Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

PubMed

Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin

2016-11-01

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Vigabatrin and lamotrigine in refractory epilepsy.

PubMed Central

Stolarek, I; Blacklaw, J; Forrest, G; Brodie, M J

1994-01-01

Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter gamma-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting > 50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy. PMID:8057114

Melatonin and childhood refractory epilepsy--a pilot study.

PubMed

Paprocka, Justyna; Dec, Renata; Jamroz, Ewa; Marszał, Elzbieta

2010-09-01

The aim of the study was to assess diurnal melatonin secretion in children with refractory epilepsy (N=74) as compared to children without epileptic seizures (N=37) and to compare melatonin secretion in children with focal and generalized refractory epilepsy. In the study group 4 subgroups were defined: children with focal symptomatic epilepsy, focal cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA method. Analysis of diurnal melatonin secretion indicated a lower level of the hormone in patients with refractory epilepsy. The daily rhythm of melatonin secretion in the study group was maintained, with a peak shift of melatonin secretion especially visible in the subgroup with generalized symptomatic refractory epilepsy in the age group between 6 months and 3 years of age. The hypothesis may be formed that a lowered level of melatonin in the study group in relation to the comparison group is the consequence of the natural course of epilepsy or is influenced by antiepileptic drugs.

Parahippocampal epilepsy with subtle dysplasia: A cause of "imaging negative" partial epilepsy.

PubMed

Pillay, Neelan; Fabinyi, Gavin C A; Myles, Terry S; Fitt, Gregory J; Berkovic, Samuel F; Jackson, Graeme D

2009-12-01

Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T(1)- and T(2)-weighted images with relative preservation of the gray-white matter boundary on T(1)-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.

Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

PubMed

Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

2014-03-01

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases.

PubMed

Verrotti, Alberto; Loiacono, Giulia; Rossi, Alessandra; Tartaro, Armando; Delli Pizzi, Andrea; Coppola, Giangennaro

2015-07-01

Schizencephaly is an uncommon malformation of cortical development. Patients with schizencephaly present with a broad range of severe neurologic symptoms including pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and it is also effective for refractory partial seizures. We report 3 cases of pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable epilepsy associated with bilateral open-lip schizencephaly and septo-optic dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the introduction of rufinamide as adjunctive drug led to a dramatic decline in the number of seizures and an improvement in EEG epileptic activity without side effects. Rufinamide seems to be efficacious and safe in patients with epileptic encephalopathies associated with pharmacoresistant epilepsy; further and larger clinical reports and controlled studies could confirm the usefulness of this anticonvulsant drug. © The Author(s) 2014.

Management of refractory epilepsy.

PubMed

Muñana, Karen R

2013-05-01

The term refractory epilepsy is utilized in veterinary medicine to describe a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional antiepileptic drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. Consequently, there is much interest in identifying ways to more effectively treat this population of animals. More than a dozen new antiepileptic drugs have been approved for humans over the last 2 decades, and several of these drugs, including gabapentin, zonisamide, levetiracetam, and pregabalin, have been evaluated for the treatment of refractory seizures in veterinary patients. Nonmedical methods to treat poorly controlled epilepsy are also being explored. The 2 alternative forms of therapy that have shown the most promise in humans with epilepsy are electrical stimulation of the brain and dietary modification, both of which have also been evaluated in dogs. This overview summarizes the available data on pharmacologic as well as nonmedical treatment options for dogs and cats with refractory epilepsy. Although many forms of therapy are currently being utilized in clinical practice, our knowledge of the safety and efficacy of these treatments is limited. Additional randomized controlled trials are needed to better evaluate these novel therapies for refractory epilepsy in dogs and cats. © 2013 Elsevier Inc. All rights reserved.

Anthropometric Indices in Children With Refractory Epilepsy.

PubMed

Aminzadeh, Vahid; Dalili, Setila; Ashoorian, Yalda; Kohmanaee, Shahin; Hassanzadeh Rad, Afagh

2016-01-01

We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy.

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

PubMed

Sabaz, M; Cairns, D R; Lawson, J A; Bleasel, A F; Bye, A M

2001-05-01

To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

PubMed

Castillo, Sergio M; Schmidt, Dieter B; White, Sarah; Shukralla, Arif

2016-11-15

Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long-term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.

Illness identity in young adults with refractory epilepsy.

PubMed

Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

2018-03-01

Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Dietary therapy is the best option for refractory nonsurgical epilepsy.

PubMed

Felton, Elizabeth A; Cervenka, Mackenzie C

2015-09-01

Ketogenic diet therapies for epilepsy have been described since the fifth century and published in scientific literature since the early 1900s. Since that time, the diet's popularity has waxed and waned as newer drugs and other treatments have been introduced. However, in recent years, dietary therapy for epilepsy has been increasingly accepted by physicians and desired by patients as an alternative to new drugs and neurostimulation. The introduction of less restrictive versions of the classic ketogenic diet, such as the modified Atkins diet (MAD), have led to increased numbers of adult patients with refractory epilepsy who are initiating dietary treatment. Approximately half of adults and children who start a ketogenic diet have a >50% seizure reduction, which is impressive given that these patients typically have medically refractory epilepsy. We believe that ketogenic dietary treatment is the best option for children and adults with refractory nonsurgical epilepsy due to its efficacy, rapid seizure reduction, synergistic effects with other antiseizure treatments, known and treatable side effects, potential to treat comorbid medical conditions, and worldwide availability. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy

PubMed Central

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine – a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and refractory cases, either as monotherapy or as adjunctive treatment. PMID:27307737

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy.

PubMed

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine - a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and refractory cases, either as monotherapy or as adjunctive treatment.

Dietary therapy is not the best option for refractory nonsurgical epilepsy.

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

The ketogenic diet (KD) is currently a well-established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow-up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

New insights into the clinical management of partial epilepsies.

PubMed

Hirsch, E; de Saint-Martin, A; Arzimanoglou, A

2000-01-01

The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of epileptic syndromes. Partial epilepsies are heterogeneous and can be divided into idiopathic, cryptogenic, and symptomatic epilepsies. The most common of the idiopathic localization-related epilepsies is benign epilepsy with rolandic or centrotemporal spikes (BECTS). Seizures remain rare and the use of antiepileptic drug (AED) treatment in all patients does not appear justified. Children who present with some of the electroclinical characteristics of BECTS may also display severe unusual neurologic, neuropsychological, or atypical symptoms. In some cases, carbamazepine has been implicated as a triggering factor. Primary reading epilepsy and idiopathic occipital lobe epilepsies with photosensitivity are examples of an overlap between idiopathic localization-related and generalized epilepsies and respond well to sodium valproate. Autosomal dominant nocturnal frontal lobe epilepsy and benign familial infantile convulsions are recently described syndromes, differing in several ways from classical idiopathic localization-related epileptic syndromes. In cryptogenic or symptomatic epilepsy, the topography of the epileptogenic zone might influence drug efficacy. An individualized approach to AED selection, tailored to each patient's needs, should be used. Resistance of seizures to antiepileptic therapy may be due to diagnostic and/or treatment error or may be the result of noncompliance. Increasing the dosage, discontinuation or replacement of a drug, or addition of a second drug is indicated in truly resistant cases. The use of more than two AEDs rarely optimizes seizure control, and in some cases reduction of treatment may improve seizure control while lessening side effects. EEG-video assessment of patients with refractory epilepsy is important. Indications for and timing of epilepsy surgery should be reconsidered. Surgical therapy should probably be used more often and earlier than it is at present.

Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

PubMed

Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

2016-03-01

Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno- and chemotherapies, with eventual partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

PubMed Central

Tang, Fei; Hartz, Anika M. S.; Bauer, Björn

2017-01-01

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy. PMID:28729850

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

PubMed

Hirsch, Lawrence J; Gaspard, Nicolas; van Baalen, Andreas; Nabbout, Rima; Demeret, Sophie; Loddenkemper, Tobias; Navarro, Vincent; Specchio, Nicola; Lagae, Lieven; Rossetti, Andrea O; Hocker, Sara; Gofton, Teneille E; Abend, Nicholas S; Gilmore, Emily J; Hahn, Cecil; Khosravani, Houman; Rosenow, Felix; Trinka, Eugen

2018-04-01

We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

PubMed

Cilio, Maria Roberta; Bianchi, Roberto; Balestri, Martina; Onofri, Alfredo; Giovannini, Simona; Di Capua, Matteo; Vigevano, Federico

2009-09-01

To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

PubMed

Ganguli, Malika P; Upton, Adrian R M; Kamath, Markad V

2017-01-01

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

Topiramate in Long-Term Treatment of Epilepsy in the Intellectually Disabled

ERIC Educational Resources Information Center

Arvio, M.; Sillanpaa, M.

2005-01-01

To study the effectiveness of topiramate (TPM) in refractory epilepsy in patients who have intellectual disability (ID). A representative population sample of 57 patients with ID (age range 261, mean 32.8) was administered add-on TPM for drug-refractory epilepsy. Results Seizure freedom for at least for 6months was attained by 10 (17%), and…

[Autism spectrum disorder and epilepsy: the role of ketogenic diet].

PubMed

Garcia-Penas, J J

2016-01-01

Between 5-40% of autistic patients will develop epilepsy. Most individuals with autism and epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. For this population, alternative treatments such as ketogenic diet (KD) can be highly efficacious and should be seriously considered. To discuss the use of the KD in refractory pediatric epilepsy and its role in patients with autism and epilepsy. KD is an effective and well-tolerated treatment for refractory childhood epilepsy, including those patients who associate autism and epilepsy. Accurate characterization of the electroclinical epilepsy syndrome is the key to deciding when to consider the KD. Otherwise, the positive effect of KD for treating mitochondrial oxidative disorders and different models of autistic animals suggest that KD could be a good alternative treatment for autistic patients. Based on the demonstrated efficacy of KD in patients who associate both epilepsy and autism, KD treatment has been recently used in the treatment of autism spectrum disorders; however, there is lacking of controlled studies to define the real efficacy of this therapy. A well designed randomized controlled study is needed to determine whether KD is really efficacious for these patients.

The ketogenic diet and other dietary treatments for refractory epilepsy in children

PubMed Central

Sharma, Suvasini; Jain, Puneet

2014-01-01

The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. PMID:25221391

Investigation of magnetic resonance imaging texture analysis as an aid tool for characterization of refractory epilepsies.

PubMed

Baldissin, Maurício Martins; Souza, Edna Marina de

2013-12-01

Refractory epilepsies are syndromes for which therapies that employ two or more antiepileptic drugs, separately or in association, do not result in control of crisis. Patients may present focal cortical dysplasia or diffuse dysplasia and/or hippocampal atrophic alterations that may not be detectable by a simple visual analysis in magnetic resonance imaging. The aim of this study was to evaluate MRI texture in regions of interest located in the hippocampi, limbic association cortex and prefrontal cortex of 20 patients with refractory epilepsy and to compare them with the same areas in 20 healthy individuals, in order to find out if the texture parameters could be related to the presence of the disease. Of the 11 texture parameters calculated, three indicated the existence of statistically significant differences between the studied groups. Such findings suggest the possibility of this technique contributing to studies of refractory epilepsies.

Treatment of depression in patients with epilepsy.

PubMed

Noe, Katherine H; Locke, Dona E C; Sirven, Joseph I

2011-08-01

In this article, we review the current best evidence for the treatment of depression in patients with epilepsy. Depression is a common epilepsy comorbidity, but it is often unrecognized. The most important step in appropriately managing mood disorders in this population is making the diagnosis. Clinical vigilance and routine use of a validated screening tool can improve detection and quality of care. As is increasingly the case for the general population, persons with epilepsy are often interested in exploring alternative therapies for chronic conditions, including depression. Unfortunately, the benefit of complementary and alternative therapies for depression currently is largely unproven for persons with a seizure history, although an early study of exercise for mild depression has shown some benefit. Concerns about drug interactions, side effects, and expense may be barriers to the prescription of antidepressant medications for people requiring chronic antiepileptic drug (AED) therapy. For this reason, use of an AED with mood-stabilizing properties has appeal and may be appropriate for selected individuals with mild depressive symptoms. Undue fear of lowering seizure threshold should not preclude the prescription of an antidepressant medication, as the perceived risks are often overestimated and rarely outweigh the risk of leaving depression untreated. At present, the best evidence for efficacy and safety support the use of citalopram, sertraline, or mirtazapine as initial pharmacotherapy, whereas bupropion should be avoided. Start low, go slow, and use the lowest effective dose. Cognitive behavioral therapy is a valuable adjunct to antidepressant therapy in this population. For people with refractory partial epilepsy and refractory depression, vagus nerve stimulation has some appeal, in that it may be beneficial for both conditions, but the efficacy of vagus nerve stimulation in improving mood in patients with epilepsy remains unclear.

Lateralizing value of unilateral relative ictal immobility in patients with refractory focal seizures--Looking beyond unilateral automatisms.

PubMed

Agarwal, Priya; Kaul, Bhavna; Shukla, Garima; Srivastava, Achal; Singh, Mamta Bhushan; Goyal, Vinay; Behari, Madhuri; Suri, Ashish; Gupta, Aditya; Garg, Ajay; Gaikwad, Shailesh; Bal, C S

2015-12-01

Ictal motor phenomena play a crucial role in the localization of seizure focus in the management of refractory focal epilepsy. While the importance of unilateral automatisms is well established, little attention is paid to the contralateral relatively immobile limb. In cases where automatisms mimic clonic or dystonic movements and in the absence of previously well-established signs, unilateral relative ictal immobility (RII) is potentially useful as a lateralizing sign. This study was carried out to examine the lateralizing value of this sign and to define its characteristics among patients of refractory focal epilepsy. VEEGs of 69 consecutive patients of refractory focal epilepsy who had undergone epilepsy surgery at our center over last four years were reviewed and analyzed for the presence of RII. Unilateral RII was defined as a paucity of movement in one limb lasting for at least 10s while the contralateral limb showed purposive or semi-purposive movements (in the absence of tonic or dystonic posturing or clonic movements in the involved limb). The findings were seen in the light of VEEG, radiological and nuclear imaging data, and with post-surgical outcome. Unilateral RII as a lateralizing sign was found in 24 of 69 patients (34.78%), consisting of both temporal and extra temporal epilepsy, with 100% concordance with VEEG and MRI data. All patients demonstrating this sign had a good post-surgical outcome. RII, when well characterized is a frequent and reliable lateralizing sign in patients of refractory focal epilepsy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

PubMed

Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

2004-12-01

Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

Evaluation of nutritional status in children with refractory epilepsy.

PubMed

Bertoli, S; Cardinali, S; Veggiotti, P; Trentani, C; Testolin, G; Tagliabue, A

2006-04-26

children affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy. 17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 +/- 3,2 years; Body Mass Index 15,7 +/- 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age. 40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) x 100] was < 60% for calcium iron and zinc. many children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care.

Sleep and Epilepsy: Strange Bedfellows No More.

PubMed

St Louis, Erik K

2011-09-01

Ancient philosophers and theologians believed that altered consciousness freed the mind to prophesy the future, equating sleep with seizures. Only recently has the bidirectional influences of epilepsy and sleep upon one another received more substantive analysis. This article reviews the complex and increasingly recognized interrelationships between sleep and epilepsy. NREM sleep differentially activates interictal epileptiform discharges during slow wave (N3) sleep, while ictal seizure events occur more frequently during light NREM stages N1 and N2. The most commonly encountered types of sleep-related epilepsies (those with preferential occurrence during sleep or following arousal) include frontal and temporal lobe partial epilepsies in adults, and benign epilepsy of childhood with centrotemporal spikes (benign rolandic epilepsy) and juvenile myoclonic epilepsy in children and adolescents. Comorbid sleep disorders are frequent in patients with epilepsy, particularly obstructive sleep apnea in refractory epilepsy patients which may aggravate seizure burden, while treatment with nasal continuous positive airway pressure often improves seizure frequency. Distinguishing nocturnal events such as NREM parasomnias (confusional arousals, sleep walking, and night terrors), REM parasomnias including REM sleep behavior disorder, and nocturnal seizures if frequently difficult and benefits from careful history taking and video-EEG-polysomnography in selected cases. Differentiating nocturnal seizures from primary sleep disorders is essential for determining appropriate therapy, and recognizing co-existent sleep disorders in patients with epilepsy may improve their seizure burden and quality of life.

Vagus Nerve Stimulation in Intractable Childhood Epilepsy: a Korean Multicenter Experience

PubMed Central

You, Su Jeong; Kang, Hoon-Chul; Kim, Heung Dong; Kim, Deok-Soo; Hwang, Yong Soon; Kim, Dong Suk; Lee, Jung-Kyo; Park, Sang Keun

2007-01-01

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved altertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events. PMID:17596651

Clinical Outcomes and Quality of Life Following Surgical Treatment for Refractory Epilepsy

PubMed Central

Liu, Shi-Yong; Yang, Xiao-Lin; Chen, Bing; Hou, Zhi; An, Ning; Yang, Mei-Hua; Yang, Hui

2015-01-01

Abstract Surgery for refractory epilepsy is widely used but the efficacy of this treatment for providing a seizure-free outcome and better quality of life remains unclear. This study aimed to update current evidence and to evaluate the effects of surgery on quality of life in patients with refractory epilepsy. A systematic review and meta-analysis of the literature were conducted and selected studies included 2 groups of refractory epilepsy patients, surgical and nonsurgical. The studies were assessed using the Newcastle–Ottawa Scale. The primary outcome was the seizure-free rate. The secondary outcome was quality of life. Adverse events were also reviewed. After screening, a total of 20 studies were selected: 8 were interventional, including 2 randomized controlled trials, and 12 were observational. All of the studies comprised 1959 patients with refractory epilepsy. The seizure-free rates were significantly higher for patients who received surgery compared with the patients who did not; the combined odds ratio was 19.35 (95% CI = 12.10–30.95, P < 0.001). After adjusting for publication bias the combined odds ratio was 10.25 (95% CI = 5.84–18.00). In both the interventional and observational studies, patients treated surgically had a significantly better quality of life compared with the patients not treated surgically. Complications were listed in 3 studies and the rates were similar in surgical and nonsurgical patients. Our meta-analysis found that for patients with refractory epilepsy, surgical treatment appears to provide a much greater likelihood of seizure-free outcome than nonsurgical treatment, although there is a need for more studies, particularly randomized studies, to confirm this conclusion. Based on more limited data, surgical treatment also appeared to provide a better quality of life and did not seem to increase complications. PMID:25674741

Epilepsy surgery in context of neurocysticercosis

PubMed Central

Singh, Gagandeep; Chowdhary, Ashwani Kumar

2014-01-01

The association between neurocysticercosis (NCC) and epilepsy is well known and NCC is an important risk factor for epileptic seizures in many Taenia solium-endemic regions of the world. However, while the relationship between NCC and epilepsy is well known, the association between NCC and medically refractory (or surgically remediable epilepsy) has received little attention in the past. Our experience and review of the sparse literature available suggests that NCC is causally related to surgically remediable epilepsy albeit uncommonly so and that association derives its underpinnings from several different scenarios: (1) Medically refractory lesional epilepsy, in which seizures arise from the vicinity of the calcified neurocysticercus lesion (CNL), (2) Medically refractory epilepsy with dual pathology type of relationship between the hippocampal sclerosis (HS) and CNL in which both have been unequivocally demonstrated to give rise to independent seizures and (3) Mesial temporal lobe epilepsy due to HS with a distantly-located CNL, which is in itself not epileptogenic. A major point of controversy revolves around whether or not there exists a causal association between the CNL and HS. We believe that an association exists between NCC and HS and the most important factor influencing this association is the location of the CNL. Furthermore, NCC is a risk factor for medically-refractory epilepsy and that this might account for a considerable proportion of the intractable epilepsy population in endemic regions; the association has been largely ignored owing to the lack of availability of presurgical work-up facilities in these regions. Finally, from a clinical standpoint of presurgical evaluation, patients with CNL and HS should be evaluated on a case by case basis owing to disparate settings underlying the association. PMID:24791092

The impact of family factors on IQ in pediatric medically refractory epilepsy.

PubMed

Puka, Klajdi; Smith, Mary Lou; Widjaja, Elysa

2017-02-01

To evaluate whether family factors were associated with intellectual functioning among children with medically refractory epilepsy, and whether family factors moderate the relationship between patient/epilepsy-related variables and intellectual functioning. Children aged 4 to 18 years with medically refractory epilepsy who were evaluated for surgical candidacy were recruited. The authors assessed the association of intellectual quotient (IQ) with patient, epilepsy, and family factors. Family factors included parental education, household income, and validated parent-report measures of family functioning, family mastery and social support, and family demands. Univariable analyses showed that higher IQ scores were associated with an older age of epilepsy onset (β = .260, p = .009), fewer antiepileptic drugs (β = .248, p = .013), a shorter duration (β = .384, p < .001) and percentage of life with epilepsy (β = .419, p < .001), unilobar epileptogenic foci relative to multilobar foci (β = .274, p = .006), and lower family demands (β = .211, p = .035). In multivariable analysis, unilobar epileptogenic foci (p = .010) and a shorter percentage of life with epilepsy (p = .001) remained significant predictors of IQ. Exploratory moderation analyses found the relationship between the extent of epileptogenic foci and IQ to be moderated by family demands (p = .004); specifically, patients with unilobar epileptogenic onset had similar IQ scores irrespective of family demands, whereas patients with multilobar foci had lower IQ scores with increasing family demands. Family factors did not have a large impact on IQ among children with medically refractory epilepsy, although the moderating effect of family demands deserves further study. Epilepsy-related factors in this patient group may weaken the link between child IQ and family factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pharmacological considerations in the use of stiripentol for the treatment of epilepsy.

PubMed

Verrotti, Alberto; Prezioso, Giovanni; Stagi, Stefano; Paolino, Maria Chiara; Parisi, Pasquale

2016-01-01

Despite the fact that more than 20 antiepileptic drugs (AEDs) are currently available, about one-third of patients still present drug resistance. Further efforts are required to develop novel and more efficacious therapeutic strategies, especially for refractory epileptic syndromes showing few and anecdotic therapeutic options. Stiripentol (STP) is a second generation AED that shows GABAergic activity, with immature brain selectivity, and an indirect metabolic action on co-administered AEDs. Two pivotal studies demonstrated STP efficacy in patients with Dravet syndrome with refractory partial seizures, and marketing authorization in Europe, Canada and Japan was granted thereafter. Post-marketing surveys reported a good efficacy and tolerability profile. In addition, interesting data is currently emerging regarding off-label experimentation of STP in other forms of epilepsy. STP is an important addition to the limited treatment options available for patients resistant to common AEDs. The possibility to inhibit seizures through the metabolic pathway of lactate dehydrogenase and the inhibitory effects on the entry of Na(+) and Ca(2+) are the most recent findings to emerge about STP and could be proof of its neuroprotective action. Moreover, its positive effects on cognitive function, its good safety and tolerability profile and the increasing data about STP efficacy on other refractory epileptic syndromes may prove to be fertile grounds for further investigation.

Clinical services for adults with an intellectual disability and epilepsy: A comparison of management alternatives.

PubMed

Wagner, Adam P; Croudace, Tim J; Bateman, Naomi; Pennington, Mark W; Prince, Elizabeth; Redley, Marcus; White, Simon R; Ring, Howard

2017-01-01

Intellectual disability (ID) is relatively common in people with epilepsy, with prevalence estimated to be around 25%. Surprisingly, given this relatively high frequency, along with higher rates of refractory epilepsy than in those without ID, little is known about outcomes of different management approaches/clinical services treating epilepsy in adults with ID-we investigate this area. We undertook a naturalistic observational cohort study measuring outcomes in n = 91 adults with ID over a 7-month period (recruited within the period March 2008 to April 2010). Participants were receiving treatment for refractory epilepsy (primarily) in one of two clinical service settings: community ID teams (CIDTs) or hospital Neurology services. The pattern of comorbidities appeared important in predicting clinical service, with Neurologists managing the epilepsy of relatively more of those with neurological comorbidities whilst CIDTs managed the epilepsy of relatively more of those with psychiatric comorbidities. Epilepsy-related outcomes, as measured by the Glasgow Epilepsy Outcome Scale 35 (GEOS-35) and the Epilepsy and Learning Disabilities Quality of Life Scale (ELDQoL) did not differ significantly between Neurology services and CIDTs. In the context of this study, the absence of evidence for differences in epilepsy-related outcomes amongst adults with ID and refractory epilepsy between mainstream neurology and specialist ID clinical services is considered. Determining the selection of the service managing the epilepsy of adults with an ID on the basis of the skill sets also required to treat associated comorbidities may hence be a reasonable heuristic.

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2001-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (January 1966 to April 2001) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1.61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available precludes any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2000-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available preclude any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats.

PubMed

Shao, Yiye; Wang, Cuicui; Hong, Zhen; Chen, Yinghui

2016-03-01

It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up-regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase (MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug (AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38MAPK could participate in drug resistance in refractory epilepsy through the regulation of P-gp. We show that the specific inhibitor of p38MAPK could down-regulate the expression of multidrug transporter (P-glycoprotein) in blood-brain barrier, increase the concentration of antiepileptic drugs in the hippocampal extracellular fluid and reduce anti-epileptic drug resistance in refractory epileptic rats. We propose that the p38MAPK signaling pathway participates in drug resistance in refractory epilepsy through the regulation of P-glycoprotein expression. © 2015 International Society for Neurochemistry.

Evaluation of nutritional status in children with refractory epilepsy

PubMed Central

Bertoli, S; Cardinali, S; Veggiotti, P; Trentani, C; Testolin, G; Tagliabue, A

2006-01-01

Background children affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy. Methods 17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 ± 3,2 years; Body Mass Index 15,7 ± 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age. Results 40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) × 100] was < 60% for calcium iron and zinc. Conclusion many children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care. PMID:16640779

Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

PubMed

McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

2013-11-27

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Pharmacological Properties of (S)-N-[(6-Chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112)

PubMed Central

McComsey, David F.; Smith-Swintosky, Virginia L.; Parker, Michael H.; Brenneman, Douglas E.; Malatynska, Ewa; White, H. Steve; Klein, Brian D.; Wilcox, Karen S.; Milewski, Michael E.; Herb, Mark; Finley, Michael F. A.; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B.; Maryanoff, Bruce E.

2014-01-01

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such “neurostabilizers” have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4–9, 10a–i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels, and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies. PMID:24205976

The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach?

PubMed

Löscher, Wolfgang

2017-07-01

Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring. More recently, it was proposed that, instead of monitoring SRS, chemical or electrical induction of acute seizures in epileptic rodents may be used as a surrogate for testing the efficacy of novel ASDs against refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute seizures, when such seizures were induced by pentylenetetrazole (PTZ) in epileptic rather than nonepileptic rats, whereas this was not observed when using the maximal electroshock seizure test. Subsequent studies confirmed the loss of anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic mice, but several other ASDs were more potent against PTZ in epileptic than nonepileptic mice. This was also observed when using the 6-Hz model of partial seizures in epileptic mice, in which the potency of levetiracetam, in particular, was markedly increased compared to nonepileptic animals. Overall, these observations suggest that performing acute seizure tests in epileptic rodents provides valuable information on the pharmacological profile of ASDs, in particular those with mechanisms inherent to disease-induced brain alterations. However, it appears that further work is needed to define optimal approaches for acute seizure induction and generation of epileptic/drug refractory animals that would permit reliable screening of new ASDs with improved potential to provide seizure control in patients with pharmacoresistant epilepsy.

Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

PubMed Central

Lerner, Jason T; Salamon, Noriko; Sankar, Raman

2010-01-01

Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk. PMID:21127692

The social context and the need of information from patients with epilepsy: evaluating a tertiary referral service.

PubMed

Freitas-Lima, Priscila; Monteiro, Edna Almeida; Macedo, Lígia Ribeiro Horta; Funayama, Sandra Souza; Ferreira, Flávia Isaura Santi; Matias Júnior, Ivair; Angelis, Geisa; Nogueira, Adriana Maria Arantes; Alexandre, Veriano; Velasco, Tonicarlo Rodrigues; Pinheiro-Martins, Ana Paula; Sakamoto, Américo Ceiki

2015-04-01

Characterize the social profile and the need of information from patients with refractory epilepsy. A semi-structured questionnaire was applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy and any doubts about epilepsy. Patients were highly dependent on having a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the population was unemployed, and 26% confirmed receiving social security benefits due to epilepsy. Twenty-nine percent of the population reached high school. Eighty-five percent of the patients had at least one doubt about epilepsy; treatment and epilepsy aspects in general were the main topics. As observed in developed countries, patients with refractory epilepsy from a developing country also have high rates of unemployment and low educational levels. The results raise a concern about the need of information about epilepsy by patients and their families, urging the necessity to invest in strategies to solve this deficiency in knowledge.

Response to Early AED Therapy and Its Prognostic Implications

PubMed Central

French, Jacqueline A.

2002-01-01

Determining the prognosis of patients when they first present with epilepsy is a difficult task. Several clinical studies have shed light on this very important topic. Potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome. One predictor of the refractory state appears to be early response to AED therapy. Inadequate seizure control after initial treatment is a poor prognostic sign. Recent research into genetic causes of the refractory state has included investigation of the multiple drug resistance gene, and polymorphisms at drug targets. More work is needed to determine the causes and predictors of drug resistance. PMID:15309146

Stimulation of the bilateral anterior nuclei of the thalamus in the treatment of refractory epilepsy: two cases of subcortical band heterotopia.

PubMed

Franco, Ana; Pimentel, José; Campos, Alexandre Rainha; Morgado, Carlos; Pinelo, Sara; Ferreira, António Gonçalves; Bentes, Carla

2016-12-01

Subcortical band heterotopia is a neuronal migration disorder that may cause refractory epilepsy. In these patients, resective surgery has yielded inadequate results. Deep brain stimulation of the anterior nuclei of the thalamus has been used for the treatment of refractory epilepsy with good results. We describe the first two patients with subcortical band heterotopia who were submitted to deep brain stimulation of the anterior nuclei of the thalamus, with evaluation of seizure outcome after 12 and 18 months of follow-up. At these times, both showed a >50% decrease in seizure frequency and an increase in seizure freedom. Both patients had a depressive syndrome after surgery that responded fully to anti-depressive medication in one patient and partly in the other. In both, deep brain stimulation of the anterior nuclei of the thalamus was associated with good seizure outcome. This procedure can therefore be considered in the treatment of patients with subcortical band heterotopia and refractory epilepsy. Depression may be a transient adverse event of the surgery or stimulation, however, its aetiology is probably multifactorial.

Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy.

PubMed

Muramatsu, Kazuhiro; Sawaura, Noriko; Ogata, Tomomi; Makioka, Nishiki; Tomita, Keiko; Motojima, Toshino; Ida, Kuniko; Hazama, Kyoko; Arakawa, Hirokazu

2017-03-01

Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status. Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA.

PubMed

Villanueva, Vicente; López-Gomáriz, Elena; López-Trigo, Javier; Palau, Juan; García, Manuel; Villarroya, Teresa; Bonet, Macarena; Santafé, Consuelo

2012-03-01

There has been little long-term success with polytherapy for patients with refractory partial-onset epilepsy. The rational combination of antiepileptic drugs based on their mechanism of action may help improve treatment efficacy and tolerability. Lacosamide, a novel sodium channel blocker (SCB), was investigated in 158 patients with partial-onset epilepsy in the prospective, multicenter, observational, RELACOVA cohort study conducted in Spain. After 12 months' treatment with lacosamide, 47% of patients were responders (≥50% reduction in seizure frequency) and 24% were seizure free. Lacosamide was well tolerated; dizziness was the most frequent adverse event. Efficacy was better (responder rate, 65% vs 38%; seizure free rate, 35% vs 17%) and there was a lower adverse event rate (33% vs 58%) in patients receiving non-SCBs (n=49) versus those receiving SCBs (n=104) as concomitant therapy at baseline. Further investigation of lacosamide combination therapy is warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Leading up to saying "yes": A qualitative study on the experience of patients with refractory epilepsy regarding presurgical investigation for resective surgery.

PubMed

Shih, Patti; Nikpour, Armin; Bleasel, Andrew; Herkes, Geoffrey; Mitchell, Rebecca; Seah, Rebecca; Mumford, Virginia; Braithwaite, Jeffrey; Vagholkar, Sanjyot; Rapport, Frances

2018-06-01

Adult patients with refractory epilepsy who are potential candidates for resective surgery undergo a period of presurgical investigation in tertiary epilepsy centers (TECs), where they engage extensively with healthcare professionals and receive a range of treatment-related information. This qualitative study aimed to examine the experiences of adult patients with refractory epilepsy leading up to and during presurgical investigation and how their perceptions of resective surgery are shaped. In-depth interviews with 12 patients and six epilepsy specialist clinicians and 12 observations of routine patient-clinician consultations took place at two TECs in Sydney, Australia. Data were thematically analyzed via group work. Patients reflected on prior experiences of poor seizure control and inadequate antiepileptic drug management and a lack of clarity about their condition before referral to tertiary care. Poor continuity of care and disrupted care transitions affected patients from regional locations. Tertiary referral increased engagement with personalized information about refractory epilepsy, which intensified during presurgical assessments with additional hospital visits and consultations. Experiential information, such as testimonials of other patients, influenced perceptions of surgery and fostered more trust and confidence towards healthcare professionals. Qualitative inquiry detailed multifaceted effects of information on patients' overall treatment trajectory and experience of healthcare. Earlier patient identification for surgical assessments should be accompanied by access to good quality information at primary and community care levels and strengthened referral processes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Paroxysmal events during prolonged video-video electroencephalography monitoring in refractory epilepsy.

PubMed

Sanabria-Castro, A; Henríquez-Varela, F; Monge-Bonilla, C; Lara-Maier, S; Sittenfeld-Appel, M

2017-03-16

Given that epileptic seizures and non-epileptic paroxysmal events have similar clinical manifestations, using specific diagnostic methods is crucial, especially in patients with drug-resistant epilepsy. Prolonged video electroencephalography monitoring during epileptic seizures reveals epileptiform discharges and has become an essential procedure for epilepsy diagnosis. The main purpose of this study is to characterise paroxysmal events and compare patterns in patients with refractory epilepsy. We conducted a retrospective analysis of medical records from 91 patients diagnosed with refractory epilepsy who underwent prolonged video electroencephalography monitoring during hospitalisation. During prolonged video electroencephalography monitoring, 76.9% of the patients (n=70) had paroxysmal events. The mean number of events was 3.4±2.7; the duration of these events was highly variable. Most patients (80%) experienced seizures during wakefulness. The most common events were focal seizures with altered levels of consciousness, progressive bilateral generalized seizures and psychogenic non-epileptic seizures. Regarding all paroxysmal events, no differences were observed in the number or type of events by sex, in duration by sex or age at onset, or in the number of events by type of event. Psychogenic nonepileptic seizures were predominantly registered during wakefulness, lasted longer, started at older ages, and were more frequent in women. Paroxysmal events recorded during prolonged video electroencephalography monitoring in patients with refractory epilepsy show similar patterns and characteristics to those reported in other latitudes. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

Epilepsy Surgery for Individuals with TSC

MedlinePlus

... AC, van der Grond J (2003) Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber ... tuberous sclerosis complex. Epilepsy Behav 20:561-565 Shields WD (2004) Surgical Treatment of Refractory Epilepsy. Curr ...

The effectiveness and safety of lacosamide in children with epilepsy in a clinical practice setting.

PubMed

Sanmartí-Vilaplana, Francesc; Díaz-Gómez, Asunción

2018-02-01

Seizures in up to 30% of children with epilepsy become refractory to treatment, decreasing their quality of life. Studies suggest that lacosamide may be effective in pediatric patients with refractory epilepsy. To assess the effectiveness and safety of lacosamide in a population of children with mostly focal refractory epilepsy. Retrospective analysis of children aged <18years presenting to a single hospital in Spain. Data from baseline, and 3, 6, and 12months after lacosamide initiation were collected and analyzed. Response to lacosamide was categorized by seizure frequency (seizure freedom or ≥75%, ≥50%, and <50% reduction in seizures). One hundred ninety-one pediatric patients (~55% male) with focal epilepsy treated with lacosamide were included. The mean age at lacosamide initiation was 9.4years, and the mean duration of epilepsy was 5.4years. Seizure-free rates at 3, 6, and 12months were 9.7%, 11.8%, and 16.0%. At 12months, 44.4% of the population had a ≥50% reduction in seizure frequency. When analyzing response according to the number of previous/concomitant AEDs, those patients who received ≤2 previous AEDs/fewer concomitant AEDs had significantly greater response rates than those who received greater numbers of previous/concomitant AEDs; however, no predictive factors for response were identified. The most common adverse events were seizure number increased (14.7%), diplopia (5.2%), dizziness (3.7%), ataxia (2.1%), and drowsiness (2.1%). Lacosamide use in children with refractory focal epilepsy can result in a reduction in seizure rate that improves progressively over time with few adverse effects, making lacosamide a promising option in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Developing the Pediatric Refractory Epilepsy Questionnaire: a pilot study.

PubMed

Purusothaman, Vaishnavi; Ryther, Robin C C; Bertrand, Mary; Harker, Lisa A; Jeffe, Donna B; Wallendorf, Michael; Smyth, Matthew D; Limbrick, David D

2014-08-01

Up to 14% of children with epilepsy continue to experience seizures despite having appropriate medical therapy and develop medically refractory epilepsy (MRE). Assessing clinical outcomes and therapeutic efficacy in children with MRE undergoing palliative epilepsy surgery has been challenging because of the lack of a quantitative instrument capable of estimating the clinical status of these patients. The ideal instrument would at once consider seizure control, neurodevelopment, caregiver burden, and quality of life. The purpose of this study was to develop and pilot the Pediatric Refractory Epilepsy Questionnaire (PREQ), a quantitative instrument to assess the severity and individual burden of epilepsy in children with MRE undergoing palliative epilepsy treatments. The caregivers of 25 patients with MRE completed the PREQ and the Quality of Life in Childhood Epilepsy (QOLCE) measure and participated in a semistructured interview. Medical records of the patients were reviewed, an Early Childhood Epilepsy Severity Scale (E-CHESS) score was calculated, and a Global Assessment of Severity of Epilepsy (GASE) score was obtained for each patient. The initial PREQ was modified based on the analysis of responses, association with previously validated scales, comments from caregivers, and expertise of the PREQ panelists. Pediatric Refractory Epilepsy Questionnaire subscale scores were calculated based on clinical paradigm and compared with independent measures of seizure severity and quality of life. Significant correlations were observed between the seizure severity subscale and the GASE score (r=0.55) and between the mood subscale and the well-being score (r=0.61) on the QOLCE. Significant correlations were also observed between the caregiver rating of seizure severity and the GASE score (r=0.53), the social activity score (r=0.57), and the behavior score (r=0.43) on the QOLCE. Correlations between the caregiver rating of quality of life and the quality of life score (r=0.58) and the number of AEDs used (r=0.45) were also significant. This pilot study is an initial, critical step in the development of the PREQ. The significant correlations between the PREQ subscales and the external epilepsy severity and quality of life measures lend preliminary support to our hypothesis that the PREQ is assessing the severity of epilepsy along with other important domains, such as mood, neurodevelopment, and quality of life. A larger prospective study of this modified PREQ is currently underway to further develop the PREQ. Copyright © 2014 Elsevier Inc. All rights reserved.

Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

PubMed

Morrell, Martha J

2011-09-27

This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Video electroencephalogram telemetry in temporal lobe epilepsy

PubMed Central

Mani, Jayanti

2014-01-01

Temporal lobe epilepsy (TLE) is the most commonly encountered medically refractory epilepsy. It is also the substrate of refractory epilepsy that gives the most gratifying results in any epilepsy surgery program, with a minimum use of resources. Correlation of clinical behavior and the ictal patterns during ictal behavior is mandatory for success at epilepsy surgery. Video electroencephalogram (EEG) telemetry achieves this goal and hence plays a pivotal role in pre-surgical assessment. The role of telemetry is continuously evolving with the advent of digital EEG technology, of high-resolution volumetric magnetic resonance imaging and other functional imaging techniques. Most of surgical selection in patients with TLE can be done with a scalp video EEG monitoring. However, the limitations of the scalp EEG technique demand invasive recordings in a selected group of TLE patients. This subset of the patients can be a challenge to the epileptologist. PMID:24791089

Need for surgical treatment of epilepsy and excision of tumors and post-traumatic epileptogenic lesions in Kinshasa, RDC.

PubMed

Ntsambi-Eba, G; Beltchika Kalubye, A; Kalala Okito, J P

2017-11-01

Surgery is a treatment to consider in epilepsy when the condition is refractory or epileptic events are related to a clearly identified brain abnormality. The tropical climate of the DRC explains the high risk of epilepsy and the potentially large number of refractory cases. The number of patients with epilepsy in Kinshasa is estimated to be at least 120 000, and almost one third may be refractory. Hence, the need to integrate the use of surgery in the treatment of this disease. Most neurosurgical techniques used for treating epilepsy are practiced with a neurosurgical microscope and neuronavigation. In most developing countries, neither the material conditions for optimum realization of these surgical techniques nor the equipment for epilepsy investigation are close to fully available. Nonetheless, the selection of a large number of patients for surgery often does not require the use of all these explorations.The current availability in Kinshasa of the equipment for the basic investigation of epilepsy, such as EEG and MRI instruments, and the experience of the local neurological/neurosurgical team together make it possible to diagnose this pathology and treat it surgically when necessary. The creation of a multidisciplinary team for epilepsy will enable the selection of candidates who can most effectively benefit from surgical treatment. This surgery should focus initially on well circumscribed lesions that do not require sophisticated methods of investigation and can be removed relatively easily, with a high probability of seizure suppression.

Outcome after temporal lobectomy in patients with medically-refractory mesial temporal epilepsy in Iran.

PubMed

Asadi-Pooya, Ali A; Rakei, Seyed M; Kamgarpour, Ahmad; Taghipour, Mousa; Ashjazadeh, Nahid; Razmkon, Ali; Zare, Zahra; Bagheri, Mohammad H

2017-06-01

Epilepsy surgery has been proved to be feasible and cost-effective in developing countries. In the current paper, we discussed the outcome of patients with mesial temporal lobe epilepsy (MTLE) and medically-refractory seizures who had surgery at our center in Shiraz, Iran. Patients aged 18 years and older with refractory MTLE and mesial temporal sclerosis operated at Namazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran from May 2009 through December 2011 were enrolled. Presurgical evaluation included clinical history, neurological examination, 2-hour video-EEG recording, and 1.5-T MRI. All patients were submitted to standard temporal lobectomy at the side determined by MRI and video-EEG. Twenty-two patients (12 women and 10 men) underwent surgery between May 2009 and December 2011. All patients were followed postoperatively for at least 12 months (mean=24.8±7.7 months; minimum=12 months; maximum=36 months). At the last follow-up visit, 18 patients (81.8%) had a good outcome (15 patients [68.2%] had Engel class 1 and three others had Engel class 2). The total cost of presurgical evaluation and epilepsy surgery at our center was less than $500. Resources are limited for the vast majority of medically-refractory patients with epilepsy who live in the developing countries. However, it is feasible to select good surgical candidates for anterior temporal lobectomy relying on the clinical history and examination, MRI and interictal EEG. Broader application of epilepsy surgery should be encouraged in countries with limited financial resources.

Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

PubMed

Pedreira, C; Vaudano, A E; Thornton, R C; Chaudhary, U J; Vulliemoz, S; Laufs, H; Rodionov, R; Carmichael, D W; Lhatoo, S D; Guye, M; Quian Quiroga, R; Lemieux, L

2014-10-01

Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Do gene polymorphism in IL-1β, TNF-α and IL-6 influence therapeutic response in patients with drug refractory epilepsy?

PubMed

Tiwari, Prabhakar; Dwivedi, Rekha; Mansoori, Nasim; Alam, Rizwan; Chauhan, Ugam Kumari; Tripathi, Manjari; Mukhopadhyay, Asok Kumar

2012-09-01

Pro-inflammatory cytokines may play an important pathophysiological role in patients with epilepsy. To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1β-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy. The comparative frequency of polymorphism was determined in rs16944, rs1800629 and rs1800795 using PCR-RFLP in a group of 120 persons with epilepsy (PWE) and 110 ethnically matched healthy subjects of comparable age and sex in the North Indian population. Alleles and genotypes of rs16944, rs1800629 and rs1800795 were not found to influence the odds ratio of having susceptibility to epilepsy. Also gene-gene interaction of possible nine combinations of these genes did not show any positive association with epilepsy. The genotype and allelic frequency of rs1800795 showed a significant association (p<0.05) in seizure frequency (number of seizures/6-months) and drug refractory epilepsy. However, the genotype and allelic frequency of rs16944 and rs1800629 were not found to have such effect. This study demonstrates that the rs16944, rs1800629 and rs1800795 polymorphism does not act as a strong susceptibility factor for epilepsy in North Indian population. The genotypic association of rs1800795 with seizure frequency and drug-refractory epilepsy raises the issue that a specific set of polymorphic genes can influence seizures and therapeutic response in epilepsy. Copyright © 2012 Elsevier B.V. All rights reserved.

Reasons for uncontrolled seizures in adults; the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas

2013-05-01

We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Comparing neurostimulation technologies in refractory focal-onset epilepsy.

PubMed

Gooneratne, Inuka Kishara; Green, Alexander L; Dugan, Patricia; Sen, Arjune; Franzini, Angelo; Aziz, Tipu; Cheeran, Binith

2016-11-01

For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5 years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Peri-ictal ECG changes in childhood epilepsy: implications for detection systems.

PubMed

Jansen, Katrien; Varon, Carolina; Van Huffel, Sabine; Lagae, Lieven

2013-10-01

Early detection of seizures could reduce associated morbidity and mortality and improve the quality of life of patients with epilepsy. In this study, the aim was to investigate whether ictal tachycardia is present in focal and generalized epileptic seizures in children. We sought to predict in which type of seizures tachycardia can be identified before actual seizure onset. Electrocardiogram segments in 80 seizures were analyzed in time and frequency domains before and after the onset of epileptic seizures on EEG. These ECG parameters were analyzed to find the most informative ones that can be used for seizure detection. The algorithm of Leutmezer et al. was used to find the temporal relationship between the change in heart rate and seizure onset. In the time domain, the mean RR shows a significant difference before compared to after onset of the seizure in focal seizures. This can be observed in temporal lobe seizures as well as frontal lobe seizures. Calculation of mean RR interval has a high specificity for detection of ictal heart rate changes. Preictal heart rate changes are observed in 70% of the partial seizures. Ictal heart rate changes are present only in partial seizures in this childhood epilepsy study. The changes can be observed in temporal lobe seizures as well as in frontal lobe seizures. Heart rate changes precede seizure onset in 70% of the focal seizures, making seizure detection and closed-loop systems a possible therapeutic alternative in the population of children with refractory epilepsy. © 2013.

Lacosamide as adjunctive therapy in refractory epilepsy in adults: a systematic review.

PubMed

Paquette, Vanessa; Culley, Celia; Greanya, Erica D; Ensom, Mary H H

2015-02-01

To review the evidence for efficacy and safety of lacosamide in adult patients with refractory epilepsy and refractory status epilepticus (RSE). A systematic literature search of MEDLINE, PubMed, EMBASE, IPA, Google and Google Scholar (through October 2014) was performed. Fourteen studies assessing lacosamide in 3509 refractory epilepsy patients were included. In 3 RCTs, more patients had at least 50% reduction in seizure frequency with lacosamide compared to placebo with 38.3-41.1%, 38.1-41.2%, and 18.3-25.8%, in the 400 mg/day, 600 mg/day, and placebo groups, respectively. In non-comparative trials, 18-69% of patients achieved at least 50% reduction in seizure frequency, and 1.7-26.2% achieved seizure freedom. Non-responders were documented in two trials, with 26.2-34% having no response. Thirteen studies assessing lacosamide in 390 RSE patients were included. When assessing lacosamide's ability to terminate RSE, one comparative cohort study found no improvement in SE duration or seizure control with addition of lacosamide. Another study documented no difference compared to use of phenytoin. Eleven descriptive studies using lacosamide as add-on RSE therapy revealed seizure termination rates of 0-100% (median 64.7%). In all patients receiving lacosamide, dizziness (21.8%), vision disturbances (10.4%), drowsiness (7.4%), headache (7.0%), nausea (6.5%), and coordination problems (5.8%) were the most common adverse effects. Based on evidence to date, adjunctive lacosamide is a treatment option to reduce seizure frequency in patients with refractory epilepsy and terminate seizures in patients with RSE. The safety information summary can be used to advise patients of potential adverse effects. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy.

PubMed

Klinger, Neil V; Mittal, Sandeep

2016-01-01

Epilepsy affects 50 million people worldwide and about 30% of these patients will not be adequately controlled with antiepileptic drugs (AEDs) alone. For patients where resective surgery is not indicated, deep brain stimulation (DBS) may be an effective alternative. The majority of available literature targets the thalamic nuclei (anterior; centromedian), subthalamic nucleus, hippocampus, and cerebellum. Here, we review patient outcomes and adverse events related to DBS to these various targets. Data show DBS may be a safe and effective treatment option for refractory epilepsy. Copyright © 2015. Published by Elsevier B.V.

Detection of Focal Cortical Dysplasia Lesions in MRI Using Textural Features

NASA Astrophysics Data System (ADS)

Loyek, Christian; Woermann, Friedrich G.; Nattkemper, Tim W.

Focal cortical dysplasia (FCD) is a frequent cause of medically refractory partial epilepsy. The visual identification of FCD lesions on magnetic resonance images (MRI) is a challenging task in standard radiological analysis. Quantitative image analysis which tries to assist in the diagnosis of FCD lesions is an active field of research. In this work we investigate the potential of different texture features, in order to explore to what extent they are suitable for detecting lesional tissue. As a result we can show first promising results based on segmentation and texture classification.

The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy.

PubMed

Steinhoff, Bernhard J; Somerville, Ernest R; Van Paesschen, Wim; Ryvlin, Philippe; Schelstraete, Isabelle

2007-08-01

The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study aimed to evaluate the safety and efficacy of levetiracetam (Keppra, LEV) as add-on therapy for refractory partial seizures in clinical practice. This Phase IV, 16-week, open-label study recruited patients > or =16-year old with treatment-resistant partial seizures. LEV (1000 mg/day) was added to a stable concomitant antiepileptic drug regimen. LEV dosage was adjusted based on seizure control and tolerability to a maximum of 3000 mg/day. 1541 patients (intent-to-treat population) were recruited including 1346 (87.3%) who completed the study and 77.0% who declared further continuing on LEV after the trial. Overall, 50.5% of patients reported at least one adverse event that was considered related to LEV treatment. The most frequently reported drug-related adverse events were mild-to-moderate somnolence, fatigue, dizziness and headache. Serious adverse events considered related to LEV occurred in 1.0% of patients. 7.5% of patients reported adverse events as the most important reason for study drug discontinuation. The median reduction from baseline in the frequency of all seizures was 50.2%; 15.8% of patients were seizure free; 50.1% had seizure frequency reduction of > or =50%. At the end of the study, 60.4% of patients were considered by the investigator to show marked or moderate improvement. There was a significant improvement in health-related quality of life as assessed with the QOLIE-10-P (total score increasing from 55.6 to 61.6; p<0.001). This community-based study suggests that LEV is well tolerated and effective as add-on therapy for refractory partial seizures in adults. These data provide supportive evidence for the safety and efficacy of LEV demonstrated in the pivotal Phase III placebo-controlled studies.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis

PubMed Central

Wilfong, Angus A.; Mays, Maxwell; Talley, Christina M.; Agricola, Karen; Tudor, Cindy; Capal, Jamie; Holland-Bouley, Katherine; Franz, David Neal

2016-01-01

Objective: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). Methods: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. Results: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. Conclusions: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. Classification of evidence: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control. PMID:27815402

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy.

PubMed

Kim, Jon Soo; Kim, Hunmin; Lim, Byung Chan; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Hwang, Hee

2014-06-01

To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients' epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2-17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1-6) and the mean duration of follow-up was 10.1 (range, 6.1-13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4-9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Left Frontal Meningioangiomatosis Associated with Type IIIc Focal Cortical Dysplasia Causing Refractory Epilepsy and Literature Review.

PubMed

Roux, Alexandre; Mellerio, Charles; Lechapt-Zalcman, Emmanuelle; Still, Megan; Zerah, Michel; Bourgeois, Marie; Pallud, Johan

2018-06-01

We report the surgical management of a lesional drug-resistant epilepsy caused by a meningioangiomatosis associated with a type IIIc focal cortical dysplasia located in the left supplementary motor area in a young male patient. A first anatomically based partial surgical resection was performed on an 11-year-old under general anesthesia without intraoperative mapping, which allowed for postoperative seizure control (Engel IA) for 6 years. The patient then exhibited intractable right sensatory and aphasic focal onset seizures despite 2 appropriate antiepileptic drugs. A second functional-based surgical resection was performed using intraoperative corticosubcortical functional mapping with direct electrical stimulation under awake conditions. A complete surgical resection was performed, and a left partial supplementary motor area syndrome was observed. At 6 months postoperatively, the patient is seizure free (Engel IA) with an ongoing decrease in antiepileptic drug therapy. Intraoperative functional brain mapping can be applied to preserve the brain function and networks around a meningioangiomatosis to facilitate the resection of potentially epileptogenic perilesional dysplastic cortex and to tailor the extent of resection to functional boundaries. Copyright © 2018 Elsevier Inc. All rights reserved.

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Does surgery help in reducing stigma associated with drug refractory epilepsy in children?

PubMed

Bajaj, Jitin; Tripathi, Manjari; Dwivedi, Rekha; Sapra, Savita; Gulati, Sheffali; Garg, Ajay; Tripathi, Madhavi; Bal, Chandra S; Chandra, Sarat P

2018-03-01

Epilepsy has several comorbidities and associated stigma. Stigma associated with epilepsy is well known and prevalent worldwide. Surgical treatment is an established treatment for drug refractory epilepsy. Following surgery in children, it is possible that the stigma may reduce, but such an effect has not been studied earlier. Analysis of prospectively collected data was performed for pediatric patients at a single tertiary center for treating epilepsy. Child stigma scale, as described by Austin et al., was used to evaluate stigma both pre- and postoperatively. Analysis was done using Paired t test. In this study, following surgery, there was significant reduction of stigma (P<0.001). This was proportional to the reduction in seizures, though there were 9 (30%) patients, who due to persistent neurodisability did not have any reduction of stigma despite having good seizure outcome. Surgery in drug-resistant epilepsy helps in reducing stigma. Seizure reduction is probably not the only factor responsible for a change in stigma outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

PubMed

Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

2010-11-01

Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be relatively common, and not typically associated with hippocampal sclerosis, is an appropriate target for contemporary approaches to complex disorders such as genome-wide association studies for common genetic variants or deep sequencing for rare variants.

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PubMed

Uthman, Basim M; Bazil, Carl W; Beydoun, Ahmad; Schulze-Bonhage, Andreas; Benabou, Reina; Whalen, Ed; Emir, Birol; Griesing, Teresa; Leon, Teresa

2010-06-01

To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Getting the best outcomes from epilepsy surgery

PubMed Central

Vakharia, Vejay N.; Witt, Juri‐Alexander; Elger, Christian E.; Staba, Richard; Engel, Jerome

2018-01-01

Neurosurgery is an underutilized treatment that can potentially cure drug‐refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug‐refractory focal epilepsies. Ann Neurol 2018;83:676–690 PMID:29534299

[Rational combinations of antiepileptic drugs for refractory epilepsy].

PubMed

Yoshino, Aihide

2011-04-01

Although epilepsy surgery is most effective for patients with intractable epilepsy, a majority of them is not eligible for the surgery. Most of patients with refractory epilepsy are eventually treated with polypharmacy in hope of seizure control. Therefore, rational combinations of antiepileptic drugs are needed to control intractable seizures. Drug combinations should be rationally chosen based on the evidence of synergic efficacy and on avoidance of neurotoxicity. Several clinical studies suggest that the combination of valproate with lamotrigine has synergic antiepileptic effect. It has also been reported that the combination of carbamazepine with lamotrigine paradoxically decreases efficacy and increases toxicity. Animal studies using isobolography suggest that the combinations of topiramate with lamotrigine or levetiracetam are also promising on both seizure control and neurotoxicity. Clinical research is needed to examine these combinations.

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

PubMed

Hausman-Kedem, Moran; Menascu, Shay; Kramer, Uri

2018-04-16

The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d. Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation. Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports. Randomized controlled trials are necessary to assess its true efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Heart rate changes in partial seizures: analysis of influencing factors among refractory patients

PubMed Central

2014-01-01

Background We analyzed the frequency of heart rate (HR) changes related to seizures, and we sought to identify the influencing factors of these changes during partial seizures, to summarize the regularity of the HR changes and gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. To date, detailed information on influencing factors of HR changes related to seizures by multiple linear regression analysis remains scarce. Methods Using video-electroencephalograph (EEG)-electrocardiograph (ECG) recordings, we retrospectively assessed the changes in the HR of 81 patients during a total of 181 seizures, including 27 simple partial seizures (SPS), 110 complex partial seizures (CPS) and 44 complex partial seizures secondarily generalized (CPS-G). The epileptogenic focus and the seizure type, age, gender, and sleep/wakefulness state of each patient were evaluated during and after the seizure onset. The HR changes were evaluated in the stage of epilepsy as time varies. Results Of the 181 seizures from 81 patients with ictal ECGs, 152 seizures (83.98%) from 74 patients were accompanied by ictal tachycardia (IT). And only 1 patient was accompanied by ictal bradycardia (IB). A patient has both IT and IB. We observed that HR difference was independently correlated with side, type and sleep/wakefulness state. In this analysis, the HR changes were related to the side, gender, seizure type, and sleep/wakefulness state. Right focus, male, sleep, and CPS-G showed more significant increases than that were observed in left, female, wakefulness, SPS and CPS. HR increases rapidly within 10 seconds before seizure onset and ictus, and typically slows to normal with seizure offset. Conclusion CPS-G, sleep and right focus led to higher ictal HR. The HR in the stage of epilepsy has regularly been observed to change to become time-varying. The risk factors of ictal HR need to be controlled along with sleep, CPS-G and right focus. Our study first explains that the HR in seizures has a regular evolution varying with time. Our study might help to further clarify the basic mechanisms of interactions between heart and brain, making seizure detection and closed-loop systems a possible therapeutic alternative in refractory patients. PMID:24950859

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

PubMed

Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

2015-09-01

Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Initial experience with SPECT imaging of the brain using I-123 p-iodoamphetamine in focal epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaManna, M.M.; Sussman, N.M.; Harner, R.N.

1989-06-01

Nineteen patients with complex partial seizures refractory to medical treatment were examined with routine electroencephalography (EEG), video EEG monitoring, computed tomography or magnetic resonance imaging, neuropsychological tests and interictal single photon emission computed tomography (SPECT) with I-123 iodoamphetamine (INT). In 18 patients, SPECT identified areas of focal reduction in tracer uptake that correlated with the epileptogenic focus identified on the EEG. In addition, SPECT disclosed other areas of neurologic dysfunction as elicited on neuropsychological tests. Thus, IMP SPECT is a useful tool for localizing epileptogenic foci and their associated dynamic deficits.

Epileptic seizure predictors based on computational intelligence techniques: a comparative study with 278 patients.

PubMed

Alexandre Teixeira, César; Direito, Bruno; Bandarabadi, Mojtaba; Le Van Quyen, Michel; Valderrama, Mario; Schelter, Bjoern; Schulze-Bonhage, Andreas; Navarro, Vincent; Sales, Francisco; Dourado, António

2014-05-01

The ability of computational intelligence methods to predict epileptic seizures is evaluated in long-term EEG recordings of 278 patients suffering from pharmaco-resistant partial epilepsy, also known as refractory epilepsy. This extensive study in seizure prediction considers the 278 patients from the European Epilepsy Database, collected in three epilepsy centres: Hôpital Pitié-là-Salpêtrière, Paris, France; Universitätsklinikum Freiburg, Germany; Centro Hospitalar e Universitário de Coimbra, Portugal. For a considerable number of patients it was possible to find a patient specific predictor with an acceptable performance, as for example predictors that anticipate at least half of the seizures with a rate of false alarms of no more than 1 in 6 h (0.15 h⁻¹). We observed that the epileptic focus localization, data sampling frequency, testing duration, number of seizures in testing, type of machine learning, and preictal time influence significantly the prediction performance. The results allow to face optimistically the feasibility of a patient specific prospective alarming system, based on machine learning techniques by considering the combination of several univariate (single-channel) electroencephalogram features. We envisage that this work will serve as benchmark data that will be of valuable importance for future studies based on the European Epilepsy Database. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development of perampanel in epilepsy.

PubMed

Satlin, A; Kramer, L D; Laurenza, A

2013-01-01

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors play a key role in mediating glutamatergic transmission in the cortex. Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile) is a potent, orally active, highly selective, non-competitive AMPA-type glutamate receptor antagonist, identified via a focused discovery program at Eisai Research Laboratories. Development of perampanel as adjunctive therapy for the treatment of partial-onset seizures was planned in keeping with regulatory guidance and guidelines on antiepileptic drug (AED) development. This is the first AED with a specific action on glutamate-mediated excitatory neurotransmission to show evidence of efficacy and tolerability in reducing treatment-refractory partial-onset seizures in Phase III clinical trials. Perampanel (Fycompa(®)) has been approved in the EU and the United States for adjunctive treatment of partial-onset seizures. © 2013 John Wiley & Sons A/S.

Epilepsy surgery and neurocysticercosis: Assessing the role of the cysticercotic lesion in medically-refractory epilepsy.

PubMed

Escalaya, Alejandro L; Burneo, Jorge G

2017-11-01

There is increasing evidence of the existence of refractoriness to treatment with antiepileptic medications in those with NCC-related epilepsy. We performed a systematic review with the objective to determine the role of a cysticercotic lesion in this group of patients. We sought those manuscripts, including case reports, describing patients with NCC-related medically-intractable epilepsy who underwent epilepsy surgery and were seizure-free a year after. Only 10 manuscripts fulfilled inclusion and exclusion criteria. Three different clinical presentations were identified: 1) the cysticercotic lesion was epileptogenic, 2) there was dual pathology, including the cysticercotic lesion, with the other lesion usually being hippocampal sclerosis, and 3) the cysticercotic lesion was not related to the epileptogenic focus. In the case of an epileptogenic cysticercotic lesion, the presence of gliosis appeared to be the culprit for epileptogenicity. More studies using large cohorts of patients might be able to confirm our findings. This article is part of a Special issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Iterative Structural and Functional Synergistic Resolution Recovery (iSFS-RR) Applied to PET-MR Images in Epilepsy

NASA Astrophysics Data System (ADS)

Silva-Rodríguez, J.; Cortés, J.; Rodríguez-Osorio, X.; López-Urdaneta, J.; Pardo-Montero, J.; Aguiar, P.; Tsoumpas, C.

2016-10-01

Structural Functional Synergistic Resolution Recovery (SFS-RR) is a technique that uses supplementary structural information from MR or CT to improve the spatial resolution of PET or SPECT images. This wavelet-based method may have a potential impact on the clinical decision-making of brain focal disorders such as refractory epilepsy, since it can produce images with better quantitative accuracy and enhanced detectability. In this work, a method for the iterative application of SFS-RR (iSFS-RR) was firstly developed and optimized in terms of convergence and input voxel size, and the corrected images were used for the diagnosis of 18 patients with refractory epilepsy. To this end, PET/MR images were clinically evaluated through visual inspection, atlas-based asymmetry indices (AIs) and SPM (Statistical Parametric Mapping) analysis, using uncorrected images and images corrected with SFS-RR and iSFS-RR. Our results showed that the sensitivity can be increased from 78% for uncorrected images, to 84% for SFS-RR and 94% for the proposed iSFS-RR. Thus, the proposed methodology has demonstrated the potential to improve the management of refractory epilepsy patients in the clinical routine.

Parenting stress in parents of children with refractory epilepsy before and after vagus nerve stimulation implantation.

PubMed

Li, Sung-Tse; Chiu, Nan-Chang; Kuo, Yung-Ting; Shen, Ein-Yiao; Tsai, Pei-Chieh; Ho, Che-Sheng; Wu, Wen-Hsiang; Chen, Juei-Chao

2017-12-01

The purpose of this study was to evaluate parenting stress in parents of children with refractory epilepsy before and after their children received vagus nerve stimulation (VNS) implantation. Parents of children with refractory epilepsy completed the Parenting Stress Index (PSI) under a psychologist's assessment before and at least 12 months after their children received VNS implantation. The PSI questionnaire measures parenting stress in two domains; a parent domain with seven subscales, and a child domain with six. Age, gender, epilepsy comorbidity, VNS implantation date, seizure frequency, and anticonvulsant history before and after VNS implantation were obtained from reviews of medical charts. In total, 30 parents completed the first and follow-up PSI questionnaires. Seventeen of their children (56.7%) were boys. The children aged from 1 to 12 years (7.43 ± 3.59 years, mean ± SD). After VNS implantation, the mean total parenting stress scores decreased from 282.1 ± 38.0 to 272.4 ± 42.9. A significant decrease was found on the spouse subscale of the parent domain. For the parents of boys, the mean total parenting stress scores decreased significantly. The mean total parenting stress scores also decreased significantly for parents of epileptic children without autism and who did not taper off the number of different anticonvulsants used after VNS. VNS is an advisable choice to treat refractory epilepsy. Our study showed that 12 months or more after VNS implantation, seizure frequency and parenting stress typically decreased. However, in some special cases the parenting stress may increase, and external help may be required to support these patients and their parents. Copyright © 2017. Published by Elsevier B.V.

Epilepsy Surgery: An Evidence Summary

PubMed Central

2012-01-01

Background The Medical Advisory Secretariat, the predecessor of Health Quality Ontario, published an evidence-based analysis on functional brain imaging. This analysis highlighted the low uptake of epilepsy surgery in Ontario and internationally. Objective The objective of this analysis was to review the effectiveness of epilepsy surgery at reducing seizure frequency, as well as the safety of epilepsy surgery. Data Sources The literature search included studies published between January 1995 and March 2012. Search terms included epilepsy, surgery, resection, safety, and complications. Review Methods Studies were eligible for inclusion if they included at least 20 patients undergoing surgery; had a comparison group of patients with epilepsy who were not undergoing surgery; and reported follow-up periods of at least 1 year. Outcomes of interest included seizure frequency and complications associated with surgery. Results Six systematic reviews reported pooled seizure-free rates that ranged from 43% to 75%. Two randomized controlled trials compared the effectiveness of epilepsy surgery with no surgery in patients with drug-refractory epilepsy. Both trials reported significant improvements in the seizure frequency in the surgery group compared with the nonsurgery group. Eight retrospective cohort studies reported on the safety of epilepsy surgery. Of the 2,725 patients included in these studies, there were 3 deaths reportedly related to surgery. Other complications included hemiparesis, infection, and visual field defects. The studies had long follow-up periods ranging from a mean of 2 to 7 years. Limitations The most recent randomized controlled trial was stopped early due to slow enrolment rates. Thus results need to be interpreted with caution. Conclusions There is high quality evidence that epilepsy surgery is effective at reducing seizure frequency. Two randomized controlled trials compared surgery to no surgery in patients with drug-refractory epilepsy. Both demonstrated significant reductions in seizure frequency. There are some complications associated with epilepsy surgery. In the published literature identified, we observed a 0.1% mortality rate associated with the surgery. Plain Language Summary About 30% of patients with epilepsy continue to have seizures despite optimal drug treatment. In some of these patients, surgery to control the number of seizures may be an option. Patients are carefully selected based on frequency of seizures, location of seizure in the brain, and type of seizures. There is good evidence to indicate that surgery is an effective and safe option for some patients with drug-refractory epilepsy. PMID:23074427

Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: A systematic review.

PubMed

Ortiz de la Rosa, Johann Sebastián; Ladino, Lady Diana; Rodríguez, Paula Juliana; Rueda, María Camila; Polanía, Juan Pablo; Castañeda, Angie Catalina

2018-03-01

Lacosamide, is one of the newer antiepileptic drug approved for focal drug-resistant epilepsy as an add-on treatment in patients older than 16 years. However, there is growing evidence of its use, safety and efficacy in children. We aim to evaluate efficacy and tolerability of lacosamide in focal and generalized drug-resistant epilepsy and refractory status epilepticus in the pediatric population. We conducted a systematic review on MEDLINE, EMBASE, COCHRANE, Google Scholar and Scielo from January 2008 to January 2017. The primary outcome was the efficacy of lacosamide in children with drug-resistant epilepsy and refractory status epilepticus. Efficacy and adverse events attributed to lacosamide were extracted from each publication and systematically reported. We performed no meta-analyses due to limited available data. Of 175 abstracts identified by the search, 82 were reviewed as full-text. Twenty-six articles fulfilled eligibility criteria and described outcomes in 797 patients (57% male). The majority of studies were retrospective (69%) small series (84%). On average 51% of patients had 50% or greater seizure reduction. The mean seizure freedom rate was 24%. Adverse effects occurred in 18-59% of patients. The main events were dizziness, sedation, gastrointestinal upset, mood and behavioral changes. Half of the patients with Lennox Gastaut syndrome showed 50% or greater seizure reduction, 32% did not response to lacosamide and 17% suffered seizure aggravation. Current evidence shows lacosamide as a good option in pediatric patients with focal drug-resistant epilepsy and refractory status epilepticus as an add-on therapy given its efficacy on seizure control and safety profile. The use of lacosamide in Lennox-Gastaut syndrome shows conflicting data. Large randomized controlled studies in the pediatric population are necessary to substantiate these findings. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

PubMed

Sidhu, Meneka K; Thompson, Pamela J; Wandschneider, Britta; Foulkes, Alexandra; de Tisi, Jane; Stretton, Jason; Perona, Marina; Thom, Maria; Bonelli, Silvia B; Burdett, Jane; Williams, Elaine; Duncan, John S; Matarin, Mar

2018-06-27

Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE. © 2018 John Wiley & Sons Ltd.

When should temporal-lobe epilepsy be treated surgically?

PubMed

Spencer, Susan S

2002-10-01

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Epilepsy Care in Ontario: An Economic Analysis of Increasing Access to Epilepsy Surgery

PubMed Central

Bowen, James M.; Snead, O. Carter; Chandra, Kiran; Blackhouse, Gord; Goeree, Ron

2012-01-01

Background In August 2011 a proposed epilepsy care model was presented to the Ontario Health Technology Advisory Committee (OHTAC) by an Expert Panel on a Provincial Strategy for Epilepsy Care in Ontario. The Expert Panel recommended leveraging existing infrastructure in the province to provide enhanced capacity for epilepsy care. The point of entry for epilepsy care and the diagnostic evaluation for surgery candidacy and the epilepsy surgery would occur at regional and district epilepsy centres in London, Hamilton, Toronto, and Ottawa and at new centres recommended for northern and eastern Ontario. This economic analysis report was requested by OHTAC to provide information about the estimated budgetary impact on the Ontario health care system of increasing access to epilepsy surgery and to examine the cost-effectiveness of epilepsy surgery in both children and adults. Methods A prevalence-based “top-down” health care system budgetary impact model from the perspective of the Ministry of Health and Long-Term Care was developed to estimate the potential costs associated with expanding health care services to increase access to epilepsy care in general and epilepsy surgery in particular. A 5-year period (i.e., 2012–2016) was used to project annual costs associated with incremental epilepsy care services. Ontario Health Survey estimates of epilepsy prevalence, published epilepsy incidence data, and Canadian Census results for Ontario were used to approximate the number of individuals with epilepsy in the province. Applying these population estimates to data obtained from a recent field evaluation study that examined patterns of care and costs associated with epilepsy surgery in children, a health care system budget impact was calculated and the total costs and incremental costs associated with increasing access to surgery was estimated. In order to examine the cost-effectiveness of epilepsy surgery in children, a decision analysis compared epilepsy surgery to continued medical management in children with medically intractable epilepsy. Data from the field evaluation were combined with various published data to estimate the costs and outcomes for children with drug-refractory epilepsy over a 20-year period. Outcomes were defined as the number of quality-adjusted life years (QALYs) accumulated over 20 years following epilepsy surgery. Results There are about 20,981 individuals with medically intractable epilepsy in Ontario. Of these, 9,619 (1,441 children and 8,178 adults) could potentially be further assessed at regional epilepsy centres for suitability for epilepsy surgery, following initial evaluation at a district epilepsy care centre. The health care system impact analysis related to increasing access to epilepsy surgery in the Ontario through the addition of epilepsy monitoring unit (EMU) beds with video electroencephalography (vEEG) monitoring (total capacity of 15 pediatric EMU beds and 35 adult EMU beds distributed across the province) and the associated clinical resources is estimated to require an incremental $18.1 million (Cdn) annually over the next 5 years from 2012 to 2016. This would allow for about 675 children and 1050 adults to be evaluated each year for suitability for epilepsy surgery representing a 150% increase in pediatric epilepsy surgery evaluation and a 170% increase in adult epilepsy surgery evaluation. Epilepsy surgery was found to be cost-effective compared to continued medical management in children with drug-refractory epilepsy with the incremental cost-effectiveness ratio of $25,020 (Cdn) to $69,451 (Cdn) per QALY for 2 of the scenarios examined. In the case of choosing epilepsy surgery versus continued medical management in children known to be suitable for surgery, the epilepsy surgery was found to be less costly and provided greater clinical benefit, that is, it was the dominant strategy. Conclusion Epilepsy surgery for medically intractable epilepsy in suitable candidates has consistently been found to provide favourable clinical outcomes and has been demonstrated to be cost-effective in both adult and child patient populations. The first step to increasing access to epilepsy surgery is to provide access to evidence-based care for all patients with epilepsy, both adults and children, through the provision of resources to expand EMU bed capacity and associated clinical personnel across the province of Ontario. Plain Language Summary Epilepsy, characterized by recurrent, unpredictable, and spontaneous seizures, affects approximately 70,000 people in Ontario. About 30% continue to suffer from seizures despite using 2 or more anti-seizure medications. For these individuals epilepsy surgery is a treatment option to stop the seizures or at least reduce their frequency. Awareness of this treatment option is not widespread and people are not commonly referred to those hospitals in Ontario where this surgery is available. A proposal to increase access to epilepsy care and surgery has been made by an expert committee that provided a report to the Ontario Health Technology Advisory Committee (OHTAC). In order to address the lack of access of patients with medically intractable epilepsy to the possibility of curative surgical treatment, it is necessary to design a system that provides equal availability of evidence-based treatment for all epilepsy patients in Ontario, both adults and children. To this end, the establishment of district epilepsy care centres and the further development of the existing regional epilepsy care centres in the province have been proposed. This report outlines the estimated additional funds that will be required to implement the proposal. It also examines the cost-effectiveness of referral to these centres and epilepsy surgery. For the 21,000 people in the province with drug-refractory epilepsy, referral to an epilepsy monitoring unit (EMU) located at one of the epilepsy care centres is the first step to determining if epilepsy surgery is an option for them. The expert committee proposal suggests that the number of EMU beds be increased from the current 19 to 50 to allow for the assessment of those individuals with drug-refractory epilepsy. The health care system budget impact model presented in this report estimates that it would cost approximately $18 million (Cdn) each year over the next 5 years to increase the number of EMU beds and expand associated epilepsy care centres to permit the systematic evidence-based care of all Ontarians with epilepsy and evaluate more people for surgery candidacy. This amount would provide appropriate care for patients with epilepsy and ensure that about 675 children and 1050 adults could be assessed each year for suitability for epilepsy surgery. Surgery could then be made available to just over 300 people per year. Epilepsy surgery over the long term is a less expensive treatment alternative for adults and children with medically refractory epilepsy compared with continued drug treatment. In addition, drug treatment does not always work for some patients; nor does it necessarily provide improved quality of life. This report includes a cost-effectiveness analysis comparing referral for assessment for epilepsy surgery with continuing medical management in children with drug-refractory epilepsy. In all the cases examined epilepsy surgery provides good value for money over a 20-year period. Similar studies have found that the benefits from epilepsy surgery outweigh those of continuing medical management in adult patients with medically refractory epilepsy. PMID:23074428

Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody-positive refractory epilepsy.

PubMed

Liimatainen, Suvi; Peltola, Jukka; Hietaharju, Aki; Sabater, Lidia; Lang, Bethan

2014-03-01

Over the last few years autoantibodies against neuronal proteins have been identified in several forms of autoimmune encephalitis and epilepsy. NMDA receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies are mainly associated with limbic encephalitis (LE) whereas glutamic acid decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more commonly detected in patients with chronic epilepsy. Clinical features vary between these antibodies suggesting the specificity of different neuronal antibodies in seizures. Serum samples of 14 GADA positive and 24 ACL positive patients with refractory epilepsy were analyzed for the presence of VGKC or NMDAR antibodies. No positive VGKC or NMDAR antibodies were found in these patients. The results confirm the different significance of these neuronal antibodies in seizure disorders. Different autoantibodies have different significance in seizures and probably have different pathophysiological mechanisms of actions. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of lacosamide on cognition, quality-of-life measures, and quality of life in patients with refractory partial epilepsy.

PubMed

Lancman, Marcelo E; Fertig, Evan J; Trobliger, Robert W; Perrine, Kenneth; Myers, Lorna; Iyengar, Sloka S; Malik, Munazza

2016-08-01

The objective of this study was to examine cognitive and quality-of-life measures/quality of life outcomes with adjunctive lacosamide therapy in patients with treatment-resistant partial epilepsy. This was a prospective, open-label, nonblinded, adjunctive therapy test-retest (within subjects) study of patients with treatment-resistant partial epilepsy in which outcome (cognitive functioning and mood/quality of life) was measured in the same subject before and after adjunctive lacosamide administration for 24weeks. The cognitive assessment included the following: Controlled Oral Word Association Test, Buschke Selective Reminding Test, Brief Visuospatial Memory Test-Revised, Stroop Color Word Test, Symbol Digit Modalities Test, Digit Span, Digit Cancellation, and Trails A and B. The quality-of-life measures/quality-of-life assessment included the following: Beck Depression Inventory-II, Profile of Mood States, and Quality of Life Inventory-89. Lacosamide was started at 100mg (50mg twice daily) and could be titrated as needed up to 400mg/day (200mg twice daily). Baseline concomitant AEDs were kept constant. Composite scores were calculated for a pre-post difference score for the cognitive and mood/quality-of-life measures separately and used in regression analyses to correct for the effects of age, education, seizure frequency, seizure severity, dose of lacosamide, and number of AEDs at baseline. Thirty-four patients were enrolled (13 males, 21 females). Mean age was 38.8±2.43years. Mean seizure frequency decreased significantly from 2.0±2.55 seizures per week at baseline to 1.02±1.72 seizures per week at posttreatment (t=4.59, p<.0001) with a 50% responder rate seen in 18 patients (52.9%). No significant differences were found on the composite scores of the cognitive or the mood/quality-of-life measures after 6months of lacosamide. Lacosamide appeared to have low risks of significant changes in cognition or mood/quality of life. In addition, the present study supports prior studies that have proven lacosamide as an effective adjunctive therapy for the treatment of resistant partial epilepsy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

PubMed Central

Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

2010-01-01

Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

PubMed

Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

2017-02-01

Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Stereotactic Laser Ablation for Medically Intractable Epilepsy: The Next Generation of Minimally Invasive Epilepsy Surgery

PubMed Central

LaRiviere, Michael J.; Gross, Robert E.

2016-01-01

Epilepsy is a common, disabling illness that is refractory to medical treatment in approximately one-third of patients, particularly among those with mesial temporal lobe epilepsy. While standard open mesial temporal resection is effective, achieving seizure freedom in most patients, efforts to develop safer, minimally invasive techniques have been underway for over half a century. Stereotactic ablative techniques, in particular, radiofrequency (RF) ablation, were first developed in the 1960s, with refinements in the 1990s with the advent of modern computed tomography and magnetic resonance-based imaging. In the past 5 years, the most recent techniques have used MRI-guided laser interstitial thermotherapy (LITT), the development of which began in the 1980s, saw refinements in MRI thermal imaging through the 1990s, and was initially used primarily for the treatment of intracranial and extracranial tumors. The present review describes the original stereotactic ablation trials, followed by modern imaging-guided RF ablation series for mesial temporal lobe epilepsy. The developments of LITT and MRI thermometry are then discussed. Finally, the two currently available MRI-guided LITT systems are reviewed for their role in the treatment of mesial temporal lobe and other medically refractory epilepsies. PMID:27995127

Spatial memory for asymmetrical dot locations predicts lateralization among patients with presurgical mesial temporal lobe epilepsy.

PubMed

Brown, Franklin C; Hirsch, Lawrence J; Spencer, Dennis D

2015-11-01

This study examined the ability of an asymmetrical dot location memory test (Brown Location Test, BLT) and two verbal memory tests (Verbal Selective Reminding Test (VSRT) and California Verbal Learning Test, Second Edition (CVLT-II)) to correctly lateralize left (LTLE) or right (RTLE) mesial temporal lobe epilepsy that was confirmed with video-EEG. Subjects consisted of 16 patients with medically refractory RTLE and 13 patients with medically refractory LTLE who were left hemisphere language dominant. Positive predictive values for lateralizing TLE correctly were 87.5% for the BLT, 72.7% for the VSRT, and 80% for the CVLT-II. Binary logistic regression indicated that the BLT alone correctly classified 76.9% of patients with left temporal lobe epilepsy and 87.5% of patients with right temporal lobe epilepsy. Inclusion of the verbal memory tests improved this to 92.3% of patients with left temporal lobe epilepsy and 100% correct classification of patients with right temporal lobe epilepsy. Though of a limited sample size, this study suggests that the BLT alone provides strong laterality information which improves with the addition of verbal memory tests. Copyright © 2015 Elsevier Inc. All rights reserved.

[Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review].

PubMed

Araya-Quintanilla, F; Celis-Rosati, A; Rodriguez-Leiva, C; Silva-Navarro, C; Silva-Pinto, Y; Toro-Jeria, B

2016-05-16

Epilepsy is a brain disorder that affects both children and adults. From the 1920s the ketogenic diet has gained prestige as another treatment option for patients with refractory epilepsy. A summary of the evidence will be made through a systematic review of randomized clinical trials that have compared a single ketogenic diet with other diet for the management of these patients. To determine the effectiveness of the ketogenic diet in reducing episodes of seizures in patients with refractory epilepsy. The search strategy included randomized controlled trials and controlled clinical trials. Databases used were Medline, LILACS, Central and CINAHL. Six articles that met our elegibility criteria. There is limited evidence that the ketogenic diet compared to the medium-chain triglyceride diet is more effective in reducing the frequency of seizures. There is also moderate evidence that classical ketogenic diet compared to the gradual diet (2.5:1 and 3:1) is more effective in reducing seizures. There is moderate evidence that classical ketogenic diet compared to Atkins diet is more effective in reducing the frequency of seizure. The decision to apply this type of diet should also be based on costs, preferences and safety of treatment. It should also take into account the likelihood that studies have indexing problems have been left out of the review.

Reoperation for refractory epilepsy in childhood: a second chance for selected patients.

PubMed

Ramantani, Georgia; Strobl, Karl; Stathi, Angeliki; Brandt, Armin; Schubert-Bast, Susanne; Wiegand, Gert; Korinthenberg, Rudolf; Stephani, Ulrich; van Velthoven, Vera; Zentner, Josef; Schulze-Bonhage, Andreas; Bast, Thomas

2013-10-01

Reoperations account for >10% in pediatric epilepsy surgery cohorts, and they are especially relevant in young children with catastrophic epilepsy. To determine surgical outcomes and their predictive factors in reoperations for refractory epilepsy in childhood. We retrospectively analyzed presurgical findings, resections, and outcomes of 23 consecutive children who underwent reoperations from 2000 to 2011. Etiology included cortical dysplasia with/without glioneuronal tumor in 19 patients (83%), sole glioneuronal tumor in 2, and tuberous sclerosis and Rasmussen encephalitis in 1 each. The reasons for the failure of the initial surgery were functional considerations in 8 (35%), incorrect delineation of the epileptogenic zone in 8 (35%), and resection not performed as initially planned in 7 (30%) cases. Final procedures included 8 (35%) intralobar, 8 (35%) multilobar resections, and 7 (30%) hemispherotomies. Following reoperations, 14 (61%) patients were seizure free, 6 (26%) showed significant or worthwhile improvement, and 3 (13%) did not respond to surgery. Six of 8 patients who underwent the first resection before the age of 3 years, 6 of 8 whose first resection was limited by functional considerations, and all 7 with hemispherotomy as the final resection achieved seizure freedom after reoperation. Reoperation is particularly beneficial for selected children with refractory epilepsy associated with cortical dysplasia that did not respond to an initial limited and/or early resection but achieved seizure freedom after extensive procedures. When indicated, reoperation should be performed at the youngest possible age to profit from higher functional plasticity in compensating for neurological deficit.

Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

PubMed

Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier

2015-11-01

The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.

Methodological issues associated with clinical trials in epilepsy.

PubMed

Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Russo, Emilio; Cianci, Vittoria; Ascoli, Michele; De Sarro, Giovambattista; Aguglia, Umberto

2017-10-01

despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future. Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or 'time-to-event' design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient's ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed. Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients' and clinicians' needs.

Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy.

PubMed

Hisada, K; Morioka, T; Nishio, S; Yamamoto, T; Fukui, M

2001-12-01

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

PubMed

Zhu, Xi; He, Zhongqiong; Luo, Cheng; Qiu, Xiangmiao; He, Shixu; Peng, Anjiao; Zhang, Lin; Chen, Lei

2018-03-15

To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Tailored unilobar and multilobar resections for orbitofrontal-plus epilepsy.

PubMed

Serletis, Demitre; Bulacio, Juan; Alexopoulos, Andreas; Najm, Imad; Bingaman, William; González-Martínez, Jorge

2014-10-01

Surgery for frontal lobe epilepsy often has poor results, likely because of incomplete resection of the epileptogenic zone. To present our experience with a series of patients manifesting 2 different anatomo-electro-clinical patterns of refractory orbitofrontal epilepsy, necessitating different surgical approaches for resection in each group. Eleven patients with refractory epilepsy involving the orbitofrontal region were consecutively identified over 3 years in whom stereoelectroencephalography identified the epileptogenic zone. All patients underwent preoperative evaluation, stereoelectroencephalography, and postoperative magnetic resonance imaging. Demographic features, seizure semiology, imaging characteristics, location of the epileptogenic zone, surgical resection site, and pathological diagnosis were analyzed. Surgical outcome was correlated with type of resection. Five patients exhibited orbitofrontal plus frontal epilepsy with the epileptogenic zone consistently residing in the frontal lobe; after surgery, 4 patients were free of disabling seizures (Engel I) and 1 patient improved (Engel II). The remaining 6 patients had multilobar epilepsy with the epileptogenic zone located in the orbitofrontal cortex associated with the temporal polar region (orbitofrontal plus temporal polar epilepsy). After surgery, all 6 patients were free of disabling seizures (Engel I). Pathology confirmed focal cortical dysplasia in all patients. We report no complications or mortalities in this series. Our findings highlight the importance of differentiating between orbitofrontal plus frontal and orbitofrontal plus temporal polar epilepsy in patients afflicted with seizures involving the orbitofrontal cortex. For identified cases of orbitofrontal plus temporal polar epilepsy, a multilobar resection including the temporal pole may lead to improved postoperative outcomes with minimal morbidity or mortality.

Update on diagnosis and management of childhood epilepsies.

PubMed

Zuberi, Sameer M; Symonds, Joseph D

2015-01-01

To review the current evidence base for the diagnosis and management of the childhood epilepsies and to draw attention to the current gaps in this evidence base. The focus will be on therapeutic aspects. Current International League Against Epilepsy (ILAE) terminology will be described and used throughout the discussion. The review will draw attention to recent advances that have been made in both our understanding and treatment of the childhood epilepsies. Potential future directions for research and treatment options will be discussed. Original articles relevant to the subject were obtained from the MedLine database using pertinent MeSH terms. Relevant papers were read and assimilated. Citation searching was used. Epilepsy is a major cause of global disease burden. Childhood epilepsies are a heterogeneous group of conditions. A multi-axial diagnostic approach should be taken prior to making treatment and management decisions for any individual patient. For the majority of patients, successful control of seizures can be achieved with a single medication. However, a significant minority develops refractory disease. Epilepsy surgery can provide cure for a carefully selected group of these cases. There remain significant gaps the evidence base for treatment in several areas of childhood epilepsy. Concerted multi-center efforts should be made to try to close these gaps. A personalized medicine approach may help to reduce the proportion of refractory cases of childhood epilepsy in future. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Reasons for uncontrolled seizures in children: the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2012-11-01

We investigated the various possible reasons for uncontrolled seizures in patients under 18 years of age to determine the impact of pseudointractability. We also investigated the various forms of pseudointractability in children with uncontrolled seizures. In this cross-sectional retrospective chart review study, all patients under 18 years of age with their first seizure occurring at least 6 months prior to the referral date, taking at least one antiepileptic drug (AED), and having at least one seizure in the past 3 months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: poor adherence; wrong medication; wrong dose of the correct medication; diagnosis other than epilepsy; and finally, medically refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's Exact tests to determine potentially significant differences, and a P value less than 0.05 was considered significant. During the study period, 198 patients were referred to us due to uncontrolled seizures. Ninety patients (45%) were taking one AED, 55 (28%) were taking two AEDs, and 53 (27%) patients were taking more than two AEDs at the time of referral. Four percent of these patients did not have epilepsy. Forty-seven percent of the children with uncontrolled seizures had medically refractory epilepsy; 37% were taking the wrong AEDs; 10% were taking suboptimal doses of AEDs; and 2% had poor drug adherence. Uncontrolled seizures in children are a commonly encountered problem, particularly at epilepsy clinics. One should consider all possible reasons for these uncontrolled seizures, including non-epileptic seizures, pseudointractability, and medically refractory epilepsy. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2012 Elsevier Inc. All rights reserved.

Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

PubMed

Gofshteyn, Jacqueline S; Wilfong, Angus; Devinsky, Orrin; Bluvstein, Judith; Charuta, Joshi; Ciliberto, Michael A; Laux, Linda; Marsh, Eric D

2017-01-01

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

Impact of sleep duration on seizure frequency in adults with epilepsy: a sleep diary study.

PubMed

Cobabe, Maurine M; Sessler, Daniel I; Nowacki, Amy S; O'Rourke, Colin; Andrews, Noah; Foldvary-Schaefer, Nancy

2015-02-01

Prolonged sleep deprivation activates epileptiform EEG abnormalities and seizures in people with epilepsy. Few studies have addressed the effect of chronic partial sleep deprivation on seizure occurrence in populations with epilepsy. We tested the primary hypothesis that partial sleep deprivation over 24- and 72-hour periods increases seizure occurrence in adults with epilepsy. Forty-four subjects completed a series of self-reported instruments, as well as 1-month sleep and seizure diaries, to characterize their sleep and quality of life. Diaries were used to determine the relationship between seizure occurrence and total sleep time 24 and 72h before seizure occurrence using random effects models and a logistic regression model fit by generalized estimating equations. A total of 237 seizures were recorded during 1295 diary days, representing 5.5±7.0 (mean±SD) seizures per month. Random effects models for 24- and 72-hour total sleep times showed no clinically or statistically significant differences in the total sleep time between preseizure periods and seizure-free periods. The average 24-hour total sleep time during preseizure 24-hour periods was 8min shorter than that during seizure-free periods (p=0.51). The average 72-hour total sleep time during preseizure periods was 20min longer than that during seizure-free periods (p=0.86). The presence of triggers was a significant predictor of seizure occurrence, with stress/anxiety noted most often as a trigger. Mean total sleep time was 9h, and subjects took an average of 12±10 naps per month, having a mean duration of 1.9±1.2h. Daytime sleepiness, fatigue, and insomnia symptoms were commonly reported. Small degrees of sleep loss were not associated with seizure occurrence in our sample of adults with epilepsy. Our results also include valuable observations of the altered sleep times and frequent napping habits of adults with refractory epilepsy and the potential contribution of these habits to quality of life and seizure control. Copyright © 2014 Elsevier Inc. All rights reserved.

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

PubMed

Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

2015-12-01

We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Behavioral effects and somnolence due to levetiracetam versus oxcarbazepine - a retrospective comparison study of North Indian patients with refractory epilepsy.

PubMed

Shukla, Garima; Gupta, Anupama; Agarwal, Priya; Poornima, Shivani

2016-11-01

Levetiracetam (LEV) is often chosen early in the treatment of refractory epilepsy; however, its adverse effects have largely been studied as part of clinical trials. Oxcarbazepine and valproate (VPA) are the other commonly used AEDs and, hence, serve as good comparators. This study was conducted to evaluate behavioral abnormalities and somnolence among patients with epilepsy being treated with LEV and/or OXC compared with those receiving VPA. Data of consecutive patients attending our intractable epilepsy clinic over a 2 1/2-year period were reviewed, and patients with at least one seizure a month, who had been initiated on either or a combination of LEV, VPA, or OXC, were included for analysis. Data regarding behavioral adverse effects, daytime somnolence (EDS), and weight changes were collected apart from those regarding any major effect necessitating dose reduction or discontinuation of the AED. Among a total of 445 patients screened, 292 (93 F, median age: 21years [range: 8-54]; 237 focal and 55 generalized epilepsy) fulfilled inclusion criteria. Median epilepsy duration was 11years. Levetiracetam had been introduced in 114 patients, VPA in 134, and OXC in 151 during the study period. Twenty-three were on LEV+OXC, 27 on LEV+VPA, and 33 on VPA+OXC. Behavioral disturbances (irritability, obsessive manifestations, aggressiveness, and frank psychosis) were observed in 43 patients; 23 on introduction of LEV (20.2%); LEV was discontinued in 10 (9%). Daytime somnolence was reported by 28 patients, 15 on OXC (10%); 8 received oral modafinil for the same, while none discontinued this AED. Only one patient on LEV and 3 on VPA reported EDS. Menstrual disturbances were reported by 9, weight gain by 3, and severe hair loss by 2 females on VPA. Behavioral disturbances with levetiracetam are common among patients with refractory epilepsy while somnolence is common with oxcarbazepine. Antiepileptic drugs should be selected with this in perspective. Copyright © 2016 Elsevier Inc. All rights reserved.

Harnessing the Power of Metabolism for Seizure Prevention: Focus on Dietary Treatments

PubMed Central

Hartman, Adam L.; Stafstrom, Carl E.

2012-01-01

The continued occurrence of refractory seizures in at least one-third of children and adults with epilepsy, despite the availability of almost 15 conventional and novel anticonvulsant drugs, speaks to a dire need to develop novel therapeutic approaches. Cellular metabolism, the critical pathways by which cells access and utilize energy, is critical for normal neuronal function. Furthermore, mounting evidence suggests direct links between energy metabolism and cellular excitability. The high-fat, low-carbohydrate ketogenic diet has been used as a treatment for drug-refractory epilepsy for almost a century. Yet, the multitude of alternative therapies to target aspects of cellular metabolism and hyperexcitability is almost untapped. Approaches discussed in this review offer a wide diversity of therapeutic targets that might be exploited by investigators in the search for safer and more effective epilepsy treatments. PMID:23110824

AED Strategy after Refractory Epilepsy Surgery.

PubMed

Zigouris, Andreas; Alexiou, George A; Themistocleous, Marios S; Voulgaris, Spyridon

2017-01-01

Post-epilepsy surgery antiepileptic drug discontinuation (AED) practices remain unclear and little evidence about the optimum timing exists. In the present study, we reviewed the types of surgery for epilepsy and their outcome. The current concepts for discontinuation of AED after surgery are presented and all contributing factors that should be taken into consideration are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis

PubMed Central

Spatola, M.; Dalmau, J.

2018-01-01

Purpose of review To assess the seizure manifestations and risk of epilepsy in encephalitis associated to antibodies against neuronal cell-surface (AE) or myelin-associated antigens, and to review several chronic epileptic disorders including, Rasmussen’s encephalitis (RE), fever-induced refractory epileptic syndromes (FIRES), and new-onset refractory status epilepticus (NORSE). Recent findings Seizures are a frequent manifestation of AE. Some AE may associate with characteristic features: faciobrachial dystonic seizures (anti-LGI1 encephalitis), EEG extreme delta brush (anti-NMDAR), or multifocal FLAIR-MRI abnormalities (anti-GABAAR). In anti-LGI1 encephalitis, cortical, limbic, and basal ganglia dysfunction results in different types of seizures. AE or myelin-antibody associated syndromes are often immunotherapy-responsive and appear to have a low risk for chronic epilepsy. In contrast patients with seizures related to GAD65-antibodies (an intracellular antigen) frequently develop epilepsy and have suboptimal response to treatment (including surgery). RE or FIRES may occur with autoantibodies of unclear significance and rarely respond to immunotherapy. A study of patients with NORSE showed that 30% developed chronic epilepsy. Summary Although seizures are frequent in all types of AE, the risk for chronic epilepsy is dependent on the antigen: lower if located on the cell-surface, and higher if intracellular. For other disorders (RE, FIRES, NORSE) the prognosis remains poor. PMID:28234800

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

PubMed

Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

2018-07-01

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market.

PubMed

Mäkinen, Jussi; Peltola, Jukka; Raitanen, Jani; Alapirtti, Tiina; Rainesalo, Sirpa

2017-07-01

The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan-Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.

The three stages of epilepsy in patients with CDKL5 mutations.

PubMed

Bahi-Buisson, Nadia; Kaminska, Anna; Boddaert, Nathalie; Rio, Marlène; Afenjar, Alexandra; Gérard, Marion; Giuliano, Fabienne; Motte, Jacques; Héron, Delphine; Morel, Marie Ange N'guyen; Plouin, Perrine; Richelme, Christian; des Portes, Vincent; Dulac, Olivier; Philippe, Christophe; Chiron, Catherine; Nabbout, Rima; Bienvenu, Thierry

2008-06-01

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are responsible for a severe encephalopathy with early epilepsy. So far, the electroclinical phenotype remains largely unknown and no clear genotype-phenotype correlations have been established. To characterize the epilepsy associated with CDKL5 mutations and to look for a relationship between the genotype and the course of epilepsy. We retrospectively analyzed the electroclinical phenotypes of 12 patients aged from 2.5 to 19 years diagnosed with pathogenic CDKL5 mutations and one patient with a novel intronic sequence variation of uncertain pathogenicity and examined whether the severity of the epilepsy was linked to the type and location of mutations. The epilepsy course reveals three successive stages: (Stage I) early epilepsy (onset 1-10 weeks) with normal interictal electroencephalogram (EEG) (10/13) despite frequent convulsive seizures; (Stage II) epileptic encephalopathy with infantile spasms (8/8) and hypsarrhythmia (8/8). At the age of evaluation, seven patients were seizure free and six had developed refractory epilepsy (stage III) with tonic seizures and myoclonia (5/6). Interestingly, the patients carrying a CDKL5 mutations causing a truncation of the catalytic domain tended to develop a more frequent refractory epilepsy than patients with mutations located downstream (4/6, 66.6% versus 1/6, 16%) although, these trends are not yet significant. Our data contribute to a better definition of the epileptic phenotype in CDKL5 mutations, and might give some clues to a potential relationship between the phenotype and the genotype in these patients.

New insights into the mechanisms of the ketogenic diet

PubMed Central

Boison, Detlev

2017-01-01

Purpose of review High-fat, low-carbohydrate ketogenic diets (KDs) have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of KDs has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of KD therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by KD therapies. Recent findings KDs act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium chain triclycerides, contributes to seizure control through direct AMPA receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. KD therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Summary KD therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy. PMID:28141738

The long-term outcomes of epilepsy surgery

PubMed Central

Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections. PMID:29768433

The long-term outcomes of epilepsy surgery.

PubMed

Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.

Temporal lobe epilepsy is a predisposing factor for sleep apnea: A questionnaire study in video-EEG monitoring unit.

PubMed

Yildiz, F Gokcem; Tezer, F Irsel; Saygi, Serap

2015-07-01

The interaction between epilepsy and sleep is known. It has been shown that patients with epilepsy have more sleep problems than the general population. However, there is no recent study that compares the frequency of sleep disorders in groups with medically refractory temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). The main purpose of this study was to investigate the occurrence of sleep disorders in two subtypes of epilepsy by using sleep questionnaire forms. One hundred and eighty-nine patients, out of 215 who were monitored for refractory epilepsy and were followed by the video-EEG monitoring unit, were divided into a group with TLE and a group with ETLE. The medical outcome study-sleep scale (MOS-SS), Epworth sleepiness scale (ESS), and sleep apnea scale of the sleep disorders questionnaire (SD-SDQ) were completed after admission to the video-EEG monitoring unit. The total scores in the group with TLE and group with ETLE were compared. Of the patients, TLE was diagnosed in 101 (53.4%) (45 females), and ETLE was diagnosed in 88 (46.6%) (44 females). Comparison of MOS-SS and Epworth sleepiness scale scores in the two subgroups did not reveal significant differences. In the group with TLE, SD-SDQ scores were significantly higher compared to that in the group with ETLE. Patients with temporal lobe epilepsy have higher risk of obstructive sleep apnea (OSA) according to their reported symptoms. Detection of OSA in patients with epilepsy by using questionnaire forms may decrease the risk of ictal or postictal respiratory-related 'Sudden Unexpected Death in Epilepsy'. Copyright © 2015 Elsevier Inc. All rights reserved.

[A study of epilepsy according to the age at onset and monitored for 3 years in a regional reference paediatric neurology unit].

PubMed

Ochoa-Gómez, Laura; López-Pisón, Javier; Lapresta Moros, Carlos; Fuertes Rodrigo, Cristina; Fernando Martínez, Ruth; Samper-Villagrasa, Pilar; Monge-Galindo, Lorena; Peña-Segura, José Luis; García-Jiménez, María Concepción

2017-01-01

A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Genetics Home Reference: malignant migrating partial seizures of infancy

MedlinePlus

... of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures ... infantile epileptic encephalopathy 14 EIEE14 malignant migrating partial epilepsy of infancy migrating partial epilepsy of infancy migrating ...

Genetics Home Reference: autosomal dominant partial epilepsy with auditory features

MedlinePlus

... Twitter Home Health Conditions ADPEAF Autosomal dominant partial epilepsy with auditory features Printable PDF Open All Close ... the expand/collapse boxes. Description Autosomal dominant partial epilepsy with auditory features ( ADPEAF ) is an uncommon form ...

[National consensus on the ketogenic diet].

PubMed

Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

2014-09-01

Epilepsy is a chronic disease with onset in infancy affecting 0.5-1% of the population. One third of the patients is refractory to antiepileptic drugs and they pose a challenge for the health care team. The ketogenic diet is an effective, non-pharmacological, alternative treatment for the management of refractory epilepsy. There is a need to establish guidelines for the adequate and increased use of the ketogenic diet in Spanish-speaking countries. The National Committee on the Ketogenic Diet, consisting of paediatric neurologists, clinical nutritionists, and dietitians, of the Argentine Society of Child Neurology has developed this consensus statement to standardize the use of the ketogenic diet based on the literature and clinical experience. Patient selection, pre-treatment family counseling, drug interactions, micronutrient supplementation, adverse effects, and discontinuation of the diet are discussed. The ketogenic diet is an effective treatment for children with refractory epilepsy. Education and collaboration of the patient and their family is essential. The patient should be managed by an experienced multidisciplinary team using a protocol. The formation of a national multidisciplinary team and the publication of this document provide possibilities for new centers to integrate the ketogenic diet into their treatment options.

Music therapy as a non-pharmacological treatment for epilepsy.

PubMed

Liao, Huan; Jiang, Guohui; Wang, Xuefeng

2015-01-01

Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies.

The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

ERIC Educational Resources Information Center

Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

2009-01-01

Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

Determining Surgical Candidacy in Temporal Lobe Epilepsy

PubMed Central

Mansouri, Alireza; Fallah, Aria; Valiante, Taufik A.

2012-01-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy that is amenable to surgical treatment. In the carefully selected patient, excellent seizure outcome can be achieved with minimal or no side effects from surgery. This may result in improved psychosocial functioning, achieving higher education, and maintaining or gaining employment. The objective of this paper is to discuss the surgical selection process of a patient with TLE. We define what constitutes a patient that has medically refractory TLE, describe the typical history and physical examination, and distinguish between mesial TLE and neocortical TLE. We then review the role of routine (ambulatory/sleep-deprived electroencephalography (EEG), video EEG, magnetic resonance imaging (MRI), neuropsychological testing, and Wada testing) and ancillary preoperative testing (positron emission tomography, single-photon emission computed tomography (SPECT), subtraction ictal SPECT correlated to MRI (SISCOM), magnetoencephalography, magnetic resonance spectroscopy, and functional MRI) in selecting surgical candidates. We describe the surgical options for resective epilepsy surgery in TLE and its commonly associated risks while highlighting some of the controversies. Lastly, we present teaching cases to illustrate the presurgical workup of patients with medically refractory TLE. PMID:22957238

Temporal lobe origin is common in patients who have undergone epilepsy surgery for hypermotor seizures.

PubMed

Arain, Amir M; Azar, Nabil J; Lagrange, Andre H; McLean, Michael; Singh, Pradumna; Sonmezturk, Hasan; Konrad, Peter; Neimat, Joseph; Abou-Khalil, Bassel

2016-11-01

Hypermotor seizures are most often reported from the frontal lobe but may also have temporal, parietal, or insular origin. We noted a higher proportion of patients with temporal lobe epilepsy in our surgical cohort who had hypermotor seizures. We evaluated the anatomic localization and surgical outcome in patient with refractory hypermotor seizures who had epilepsy surgery in our center. We identified twenty three patients with refractory hypermotor seizures from our epilepsy surgery database. We analyzed demographics, presurgical evaluation including semiology, MRI, PET scan, interictal/ictal scalp video-EEG, intracranial recording, and surgical outcomes. We evaluated preoperative variables as predictors of outcome. Most patients (65%) had normal brain MRI. Intracranial EEG was required in 20 patients (86.9%). Based on the presurgical evaluation, the resection was anterior temporal in fourteen patients, orbitofrontal in four patients, cingulate in four patients, and temporoparietal in one patient. The median duration of follow-up after surgery was 76.4months. Fourteen patients (60%) had been seizure free at the last follow up while 3 patients had rare disabling seizures. Hypermotor seizures often originated from the temporal lobe in this series of patients who had epilepsy surgery. This large proportion of temporal lobe epilepsy may be the result of a selection bias, due to easier localization and expected better outcome in temporal lobe epilepsy. With extensive presurgical evaluation, including intracranial EEG when needed, seizure freedom can be expected in the majority of patients. Copyright © 2016. Published by Elsevier Inc.

Better evidence for earlier assessment and surgical intervention for refractory epilepsy (The BEST study): a mixed methods study protocol.

PubMed

Rapport, Frances; Shih, Patti; Mitchell, Rebecca; Nikpour, Armin; Bleasel, Andrew; Herkes, Geoffrey; Vagholkar, Sanjyot; Mumford, Virginia

2017-08-21

One-third of patients with refractory epilepsy may be candidates for resective surgery, which can lead to positive clinical outcomes if efficiently managed. In Australia, there is currently between a 6-month and 2-year delay for patients who are candidates for respective epilepsy surgery from the point of referral for surgical assessment to the eventual surgical intervention. This is a major challenge for implementation of effective treatment for individuals who could potentially benefit from surgery. This study examines implications of delays following the point of eligibility for surgery, in the assessment and treatment of patients, and the factors causing treatment delays. Mixed methods design: Observations of qualitative consultations, patient and healthcare professional interviews, and health-related quality of life assessments for a group of 10 patients and six healthcare professionals (group 1); quantitative retrospective medical records' reviews examining longitudinal outcomes for 50 patients assessed for, or undergoing, resective surgery between 2014 and 2016 (group 2); retrospective epidemiological study of all individuals hospitalised with a diagnosis of epilepsy in New South Wales (NSW) in the last 5 years (2012-2016; approximately 11 000 hospitalisations per year, total 55 000), examining health services' use and treatment for individuals with epilepsy, including refractory surgery outcomes (group 3). Ethical approval has been granted by the North Sydney Local Health District Human Research Ethics Committee (HREC/17/HAWKE/22) and the NSW Population & Health Services Research Ethics Committee (HREC/16/CIPHS/1). Results will be disseminated through publications, reports and conference presentations to patients and families, health professionals and researchers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Surgical treatment for medically refractory focal epilepsy in a patient with fragile X syndrome.

PubMed

Kenmuir, Cynthia; Richardson, Mark; Ghearing, Gena

2015-10-01

Medication resistant temporal lobe epilepsy occurs in a small population of patients with fragile X syndrome. We present the case of a 24-year-old man with medically refractory temporal lobe epilepsy and fragile X syndrome who underwent left anterior temporal lobectomy resulting in cessation of seizures. Our patient was diagnosed with fragile X syndrome with a fully mutated, fully methylated FMR1 gene resulting in 572 CGG repeats. He developed seizures initially controlled with Depakote monotherapy, but progressed to become medically refractive to combination treatment with Depakote, lamotrigine and zonisamide. Prolonged video EEG monitoring revealed interictal left temporal sharp waves and slowing as well as subclinical and clinical seizures, each with left temporal onset. 3T MRI was consistent with left mesial temporal sclerosis. After discussing the case in our multidisciplinary surgical epilepsy conference, he was referred for presurgical evaluation including neuropsychological testing and Wada testing. He underwent an asleep left anterior temporal lobectomy, sparing the superior temporal gyrus. Pathology showed neuronal loss and gliosis in the hippocampus and amygdala. Twelve months after surgery, the patient has not experienced a seizure. He is described by his parents as less perseverative and less restless. We have presented the case of a 24 year-old-man with fragile X syndrome who underwent successful left anterior temporal lobectomy for the treatment of medically refractory epilepsy who is now seizure free without further functional impairment. This case report demonstrates the feasibility of surgical treatment for a patient with comorbid fragile X syndrome and mesial temporal sclerosis. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis.

PubMed

Spatola, Marianna; Dalmau, Josep

2017-06-01

The aim of this study was to assess the seizure manifestations and risk of epilepsy in encephalitis associated with antibodies against neuronal cell-surface (autoimmune encephalitis) or myelin-associated antigens, and to review several chronic epileptic disorders, including Rasmussen's encephalitis, fever-induced refractory epileptic syndromes (FIRES) and new-onset refractory status epilepticus (NORSE). Seizures are a frequent manifestation of autoimmune encephalitis. Some autoimmune encephalitis may associate with characteristic features: faciobrachial dystonic seizures (anti-LGI1 encephalitis), electroencephalogram extreme delta brush (anti-NMDAR) or multifocal FLAIR-MRI abnormalities (anti-GABAAR). In anti-LGI1 encephalitis, cortical, limbic and basal ganglia dysfunction results in different types of seizures. Autoimmune encephalitis or myelin-antibody associated syndromes are often immunotherapy-responsive and appear to have a low risk for chronic epilepsy. In contrast patients with seizures related to GAD65-antibodies (an intracellular antigen) frequently develop epilepsy and have suboptimal response to treatment (including surgery). Rasmussen's encephalitis or FIRES may occur with autoantibodies of unclear significance and rarely respond to immunotherapy. A study of patients with NORSE showed that 30% developed chronic epilepsy. Although seizures are frequent in all types of autoimmune encephalitis, the risk for chronic epilepsy is dependent on the antigen: lower if located on the cell-surface, and higher if intracellular. For other disorders (Rasmussen's encephalitis, FIRES, NORSE), the prognosis remains poor.

Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

ERIC Educational Resources Information Center

Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

An observational study on outcome of hemispherotomy in children with refractory epilepsy.

PubMed

Panigrahi, Manas; Krishnan, Shyam Sundar; Vooturi, Sudhindra; Vadapalli, Rammohan; Somayajula, Shanmukhi; Jayalakshmi, Sita

2016-12-01

The current study aimed to evaluate the clinical characteristics and outcome of hemispherotomy in children with refractory hemispherical epilepsy. Retrospective analysis of data in twenty one children aged ≤12 years who underwent hemispherotomy and had at least two years post surgery follow-up was performed. Sixteen children underwent Delalande's vertical para-sagittal hemispherotomy (VPH), while lateral peri-insular functional hemispherotomy was performed in the rest. The average age of onset for epilepsy in the study population was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years. The mean age at surgery of the study population was 6.8 ± 2.8 years. Six (28.5%) children were girls. Gliosis due to presumed childhood infarct was most common etiology, observed in 13 (62.0%) of the children, followed by Rasmussen's encephalitis in six (28.5%). There was no significant difference between the surgery groups for the reported acute post operative seizures (APOS) (20.0% vs. 25.0%; p = 1.000). At last follow up 90.5% patients were seizure free; there was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p = 0.228). When analyzed for outcome between the etiologies, seizure freedom was similar for gliosis due to infarct (76.9%), Rassmussens encephalitis (83.3%) and malformations of cortical development (MCD) (100.0%). Moreover, improved quality of life in epilepsy (QOLIE) scores was observed in 80.0% of the lateral peri-insular functional hemispherotomy group and 87.5% children in VPH group at the last follow-up. Gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions in the current study. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients.

PubMed

Ryvlin, P; Bouvard, S; Le Bars, D; De Lamérie, G; Grégoire, M C; Kahane, P; Froment, J C; Mauguière, F

1998-11-01

We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery.

The consequences of idiopathic partial epilepsies in relation to neuropsychological functioning: a closer look at the associated mathematical disability.

PubMed

Sart, Z Hande; Demirbilek, Veysi; Korkmaz, Bariş; Slade, Peter D; Dervent, Ayşin; Townes, Brenda D

2006-03-01

Although the seizure prognosis is mostly favorable in idiopathic partial epilepsies, there is some empirical evidence showing that subtle neuropsychological impairments, with a consequent risk of academic underachievement, are not rare. We investigated neuropsychological functioning including attention, memory, visuomotor ability, and executive functioning with a closer look at the associated mathematical ability in patients with idiopathic partial epilepsies. A battery of age-appropriate, neuropsychological and mathematics achievement tests was administered to 30 participants with idiopathic partial epilepsy [13 children with benign epilepsy with centrotemporal spikes (BECTS), 17 children with idiopathic childhood occipital epilepsies (ICOE)], and to 30 healthy participants matched for age, sex, handedness, and socioeconomic status. Results did not support any impairment in overall neuropsychological functioning in participants with idiopathic partial epilepsies, whereas, isolated deficits did exist. The mean performance of the IPE group was significantly lower than the control group in six out of 12, neuropsychological measures: drawing (p < 0.01), digit span (p < 0.05), verbal learning (p < 0.01), object assembly (p < 0.01), similarities (p < 0.05), and vocabulary (p < 0.001). Results suggested that one should be cautious regarding neuropsychological and academic prognosis in the so-called benign idiopathic partial epilepsies of childhood.

Antiepileptic effect of olanzapine in epilepsy patients with atypical depressive comorbidity.

PubMed

Qiu, Xiangmiao; Zingano, Bianca; He, Shixu; Zhu, Xi; Peng, Anjiao; Duan, Jianan; Wolf, Peter; Chen, Lei

2018-06-15

Depression is relatively common among patients with epilepsy, but often with predominant atypical symptoms. Some antiepileptic drugs show positive psychotropic effects, but these are not always sufficient to stabilize mood in epilepsy patients. Antidepressants are recommended to treat atypical depression but are not always effective and present a certain risk of seizure provocation. Thus, new treatment options are welcome. Here, we describe three cases of refractory epilepsy with atypical depression in which olanzapine, contrary to its earlier reported proconvulsant effect, showed excellent antidepressant action and resulted in seizure control. Possible mechanisms of this action are discussed.

New insights into the mechanisms of the ketogenic diet.

PubMed

Boison, Detlev

2017-04-01

High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by ketogenic diet therapies. Ketogenic diets act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium-chain triclycerides, contributes to seizure control through direct α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. Ketogenic diet therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Ketogenic diet therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

Nonvisual spatial navigation fMRI lateralizes mesial temporal lobe epilepsy in a patient with congenital blindness.

PubMed

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; König, Kristina; Jokeit, Hennric

2015-01-01

Nonvisual spatial navigation functional magnetic resonance imaging (fMRI) may help clinicians determine memory lateralization in blind individuals with refractory mesial temporal lobe epilepsy (MTLE). We report on an exceptional case of a congenitally blind woman with late-onset left MTLE undergoing presurgical memory fMRI. To activate mesial temporal structures despite the lack of visual memory, the patient was requested to recall familiar routes using nonvisual multisensory and verbal cues. Our findings demonstrate the diagnostic value of a nonvisual fMRI task to lateralize MTLE despite congenital blindness and may therefore contribute to the risk assessment for postsurgical amnesia in rare cases with refractory MTLE and accompanying congenital blindness.

Cannabidiol as potential treatment in refractory pediatric epilepsy.

PubMed

Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

2016-01-01

In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma.

PubMed

Guimarães, Catarina A; Franzon, Renata C; Souza, Elisabete A P; Schmutzler, Kátia M R S; Montenegro, Maria Augusta; Queiroz, Luciano de S; Cendes, Fernando; Guerreiro, Marilisa M

2004-10-01

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.

Vagal Nerve Stimulator Malfunction with Change in Neck Position: Case Report and Literature Review.

PubMed

D'Agostino, Erin; Makler, Vyacheslav; Bauer, David F

2018-06-01

Vagal nerve stimulation is a safe and well-tolerated treatment for drug-resistant epilepsy. Complications and failure of the device can result from lead fracture, device malfunction, disconnection, or battery displacement and can result in a variety of symptoms. We present an interesting case of stimulator malfunction with increased impedance change seen only with a change in head position. The patient is a 25-year-old male with a vagal nerve stimulator (VNs) placed for medically refractory epilepsy who presented with neck pain and an electrical pulling sensation in his neck whenever he turned his head to the right. Initial interrogation of the VNs showed normal impedance. Subsequent interrogation with the patient's head turned found increased impedance only when the head was turned to the right. The patient had successful removal and replacement of the device with resolution of his preoperative complaints. Partial lead fracture was seen at explant. VNs malfunction can present in atypical ways. Positional maneuvers may help with its timely diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy.

PubMed

Thakur, Anamika; Sahai, A K; Thakur, J S

2011-04-01

Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy. Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD(50) and CD(99) values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100-300 mg/kg), lamotrigine (3-12 mg/kg) and flunarizine (5-20 mg/kg), and then each group of mice was injected with CD(99) dose of PTZ (65mg/kg i.p.). Another group of mice received single ED(50) dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal-Wallis ANOVA on Ranks test. As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection. As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.

Neuroimaging evaluation in refractory epilepsy

PubMed Central

Granados, Ana M; Orejuela, Juan F

2015-01-01

Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

Adenosinergic signaling in epilepsy.

PubMed

Boison, Detlev

2016-05-01

Despite the introduction of at least 20 new antiepileptic drugs (AEDs) into clinical practice over the past decades, about one third of all epilepsies remain refractory to conventional forms of treatment. In addition, currently used AEDs have been developed to suppress neuronal hyperexcitability, but not necessarily to address pathogenic mechanisms involved in epilepsy development or progression (epileptogenesis). For those reasons endogenous seizure control mechanisms of the brain may provide alternative therapeutic opportunities. Adenosine is a well characterized endogenous anticonvulsant and seizure terminator of the brain. Several lines of evidence suggest that endogenous adenosine-mediated seizure control mechanisms fail in chronic epilepsy, whereas therapeutic adenosine augmentation effectively prevents epileptic seizures, even those that are refractory to conventional AEDs. New findings demonstrate that dysregulation of adenosinergic mechanisms are intricately involved in the development of epilepsy and its comorbidities, whereas adenosine-associated epigenetic mechanisms may play a role in epileptogenesis. The first goal of this review is to discuss how maladaptive changes of adenosinergic mechanisms contribute to the expression of seizures (ictogenesis) and the development of epilepsy (epileptogenesis) by focusing on pharmacological (adenosine receptor dependent) and biochemical (adenosine receptor independent) mechanisms as well as on enzymatic and transport based mechanisms that control the availability (homeostasis) of adenosine. The second goal of this review is to highlight innovative adenosine-based opportunities for therapeutic intervention aimed at reconstructing normal adenosine function and signaling for improved seizure control in chronic epilepsy. New findings suggest that transient adenosine augmentation can have lasting epigenetic effects with disease modifying and antiepileptogenic outcome. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Treatment of refractory status epilepticus with topiramate. Report of three cases].

PubMed

Soler, Bernardita; Godoy, Jaime; Mellado Talesnik, Patricio

2009-07-01

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50%. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

PubMed

Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

2014-12-01

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Epilepsy with dual pathology: surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis.

PubMed

Kim, Dong W; Lee, Sang K; Nam, Hyunwoo; Chu, Kon; Chung, Chun K; Lee, Seo-Young; Choe, Geeyoung; Kim, Hyun K

2010-08-01

The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial. We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology. A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02). We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS. Wiley Periodicals, Inc. © 2009 International League Against Epilepsy.

High-frequency oscillations (HFOs) in clinical epilepsy

PubMed Central

Jacobs, J.; Staba, R.; Asano, E.; Otsubo, H.; Wu, J.Y.; Zijlmans, M.; Mohamed, I.; Kahane, P.; Dubeau, F.; Navarro, V.; Gotman, J.

2013-01-01

Epilepsy is one of the most frequent neurological diseases. In focal medically refractory epilepsies, successful surgical treatment largely depends on the identification of epileptogenic zone. High-frequency oscillations (HFOs) between 80 and 500 Hz, which can be recorded with EEG, may be novel markers of the epileptogenic zone. This review discusses the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. HFOs are clearly linked to the seizure onset zone, and the surgical removal of regions generating them correlates with a seizure free post-surgical outcome. Moreover, HFOs reflect the seizure-generating capability of the underlying tissue, since they are more frequent after the reduction of antiepileptic drugs. They can be successfully used in pediatric epilepsies such as epileptic spasms and help to understand the generation of this specific type of seizures. While mostly recorded on intracranial EEGs, new studies suggest that identification of HFOs on scalp EEG or magnetoencephalography (MEG) is possible as well. Thus not only patients with refractory epilepsies and invasive recordings but all patients might profit from the analysis of HFOs. Despite these promising results, the analysis of HFOs is not a routine clinical procedure; most results are derived from relatively small cohorts of patients and many aspects are not yet fully understood. Thus the review concludes that even if HFOs are promising biomarkers of epileptic tissue, there are still uncertainties about mechanisms of generation, methods of analysis, and clinical applicability. Large multicenter prospective studies are needed prior to widespread clinical application. PMID:22480752

Neuropsychology Outcomes Following Trephine Epilepsy Surgery: The Inferior Temporal Gyrus Approach for Amygdalohippocampectomy in Medically Refractory Mesial Temporal Lobe Epilepsy.

PubMed

Schoenberg, Mike R; Clifton, William E; Sever, Ryan W; Vale, Fernando L

2018-06-01

Surgery is indicated in cases of mesial temporal lobe epilepsy(MTLE) that are refractory to medical management. The inferior temporal gyrus (ITG) approach provides access to the mesial temporal lobe (MTL) structures with minimal tissue disruption. Reported neuropsychology outcomes following this approach are limited. To report neuropsychological outcomes using an ITG approach to amygdalohippocampectomy (AH) in patients with medically refractory MTLE based on a prospective design. Fifty-four participants had Engel class I/II outcome following resection of MTL using the ITG approach. All participants had localization-related epilepsy confirmed by long-term surface video-electroencephalography and completed pre/postsurgical evaluations that included magnetic resonance imaging (MRI), Wada test or functional MRI, and neuropsychology assessment. Clinical semiology/video-electroencephalography indicated that of the 54 patients, 28 (52%) had left MTLE and 26 (48%) had right MTLE. Dominant hemisphere resections were performed on 23 patients (43%), nondominant on 31(57%). Twenty-nine (29) had pathology-confirmed mesial temporal sclerosis (MTS). Group level analyses found declines in verbal memory for patients with language-dominant resections (P < .05). No significant decline in neuropsychological measures occurred for patients with MTS. Participants without MTS who underwent a language-dominant lobe resection exhibited a significant decline in verbal and visual memory (P < .05). Nondominant resection participants did not exhibit significant change in neuropsychology scores (P > .05). Neuropsychology outcomes of an ITG approach for selective mesial temporal resection are comparable to other selective AH techniques showing minimal adverse cognitive effects. These data lend support to the ITG approach for selective AH as an option for MTLE.

Impact of social factors on the quality of life of patients with refractory epilepsy.

PubMed

Viteva, E

2013-06-01

To assess the impact of social factors on the quality of life of Bulgarian patients with refractory epilepsy. We have studied 70 patients with refractory epilepsy (RE) and 70 patients with pharmacosensitive epilepsy. All of them were between 18 and 65 years of age, without cognitive decline, progressive somatic or neurological disease or recent seizures. All participants were inquired about their education,employment, marital status, and driving. Only the patients with RE completed QOLIE-89. Twenty-five (35.71%) of the participants with RE were not married; 16 (22.86%) of them had an elementary education, 44 (62.86%) - a secondary education, and 10 (14.29%) - a university education.Nineteen (27.4%) participants were employed, 41 (58.57%) were recognized disabled, 10 (14.29%)were unemployed. Two (2.86%) of the patients with RE were drivers. We found out that the marital status did not change the quality of life. The university education correlated with a higher assessment of the “overall health” subscale (50%). The limited or lacking employment had a negative impact on the assessment of the following subscales: “pain”, “health discouragement”, “sexual relations”, “emotional well-being”, “memory”, “work/driving/social function”, “overall health”, “overall quality of life” and the overall score of QOLIE-89. The possibility of driving correlated with more worries about adverse events from antiepileptic drugs. The limited or lacking employment has a negative impact on most aspects of the quality of life, while education and driving influence single aspects of the quality of life.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

Partial (focal) seizure

MedlinePlus

... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

PubMed

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

PubMed

Hussain, Shaun A; Shin, Ji Hyun; Shih, Evan J; Murata, Kristina K; Sewak, Sarika; Kezele, Michele E; Sankar, Raman; Matsumoto, Joyce H

2016-02-01

Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.

PubMed

Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong

2011-01-01

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.

Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of >100 patients.

PubMed

Lim, Zhan; Wong, Kingsley; Olson, Heather E; Bergin, Ann M; Downs, Jenny; Leonard, Helen

2017-08-01

Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures. The International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital. Data regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3-33.9 years), with median age of 6 weeks (range = 1 day-65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9-24). Changes in seizure activity after commencing KD were reported for two-thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one-third (31.7%) experienced side effects during the diet. At ascertainment, only one-third (32%) remained on the diet, with lack of long-term efficacy as the main reason for diet cessation (51%, 36 of 70). Benefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long-term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: a decision analysis.

PubMed

Akama-Garren, Elliot H; Bianchi, Matt T; Leveroni, Catherine; Cole, Andrew J; Cash, Sydney S; Westover, M Brandon

2014-11-01

Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

PubMed

Asadi-Pooya, Ali A; Sperling, Michael R

2015-08-01

To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neuronal zinc-α2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats.

PubMed

Liu, Ying; Wang, Teng; Liu, Xi; Wei, Xin; Xu, Tao; Yin, Maojia; Ding, Xueying; Mo, Lijuan; Chen, Lifen

2017-08-15

Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used. The existence and level of ZAG in the brain were identified using immunohistochemistry, double-labeled immunofluorescence and western blot, and the expression level of AZGP1 mRNA was determined with quantitative real-time polymerase chain reaction (qrt-PCR). To explore the potential biological role of ZAG in the brain, co-immunoprecipitation (Co-IP) of phosphorylated ERK (p-ERK), TGF-β1 and ZAG was also performed. ZAG was found in the cytoplasm of neurons in brain tissue from both patients and rats. The levels of AZGP1 mRNA and ZAG were lower in refractory TLE patients and PTZ-kindled rats than in controls. In addition, the ZAG level decreased as PTZ kindling continued. Co-IP identified direct binding between p-ERK, TGF-β1 and ZAG. ZAG was found to be synthesized in neurons, and both the AZGP1 mRNA and ZAG protein levels were decreased in epilepsy patients and rat models. The reduction in ZAG may participate in the pathogenesis and pathophysiology of epilepsy by interacting with p-ERK and TGF-β1, promoting inflammation, regulating the metabolism of ketone bodies, or affecting other epilepsy-related molecules. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Perampanel as adjunctive therapy in highly refractory epilepsies: Real-world data from an Italian tertiary care epilepsy centre.

PubMed

Morano, Alessandra; Fattouch, Jinane; Albini, Mariarita; Casciato, Sara; Fanella, Martina; Basili, Luca Manfredi; Viganò, Alessandro; Manfredi, Mario; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

2018-07-15

Perampanel (PER) is a selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, licensed as adjunctive therapy in focal epilepsy and primary generalized tonic-clonic seizures (pGTCSs). We performed a retrospective study on highly refractory adult patients taking PER, with 1-year follow-up. Retention rate represented the primary outcome of our work; seizure frequency reduction (≥50%), "switch rate" and proportion of adverse events (AEs) were evaluated as secondary endpoints. Eighty-nine subjects (47 females, age range: 19-78 years) were included. Seventy-three had focal epilepsy (FE), 9 generalized epilepsy and 7 epileptic encephalopathy. All patients were highly drug-resistant (medication failures: 5-17). Retention rate was 87.6%, 63% and 51.7% at 3, 6 and 12 months. Responders were 27/89 (30.3%), with 8/27 seizure-free. The number of previous treatment failures and the concomitant use of enzyme inducers negatively influenced clinical response, whereas no correlation was documented between PER dose and outcome. Responder proportion was more satisfying in structural FE than in FE of unknown etiology (33% versus 20%), and in secondarily GTCSs than focal seizures (54% vs 28%), whereas pGTCSs showed a lower reponse rate (25%). Mild-to-moderate AEs (mainly dizziness, gait disturbances and psychiatric effects) were reported by 40% of patients; serious psychiatric AEs usually occurred in subjects with psychiatric comorbidities. Our study confirms the tolerability and effectiveness of PER in highly drug-resistant patients with different epilepsy syndromes and aetiologies. Copyright © 2018 Elsevier B.V. All rights reserved.

Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet.

PubMed

Lauritzen, Fredrik; Eid, Tore; Bergersen, Linda H

2015-01-01

Epilepsy is a serious neurological disorder that affects approximately 1 % of the general population, making it one of the most common disorders of the central nervous system. Furthermore, up to 40 % of all patients with epilepsy cannot control their seizures with current medications. More efficacious treatments for medication refractory epilepsy are therefore needed. A better understanding of the mechanisms that cause this disorder is likely to facilitate the discovery of such treatments. Impairment in cerebral energy metabolism has been proposed as a possible causative factor in the pathogenesis of temporal lobe epilepsy (TLE), which is one of the most common types of medication-refractory epilepsies in adults. In this review, we will discuss some of the current hypotheses regarding the possible causal relationship between brain energy metabolism and TLE. Emphasis will be placed on the role of energy substrates (lactate and ketone bodies) and their transporter molecules, particularly monocarboxylate transporters 1 and 2 (MCT1 and MCT2). We recently reported that the cellular distribution of MCT1 and MCT2 is perturbed in the hippocampus in patients with TLE. The changes may be an adaptive response aimed at keeping high levels of lactate in the epileptic tissue, which may serve to counteract epileptic activity by downregulating cAMP levels through the lactate receptor GPR81, newly discovered in hippocampus. We propose that the perturbation of MCTs may be further involved in the pathophysiology of TLE by influencing brain energy homeostasis, mitochondrial function, GABA-ergic and glutamatergic neurotransmission, and flux of lactate through the brain.

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study.

PubMed

Toupin, Jean-François; Lortie, Anne; Major, Philippe; Diadori, Paola; Vanasse, Michel; Rossignol, Elsa; D'Anjou, Guy; Perreault, Sebastien; Larbrisseau, Albert; Carmant, Lionel; Birca, Ala

2015-12-01

Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste-Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow-up visit. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2-20.7 years) at the initiation of treatment. The average length of follow-up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow-up visit, respectively. One became seizure-free. Adverse effects were reported in 11 patients and none were severe. Responders and non-responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.

Right fronto-limbic atrophy is associated with reduced empathy in refractory unilateral mesial temporal lobe epilepsy.

PubMed

Toller, Gianina; Adhimoolam, Babu; Rankin, Katherine P; Huppertz, Hans-Jürgen; Kurthen, Martin; Jokeit, Hennric

2015-11-01

Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain structures for human empathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet.

PubMed

Alberti, María J; Agustinho, Ariela; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; De Martini, Martha G; Diez, Cecilia; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Ríos, Viviana; Sosa, Patricia; Vaccarezza, María; Viollaz, Rocío; Panico, Luis

2016-02-01

The ketogenic diet, a non-drug treatment with proven effectiveness, has been the most commonly used therapy in the past decade for the management of refractory epilepsy in the pediatric population. Compared to adding a new drug to a pre-existing treatment, the ketogenic diet is highly effective and reduces the number of seizures by 50-90% in approximately 45-60% of children after six months of treatment. For this reason, the Argentine Society of Pediatric Neurology established the Ketogenic Diet Working Group. It is integrated by pediatric dietitians, pediatricians, pediatric neurologists and B.S. in Nutrition, who developed recommendations for the optimal management of patients receiving the classical ketogenic diet based on expert consensus and scientific publications in this field. Sociedad Argentina de Pediatría.

A comparison of the efficacy and tolerability of oxcarbazepine oral suspension between infants and children with epilepsy: a retrospective chart review at a single medical center in Taiwan.

PubMed

Wei, Shu-Hao; Liu, Cheng-Chao; Fan, Pi-Chuan

2014-02-01

Few clinical studies have assessed the efficacy and safety of oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly in infants. The aim of this study was to investigate and compare the efficacy, tolerability, and side effects of OXC oral suspension in Taiwanese infants and children with various types of epilepsy. A retrospective review of the efficacy, tolerability, and side effects of OXC oral suspension in a tertiary medical center in Taiwan was conducted and included children (1-9 years old) and infants (<1 year old) diagnosed with epilepsy, which was classified into idiopathic partial, symptomatic partial, or multifocal subtypes. The OXC oral suspension (Trileptal(®); Novartis) was given in a gradual dose titration, from an initial 7.5 mg/kg/day to 30 mg/kg/day within 1 month in all cases. A total of 20 infants and 38 children were identified. There were no statistically significant differences between the children and infants in efficacy (75 vs. 82 %, p = 0.734) and adverse effects (30 vs. 21 %, p = 0.525) after OXC oral suspension treatment. The efficacy was significantly correlated with the epilepsy subtype (p < 0.01) and the number of combined antiepileptic drugs (AEDs) before OXC treatment (p < 0.01) in both groups. The patients with idiopathic and symptomatic partial epilepsy responded better to OXC oral suspension than those with multifocal epilepsy. OXC oral suspension is effective and well tolerated in both infants and children with partial epilepsy in Taiwan. Treatment efficacy was related to epilepsy subtype and number of combined AEDs before OXC treatment. Monotherapy had an excellent therapeutic response in partial epilepsy but not in multifocal epilepsy.

Determination of SCN1A genetic variants in Mexican patients with refractory epilepsy and Dravet syndrome.

PubMed

Jiménez-Arredondo, R E; Brambila-Tapia, A J L; Mercado-Silva, F M; Magaña-Torres, M T; Figuera, L E

2017-05-18

Mutations in the SCN1A gene can result in syndromes associated with epilepsy, including the Dravet syndrome (DS). However, the prevalence of such mutations in these diseases varies widely between different studies, and has not been examined in Mexican patients with epilepsy. Therefore, the objective of this study was to determine the frequency of SCN1A mutations (in the exon 26) in a cohort of Mexican patients with DS and refractory epilepsy (RE). We recruited 24 Mexican patients (14 males and 10 females), of which 15 were diagnosed with RE and 9 were diagnosed with DS. The SCN1A gene was sequenced to uncover mutations in exon 26. We detected 2 novel genotypes in 2 DS patients. One was a synonymous variant, c.5418 G > A (E1806E), and the other was a missense variant, c. 5324 T > C (L1775P). The missense mutation was predicted to be damaging with a score of 100% by the PolyPhen-2 program. The frequency of pathogenic variants was 4.17% in all the patients and 11.1% in DS patients, which, together with other publications, emphasize that specific and more severe phenotypes are associated with SCN1A mutations.

Variable outcome for epilepsy after neonatal hypoglycaemia.

PubMed

Fong, Choong Yi; Harvey, A Simon

2014-11-01

To evaluate the electroclinical features of epilepsy secondary to neonatal hypoglycaemia. This was a retrospective study of children who had seizures beyond infancy after neonatal hypoglycaemia treated at The Royal Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal asphyxia were excluded. Clinical details were obtained from medical records. Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were reviewed. Eleven patients met the inclusion criteria (six males, five females; mean age 10y 5mo, range 4-18y at the time of review). Age at seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in nine and generalized tonic in two patients. MRI showed gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe in all. Predominant EEG findings were stereotyped occipital sharp-slow discharges in five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and generalized slow spike-wave and fast activity in two. Seizures were infrequent or remitted in six of the nine children with focal occipital seizures, and frequent and refractory in both children with generalized seizures. Despite the common antecedent and bilateral occipital lobe injury, the seizure manifestations and course of epilepsy after neonatal hypoglycaemia were variable, with mild occipital, refractory occipital, and symptomatic generalized epilepsy recognized. © 2014 Mac Keith Press.

Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

PubMed

Walsh, Jordana; Thomas, Rhys H; Church, Carla; Rees, Mark I; Marson, Anthony G; Baker, Gus A

2014-06-01

The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery. Copyright © 2014. Published by Elsevier Inc.

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Medical management of refractory epilepsy--practical treatment with novel antiepileptic drugs.

PubMed

Ben-Menachem, Elinor

2014-01-01

The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Presurgical evaluation for partial epilepsy: Relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal ictal EEG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engel, J. Jr.; Henry, T.R.; Risinger, M.W.

1990-11-01

One hundred fifty-three patients with medically refractory partial epilepsy underwent chronic stereotactic depth-electrode EEG (SEEG) evaluations after being studied by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and scalp-sphenoidal EEG telemetry. We carried out retrospective standardized reviews of local cerebral metabolism and scalp-sphenoidal ictal onsets to determine when SEEG recordings revealed additional useful information. FDG-PET localization was misleading in only 3 patients with temporal lobe SEEG ictal onsets for whom extratemporal or contralateral hypometabolism could be attributed to obvious nonepileptic structural defects. Two patients with predominantly temporal hypometabolism may have had frontal epileptogenic regions, but ultimate localization remains uncertain. Scalp-sphenoidalmore » ictal onsets were misleading in 5 patients. For 37 patients with congruent focal scalp-sphenoidal ictal onsets and temporal hypometabolic zones, SEEG recordings never demonstrated extratemporal or contralateral epileptogenic regions; however, 3 of these patients had nondiagnostic SEEG evaluations. The results of subsequent subdural grid recordings indicated that at least 1 of these patients may have been denied beneficial surgery as a result of an equivocal SEEG evaluation. Weighing risks and benefits, it is concluded that anterior temporal lobectomy is justified without chronic intracranial recording when specific criteria for focal scalp-sphenoidal ictal EEG onsets are met, localized hypometabolism predominantly involves the same temporal lobe, and no other conflicting information has been obtained from additional tests of focal functional deficit, structural imaging, or seizure semiology.« less

Genetics of Severe Early Onset Epilepsies

ClinicalTrials.gov

2017-08-24

Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions

Epileptogenesis and companion animals.

PubMed

Patterson, Edward Ned E

2013-05-01

Epileptogenesis is the process by which a normal brain develops into an epileptic brain. There are 3 distinct phases of epileptogenesis-the latent period before seizures occur, the occurrence of recurrent seizures, and in about 30% of patients, the development of refractory epilepsy. Understanding the basic epileptic circuit abnormalities associated with recurrent seizures via aberrations in glutamate, gamma-aminobutyric acid, and ligand- and voltage-gated ion channel activity can help the small-animal practitioner understand the mechanism of action of the antiepileptic drugs currently used for dogs and cats for new-onset and refractory epilepsy. Understanding the latest research results and theories about the pathophysiology of the latent period of epileptogenesis, where recurrent seizures have not yet developed, would help the practitioner understand possible target areas for future treatments to treat epilepsy by preventing it rather than just symptomatically preventing recurrent seizures. The current areas of focus of research on the latent period include neurodegeneration, neurogenesis, axonal sprouting, glial cell activation, invasion of inflammatory cells, angiogenesis, and subclinical alteration of ligand- and receptor-gated ion channels. © 2013 Elsevier Inc. All rights reserved.

Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: A case report.

PubMed

Gagnon, Maude-Marie; Savard, Martin; Mourabit Amari, Karim

2016-04-01

Autoimmune encephalitis is an inflammatory disorder of the brain that may be associated with different neuronal antibodies. Recently, an increasing number of valuable autoantibodies have been identified, including GABAAR antibodies, which appear to be associated with a severe form of encephalitis with refractory status epilepticus. We report here on a patient with encephalitis associated with GAD65 and GABAAR antibodies, an entity that remains an understudied topic, with an unanticipated clinical presentation and we describe the longitudinal follow-up. We report a case of encephalitis associated with GAD65 and GABAAR antibodies; we describe clinical and paraclinical features and the longitudinal follow-up. Our case presented with dysgueusia, dysosmia and episodes of hyperventilation that evolved into a refractory status epilepticus. Multiple anticonvulsant drugs were required. An aggressive immunotherapy was associated with a relative favorable outcome, in regard of epilepsy and cognitive functions. However, a relapse occurred and a full recovery was not observed at the last follow-up visit. There was no correlation between GAD65 antibodies titers and disease activity. Autoimmune encephalitis associated with GABAAR and GAD65 antibodies might be a severe and refractory disease. The appropriate treatment is currently unknown for those patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis.

PubMed

Vanhaesebrouck, An E; Posch, Barbara; Baker, Sam; Plessas, Ioannis N; Palmer, Anthony C; Constantino-Casas, Fernando

2012-12-01

A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called 'dual pathology' of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

2015-04-01

A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

Valproate and epilepsy: for women as well as men.

PubMed

Lawthom, Charlotte

2018-06-01

Sodium valproate remains the best drug for idiopathic generalised epilepsy. For men with the latter diagnosis, this is the drug of choice. Sodium valproate has an unacceptably high level of major fetal malformation and also causes learning disabilities in many children exposed to the drug in utero. Women of reproductive age should not normally be offered this drug. There are many women with refractory epilepsy who would benefit from this drug and who are not planning pregnancy. Individualised epilepsy care is the gold standard, not blanket bans on drug choice based on gender. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Coexistence of meningoencephalocele and hippocampal sclerosis: a new type of dual pathology.

PubMed

Martinoni, Matteo; Marucci, Gianluca; Gagliardini, Gabriele; Tinuper, Paolo; Michelucci, Roberto; Giulioni, Marco

2017-05-01

Both temporal lobe meningoencephalocele (TE) and hippocampal sclerosis (HS) are causes of drug-resistant temporal lobe epilepsy. Spontaneous TE constitutes a rare but well-known and increasingly recognised cause of refractory epilepsy. It is well known that HS may be associated with another neocortical lesion (dual pathology). Here we report for the first time a new type of dual pathology; namely, the coexistence of temporal pole meningoencephalocele and HS.

Low Rate of Intraoperative Seizures During Awake Craniotomy in a Prospective Cohort with 374 Supratentorial Brain Lesions: Electrocorticography Is Not Mandatory.

PubMed

Boetto, Julien; Bertram, Luc; Moulinié, Gérard; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

2015-12-01

Awake craniotomy (AC) in brain lesions has allowed an improvement of both oncologic and functional results. However, intraoperative seizures (IOSs) were reported as a cause of failure of AC. Here, we analyze the incidence, risk factors, and consequences of IOSs in a prospective cohort of 374 ACs without electrocorticography (ECoG). We performed a prospective study including all patients who underwent AC for an intra-axial supratentorial cerebral lesion from 2009-2014 in our department. Occurrence of IOS was analyzed with respect to medical and epilepsy history, tumor characteristics, operative technique, and postoperative outcomes. The study comprised 374 patients with a major incidence of low-grade glioma (86%). Most of the patients (83%) had epilepsy history before surgery (20% had intractable seizures). Preoperative mean Karnofsky performance scale (KPS) score was 91. IOSs occurred in 13 patients (3.4%). All IOSs were partial seizures, which quickly resolved by irrigation with cold Ringer lactate. No procedure failed because of IOS, and the rate of aborted AC whatever the cause was nil. Mean stimulation current intensity for cortical and subcortical mapping was 2.25 ± 0.6 mA. Presurgical refractory epilepsy was not associated with a higher incidence of IOS. Three months after surgery, no patients had severe or disabling permanent worsening, even within the IOS group (mean KPS score of 93.7). AC for intra-axial brain lesion can be safely and reproducibly achieved without ECoG, with a low rate of IOS and excellent functional results, even in patients with preoperative intractable epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic Devices for Epilepsy

PubMed Central

Fisher, Robert S.

2011-01-01

Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

PubMed

Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

2016-12-23

Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic drugs) is necessary to answer the title question.

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: A decision analysis

PubMed Central

Akama-Garren, Elliot H.; Bianchi, Matt T.; Leveroni, Catherine; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon

2016-01-01

SUMMARY Objectives Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. Methods We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. Results For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. Significance Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis. PMID:25244498

Refractory status epilepticus in children with and without prior epilepsy or status epilepticus.

PubMed

Sánchez Fernández, Iván; Jackson, Michele C; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Gaínza-Lein, Marina; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L; Mikati, Mohamad A; Peariso, Katrina; Riviello, James; Tasker, Robert C; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

2017-01-24

To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month-21 years of age) with rSE. We enrolled 189 participants (53% male) with a median (25th-75th percentile) age of 4.2 (1.3-9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5-60] vs 16.5 [5-42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46-190] vs 50.5 [28-116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5-22.3] vs 20 [5-60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3-124] vs 65 [32.5-156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. © 2016 American Academy of Neurology.

Low Glycemic Index Treatment in pediatric refractory epilepsy: the first Middle East report.

PubMed

Karimzadeh, Parvaneh; Sedighi, Mostafa; Beheshti, Maryam; Azargashb, Enzollah; Ghofrani, Mohammad; Abdollahe-Gorgi, Fatemeh

2014-08-01

Intractable epilepsy is a challenging aspects of pediatric epilepsy. This study was conducted to determine the efficacy and tolerability of Low Glycemic Index Treatment (LGIT) in pediatric patients referred to a Children's Hospital in Iran with intractable epilepsy. We studied 42 children with refractory epilepsy aged between 1.5 and 17 years of age, from October 2009 to April 2011 in the pediatric neurology department of Mofid Children's Hospital. Patient information on clinical status, seizure type, and baseline frequency, blood and urine biochemistry, neuro-imaging and the EEG were collected. LGIT was initiated on an outpatient basis and the diet was composed of 65% fat, 25% protein and 10% carbohydrate (40-60 g), and the glycemic index of foods was limited to below 50. 84% of patients were categorized as having more than one seizure per day at study entry, with the remaining children as experiencing over one seizure per week. A greater than 50% seizure reduction was observed in 71.4% of the patients after the second week, in 73.8% at the end of the first month and in 77.8% at the end of the second month. In 30% of the patients a mild increase in blood urea nitrogen (BUN) was detected. The most important reasons for discontinuation of LGIT were restrictiveness, lack of satiation and excessive meat in this diet. No significant complications were observed during the administration of the diet. LGIT is a safe and effective adjuvant antiepileptic therapy and may be used as an alternative to the ketogenic diet in conditions when this diet cannot be used. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Genetic variations and associated pathophysiology in the management of epilepsy.

PubMed

Mulley, John C; Dibbens, Leanne M

2011-01-01

The genomic era has enabled the application of molecular tools to the solution of many of the genetic epilepsies, with and without comorbidities. Massively parallel sequencing has recently reinvigorated gene discovery for the monogenic epilepsies. Recurrent and novel copy number variants have given much-needed impetus to the advancement of our understanding of epilepsies with complex inheritance. Superimposed upon that is the phenotypic blurring by presumed genetic modifiers scattering the effects of the primary mutation. The genotype-first approach has uncovered associated syndrome constellations, of which epilepsy is only one of the syndromes. As the molecular genetic basis for the epilepsies unravels, it will increasingly influence the classification and diagnosis of the epilepsies. The ultimate goal of the molecular revolution has to be the design of treatment protocols based on genetic profiles, and cracking the 30% of epilepsies refractory to current medications, but that still lies well into the future. The current focus is on the scientific basis for epilepsy. Understanding its genetic causes and biophysical mechanisms is where we are currently positioned: prizing the causes of epilepsy "out of the shadows" and exposing its underlying mechanisms beyond even the ion-channels.

Interictal spiking increases with sleep depth in temporal lobe epilepsy.

PubMed

Malow, B A; Lin, X; Kushwaha, R; Aldrich, M S

1998-12-01

To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.

Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

PubMed Central

French, JA; Baroldi, P; Brittain, ST; Johnson, JK

2014-01-01

Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediate-release OXC. PMID:24359313

Non-pharmacological interventions for people with epilepsy and intellectual disabilities.

PubMed

Jackson, Cerian F; Makin, Selina M; Marson, Anthony G; Kerr, Michael

2015-09-10

Approximately 30% of patients with epilepsy remain refractory to drug treatment and continue to experience seizures whilst taking one or more antiepileptic drugs (AEDs). Several non-pharmacological interventions that may be used in conjunction with or as an alternative to AEDs are available for refractory patients. In view of the fact that seizures in people with intellectual disabilities are often complex and refractory to pharmacological interventions, it is evident that good quality randomised controlled trials (RCTs) are needed to assess the efficacy of alternatives or adjuncts to pharmacological interventions.This is an updated version of the original Cochrane review (Beavis 2007) published in The Cochrane Library (2007, Issue 4). To assess data derived from randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities.Non-pharmacological interventions include, but are not limited to, the following.• Surgical procedures.• Specialised diets, for example, the ketogenic diet, or vitamin and folic acid supplementation.• Psychological interventions for patients or for patients and carers/parents, for example, cognitive-behavioural therapy (CBT), electroencephalographic (EEG) biofeedback and educational intervention.• Yoga.• Acupuncture.• Relaxation therapy (e.g. music therapy). For the latest update of this review, we searched the Cochrane Epilepsy Group Specialised Register (19 August 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO (19 August 2014), MEDLINE (Ovid, 1946 to 19 August 2014) and PsycINFO (EBSCOhost, 1887 to 19 August 2014). Randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities. Two review authors independently applied the inclusion criteria and extracted study data. One study is included in this review. When two surgical procedures were compared, results indicated that corpus callosotomy with anterior temporal lobectomy was more effective than anterior temporal lobectomy alone in improving quality of life and performance on IQ tests among people with epilepsy and intellectual disabilities. No evidence was found to support superior benefit in seizure control for either intervention. This is the only study of its kind and was rated as having an overall unclear risk of bias. The previous update (December 2010) identified one RCT in progress. The study authors have confirmed that they are aiming to publish by the end of 2015; therefore this study (Bjurulf 2008) has not been included in the current review. This review highlights the need for well-designed randomised controlled trials conducted to assess the effects of non-pharmacological interventions on seizure and behavioural outcomes in people with intellectual disabilities and epilepsy.

The origin of the concept of partial epilepsy.

PubMed

Eadie

1999-03-01

The International League Against Epilepsy has devised classifications which subdivide both epileptic seizures and the epilepsies and epileptic syndromes into two main types: generalized and partial. Epileptogenesis in the partial variety is believed to originate in a localized part of the cerebral cortex and results in clinical manifestations which appear to commence in only a restricted part of the sufferer's body. Use of the term 'partial' in relation to these entities has often been said to date back to James Cowles Prichard (1786-1849) who was the author of the second major work on epilepsy to be written in the UK. While Prichard certainly described 'partial epilepsy', he stated that he intended the words to refer to the fact that the disorder he described under that designation was only partly, and not fully, epileptic in nature. He did not refer to the fact that it affected only part of the body as his basis for using the term. In the absence of knowledge of localization of function in the cerebral cortex at Prichard's time of writing, he had no basis for deducing that the underlying epileptic process arose in only part of the brain. However, there is an earlier mention of the use of the word 'partial' in relation to epilepsy. This is to be found in the writings of the great Scottish physician William Cullen (1710-1790), and there is reason to believe that Prichard should have been aware of this. Cullen used 'partial' with an intention similar to the modern one, employing the word to refer to seizures which affected only part of the body. Credit for the origin of the idea of a 'partial' epilepsy should belong to Cullen; not only did he have priority over Prichard but his concept was closer to the modern one than was Prichard's. Copyright 1999 Harcourt Publishers Ltd.

The Janus-faced nature of Rasmussen's encephalitis.

PubMed

Press, Craig; Wallace, Adam; Chapman, Kevin E

2014-06-01

Rasmussen encephalitis (RE) is an inflammatory unilateral progressive medically refractory epilepsy associated with hemiparesis, cognitive dysfunction, and hemispheric atrophy. Here, we present 2 cases from our institution that demonstrate the dual nature of RE in 2 similarly aged children. Overall, 2 types of RE have been described: type 1 has a short prodromal phase and more explosive onset and type 2 has a longer prodromal of partial seizures followed by hemiparesis and atrophy. Younger patients are more likely to fit into the type 1 presentation and have been described as more likely to have dual pathology. Perhaps the patients with a more acute onset are more likely to have a dual pathology as is found in our 2 cases. We review the typical findings in RE and discuss current treatment options, highlighting new experimental treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

Bilateral perisylvian ulegyria: an under-recognized, surgically remediable epileptic syndrome.

PubMed

Schilling, Lucas P; Kieling, Renata R; Pascoal, Tharick A; Kim, Hyoung-Ihl; Lee, Min Cheol; Kim, Yun Hee; Paglioli, Eliseu; Neto, Pedro R; Costa, Jaderson C; Palmini, Andre

2013-08-01

Interest in the association of epilepsy and pseudobulbar palsy was rekindled since the identification through magnetic resonance imaging (MRI) of bilateral perisylvian polymicrogyria (PMG). Seizures are often intractable, but resective epilepsy surgery has not been recommended. However, a similar clinical picture can be encountered in patients with bilateral perisylvian destructive lesions, which fit the description of ulegyria (ULG). We report a series of patients with epilepsy and pseudobulbar palsy due to bilateral perisylvian ULG (BP-ULG), show that hippocampal sclerosis (HS) is often associated and highlight the fact that in this entity, unlike in malformative bilateral perisylvian PMG, seizures may be surgically treated. The motor, cognitive, epileptologic, and imaging features of 12 patients with perisylvian ULG followed at three institutions are described. For patients with refractory seizures, we detail extracranial and intracranial electrographic recordings, surgical strategies, histopathologic analyses of the resected tissue, and outcome of surgical treatment. Descriptive statistics were used for quantitative and categorical variables. Student's t-test was used to compare means, and a p < 0.05 was considered significant. Pseudobulbar palsy and mental retardation were present in all patients with symmetrical BP-ULG. Five had refractory seizures. There was no relationship between the severity of the pseudobulbar palsy or of the mental retardation and the degree of seizure control with medication. The five patients in whom seizures were refractory to medication had significantly earlier age of onset and longer duration of epilepsy (p < 0.05). Dual pathology with associated unilateral HS was present in four. One patient with dual pathology had a temporolimbic electroclinical picture and had an anterior temporal lobectomy (ATL) based upon noninvasive evaluation. The other four had ictal semiology suggesting involvement of both temporolimbic and perisylvian cortex. Intracranial electroencephalography (EEG) showed concomitant seizure onset in the anterior temporal region and in the ipsilateral ULG in three of the four with dual pathology and in the ulegyric cortex in the one without HS. Resection guided by a combination of semiology, MRI, and extra and intracranial EEG led to complete seizure control in two and almost complete seizure control (Engel class II) in two other patients. The only surgical failure was an isolated ATL in a patient with dual pathology, and concomitant seizure onset in both lesions according to semiology and intracranial EEG. Our findings suggest that BP-ULG mimics the clinical features of bilateral perisylvian PMG. In patients with refractory seizures, recognition of this entity should lead to consideration of resective surgery despite the bilateral ULG. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

PubMed

Bradley, Lucas; Bahgat, Diaa; Sharp, Gregory; Willis, Erin; Ocal, Eylem; Albert, Gregory; Serletis, Demitre

2015-10-01

We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies.

What do patients with epilepsy tell us about language dynamics? A review of fMRI studies.

PubMed

Baciu, Monica; Perrone-Bertolotti, Marcela

2015-01-01

The objective of this review is to resume major neuroimaging findings on language organization and plasticity in patients with focal and refractory epilepsy, to discuss the effect of modulatory variables that should be considered alongside patterns of reorganization, and to propose possible models of language reorganization. The focal and refractory epilepsy provides a real opportunity to investigate various types of language reorganization in different conditions. The 'chronic' condition (induced by the epileptogenic zone or EZ) is associated with either recruitment of homologous regions of the opposite hemisphere or recruitment of intrahemispheric, nonlinguistic regions. In the 'acute' condition (neurosurgery and EZ resection), the initial interhemispheric shift (induced by the chronic EZ) could follow a reverse direction, back to the initial hemisphere. These different patterns depend on several modulatory factors and are associated with various levels of language performance. As a neuroimaging tool, functional magnetic resonance imaging enables the detailed investigation of both hemispheres simultaneously and allows for comparison with healthy controls, potentially creating a more comprehensive and more realistic picture of brain-language relations. Importantly, functional neuroimaging approaches demonstrate a good degree of concordance on a theoretical level, but also a considerable degree of individual variability, attesting to the clinical importance with these methods to establish, empirically, language localization in individual patients. Overall, the unique features of epilepsy, combined with ongoing advances in technology, promise further improvement in understanding of language substrate.

Ictal Cardiac Ryhthym Abnormalities.

PubMed

Ali, Rushna

2016-01-01

Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy.

Epilepsy and the immune system: is there a link?

PubMed

Billiau, An D; Wouters, Carine H; Lagae, Lieven G

2005-01-01

The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

Prolonged partial epilepsy: a case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, M.A.

1980-11-01

The case study of a patient with prolonged partial epilepsy is presented. There was a discrepancy between the extent of the abnormality seen on the radionuclide angiogram and that seen on the static brain scan.

Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy.

PubMed

Gales, Jordan M; Prayson, Richard A

2017-10-01

Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed. Copyright © 2017 Elsevier Inc. All rights reserved.

Multimodal investigation of epileptic networks: The case of insular cortex epilepsy.

PubMed

Zerouali, Y; Ghaziri, J; Nguyen, D K

2016-01-01

The insula is a deep cortical structure sharing extensive synaptic connections with a variety of brain regions, including several frontal, temporal, and parietal structures. The identification of the insular connectivity network is obviously valuable for understanding a number of cognitive processes, but also for understanding epilepsy since insular seizures involve a number of remote brain regions. Ultimately, knowledge of the structure and causal relationships within the epileptic networks associated with insular cortex epilepsy can offer deeper insights into this relatively neglected type of epilepsy enabling the refining of the clinical approach in managing patients affected by it. In the present chapter, we first review the multimodal noninvasive tests performed during the presurgical evaluation of epileptic patients with drug refractory focal epilepsy, with particular emphasis on their value for the detection of insular cortex epilepsy. Second, we review the emerging multimodal investigation techniques in the field of epilepsy, that aim to (1) enhance the detection of insular cortex epilepsy and (2) unveil the architecture and causal relationships within epileptic networks. We summarize the results of these approaches with emphasis on the specific case of insular cortex epilepsy. © 2016 Elsevier B.V. All rights reserved.

New-onset refractory status epilepticus

PubMed Central

Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.

2015-01-01

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517

Stiripentol add-on therapy for focal refractory epilepsy.

PubMed

Brigo, Francesco; Igwe, Stanley C; Bragazzi, Nicola Luigi

2018-05-10

This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with promising effects. To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with focal refractory epilepsy who are taking AEDs. For the latest update, we searched the following databases on 21 August 2017: Cochrane Epilepsy Specialized Register, CENTRAL , MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials. Randomised, controlled, add-on trials of stiripentol in people with focal refractory epilepsy. Review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life. On the basis of our selection criteria, we included no new studies in the present review. Only one study was included from the earlier review (32 children with focal epilepsy). This study adopted a 'responder enriched' design and found no clear evidence of a reduction in seizure frequency (≥ 50% seizure reduction) (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82, low-quality evidence) nor evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43, low-quality evidence) when add-on stiripentol was compared with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47, low-quality evidence). When specific adverse events were considered, confidence intervals were very wide and showed the possibility of substantial increases and small reductions in risks of neurological (RR 2.65, 95% CI 0.88 to 8.01, low-quality evidence) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36, low-quality evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47, low-quality evidence), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group, low-quality evidence). The external validity of this study was limited because only responders to stiripentol (i.e. patients experiencing a ≥ 50% decrease in seizure frequency compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole seemed to occur significantly more often with add-on stiripentol than with add-on placebo. Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.

Mitochondrial disorders and epilepsy.

PubMed

Desguerre, I; Hully, M; Rio, M; Nabbout, R

2014-05-01

Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis. Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy. Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Review and update of the Hong Kong Epilepsy Guideline on status epilepticus.

PubMed

Fung, E Lw; Fung, B Bh

2017-02-01

Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

PubMed

Bartolini, Luca; Whitehead, Matthew T; Ho, Cheng-Ying; Sepeta, Leigh N; Oluigbo, Chima O; Havens, Kathryn; Freilich, Emily R; Schreiber, John M; Gaillard, William D

2017-01-01

To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD). We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies. Rates of pathology subtypes differed between TLE and ETLE (χ 2 (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ 2 (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ 2 (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ 2 (6) = 13.07, p = 0.042). Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy.

PubMed

Zou, Xue-Mei; Chen, Jia-Ni; An, Dong-Mei; Hao, Nan-Ya; Hong, Zhen; Hao, Xiao-Ting; Rao, Ping; Zhou, Dong

2015-07-01

The objective of this study was to explore the efficacy of low dose of oxcarbazepine (OXC) in adult patients with newly diagnosed partial epilepsy in an actual clinical setting. The associated factors influencing the poor control of seizures were also evaluated. The epilepsy database (2010-2014) from the Epilepsy Clinic of West China Hospital was retrospectively reviewed. A total of 102 adult patients with newly diagnosed, previously untreated partial epilepsy initially treated with OXC were included, and divided into good response group (64) and poor response group (38) according to whether they were seizure-free for at least 12 months. There were 27 (26.5%) patients becoming seizure-free with OXC 600 mg/day monotherapy. The remaining 75 patients had doses of either increasing OXC to 900 mg/day (n = 59) or the addition of another antiepileptic drug (AED) (n = 16), with another 20 (19.6%) and six (5.9%) patients becoming seizure-free, respectively (P = 0.788). In addition, two (2.0%) and nine (8.8%) patients became seizure-free with OXC > 900 mg/day monotherapy and OXC ≥ 900 mg/day combination therapy, respectively. Multivariate binary logistic regression analysis revealed that the time from onset of epilepsy to treatment initiation is significantly associated with seizure control (P = 0.02). Our results indicated that OXC at low to moderate doses is effective for the treatment of Chinese adult patients with newly diagnosed, previously untreated partial epilepsy, and a longer time interval from the onset of epilepsy to the start of treatment significantly predicts poor seizure control. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

NASA Astrophysics Data System (ADS)

El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

2015-01-01

Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

Historic, clinical, and prognostic features of epileptic encephalopathies caused by CDKL5 mutations.

PubMed

Moseley, Brian D; Dhamija, Radhika; Wirrell, Elaine C; Nickels, Katherine C

2012-02-01

Mutations within the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are important causes of early-onset epileptic encephalopathies. We sought to determine the historic, clinical, and prognostic features of epilepsy secondary to CDKL5 mutations. We performed retrospective chart reviews of children at our institution with epilepsy and CDKL5 mutations. Six children were identified. One manifested a deletion in exons 10-15 of the CDKL5 gene, another manifested a single base-pair duplication in exon 3, and the rest manifested base-pair exchanges. The mean age of seizure onset was 1.8 months (range, 1-3 months). Although the majority (4/6, 67%) presented with partial-onset seizures, all children developed infantile spasms. All children demonstrated developmental delay and visual impairment. Although such mutations are X-linked, two children were boys. They did not present with more severe phenotypes than their female counterparts. Despite trials of antiepileptic drugs (mean, 5; range, 3-7), steroids/adrenocorticotropic hormone (4/6; 67%), and the ketogenic diet (6/6; 100%), all children manifested refractory seizures at last follow-up. Although no treatment eliminated seizures, topiramate, vigabatrin, and the ketogenic diet were most helpful at reducing seizure frequency. Copyright © 2012 Elsevier Inc. All rights reserved.

Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

PubMed

Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

2013-12-01

Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Pre- and post-operative Wisconsin card sorting test performance in patients with temporal lobe epilepsy due to hippocampal sclerosis

PubMed Central

Tisser, Luciana; Palmini, Andre; Paglioli, Eliseu; Portuguez, Mirna; Azambuja, Ney; da Costa, Jaderson Costa; Paglioli, Eduardo; Torres, Carolina; Martinez, Jose Victor

2007-01-01

Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have a distinct neuropsychological profile, but there is still debate on whether executive dysfunction is part of this profile and also whether temporal lobe surgery can modify this dysfunction. Objective To study the presence and reversibility of executive dysfunction in patients with unilateral TLE/HS. Methods Twenty-five patients with refractory seizures due to TLE/HS underwent presurgical evaluation which included the application of the Wiconsin Card Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects matched for age and education also performed the WCST. Results Sixteen of the 25 patients (64%) completed fewer than four categories in the WCST whereas only 4 of the 22 controls (18%) did not complete at least four categories (p<0.005). In addition, the performance of the patients involved significantly more perseverative responses and errors compared to controls. The patient group demonstrated significant post-operative improvement in many measures of the WCST following SAH. Conclusions These findings support the presence of executive dysfunction in patients with TLE/HS and suggest that such dysfunction can be partially reversed by selective resection of epileptogenic mesial temporal structures. PMID:29213385

What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

PubMed

Kossoff, Eric H; Al-Macki, Nabil; Cervenka, Mackenzie C; Kim, Heung D; Liao, Jianxiang; Megaw, Katherine; Nathan, Janak K; Raimann, Ximena; Rivera, Rocio; Wiemer-Kruel, Adelheid; Williams, Emma; Zupec-Kania, Beth A

2015-09-01

Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Marijuana Use in Epilepsy: The Myth and the Reality.

PubMed

Detyniecki, Kamil; Hirsch, Lawrence

2015-10-01

Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia. Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts. This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians' and patients' opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.

Rates and predictors of seizure freedom in resective epilepsy surgery: an update

PubMed Central

Englot, Dario J.; Chang, Edward F.

2017-01-01

Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world’s population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration. PMID:24497269

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PubMed

Spencer, Susan S; Schramm, Johannes; Wyler, Allen; O'Connor, Michael; Orbach, Darren; Krauss, Gregory; Sperling, Michael; Devinsky, Orrin; Elger, Christian; Lesser, Ronald; Mulligan, Lisa; Westerveld, Michael

2002-02-01

Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Huperzine A Provides Robust and Sustained Protection against Induced Seizures in Scn1a Mutant Mice

PubMed Central

Wong, Jennifer C.; Dutton, Stacey B. B.; Collins, Stephen D.; Schachter, Steven; Escayg, Andrew

2016-01-01

De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15–20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes. Current antiepileptic drugs often fail to protect against the severe seizures and behavioral and cognitive deficits found in patients with SCN1A mutations. To address the need for more efficacious treatments for SCN1A-derived epilepsies, we evaluated the therapeutic potential of Huperzine A, a naturally occurring reversible acetylcholinesterase inhibitor. In CF1 mice, Hup A (0.56 or 1 mg/kg) was found to confer protection against 6 Hz-, pentylenetetrazole (PTZ)-, and maximal electroshock (MES)-induced seizures. Robust protection against 6 Hz-, MES-, and hyperthermia-induced seizures was also achieved following Hup A administration in mouse models of DS (Scn1a+/−) and GEFS+ (Scn1aRH/+). Furthermore, Hup A-mediated seizure protection was sustained during 3 weeks of daily injections in Scn1aRH/+ mutants. Finally, we determined that muscarinic and GABAA receptors play a role in Hup A-mediated seizure protection. These findings indicate that Hup A might provide a novel therapeutic strategy for increasing seizure resistance in DS and GEFS+, and more broadly, in other forms of refractory epilepsy. PMID:27799911

Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms

PubMed Central

d'Orsi, G; Tinuper, P; Bisulli, F; Zaniboni, A; Bernardi, B; Rubboli, G; Riva, R; Michelucci, R; Volpi, L; Tassinari, C; Baruzzi, A

2004-01-01

Objectives: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. Methods: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2–40 years). Results: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. Conclusions: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis. PMID:15146004

Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum.

PubMed

van Karnebeek, Clara D M; Tiebout, Sylvia A; Niermeijer, Jikkemien; Poll-The, Bwee Tien; Ghani, Aisha; Coughlin, Curtis R; Van Hove, Johan L K; Richter, Jost Wigand; Christen, Hans Juergen; Gallagher, Renata; Hartmann, Hans; Stockler-Ipsiroglu, Sylvia

2016-06-01

Pyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of α-aminoadipic semialdehyde/pyrroline 6' carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported. We present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions. The phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of α-aminoadipic semialdehyde/pyrroline 6' carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

PubMed Central

Carvalho, Benilton S.; Bilevicius, Elizabeth; Alvim, Marina K. M.; Lopes-Cendes, Iscia

2017-01-01

Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner. PMID:28052106

Refractory status epilepticus in children with and without prior epilepsy or status epilepticus

PubMed Central

Sánchez Fernández, Iván; Jackson, Michele C.; Abend, Nicholas S.; Arya, Ravindra; Brenton, James N.; Carpenter, Jessica L.; Chapman, Kevin E.; Gaillard, William D.; Gaínza-Lein, Marina; Glauser, Tracy A.; Goldstein, Joshua L.; Goodkin, Howard P.; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L.; Mikati, Mohamad A.; Peariso, Katrina; Riviello, James; Tasker, Robert C.; Topjian, Alexis A.; Wainwright, Mark S.; Wilfong, Angus; Williams, Korwyn

2017-01-01

Objective: To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). Methods: This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month–21 years of age) with rSE. Results: We enrolled 189 participants (53% male) with a median (25th–75th percentile) age of 4.2 (1.3–9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5–60] vs 16.5 [5–42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46–190] vs 50.5 [28–116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5–22.3] vs 20 [5–60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3–124] vs 65 [32.5–156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Conclusions: Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. PMID:28011930

Inhibition of mTOR Pathway by Rapamycin Decreases P-glycoprotein Expression and Spontaneous Seizures in Pharmacoresistant Epilepsy.

PubMed

Chi, Xiaosa; Huang, Cheng; Li, Rui; Wang, Wei; Wu, Mengqian; Li, Jinmei; Zhou, Dong

2017-04-01

The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin. Non-responders were treated for 4 weeks with vehicle only or with the mTOR pathway inhibitor rapamycin at doses of 1, 3, and 6 mg/kg. Western blotting and immunohistochemistry were used to detect the expression of phospho-S6 (P-S6) and P-gp at different time points (1 h, 8 h, 1 day, 3 days, 1 weeks, 2 weeks, and 4 weeks) after the onset of treatment. Overexpression of P-S6 and P-gp was detected in both refractory mTLE patients and non-responder rats. Rapamycin showed an inhibitory effect on P-S6 and P-gp expression 1 week after treatment in rats. In addition, the expression levels of P-S6 and P-gp in the 6 mg/kg group were significantly lower than those in the 1 mg/kg or the 3 mg/kg group at the same time points (all P < 0.05). Moreover, rapamycin decreased the duration and number of CL-induced seizures, as well as the stage of non-responders (all P < 0.05). The current study indicates that the mTOR signaling pathway plays a critical role in P-gp expression in drug-resistant epilepsy. Inhibition of the mTOR pathway by rapamycin may be a potential therapeutic approach for pharmacoresistant epilepsy.

Quality of life after surgery for intractable partial epilepsy in children: a cohort study with controls.

PubMed

Mikati, Mohamad A; Ataya, Nour; Ferzli, Jessica; Kurdi, Rana; El-Banna, Diana; Rahi, Amal; Shamseddine, Alhan; Sinno, Durriyah; Comair, Youssef

2010-08-01

Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

PubMed

Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

2016-12-01

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

A one-year prospective study of refractory status epilepticus in Modena, Italy.

PubMed

Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano

2015-08-01

Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients.

PubMed

Jähn, Johanna; Caliebe, Almuth; von Spiczak, Sarah; Boor, Rainer; Stefanova, Irina; Stephani, Ulrich; Helbig, Ingo; Muhle, Hiltrud

2013-07-01

CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years. All 4 patients had epilepsy starting with focal seizures in the first 3 months of life, evolving to epileptic spasms between the ages of 2 and 6 years and later on to tonic seizures. In 3 patients, epilepsy was resistant to antiepileptic therapy. Although there was no common EEG pattern in all patients, late hypsarrhythmia until the age of 9 years was observed in 2 patients. CDKL5-related epileptic encephalopathies are a group of refractory seizure disorders starting in early infancy. The phenomenon of late hypsarrhythmia may help define a subgroup of patients with severe and adverse outcomes.

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

PubMed Central

Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

2017-01-01

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

Clinical utility of BOLD fMRI in preoperative work-up of epilepsy

PubMed Central

Ganesan, Karthik; Ursekar, Meher

2014-01-01

Surgical techniques have emerged as a viable therapeutic option in patients with drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a comprehensive, multiparametric, and multimodal approach for precise localization of the epileptogenic focus. Various non-invasive techniques are available at the disposal of the treating physician to detect the epileptogenic focus, which include electroencephalography (EEG), video-EEG, magnetic resonance imaging (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques, single photon emission tomography (SPECT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Currently, non-invasive high-resolution MR imaging techniques play pivotal roles in the preoperative detection of the seizure focus, and represent the foundation for successful epilepsy surgery. BOLD functional magnetic resonance imaging (fMRI) maps allow for precise localization of the eloquent cortex in relation to the seizure focus. This review article focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of epilepsy patients. PMID:24851002

Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches

PubMed Central

Sharma, Suvasini; Prasad, Asuri N.

2017-01-01

Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term “metabolic epilepsy” can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Some of these disorders are amenable to specific treatment interventions; hence timely and appropriate diagnosis is critical to improve outcomes. In this review, we discuss those disorders in which epilepsy is a dominant feature and present an approach to the clinical recognition, diagnosis, and management of these disorders, with a greater focus on primarily treatable conditions. Finally, we propose a tiered approach that will permit a clinician to systematically investigate, identify, and treat these rare disorders. PMID:28671587

Patients with epilepsy and patients with psychogenic non-epileptic seizures: video-EEG, clinical and neuropsychological evaluation.

PubMed

Turner, Katherine; Piazzini, Ada; Chiesa, Valentina; Barbieri, Valentina; Vignoli, Aglaia; Gardella, Elena; Tisi, Giuseppe; Scarone, Silvio; Canevini, Maria Paola; Gambini, Orsola

2011-11-01

The incidence of psychogenic non-epileptic seizures (PNES) is 4.9/100,000/year and it is estimated that about 20-30% of patients referred to tertiary care epilepsy centers for refractory seizures have both epilepsy and PNES. The purpose of our study is to evaluate psychiatric disorders and neuropsychological functions among patients with PNES, patients with epilepsy associated with PNES and patients with epilepsy. We evaluated 66 consecutive in-patients with video-EEG recordings: 21 patients with epilepsy, 22 patients with PNES and 10 patients with epilepsy associated with PNES; 13 patients were excluded (8 because of mental retardation and 5 because they did not present seizures or PNES during the recording period). All patients with PNES had a psychiatric diagnosis (100%) vs. 52% of patients with epilepsy. Cluster B personality disorders were more common in patients with PNES. We observed fewer mood and anxiety disorders in patients with PNES compared with those with epilepsy. We did not find statistically significant differences in neuropsychological profiles among the 3 patient groups. This study can help to contribute to a better understanding of the impact of PNES manifestations, in addition to the occurrence of seizures, in order to provide patients with more appropriate clinical, psychological and social care. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Unfavorable surgical outcomes in partial epilepsy with secondary bilateral synchrony: Intracranial electroencephalography study.

PubMed

Sunwoo, Jun-Sang; Byun, Jung-Ick; Moon, Jangsup; Lim, Jung-Ah; Kim, Tae-Joon; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Chu, Kon; Kim, Manho; Chung, Chun-Kee; Jung, Ki-Young; Lee, Sang Kun

2016-05-01

Secondary bilateral synchrony (SBS) indicates bilaterally synchronous epileptiform discharges arising from a focal cortical origin. The present study aims to investigate SBS in partial epilepsy with regard to surgical outcomes and intracranial EEG findings. We retrospectively reviewed consecutive patients who underwent epilepsy surgery following extraoperative intracranial electroencephalography (EEG) study from 2008 to 2012. The presence of SBS was determined based upon the results of scalp EEG monitoring performed for presurgical evaluations. We reviewed scalp EEG, neuroimaging, intracranial EEG findings, and surgical outcomes in patients with SBS. We found 12 patients with SBS who were surgically treated for intractable partial epilepsy. Nine (75%) patients had lateralized ictal semiology and only two (16.6%) patients showed localized ictal onset in scalp EEG. Brain MRI showed epileptogenic lesion in three (25%) patients. Intracranial EEG demonstrated that ictal onset zone was widespread or non-localized in six (50%) patients. Low-voltage fast activity was the most common ictal onset EEG pattern. Rapid propagation of ictal onset was noted in 10 (83.3%) patients. Eleven patients underwent resective epilepsy surgery and only two patients (18.2%) achieved seizure-freedom (median follow-up 56 months). MRI-visible brain lesions were associated with favorable outcomes (p=0.024). Patients with SBS, compared to frontal lobe epilepsy without SBS, showed lesser localization in ictal onset EEG (p=0.029) and more rapid propagation during evolution of ictal rhythm (p=0.015). The present results suggested that resective surgery for partial epilepsy with SBS should be decided carefully, especially in case of nonlesional epilepsy. Poor localization and rapid spread of ictal onset were prominent in intracranial EEG, which might contribute to incomplete resection of the epileptogenic zone and poor surgical outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Do pets reduce the likelihood of sudden unexplained death in epilepsy?

PubMed

Terra, Vera C; Sakamoto, Américo C; Machado, Hélio R; Martins, Luciana D; Cavalheiro, Esper A; Arida, Ricardo M; Stöllberger, Claudia; Finsterer, Josef; Scorza, Fulvio A

2012-10-01

To assess the relationship between the presence of pets in homes of epilepsy patients and the occurrence of sudden unexpected death in epilepsy (SUDEP). Parents or relatives of SUDEP patients collected over a ten-year period (2000-2009) in a large epilepsy unit were asked if the patient lived together with any domestic pet at the time of death or not. Patients who did not experience SUDEP served as controls. Eleven out of the 1092 included patients (1%) experienced SUDEP, all with refractory symptomatic epilepsy, but none of them had pets in their homes at the time of death. In contrast, the frequency of pet-ownership in the control group (n=1081) was 61%. According to previous studies there are some indications that human health is directly related to companionship with animals in a way that domestic animals prevent illness and facilitate recovery of patients. Companion animals can buffer reactivity against acute stress, diminish stress perception and improve physical health. These factors may reduce cardiac arrhythmias and seizure frequency, factors related to SUDEP. Companion animals may have a positive effect on well-being, thus improving epilepsy outcome. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Temporal Lobe Epilepsy Surgery Failures: A Review

PubMed Central

Harroud, Adil; Bouthillier, Alain; Weil, Alexander G.; Nguyen, Dang Khoa

2012-01-01

Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE. PMID:22934162

Do oral contraceptives increase epileptic seizures?

PubMed

Reddy, Doodipala Samba

2017-02-01

Hormonal contraceptives are used by over 100 million people worldwide. Recently, there has been an emerging interest in studying the potential impact of oral contraceptives (OCs) on certain neurological conditions. It has been suspected for some time that hormonal birth control increases seizure activity in women with epilepsy, but there is little supportive data. Areas covered: Literature from PubMed and online sources was analyzed with respect to hormonal contraception and epilepsy or seizures. New evidence indicates that OCs can cause an increase in seizures in women with epilepsy. The epilepsy birth control registry, which surveyed women with epilepsy, found that those using hormonal contraceptives self-reported 4.5 times more seizures than those that did not use such contraceptives. A preclinical study confirmed these outcomes wherein epileptic animals given ethinyl estradiol, the primary component of OCs, had more frequent seizures that are more likely to be resistant. Expert commentary: OC pills may increase seizures in women with epilepsy and such refractory seizures are more likely to cause neuronal damage in the brain. Thus, women of child bearing age with epilepsy should consider using non-hormonal forms of birth control to avoid risks from OC pills. Additional research into the mechanisms and prospective clinical investigation are needed.

Chromia refractory brick with carbon treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, James P.; Kwong, Kyei-Sing

The disclosure provides a refractory brick system comprising a chromia refractory brick for operation in the slagging environment of an air-cooled gasifier. The chromia refractory brick comprises a ceramically-bonded porous chromia refractory having a porosity greater than 9% and having carbon deposits residing within the pores. The brick may be further comprised of Al.sub.2O.sub.3. The air-cooled gasifier generates a liquefied slag in contact with the refractory brick and generally operates at temperatures between 1250.degree. C. and 1575.degree. C. and pressures between 300 psi to 1000 psi, with oxygen partial pressures generally between 10.sup.-4 and 10.sup.-10 atm. The refractory brick performsmore » without substantial chromium carbide or chromium metal formation in the low oxygen partial pressure environment. The inclusion of carbon without chromium carbide formation provides for significant mitigation of slag penetration and significantly reduced refractory wear.« less

P-glycoprotein and multidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain.

PubMed

Potschka, H; Fedrowitz, M; Löscher, W

2001-11-16

Despite considerable advances in the pharmacotherapy of epilepsy, about 30% of epileptic patients are refractory to antiepileptic drugs (AEDs). In most cases, a patient who is resistant to one major AED is also refractory to other AEDs, although these drugs act by different mechanisms. The mechanisms that lead to drug resistance in epilepsy are not known. Recently, over-expression of multidrug transporters, such as P-glycoprotein (PGP) and multidrug resistance-associated protein (MRP), has been reported in surgically resected epileptogenic human brain tissue and suggested to contribute to the drug resistance of epilepsy. However, it is not known to what extent multidrug transporters such as PGP or MRP are involved in transport of AEDs. In the present study, we used in vivo microdialysis in rats to study whether the concentration of carbamazepine in the extracellular fluid of the cerebral cortex can be enhanced by inhibition of PGP or MRP, using the PGP inhibitor verapamil and the MRP inhibitor probenecid. Local perfusion with verapamil or probenecid via the microdialysis probe increased the extracellular concentration of carbamazepine. The data indicate that both PGP and MRP participate in the regulation of extracellular brain concentrations of the major AED carbamazepine.

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

PubMed

Azevedo de Lima, Patricia; Baldini Prudêncio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antônio Martins; Teixeira Damasceno, Nágila Raquel

2017-01-01

The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

PubMed

Royaux, E; Van Ham, L; Broeckx, B J G; Van Soens, I; Gielen, I; Deforce, D; Bhatti, S F M

2017-02-01

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome.

PubMed

Hussain, Shaun A; Zhou, Raymond; Jacobson, Catherine; Weng, Julius; Cheng, Emily; Lay, Johnson; Hung, Phoebe; Lerner, Jason T; Sankar, Raman

2015-06-01

There is a great need for safe and effective therapies for treatment of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). Based on anecdotal reports and limited experience in an open-label trial, cannabidiol (CBD) has received tremendous attention as a potential treatment for pediatric epilepsy, especially Dravet syndrome. However, there is scant evidence of specific utility for treatment of IS and LGS. We sought to document the experiences of children with IS and/or LGS who have been treated with CBD-enriched cannabis preparations. We conducted a brief online survey of parents who administered CBD-enriched cannabis preparations for the treatment of their children's epilepsy. We specifically recruited parents of children with IS and LGS and focused on perceived efficacy, dosage, and tolerability. Survey respondents included 117 parents of children with epilepsy (including 53 with IS or LGS) who had administered CBD products to their children. Perceived efficacy and tolerability were similar across etiologic subgroups. Eighty-five percent of all parents reported a reduction in seizure frequency, and 14% reported complete seizure freedom. Epilepsy was characterized as highly refractory with median latency from epilepsy onset to CBD initiation of five years, during which the patient's seizures failed to improve after a median of eight antiseizure medication trials. The median duration and the median dosage of CBD exposure were 6.8 months and 4.3mg/kg/day, respectively. Reported side effects were far less common during CBD exposure, with the exception of increased appetite (30%). A high proportion of respondents reported improvement in sleep (53%), alertness (71%), and mood (63%) during CBD therapy. Although this study suggests a potential role for CBD in the treatment of refractory childhood epilepsy including IS and LGS, it does not represent compelling evidence of efficacy or safety. From a methodological standpoint, this study is extraordinarily vulnerable to participation bias and limited by lack of blinded outcome ascertainment. Appropriately controlled clinical trials are essential to establish efficacy and safety. Copyright © 2015 Elsevier Inc. All rights reserved.

"It was five years of hell": Parental experiences of navigating and processing the slow and arduous time to pediatric resective epilepsy surgery.

PubMed

Pieters, Huibrie C; Iwaki, Tomoko; Vickrey, Barbara G; Mathern, Gary W; Baca, Christine B

2016-09-01

Children with medically refractory epilepsy stand to benefit from surgery and live a life free of seizures. However, a large proportion of potentially eligible children do not receive a timely referral for a surgical evaluation. We aimed to describe experiences during the arduous time before the referral and the parent-reported facilitators that helped them move forward through this slow time. Individual semi-structured interviews with 37 parents of children who had previously undergone epilepsy surgery at UCLA (2006-2011) were recorded, transcribed, and systematically analyzed by two independent coders using thematic analysis. Clinical data were extracted from medical records. Parents, 41.3years of age on average, were mostly Caucasian, English-speaking, mothers, married, and employed. The mean age at surgery for children was 8.2years with a mean time from epilepsy onset to surgery of 5.4years. Parental decision-making was facilitated when parents eventually received a presurgical referral and navigated to a multidisciplinary team that they trusted to care for their child with medically refractory epilepsy. Four themes described the experiences that parents used to feel a sense of moving forward. The first theme, processing, involved working through feelings and was mostly done alone. The second theme, navigating the complex unknowns of the health-care system, was more active and purposeful. Processing co-occurred with navigating in a fluid intersection, the third theme, which was evidenced by deliberate actions. The fourth theme, facilitators, explained helpful ways of processing and navigating; parents utilized these mechanisms to turn vulnerable times following the distress of their child's diagnosis into an experience of productivity. To limit parental distress and remediate the slow and arduous journey to multidisciplinary care at a comprehensive epilepsy center for a surgical evaluation, we suggest multi-pronged interventions to modify barriers associated with parents, providers, and health-care systems. Based on the facilitators that moved parents of our sample forward, we provide practical suggestions such as increased peer support, developing the role of patient navigators and communication strategies with parents before, during, and after referral to a comprehensive epilepsy center and presurgical evaluation. Published by Elsevier Inc.

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

PubMed

Mahoney, Emily C; Zeng, Andrew; Yu, Wilson; Rowe, Mackenzie; Sahai, Siddhartha; Feustel, Paul J; Ramirez-Zamora, Adolfo; Pilitsis, Julie G; Shin, Damian S

2018-05-01

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug interaction between phenytoin and valproic acid in a child with refractory epilepsy: a case report.

PubMed

Carvalho, Indira Valadê; Carnevale, Renata Cavalcanti; Visacri, Marília Berlofa; Mazzola, Priscila Gava; de Fátima Lopes Ambrósio, Rosiane; dos Reis, Marcelo Conrado; de Queiroz, Rachel Alvarenga; Moriel, Patricia

2014-04-01

There are no published reports on pediatric phenytoin toxicity, resulting from the drug interaction between phenytoin and valproic acid. A 12-year-old patient with refractory epilepsy syndrome presented with phenytoin toxicity, following a concomitant treatment with phenytoin, valproic acid, and lamotrigine. The phenytoin concentration detected in the capsules used by the patient was in accordance with the prescribed dose and was appropriate for the age and weight of the patient. However, a supratherapeutic phenytoin serum concentration was observed (21.92 µg phenytoin/mL of blood). Consequently, the phenytoin dose was reduced, and the patient was monitored; 24 hours later the patient did not present with any signs/symptoms of toxicity. Despite the appropriate phenytoin concentration in the capsules, the patient presented with phenytoin toxicity. This toxicity likely resulted from the drug interaction between phenytoin and valproic acid that leads to phenytoin displacement from plasmatic proteins and inhibits phenytoin metabolism, thereby increasing the concentration of free drug in the serum.

Relationship of number of seizures recorded on video-EEG to surgical outcome in refractory medial temporal lobe epilepsy

PubMed Central

Sainju, Rup Kamal; Wolf, Bethany Jacobs; Bonilha, Leonardo; Martz, Gabriel

2014-01-01

Introduction Surgical planning for refractory medial temporal lobe epilepsy (rMTLE) relies on seizure localization by ictal electroencephalography (EEG). Multiple factors impact the number of seizures recorded. We evaluated whether seizure freedom correlated to the number of seizures recorded, and the related factors. Methods We collected data for 32 patients with rMTLE who underwent anterior temporal lobectomy. Primary analysis evaluated number of seizures captured as a predictor of surgical outcome. Subsequent analyses explored factors that may seizure number. Results Number of seizures recorded did not predict seizure freedom. More seizures were recorded with more days of seizure occurrence (p<0.001), seizure clusters (p≤0.011) and poorly localized seizures (PLSz) (p=0.004). Regression modeling showed a trend for subjects with fewer recorded poorly localized seizures to have better surgical outcome (p=0.052). Conclusions Total number of recorded seizures does not predict surgical outcome. Patients with more PLSz may have worse outcome. PMID:22990726

Patterns of language and auditory dysfunction in 6-year-old children with epilepsy.

PubMed

Selassie, Gunilla Rejnö-Habte; Olsson, Ingrid; Jennische, Margareta

2009-01-01

In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.

The G‐protein biased partial κ opioid receptor agonist 6′‐GNTI blocks hippocampal paroxysmal discharges without inducing aversion

PubMed Central

Zangrandi, Luca; Burtscher, Johannes; MacKay, James P; Colmers, William F

2016-01-01

Background and Purpose With a prevalence of 1–2%, epilepsies belong to the most frequent neurological diseases worldwide. Although antiepileptic drugs are available since several decades, the incidence of patients that are refractory to medication is still over 30%. Antiepileptic effects of κ opioid receptor (κ receptor) agonists have been proposed since the 1980s. However, their clinical use was hampered by dysphoric side effects. Recently, G‐protein biased κ receptor agonists were developed, suggesting reduced aversive effects. Experimental Approach We investigated the effects of the κ receptor agonist U‐50488H and the G‐protein biased partial κ receptor agonist 6′‐GNTI in models of acute seizures and drug‐resistant temporal lobe epilepsy and in the conditioned place avoidance (CPA) test. Moreover, we performed slice electrophysiology to understand the functional mechanisms of 6′‐GNTI. Key Results As previously shown for U‐50488H, 6′‐GNTI markedly increased the threshold for pentylenetetrazole‐induced seizures. All treated mice displayed reduced paroxysmal activity in response to U‐50488H (20 mg·kg−1) or 6′‐GNTI (10–30 nmoles) treatment in the mouse model of intra‐hippocampal injection of kainic acid. Single cell recordings on hippocampal pyramidal cells revealed enhanced inhibitory signalling as potential mechanisms causing the reduction of paroxysmal activity. Effects of 6′‐GNTI were blocked in both seizure models by the κ receptor antagonist 5′‐GNTI. Moreover, 6′‐GNTI did not induce CPA, a measure of aversive effects, while U‐50488H did. Conclusions and Implications Our data provide the proof of principle that anticonvulsant/antiseizure and aversive effects of κ receptor activation can be pharmacologically separated in vivo. PMID:26928671

Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy.

PubMed

Puligheddu, Monica; Melis, Miriam; Pillolla, Giuliano; Milioli, Giulia; Parrino, Liborio; Terzano, Giovanni Mario; Aroni, Sonia; Sagheddu, Claudia; Marrosu, Francesco; Pistis, Marco; Muntoni, Anna Lisa

2017-10-01

Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant ADNFLE\\NFLE patients, we first demonstrated the effectiveness of fenofibrate in a mutated mouse model displaying both disease genotype and phenotype. We first tested the efficacy of fenofibrate in transgenic mice carrying the mutation in the α4-nAChR subunit (Chrna4S252F) homologous to that found in humans. Subsequently, an add-on protocol was implemented in a clinical setting and fenofibrate was administered to pharmacoresistant NFLE patients. Here, we show that a chronic fenofibrate diet markedly reduced the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced increase of IPSC frequency. Moreover, fenofibrate abolished differences between genotypes in the frequency of sleep-related movements observed under basal conditions. Patients affected by NFLE, nonresponders to traditional therapy, by means of adjunctive therapy with fenofibrate displayed a reduction of seizure frequency. Furthermore, digital video-polysomnographic recordings acquired in NFLE subjects after 6 months of adjunctive fenofibrate substantiated the significant effects on control of motor-behavioral seizures. Our preclinical and clinical studies suggest PPARα as a novel disease-modifying target for antiepileptic drugs due to its ability to regulate dysfunctional nAChRs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Sleep disturbances in children with epilepsy compared with their nearest-aged siblings.

PubMed

Wirrell, Elaine; Blackman, Marlene; Barlow, Karen; Mah, Jean; Hamiwka, Lorie

2005-11-01

The aim of the study was to compare sleep patterns in children with epilepsy with those of their non-epileptic siblings and to determine which epilepsy-specific factors predict greater sleep disturbance. We conducted a case-control study of 55 children with epilepsy (mean age 10y, range 4 to 16y; 27 males, 28 females) and their nearest-aged non-epileptic sibling (mean age 10y, range 4 to 18y; 26 males, 29 females). Epilepsy was idiopathic generalized in eight children (15%), symptomatic generalized in seven (13%), and focal in 40 (73%); the mean duration was 5 years 8 months. Parents or caregivers completed the Sleep Behavior Questionnaire (SBQ) and Child Behavior Checklist (CBCL) for patients and controls, and the Quality of Life in Childhood Epilepsy (QOLCE) for patients. Patients had a higher (more adverse) Total Sleep score (p<0.001) and scored worse than controls on nearly all subscales of the SBQ. In patients, higher Total Sleep scores were correlated with higher scores on the Withdrawn, Somatic complaints, Social problems, and Attention subscales of the CBCL, and significantly lower Total Quality of Life Scores. Refractory epilepsy, mental retardation, and remote symptomatic etiology predicted greater sleep problems in those with epilepsy. We conclude that children with epilepsy in this current study had significantly greater sleep problems than their non-epileptic siblings.

The new patient with a first seizure.

PubMed

King, Mark

2003-04-01

First seizures are common, with one in 20 people suffering a seizure at some time in their life. This article aims to outline the assessment of patients with a first seizure, including making an accurate diagnosis of both seizure type and an epilepsy syndrome, if present. Seizures are classified into generalised and partial (arising from a focal region in the brain) based on clinical and electroencephalogram findings. However, as a partial seizure may proceed to a tonic clonic phase, differentiation may be difficult. Inquiring directly about 'minor' epileptic symptoms before the episode such as absences, myoclonic jerks, visual or auditory hallucinations or feelings of déjà vu, is needed to attempt to make a epilepsy syndrome diagnosis, as this has practical implications for treatment, prognosis and genetic counselling. Generalised epilepsies should be treated initially with valproate, while partial epilepsies should be treated with carbamazepine and switched to newer agents if intolerance occurs.

Psychosocial functioning in adolescents with complex partial seizures.

PubMed

Elliott, I

1992-03-01

This pilot study examined psychosocial functioning in adolescents (age 12.5-18.5 years) with complex partial seizures. Twenty-five subjects were divided into three groups: Group I (N = 11), medically treated with uncontrolled seizures; Group II (N = 6), medically managed with controlled seizures; and Group III (N = 8), epilepsy refractory to medical management with seizure control following surgery. Psychosocial functioning was measured using the "Adolescent Psychosocial Inventory" of Batzel and Dodrill. Findings revealed significant differences (F 4.80. p less than 0.02) in psychosocial functioning between the three groups. Group I showed the poorest overall adjustment; Group II, the best adjustment; Group III was better adjusted than Group I, but less than Group II. Significant difficulties were evident in the areas of school, interpersonal, emotional, seizure adjustment and overall psychosocial functioning in Group III. No problems were evident in Group II. School, emotional and overall adjustment were moderately problematic in Group III. Analysis of biological and demographic data revealed a significant association between increased numbers of medications and poorer psychosocial functioning (r = 58, p less than 0.02). The study results provide direction for clinic and community nurse specialists to set priorities with regard to assessment and supportive interventions.

Epilepsy and the ketogenic diet: assessment of ketosis in children using breath acetone.

PubMed

Musa-Veloso, Kathy; Rarama, Exequiel; Comeau, Felix; Curtis, Rosalind; Cunnane, Stephen

2002-09-01

High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p < 0.05), but not in children on a ketogenic diet. Children who were on the ketogenic diet for longer periods of time had a significantly lower fasting breath acetone (R(2) = 0.55, p = 0.014). In one child on the ketogenic diet, breath acetone was determined hourly over a 9-h period, both by gas chromatography and by a prototype hand-held breath acetone analyzer. Preliminary results using this hand-held breath acetone analyzer are encouraging. Breath acetone may be a useful tool in examining the relationship between ketosis and seizure control and enhancing our understanding of the mechanism of the ketogenic diet.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

PubMed

Ormond, D Ryan; Clusmann, Hans; Sassen, Robert; Hoppe, Christian; Helmstaedter, Christoph; Schramm, Johannes; Grote, Alexander

2018-04-13

Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

What are the arguments for and against rational therapy for epilepsy?

PubMed

Barker-Haliski, Melissa; Sills, Graeme J; White, H Steve

2014-01-01

Although more than a dozen new anti-seizure drugs (ASDs) have entered the market since 1993, a substantial proportion of patients (~30 %) remain refractory to current treatments. Thus, a concerted effort to identify and develop new therapies that will help these patients continues. Until this effort succeeds, it is reasonable to re-assess the use of currently available therapies and to consider how these therapies might be utilized in a more efficacious manner. This applies to the selection of monotherapies in newly-diagnosed epilepsy, but perhaps, more importantly, to the choice of combination treatments in otherwise drug-refractory epilepsy. Rational polytherapy is a concept that is predicated on the combination of drugs with complementary mechanisms of action (MoAs) that work synergistically to maximize efficacy and minimize the potential for adverse events. Furthermore, rational polytherapy requires a detailed understanding of the MoA subclasses amongst available ASDs and an appreciation of the empirical evidence that supports the use of specific combinations. The majority of ASDs can be loosely categorized into those that target neurotransmission and network hyperexcitability, modulate intrinsic neuronal properties through ion channels, or possess broad-spectrum efficacy as a result of multiple mechanisms. Within each of these categories, there are discrete pharmacological profiles that differentiate individual ASDs. This chapter will consider how knowledge of MoA can help guide therapy in a rational manner, both in the selection of monotherapies for specific seizure types and syndromes, but also in the choice of drug combinations for patients whose epilepsy is not optimally controlled with a single ASD.

Sexual problems in people with refractory epilepsy.

PubMed

Henning, Oliver J; Nakken, Karl O; Træen, Bente; Mowinckel, Petter; Lossius, Morten

2016-08-01

Sexual dysfunction is an important but often neglected aspect of epilepsy. The objective of this study was to explore the prevalence and types of sexual problems in patients with epilepsy and compare the results with similar data obtained from a representative sample of the general population. At the National Centre for Epilepsy in Norway, 171 of 227 consecutive adult inpatients and outpatients with epilepsy (response rate: 75.3%) and their neurologists participated in a questionnaire study about epilepsy and sexuality. The results were compared with data available from 594 adult Norwegians who had completed the same questionnaire. Patients with epilepsy had a significantly higher prevalence of sexual problems (women: 75.3% vs. 12.0%; men: 63.3% vs. 9.6%). The most commonly reported problems (>30%) were reduced sexual desire, orgasm problems, erection problems, and vaginal dryness. The patients reported considerable dissatisfaction regarding sexual functioning. Significantly more sexual problems were found in patients of both sexes with reduced quality of life and in women with symptoms of depression. We found no significant association between sexual problems and age of epilepsy onset, type of epilepsy, or use of enzyme-inducing antiepileptic drugs. Whereas age at sexual debut did not differ between the patients with epilepsy and the general population, men with epilepsy had a lower number of partners during the last 12months, and the proportion of women with a low frequency of intercourse was higher in the group with epilepsy. In conclusion, sexual problems are significantly greater in Norwegian patients with epilepsy than in the general adult population. As no single epilepsy type or treatment could be identified as a specific predisposing factor, it seems likely that there are multiple causes underlying our results, including both organic and psychosocial factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

PubMed

Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

2016-09-01

SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = -0.63), recall (r = -0.44) and graded naming test scores (r = -0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = -0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ(2), P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections

PubMed Central

Tai, Xin You; Koepp, Matthias; Duncan, John S.; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y. W.; Reeves, Cheryl; Michalak, Zuzanna

2016-01-01

Abstract See Bernasconi (doi:10.1093/aww202) for a scientific commentary on this article. Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer’s disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer’s disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer’s disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = −0.63), recall (r = −0.44) and graded naming test scores (r = −0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = −0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ2, P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. PMID:27497924

Autonomic symptoms during childhood partial epileptic seizures.

PubMed

Fogarasi, András; Janszky, József; Tuxhorn, Ingrid

2006-03-01

To analyze systematically the occurrence and age dependence as well as the localizing and lateralizing value of ictal autonomic symptoms (ASs) during childhood partial epilepsies and to compare our results with those of earlier adult studies. Five hundred fourteen video-recorded seizures of 100 consecutive children 12 years or younger with partial epilepsy and seizure-free postoperative outcome were retrospectively analyzed. Sixty patients produced at least one AS; 43 (70%) of 61 with temporal and 17 (44%) of 39 with extratemporal lobe epilepsy (p=0.012). Apnea/bradypnea occurred more frequently in younger children (p<0.01), whereas the presence of other ASs was neither age nor gender related. Postictal coughing (p<0.01) and epigastric aura (p<0.05) localized to the temporal lobe, whereas no ASs lateralized to the seizure-onset zone. Our study shows that ASs are common in childhood focal epilepsies, appearing in infants and young children, too. As in adults, childhood central autonomic networks might have a close connection to temporal lobe structures but do not lateralize the seizure-onset zone. To our knowledge, this is the first study comprehensively assessing ASs in childhood epilepsy.

Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial.

PubMed

Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício

2015-02-01

To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Social media in epilepsy: A quantitative and qualitative analysis.

PubMed

Meng, Ying; Elkaim, Lior; Wang, Justin; Liu, Jessica; Alotaibi, Naif M; Ibrahim, George M; Fallah, Aria; Weil, Alexander G; Valiante, Taufik A; Lozano, Andres M; Rutka, James T

2017-06-01

While the social burden of epilepsy has been extensively studied, an evaluation of social media related to epilepsy may provide novel insight into disease perception, patient needs and access to treatments. The objective of this study is to assess patterns in social media and online communication usage related to epilepsy and its associated topics. We searched two major social media platforms (Facebook and Twitter) for public accounts dedicated to epilepsy. Results were analyzed using qualitative and quantitative methodologies. The former involved thematic and word count analysis for online posts and tweets on these platforms, while the latter employed descriptive statistics and non-parametric tests. Facebook had a higher number of pages (840 accounts) and users (3 million) compared to Twitter (137 accounts and 274,663 users). Foundation and support groups comprised most of the accounts and users on both Facebook and Twitter. The number of accounts increased by 100% from 2012 to 2016. Among the 403 posts and tweets analyzed, "providing information" on medications or correcting common misconceptions in epilepsy was the most common theme (48%). Surgical interventions for epilepsy were only mentioned in 1% of all posts and tweets. The current study provides a comprehensive reference on the usage of social media in epilepsy. The number of online users interested in epilepsy is likely the highest among all neurological conditions. Surgery, as a method of treating refractory epilepsy, however, could be underrepresented on social media. Copyright © 2017 Elsevier Inc. All rights reserved.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PubMed

Boon, Paul; Vonck, Kristl; van Rijckevorsel, Kenou; El Tahry, Riem; Elger, Christian E; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate; Hamer, Hajo; Reuber, Markus; Kostov, Hrisimir; Legros, Benjamin; Noachtar, Soheyl; Weber, Yvonne G; Coenen, Volker A; Rooijakkers, Herbert; Schijns, Olaf E M G; Selway, Richard; Van Roost, Dirk; Eggleston, Katherine S; Van Grunderbeek, Wim; Jayewardene, Amara K; McGuire, Ryan M

2015-11-01

This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy.

PubMed

Ngo, Ly; Sperling, Michael R; Skidmore, Christopher; Mintzer, Scott; Nei, Maromi

2017-04-01

Frequent interictal epileptiform abnormalities may correlate with poor prognosis after temporal lobe resection for refractory epilepsy. To date, studies have focused on limited resections such as selective amygdalohippocampectomy and apical temporal lobectomy without hippocampectomy. However, it is unclear whether the frequency of spikes predicts outcome after standard anterior temporal lobectomy. Preoperative scalp video-EEG monitoring data from patients who subsequently underwent anterior temporal lobectomy over a three year period and were followed for at least one year were reviewed for the frequency of interictal epileptiform abnormalities. Surgical outcome for those patients with frequent spikes (>60/h) was compared with those with less frequent spikes. Additionally, spike frequency was evaluated as a continuous variable and correlated with outcome to determine if increased spike frequency correlated with worse outcome, as assessed by modified Engel Class outcome. Forty-seven patients (18 men, 29 women; mean age 40 years at surgery) were included. Forty-six patients had standard anterior temporal lobectomy (24 right, 22 left) and one had a modified left temporal lobectomy. There was no significant difference in seizure outcome between those with frequent (57% Class I) vs. those with less frequent (58% Class I) spikes. Increased spike frequency did not correlate with worse outcome. Greater than 20 complex partial seizures/month and generalized tonic-clonic seizures within one year of surgery correlated with worse outcome. This study suggests that absolute spike frequency does not predict seizure outcome after anterior temporal lobectomy unlike in selective procedures, and should not be used as a prognostic factor in this population. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

PubMed

Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

2015-08-01

In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

New antiepileptic drugs in pediatric epilepsy.

PubMed

Hwang, Hee; Kim, Ki Joong

2008-10-01

New antiepileptic drugs (AEDs), introduced since 1993, provide more diverse options in the treatment of epilepsy. Despite the equivalent efficacy and better tolerability of these drugs, more than 25% of patients remain refractory to treatment. Moreover, the issues for pediatric patients are different from those for adults, and have not been addressed in the development and application of the new AEDs. Recently published evidence-based treatment guidelines have helped physicians to choose the most reasonable AED, although they cannot fully endorse new AEDs because of the lack of well-designed, randomized controlled trials. We review the mechanisms of action, pharmacokinetic properties, adverse reactions, efficacy, and tolerability of eight new AEDs (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin, and zonisamide), focusing on currently available treatment guidelines and expert opinions regarding pediatric epilepsy.

Cognitive outcome of surgery.

PubMed

Gallagher, Anne; Jambaqué, Isabelle; Lassonde, Maryse

2013-01-01

Epilepsy surgery is now widely accepted as an effective therapeutic option for carefully selected children with medically refractory epilepsy. The surgical procedure may cause cognitive deficits or exacerbate existing impairments, but it may also improve cognitive abilities by the restoration of functions located in adjacent or contralateral areas that had been secondarily affected by the epilepsy or the underlying pathology. Compared to adults, better cognitive outcome has been reported in children, a finding probably due to the developing state of the brain, which possesses considerable structural and functional plasticity. More extensive and effective surgery such as hemispherectomy is more commonly used in the pediatric population, and this must also influence surgical outcome. However, studies related to cognitive outcome of epilepsy surgery in children are limited, and controversial results are often reported. In this chapter, we provide a current overview of the literature on cognitive outcomes in children who undergo different types of epilepsy surgery, including focal resections as well as corpus callosotomy and hemispherectomy. Early surgical intervention appears to be a rational option for the treatment of childhood epilepsy since many cognitive deficits are linked to the epileptic process and may disappear when seizures are controlled. Copyright © 2013 Elsevier B.V. All rights reserved.

Electroencephalography in Mesial Temporal Lobe Epilepsy: A Review

PubMed Central

Javidan, Manouchehr

2012-01-01

Electroencephalography (EEG) has an important role in the diagnosis and classification of epilepsy. It can provide information for predicting the response to antiseizure drugs and to identify the surgically remediable epilepsies. In temporal lobe epilepsy (TLE) seizures could originate in the medial or lateral neocortical temporal region, and many of these patients are refractory to medical treatment. However, majority of patients have had excellent results after surgery and this often relies on the EEG and magnetic resonance imaging (MRI) data in presurgical evaluation. If the scalp EEG data is insufficient or discordant, invasive EEG recording with placement of intracranial electrodes could identify the seizure focus prior to surgery. This paper highlights the general information regarding the use of EEG in epilepsy, EEG patterns resembling epileptiform discharges, and the interictal, ictal and postictal findings in mesial temporal lobe epilepsy using scalp and intracranial recordings prior to surgery. The utility of the automated seizure detection and computerized mathematical models for increasing yield of non-invasive localization is discussed. This paper also describes the sensitivity, specificity, and predictive value of EEG for seizure recurrence after withdrawal of medications following seizure freedom with medical and surgical therapy. PMID:22957235

Ketogenic Diets: New Advances for Metabolism-Based Therapies

PubMed Central

Kossoff, Eric H.; Hartman, Adam L.

2014-01-01

Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

Surgical outcome in patients with epilepsy and dual pathology.

PubMed

Li, L M; Cendes, F; Andermann, F; Watson, C; Fish, D R; Cook, M J; Dubeau, F; Duncan, J S; Shorvon, S D; Berkovic, S F; Free, S; Olivier, A; Harkness, W; Arnold, D L

1999-05-01

High-resolution MRI can detect dual pathology (an extrahippocampal lesion plus hippocampal atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippocampal lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippocampal lesion); mesial temporal resection (removal of an atrophic hippocampus); and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippocampus). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible.

New classification of epilepsy-related neoplasms: The clinical perspective.

PubMed

Kasper, Burkhard S; Kasper, Ekkehard M

2017-02-01

Neoplastic CNS lesions are a common cause of focal epilepsy refractory to anticonvulsant treatment, i.e. long-term epilepsy-associated tumors (LEATs). Epileptogenic tumors encompass a variety of intriguing lesions, e.g. dysembryoplastic neuroepithelial tumors or gangliogliomas, which differ from more common CNS neoplasms in their clinical context as well as on histopathology. Long-term epilepsy-associated tumor classification is a rapidly evolving issue in surgical neuropathology, with new entities still being elucidated. One major issue to be resolved is the inconsistent tissue criteria applied to LEAT accounting for high diagnostic variability between individual centers and studies, a problem recently leading to a proposal for a new histopathological classification by Blümcke et al. in Acta Neuropathol. 2014; 128: 39-54. While a new approach to tissue diagnosis is appreciated and needed, histomorphological criteria alone will not suffice and we here approach the situation of encountering a neoplastic lesion in an epilepsy patient from a clinical perspective. Clinical scenarios to be supported by an advanced LEAT classification will be illustrated and discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

A case of refractary epilepsy and related pain due to dysmenorrhea solved with loading dose of lacosamide: clinical and neurophysiological correlates.

PubMed

Marchitto, Nicolino; Ceratti, Umberto; Dalmaso, Serenella; Raimondi, Gianfranco

2017-10-23

 In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer. She was treated with lamotrigine, clonazepam and levomepromazina maleato. At admission the patient shew seizures due to pain related to dysmenorrhea. In emergency we treated with verapamil hydrochloride 10 mg ev, subsequently verapamil hydrochloride 20 mg in 250 ml of saline solution as maintenance dose. Then we decided to administer a loading dose of 100 mg cpr of Lacosamide to stop the treatment with verapamil hydrochloride. With Lacosamide we solved the seizures in 24 hours.

A Functional-Genetic Scheme for Seizure Forecasting in Canine Epilepsy.

PubMed

Bou Assi, Elie; Nguyen, Dang K; Rihana, Sandy; Sawan, Mohamad

2018-06-01

The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturally-occurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEG-triggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

Neuropsychology Within a Tertiary Care Epilepsy Center.

PubMed

Morrison, Chris E; MacAllister, William S; Barr, William B

2018-05-01

Epilepsy is a prevalent condition characterized by variations in its clinical presentation, etiology, and amenability to treatment. Through history, neuropsychologists have played a significant role in performing research studies on changes in language, memory, and executive functioning in patients with epilepsy, including those undergoing surgical treatment for medically refractory seizures. These studies provided a foundation for establishing neuropsychologists as critical members of interdisciplinary clinical teams specializing in evaluation and treatment of epilepsy. This article describes a number of elements of specialized neuropsychological practice that have evolved over the years within a tertiary care epilepsy center. Through diagnostic interview and objective testing, the neuropsychologist is able to provide a more complete and objective understanding of a patient's cognitive and behavioral functioning than what is obtained by other clinicians through brief office visits. While assessment of cognition, mood, and behavior is the most commonly provided service to patients with epilepsy from all age groups, there are many instances when neuropsychologists in surgical settings are called to perform more specialized procedures, including the intracarotid amytal (Wada) procedure, electrocortical stimulation mapping of language eloquent brain regions, and functional brain imaging procedures. While working as a neuropsychologist on an interdisciplinary epilepsy care team requires specialized knowledge and clinical training, it is extremely satisfying due to the diversity of the patient population and the particular challenges resulting from the often unique manner that cognition and behavior can be affected in patients with epilepsy across the lifespan.

Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

PubMed Central

Walker, Lauren Elizabeth; Frigerio, Federica; Ravizza, Teresa; Ricci, Emanuele; Tse, Karen; Jenkins, Rosalind E.; Sills, Graeme John; Jorgensen, Andrea; Porcu, Luca; Alapirtti, Tiina; Peltola, Jukka; Brodie, Martin J.; Park, Brian Kevin; Marson, Anthony Guy; Antoine, Daniel James

2017-01-01

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 isoforms. Moreover, treatment of animals with antiinflammatory drugs during epileptogenesis prevented both disease progression and blood increase in HMGB1 isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation in larger-scale prospective studies. PMID:28504645

Art and epilepsy surgery.

PubMed

Ladino, Lady Diana; Hunter, Gary; Téllez-Zenteno, José Francisco

2013-10-01

The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process. © 2013.

Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy.

PubMed

Reddy, Doodipala Samba

2016-01-01

Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy.

Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy.

PubMed

Fan, Zhiliang; Feng, Xiaojuan; Fan, Zhigang; Zhu, Xingyuan; Yin, Shaohua

2018-05-09

Epilepsy is a type of refractory neurologic disorder mental disease, which is associated with cognitive impairments and memory dysfunction. However, the potential mechanisms of epilepsy are not well understood. Previous evidence has identified the voltage gated potassium channel complex (VGKC) as a target in various cohorts of patients with epilepsy. In the present study, the efficacy of an antibody against VGKC (anti‑VGKC) for the treatment of epilepsy in mice was investigated. A mouse model of lithium‑pilocarpine temporal lobe epilepsy was established and anti‑VGKC treatment was administered for 30 days. Memory impairment, anxiety, visual attention, inhibitory control and neuronal loss were measured in the mouse model of lithium‑pilocarpine temporal lobe epilepsy. The results revealed that epileptic mice treated with anti‑VGKC were able to learn the task and presented attention impairment, even a tendency toward impulsivity and compulsivity. It was also exhibited that anti‑VGKC treatment decreased neuronal loss in structures classically associated with attentional performance in hippocampus. Mice who received Anti‑VGKC treatment had inhibited motor seizures and hippocampal damage as compared with control mice. In conclusion, these results indicated that anti‑VGKC treatment may present benefits for improvements of the condition of motor attention impairment and cognitive competence, which suggests that VGKC may be a potential target for the treatment of epilepsy.

Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project.

PubMed

Tobochnik, Steven; Fahlstrom, Robyn; Shain, Catherine; Winawer, Melodie R

2017-07-04

To improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project. We studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband. In families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures. Our results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes. © 2017 American Academy of Neurology.

Seizure drawings: insight into the self-image of children with epilepsy.

PubMed

Stafstrom, Carl E; Havlena, Janice

2003-02-01

Epilepsy is a chronic disorder that is associated with numerous psychological challenges, especially in children. Drawings have been underutilized as a method to obtain insight into psychological issues in children with epilepsy. We asked 105 children with epilepsy, ages 5 to 18 years, to draw a picture of what it is like to have a seizure. Across ages and epilepsy syndromes, the drawings showed evidence of impaired self-concept, low self-esteem, and a sense of helplessness and vulnerability. Overall, the drawings of human figures were less developed than expected for chronological age. In some drawings, indicators of underlying depression were found. When considered by epilepsy syndrome or seizure type, some specific artistic features were noted. Children with simple partial (motor) seizures drew distorted body parts, especially limbs. Those with complex partial seizures depicted sensory symptoms and mental status changes such as confusion. Children with generalized tonic-clonic seizures showed shaking extremities. Drawings by children with absence seizures illustrated mainly staring. In conclusion, drawings are a powerful method to examine the self-concept of children with epilepsy and gain insight into their feelings about themselves and their world.

The effects of adjunctive topiramate therapy on seizure severity and health-related quality of life in patients with refractory epilepsy---a Canadian study.

PubMed

Baker, Gus A; Currie, Natalie G T; Light, Margaret J; Schneiderman, Jack H

2002-01-01

Although reduction in seizure frequency is the most common endpoint used to assess the antiepileptic efficacy, seizure frequency alone does not provide a complete picture of effectiveness, particularly in patients with refractory epilepsy. The aim of our study was to assess the effects of topiramate on seizure severity and health-related quality of life (HRQL), in addition to standard efficacy measures, in an open, multicentre, 6-month trial of patients with epilepsy uncontrolled on antiepileptic drugs other than topiramate. Two hundred and nine patients were enrolled and received topiramate for up to 6 months (initiated at 50 mg/day and titrated to a recommended dose of 200-400 mg/day) in addition to existing medication. The median reduction in seizure frequency from baseline to the post-titration period was 40.9% ( P< 0.0001). Patients also demonstrated a mean reduction in the Liverpool Seizure Severity Scale (LSSS) of 5.3 ( P< 0.0001), which was considered clinically significant. Statistically significant changes in HRQL were not observed with the SF-36, a generic measure. Tolerability of antiepileptic medication was good, with a low incidence of cognitive adverse events. The results indicate that topiramate significantly reduces seizure severity---an important aspect of HRQL---when administered as adjunctive therapy to anticonvulsant therapy. Copyright 2002 BEA Trading Ltd.

Ketogenic Diet in Refractory Childhood Epilepsy

PubMed Central

Weijenberg, Amerins; van Rijn, Margreet; de Koning, Tom J.; Brouwer, Oebele F.

2018-01-01

Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis. PMID:29872664

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

PubMed

Dilena, Robertino; Striano, Pasquale; Traverso, Monica; Viri, Maurizio; Cristofori, Gloria; Tadini, Laura; Barbieri, Sergio; Romeo, Antonino; Zara, Federico

2016-01-01

Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery. We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein. The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Clinical experience with lacosamide in Galicia: the GALACO study].

PubMed

Rodriguez-Osorio, Xiana; Lopez-Gonzalez, Francisco J; Pato-Pato, Antonio; Cebrian-Perez, Ernesto; Marey-Lopez, José; Corredera-Garcia, Enrique; Rubio-Nazabal, Eduardo; Castro-Vilanova, M Dolores; Abella-Corral, Javier; Rodriguez-Regal, Ana; Amigo-Jorrin, M Campo; Pego-Reigosa, Robustiano

2015-12-16

Lacosamide is a sodium channel blocker antiepileptic drug authorized as an adjunctive therapy for focal seizures in adolescents and adults. To analyze the efficacy and safety of lacosamide in Galicia according to its use in daily clinical practice. Retrospective observational study in patients who started treatment with lacosamide between January 2014 and June 2013 in 10 hospitals in Galicia, Spain. Its efficacy and safety at 3, 6 and 12 months after starting lacosamide was assessed. We included 184 patients with a mean age of 44.2 ± 17.4 years old; 56.5% (n = 104) were male; 173 patients constituted the efficacy population. Mean duration of epilepsy was 18.8 ± 15.5 years. Seizure frequency was 2.5 ± 1.6 episodes/month. After 12 months, 68.2% of patients (n = 118) had >= 50% improvement (responders) and among them, 54 (45.8% of responder patients) were seizure free. Twenty-three percent (n = 43) suffered from adverse events after 12 months, being dizziness (10.3%) and instability (3.3%) the most frequently reported. After the 12 month visit, 87.5% of patients (n = 161) continued treatment with lacosamide. Lacosamide provides a very good efficacy and safety profile for patients with focal refractory epilepsy. High percentage of responders may be related to a less refractory population compared to other daily clinical practice studies. It constitutes an attractive therapeutic option for the treatment of focal epilepsies.

Outcomes of Subdural Grid Electrode Monitoring in the Stereoelectroencephalography Era.

PubMed

Mullin, Jeffrey P; Sexton, Daniel; Al-Omar, Soha; Bingaman, William; Gonzalez-Martinez, Jorge

2016-05-01

Subdural grid (SDG) electrodes have been the gold standard of invasive monitoring in medically refractory epilepsy; however, in some centers, application of SDGs has been reduced by the progressive application of stereoelectroencephalography (SEEG). This study reviews the efficacy of SDG electrode monitoring after the incorporation of the SEEG methodology at our institution. We retrospectively reviewed 102 patients undergoing intracranial monitoring via SDG electrodes during the years 2010-2013 at our institution. The series includes all patients who underwent SDG placement after the incorporation of SEEG in our extraoperative invasive monitoring armamentarium. Average patient age was 29.9 years old; the series included 31 pediatric patients. There were 49 male patients and 53 female patients. The mean length of follow-up was 21.5 months. The epileptogenic zone was localized in 99 (97%) patients. Surgical resection was performed in 84 patients, and 70% experienced Engel class I freedom from seizures. Invasive monitoring via SDG electrodes continues to be an efficacious option for select patients with medically refractory epilepsy, mainly when the hypothetical epileptogenic zone is anatomically restricted to superficial cortical areas and in close relation with eloquent cortex. This is the first report of epilepsy outcomes after SDG monitoring at a center that also performs SEEG monitoring. Our results suggest a complementary benefit of performing both techniques at 1 institution. Copyright © 2016 Elsevier Inc. All rights reserved.

The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients.

PubMed

Myers, Kenneth A; Mandelstam, Simone A; Ramantani, Georgia; Rushing, Elisabeth J; de Vries, Bert B; Koolen, David A; Scheffer, Ingrid E

2017-06-01

This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1. We were invited to attend a large gathering of individuals with KdVS and their families. While there, we recruited individuals with KdVS and seizures, and performed thorough phenotyping. Additional subjects were included who approached us after the family support group brought attention to our research via social media. Inclusion criteria were genetic testing results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure. Thirty-one individuals were studied, aged 2-35 years. Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features. Twenty-one patients had prolonged seizures and, at times, refractory status epilepticus. Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in 20 of 26. MRI studies of 13 patients were reviewed, and all had structural anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common, although periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum abnormalities were also observed. One patient underwent epilepsy surgery for a lesion that proved to be an angiocentric glioma. The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Perceived self-control of seizures in patients with uncontrolled partial epilepsy.

PubMed

Lee, Sang-Ahm; No, Young-Joo

2005-03-01

Many patients with epilepsy have warning symptoms prior to seizure onset, and some of these individuals report the ability to abort or prevent these seizures. We investigated the clinical characteristics of perceived self-control of seizures in 174 patients with uncontrolled partial epilepsy. The warning symptoms were categorized as premonitory (prodrome) and as initial symptoms of simple partial seizure onset, depending on the relationship between the warning events and the ensuing seizures. About 50% of the patients with simple partial seizure onset and about 70% of those with prodrome or premonitory symptoms reported that they could abort or prevent their seizures by various self-developed techniques. Patients who attempted to abort or prevent their seizures reported success rates as high as 80%. The proportion of patients with secondary generalized seizures was significantly lower in patients who tried to abort their seizures than in those who did not (p<0.05). The ability to prevent seizures was significantly higher in patients with brain lesions on MRI than in those without lesions (p<0.05). These results suggest that spontaneously developed methods are helpful in controlling seizures in some patients with uncontrolled partial epilepsy and that the potential success of self-control methods may be influenced by structural abnormalities on brain MRI.

Seizure outcomes in non-resective epilepsy surgery: An update

PubMed Central

Englot, Dario J.; Birk, Harjus; Chang, Edward F.

2016-01-01

In approximately 30% of patients with epilepsy, seizures are refractory to medical therapy, leading to significant morbidity and increased mortality. Substantial evidence has demonstrated the benefit of surgical resection in patients with drug-resistant focal epilepsy, and in the present journal, we recently reviewed seizure outcomes in resective epilepsy surgery. However, not all patients are candidates for or amenable to open surgical resection for epilepsy. Fortunately, several non-resective surgical options are now available at various epilepsy centers, including novel therapies which have been pioneered in recent years. Ablative procedures such as stereotactic laser ablation and stereotactic radiosurgery offer minimally invasive alternatives to open surgery with relatively favorable seizure outcomes, particularly in patients with mesial temporal lobe epilepsy. For certain individuals who are not candidates for ablation or resection, palliative neuromodulation procedures such as vagus nerve stimulation, deep brain stimulation, or responsive neurostimulation may result in a significant decrease in seizure frequency and improved quality of life. Finally, disconnection procedures such as multiple subpial transections and corpus callosotomy continue to play a role in select patients with an eloquent epileptogenic zone or intractable atonic seizures, respectively. Overall, open surgical resection remains the gold standard treatment for drug-resistant epilepsy, although it is significantly under-utilized. While non-resective epilepsy procedures have not replaced the need for resection, there is hope that these additional surgical options will increase the number of patients who receive treatment for this devastating disorder - particularly individuals who are not candidates for or who have failed resection. PMID:27206422

Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?

PubMed

Avanzini, Giuliano; Depaulis, Antoine; Tassinari, Alberto; de Curtis, Marco

2013-11-01

Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

A prospective service evaluation of acceptance and commitment therapy for patients with refractory epilepsy.

PubMed

Dewhurst, Edel; Novakova, Barbora; Reuber, Markus

2015-05-01

The aims of this service evaluation were to explore the effectiveness of a psychotherapeutic treatment for patients with epilepsy based on the acceptance and commitment therapy (ACT) approach and to assess whether this treatment is likely to be cost-effective. We conducted an uncontrolled prospective study of consecutive patients with refractory epilepsy referred for outpatient psychological treatment to a single psychotherapist because of emotional difficulties related to their seizure disorder. Participants were referred by consultant neurologists, neuropsychologists, or epilepsy nurses, completed a set of validated self-report questionnaires (Short Form - 12 version 2, Generalized Anxiety Disorder - 7, Neurological Disorders Depression Inventory for Epilepsy, Work and Social Adjustment Scale, and Rosenberg Self-Esteem Scale), and reported their seizure frequency at referral, the end of therapy, and six months posttherapy. Patients received a maximum of 20 sessions of one-to-one psychological treatment supported by a workbook. Cost-effectiveness was estimated based on the calculation of quality-adjusted life year (QALY) gains associated with the intervention. Sixty patients completed the prepsychotherapy and postpsychotherapy questionnaires, among whom 41 also provided six-month follow-up data. Patients received six to 20 sessions of psychotherapy (mean=11.5, S.D.=9.6). Psychotherapy was associated with significant medium to large positive effects on depression, anxiety, quality of life, self-esteem, and work and social adjustment (ps<.001), which were sustained six months after therapy. The mean cost of the psychotherapy was £445.6, and, assuming that benefits were maintained for at least six months after the end of therapy, the cost per QALY was estimated to be £11,140 (€14,119, $18,016; the cost per QALY would be half this amount if the benefits lasted one year). The findings of this pilot study indicate that the described psychotherapeutic intervention may be a cost-effective treatment for patients with epilepsy. The results suggest that a randomized controlled trial of the psychotherapy program is justified. Copyright © 2015 Elsevier Inc. All rights reserved.

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan.

PubMed

Tsai, Jeng-Dau; Chang, Ying-Chao; Lin, Lung-Chang; Hung, Kun-Long

2016-03-01

Multiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population. We conducted a one-group pretest-posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged <18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children - IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist. Vagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (<12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children. Vagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent-child relationships, especially in young children (<12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age. Copyright © 2015 Elsevier Inc. All rights reserved.

Preliminary results of the global audit of treatment of refractory status epilepticus.

PubMed

Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S

2015-08-01

The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Alternative surgical approaches in epilepsy.

PubMed

Gigante, Paul R; Goodman, Robert R

2011-08-01

The mainstay of epilepsy surgery is the resection of a presumed seizure focus or disruption of seizure propagation pathways. These approaches cannot be applied to all patients with medically refractory epilepsy (MRE). Since 1997, vagus nerve stimulation has been a palliative adjunct to the care of MRE patients. Deep brain stimulation (DBS) in select locations has been reported to reduce seizure frequency in small studies over the past three decades. Recently published results from the SANTE (Stimulation of the Anterior Nuclei of Thalamus for Epilepsy) trial-the first large-scale, randomized, double-blind trial of bilateral anterior thalamus DBS for MRE-demonstrate a significant reduction in seizure frequency with programmed stimulation. Another surgical alternative is the RNS™ System (NeuroPace, Mountain View, CA), which uses a closed-loop system termed responsive neurostimulation to both detect apparent seizure onsets and deliver stimulation. Recently presented results from the RNS™ pivotal trial demonstrate a sustained reduction in seizure frequency with stimulation, although comprehensive trial results are pending.

Magnetic Resonance Thermometry-Guided Stereotactic Laser Ablation of Cavernous Malformations in Drug-Resistant Epilepsy: Imaging and Clinical Results

PubMed Central

McCracken, D. Jay; Willie, Jon T.; Fernald, Brad; Saindane, Amit M.; Drane, Daniel L.; Barrow, Daniel L.; Gross, Robert E.

2016-01-01

BACKGROUND Surgery is indicated for cerebral cavernous malformations (CCM) that cause medically refractory epilepsy. Real-time magnetic resonance thermography (MRT)-guided stereotactic laser ablation (SLA) is a minimally invasive approach to treating focal brain lesions. SLA of CCM has not previously been described. OBJECTIVE To describe MRT-guided SLA, a novel approach to treating CCM-related epilepsy, with respect to feasibility, safety, imaging, and seizure control in 5 consecutive patients. METHODS Five patients with medically refractory epilepsy undergoing standard presurgical evaluation were found to have corresponding lesions fulfilling imaging characteristics of CCM and were prospectively enrolled. Each underwent stereotactic placement of a saline-cooled cannula containing an optical fiber to deliver 980-nm diode laser energy via twist drill craniostomy. MR anatomic imaging was used to evaluate targeting prior to ablation. MR imaging provided evaluation of targeting and near real-time feedback regarding extent of tissue thermocoagulation. Patients maintained seizure diaries, and remote imaging (6–21 months post-ablation) was obtained in all patients. RESULTS Imaging revealed no evidence of acute hemorrhage following fiber placement within presumed CCM. MRT during treatment and immediate post-procedure imaging confirmed desired extent of ablation. We identified no adverse events or neurological deficits. Four of 5 (80%) patients achieved freedom from disabling seizures after SLA alone (Engel class 1 outcome), with follow-up ranging 12–28 months. Reimaging of all subjects (6–21 months) indicated lesion diminution with surrounding liquefactive necrosis, consistent with the surgical goal of extended lesionotomy. CONCLUSION Minimally invasive MRT-guided SLA of epileptogenic CCM is a potentially safe and effective alternative to open resection. Additional experience and longer follow-up are needed. PMID:27959970

HD-tDCS in refractory lateral frontal lobe epilepsy patients.

PubMed

Karvigh, Sanaz Ahmadi; Motamedi, Mahmoud; Arzani, Mahsa; Roshan, Javad Hasan Nia

2017-04-01

To evaluate the anticonvulsant effect of the novel high definition transcranial direct current stimulation (HD-tDCS) method on patients with refractory lateral frontal lobe epilepsy. The effects of HD-tDCS on working memory were also examined. 10 adult patients with intractable lateral frontal lobe epilepsy were studied. A central cathode electrode was placed on the epileptogenic zone according to LTM, and 20-min sessions of 2mA HD-tDCS were applied for 10 consecutive days. The primary endpoint was to make changes in the epileptiform discharges (EDs) during a 1-h EEG. Moreover, the seizure frequency based on seizure diary and neuropsychiatric parameters was evaluated. All patients tolerated HD-tDCS stimulation course without any adverse reaction. The frequency of EDs increased immediately and one month after the stimulation course by an average of 6.4% and 1.2%, respectively. However, these changes in the EDs frequency were not statistically significant (p-value >0.05). The mean seizure frequency changes showed decrement by an average of 17.9% immediately, and increment by an average of 38.1% one month after the HD-tDCS. These changes were not significant statistically (p-value >0.05). One patient experienced exacerbation of seizures during the stimulations hence dropped out of the study. Attention and working memory improved significantly immediately and one month after the HD-tDCS in all patients. Changes of EDs and mean seizure frequency caused by HD-tDCS were not statistically significant for the whole group; however, this method could improve the patients' working memory scores. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[The efficacy of lacosamide in relation to antiepileptic drug history. Clinical experiences in adult partial epilepsy].

PubMed

Barcs Gábor; Szűcs, Anna; Horváth, András; Kamondi, Anita

2015-01-30

A retrospective study in adult partial epilepsy on the efficacy of lacosamide in relation to previous antiepileptic drug experiences. We analysed 3-65 months' data on epilepsy-care of 43 pharmacoresistant partial epilepsy patients treated with lacosamide. Further analysis of antiepileptic drug history was carried out in strictly selected subgroups of patients with good and poor therapeutic response to lacosamide (10 and 9 patients, respectively) for 2-10 years long retrospective follow up. Adult patients with partial-onset seizures had been treated previously with three or more lifetime antiepileptic drugs without permanent success. Six patients (14%) were seizure free, eleven patients (25%) have experienced important improvement (their seizure-frequency decreased by at least 50%) for more than 12 months. Fourteen patients (32%) improved for less than 6 months and then have relapsed; and add-on lacosamide proved ineffective in 12 patients (28%). Those selected 10 patients successfully treated with lacosamide (seizure free for at least six months) favourably responded to carbamazepine or oxcarbazepine earlier and levetiracetam was ineffective or even caused worsening. The selected lacosamide-unresponsive nine patients responded unfavourably to carbamazepine or oxcarbazepine earlier. Fifteen patients (35%) suffered side effects as dizziness or sleepiness, in 11 of them lacosamide was combined with a "traditional" sodium-channal blocker antiepileptic drug. Lacosamide is an effective add-on antiepileptic drug in difficult-to treat adult partial epilepsy patients. Our data suggest that good lacosamide response may be expected in those patients who reacted favourably to "traditional" sodium-channel blocker carbamazepine or oxcarbazepine earlier.

Computational models of epilepsy.

PubMed

Stefanescu, Roxana A; Shivakeshavan, R G; Talathi, Sachin S

2012-12-01

Approximately 30% of epilepsy patients suffer from medically refractory epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs (AEDs). Understanding the mechanisms underlying these forms of drug-resistant epileptic seizures and the development of alternative effective treatment strategies are fundamental challenges for modern epilepsy research. In this context, computational modeling has gained prominence as an important tool for tackling the complexity of the epileptic phenomenon. In this review article, we present a survey of computational models of epilepsy from the point of view that epilepsy is a dynamical brain disease that is primarily characterized by unprovoked spontaneous epileptic seizures. We introduce key concepts from the mathematical theory of dynamical systems, such as multi-stability and bifurcations, and explain how these concepts aid in our understanding of the brain mechanisms involved in the emergence of epileptic seizures. We present a literature survey of the different computational modeling approaches that are used in the study of epilepsy. Special emphasis is placed on highlighting the fine balance between the degree of model simplification and the extent of biological realism that modelers seek in order to address relevant questions. In this context, we discuss three specific examples from published literature, which exemplify different approaches used for developing computational models of epilepsy. We further explore the potential of recently developed optogenetics tools to provide novel avenue for seizure control. We conclude with a discussion on the utility of computational models for the development of new epilepsy treatment protocols. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Profile of Epilepsy in a Regional Hospital in Al Qassim, Saudi Arabia

PubMed Central

Hamdy, Nermin A; Alamgir, Mohammad Jawad; Mohammad, El Gamri E; Khedr, Mahmoud H; Fazili, Shafat

2014-01-01

Introduction Epilepsy is a diverse set of chronic neurological disorders characterized by seizures. It is one of the most common of the serious neurological disorders. About 3% of people will be diagnosed with epilepsy at some time in their lives. Objectives We aimed to address the commonest types of seizures, their aetiologies, EEG and neuroimaging results and prognosis of patients presented to neurology services of the King Fahad Specialist Hospital- AlQassim (KFSH). Methodology In this retrospective epidemiological study we investigated the medical records of patients with epilepsy, who attended the neurology services of KFSH, during the study period (26/10/2011–26/4/2012). Results The study included 341 patients; 189 (55.4%) males and 152 (44.6%) females. Their ages ranged between 12 and 85 years (mean ± SD = 31±16.9). The majority of patients had Generalised Tonic Clonic Seizures (76.2%), followed by Complex Partial Seizures (7.6%). 73% of our patients had idiopathic epilepsy. The commonest causes for symptomatic epilepsy were Cerebro Vascular Accidents and Head trauma. Hemiplegia, mental retardation and psychiatric illness were the commonest comorbidity. 69.3% of patients had controlled seizures. Patients with idiopathic epilepsy were significantly controlled than patients with symptomatic epilepsy (P=0.01), and those using one Anti Epileptic Drug were significantly controlled compared to patients using polytherapy (P=0.0001) there was no significant relation between controlled seizure and duration of illness or hospitalization or EEG changes. Conclusion Seizure types, aetiology, drug therapy, Comorbidities and outcome in a tertiary care hospital in Saudi Arabia are similar to previous local and international studies. 35.3% of patients were hospitalized, higher rates than previous studies. Seizure control was better in generalized seizures and idiopathic epilepsy compared to complex partial seizures or partial seizures with secondary generalization and symptomatic epilepsy. PMID:25505860

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

PubMed

Strauss, Kenneth I; Elisevich, Kost V

2016-10-13

Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PubMed

Jung, Rebekka; Aull-Watschinger, Susanne; Moser, Doris; Czech, Thomas; Baumgartner, Christoph; Bonelli-Nauer, Sivlia; Pataraia, Ekaterina

2013-09-01

Epilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe. We systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies. Overall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60months, range 12-72); six patients (35.3%) were seizure free at least 12month before observation points (median duration 120.5months, range 35-155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p=0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p=0.116) and before reoperation (p=0.622) was not poorer compared to patients with congruent Video-EEG results. Reoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Epilepsy in TSC: certain etiology does not mean certain prognosis.

PubMed

Vignoli, Aglaia; La Briola, Francesca; Turner, Katherine; Scornavacca, Giulia; Chiesa, Valentina; Zambrelli, Elena; Piazzini, Ada; Savini, Miriam Nella; Alfano, Rosa Maria; Canevini, Maria Paola

2013-12-01

Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial. We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background. Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure-free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug-resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition. Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype-phenotype correlations. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Seizure-related factors and non-verbal intelligence in children with epilepsy. A population-based study from Western Norway.

PubMed

Høie, B; Mykletun, A; Sommerfelt, K; Bjørnaes, H; Skeidsvoll, H; Waaler, P E

2005-06-01

To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function and its relation to central seizure characteristics in a childhood epilepsy population and can be useful for the follow-up team in developing therapy strategies that meet the individual needs of the child with epilepsy.

Prescience as an aura of temporal lobe epilepsy.

PubMed

Sadler, R Mark; Rahey, Susan

2004-08-01

A patient with a distinct aura of prescience as a manifestation of temporal lobe epilepsy was encountered. The experience prompted a review of this ictal phenomenon among patients attending a tertiary care epilepsy outpatient clinic. A computer epilepsy database was searched for patients with simple partial sensory seizures and complex partial seizures with auras. Identified patients had charts reviewed for details of the auras; patients were contacted and asked to provide written descriptions of their experiences. Literature searches (PubMed) were done by using the terms "precognition" or "prescience" and "seizures" or "epilepsy." Standard comprehensive epilepsy textbooks were reviewed. The charts of 218 patients were reviewed from 927 in the database; three had prescience as an ictal feature. The patients' descriptions were very similar in all cases (a profound sense of "knowing" what was going to happen in their environment in the immediate future). The experience was distinct from déjà vu and other psychic experiences. All patients probably have temporal lobe epilepsy. Only one other description of prescience as an ictal feature was found in the literature. Prescience can occur as an ictal feature of temporal lobe epilepsy and represents a previously underreported psychic phenomenon. The potential lateralizing value of this symptom is yet to be determined.

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

PubMed

Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

2015-01-01

Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis

PubMed Central

Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

2015-01-01

Background Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Patients and Methods Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. Results During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Conclusions Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy. PMID:26444013

Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report.

PubMed

Kurian, Mary; Korff, Christian M; Ranza, Emmanuelle; Bernasconi, Andrea; Lübbig, Anja; Nangia, Srishti; Ramelli, Gian Paolo; Wohlrab, Gabriele; Nordli, Douglas R; Bast, Thomas

2018-01-01

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions. Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures. © 2017 Mac Keith Press.

Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial.

PubMed

Sharma, Suvasini; Goel, Shaiphali; Jain, Puneet; Agarwala, Anuja; Aneja, Satinder

2016-11-01

This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p<0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p=0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p=0.26). At 3 months, 6 children had constipation and 5 had weight loss. A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

The association between periodontal disease and seizure severity in refractory epilepsy patients.

PubMed

Costa, Andre L F; Yasuda, Clarissa Lin; Shibasaki, Wendel; Nahás-Scocate, Ana Carla Raphaelli; de Freitas, Claudio Fróes; Carvalho, Paulo Eduardo Guedes; Cendes, Fernando

2014-03-01

Periodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients. One hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented. In logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p<0.001); seizure frequency was significantly related to bad oral hygiene (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group. Our study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2

PubMed Central

Szabo, Gergely G.; Armstrong, Caren; Oijala, Mikko; Soltesz, Ivan

2014-01-01

Abstract Cover Figure Krook-Magnuson et al. report a bidirectional functional connectivity between the hippocampus and the cerebellum in a mouse model of temporal lobe epilepsy, and demonstrate that cerebellar directed on-demand optogenetic intervention can stop seizures recorded from the hippocampus. Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited. PMID:25599088

Innovations in Functional Neurosurgery and Anesthetic Implications.

PubMed

Dunn, Lauren K; Durieux, Marcel E; Elias, W Jeffrey; Nemergut, Edward C; Naik, Bhiken I

2018-01-01

Functional neurosurgery has undergone rapid growth over the last few years fueled by advances in imaging technology and novel treatment modalities. These advances have led to new surgical treatments using minimally invasive and precise techniques for conditions such as Parkinson's disease, essential tremor, epilepsy, and psychiatric disorders. Understanding the goals and technological issues of these procedures is imperative for the anesthesiologist to ensure safe management of patients presenting for functional neurosurgical procedures. In this review, we discuss the advances in neurosurgical techniques for deep brain stimulation, focused ultrasound and minimally invasive laser-based treatment of refractory epilepsy and provide a guideline for anesthesiologists caring for patients undergoing these procedures.

Seizure clusters: A common, understudied and undertreated phenomenon in refractory epilepsy.

PubMed

Komaragiri, Arpitha; Detyniecki, Kamil; Hirsch, Lawrence J

2016-06-01

Epilepsy is widely prevalent globally and has emerged as a well-studied neurological condition in the recent past. Seizure clusters, a type of seizures, and several aspects pertaining to the etiopathogenesis and management of clusters are yet to be elucidated. This review is an attempt to recapitulate the current understanding of seizure clusters based on the research that has been performed on seizure clusters. This article will provide a comprehensive review of various aspects of clusters, and discusses definitions, prevalence, risk factors, impact on quality of life, approved treatment modalities, and recent advances in management. Copyright © 2016 Elsevier Inc. All rights reserved.

The direct cost of epilepsy in the United States: A systematic review of estimates.

PubMed

Begley, Charles E; Durgin, Tracy L

2015-09-01

To develop estimates of the direct cost of epilepsy in the United States for the general epilepsy population and sub-populations by systematically comparing similarities and differences in types of estimates and estimation methods from recently published studies. Papers published since 1995 were identified by systematic literature search. Information on types of estimates, study designs, data sources, types of epilepsy, and estimation methods was extracted from each study. Annual per person cost estimates from methodologically similar studies were identified, converted to 2013 U.S. dollars, and compared. From 4,104 publications discovered in the literature search, 21 were selected for review. Three were added that were published after the search. Eighteen were identified that reported estimates of average annual direct costs for the general epilepsy population in the United States. For general epilepsy populations (comprising all clinically defined subgroups), total direct healthcare costs per person ranged from $10,192 to $47,862 and epilepsy-specific costs ranged from $1,022 to $19,749. Four recent studies using claims data from large general populations yielded relatively similar epilepsy-specific annual cost estimates ranging from $8,412 to $11,354. Although more difficult to compare, studies examining direct cost differences for epilepsy sub-populations indicated a consistent pattern of markedly higher costs for those with uncontrolled or refractory epilepsy, and for those with comorbidities. This systematic review found that various approaches have been used to estimate the direct costs of epilepsy in the United States. However, recent studies using large claims databases and similar methods allow estimation of the direct cost burden of epilepsy for the general disease population, and show that it is greater for some patient subgroups. Additional research is needed to further understand the broader economic burden of epilepsy and how it varies across subpopulations. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Priorities in pediatric epilepsy research

PubMed Central

Baca, Christine B.; Loddenkemper, Tobias; Vickrey, Barbara G.; Dlugos, Dennis

2013-01-01

The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care—particularly epilepsy specialty and behavioral health care—and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous. PMID:23966254

Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy.

PubMed

Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

2017-06-01

The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans. In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development. Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.

Priorities in pediatric epilepsy research: improving children's futures today.

PubMed

Berg, Anne T; Baca, Christine B; Loddenkemper, Tobias; Vickrey, Barbara G; Dlugos, Dennis

2013-09-24

The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care--particularly epilepsy specialty and behavioral health care--and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous.

Expression of SHANK3 in the Temporal Neocortex of Patients with Intractable Temporal Epilepsy and Epilepsy Rat Models.

PubMed

Zhang, Yanke; Gao, Baobing; Xiong, Yan; Zheng, Fangshuo; Xu, Xin; Yang, Yong; Hu, Yida; Wang, Xuefeng

2017-07-01

SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses. In the brain, SHANK3 directly or indirectly interacts with various synaptic molecules including N-methyl-D-aspartate receptor, the metabotropic glutamate receptor (mGluR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity. Recently, accumulating evidence has demonstrated that overexpression of SHANK3 could induce seizures in vivo. However, little is known about the role of SHANK3 in refractory temporal lobe epilepsy (TLE). Therefore, we investigated the expression pattern of SHANK3 in patients with intractable temporal lobe epilepsy and in pilocarpine-induced models of epilepsy. Immunofluorescence, immunohistochemistry, and western blot analysis were used to locate and determine the expression of SHANK3 in the temporal neocortex of patients with epilepsy, and in the hippocampus and temporal lobe cortex of rats in a pilocarpine-induced epilepsy model. Double-labeled immunofluorescence showed that SHANK3 was mainly expressed in neurons. Western blot analysis confirmed that SHANK3 expression was increased in the neocortex of TLE patients and rats. These results indicate that SHANK3 participates in the pathology of epilepsy.

Perampanel: a new add-on treatment for epilepsy.

PubMed

2013-02-01

Perampanel (Fycompa - Eisai) is a new antiepileptic drug marketed in the EU. It is licensed for use as adjunctive treatment of partial-onset seizuresi with or without secondarily generalised seizures in patients with epilepsy aged 12 years and older.2 Here we discuss the place of perampanel in the treatment of epilepsy.

Eslicarbazepine acetate: an update on efficacy and safety in epilepsy.

PubMed

Verrotti, Alberto; Loiacono, Giulia; Rossi, Alessandra; Zaccara, Gaetano

2014-01-01

Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

PubMed

Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

2014-11-01

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Mapping and mining interictal pathological gamma (30–100 Hz) oscillations with clinical intracranial EEG in patients with epilepsy

PubMed Central

Smart, Otis; Maus, Douglas; Marsh, Eric; Dlugos, Dennis; Litt, Brian; Meador, Kimford

2012-01-01

Localizing an epileptic network is essential for guiding neurosurgery and antiepileptic medical devices as well as elucidating mechanisms that may explain seizure-generation and epilepsy. There is increasing evidence that pathological oscillations may be specific to diseased networks in patients with epilepsy and that these oscillations may be a key biomarker for generating and indentifying epileptic networks. We present a semi-automated method that detects, maps, and mines pathological gamma (30–100 Hz) oscillations (PGOs) in human epileptic brain to possibly localize epileptic networks. We apply the method to standard clinical iEEG (<100 Hz) with interictal PGOs and seizures from six patients with medically refractory epilepsy. We demonstrate that electrodes with consistent PGO discharges do not always coincide with clinically determined seizure onset zone (SOZ) electrodes but at times PGO-dense electrodes include secondary seizure-areas (SS) or even areas without seizures (NS). In 4/5 patients with epilepsy surgery, we observe poor (Engel Class 4) post-surgical outcomes and identify more PGO-activity in SS or NS than in SOZ. Additional studies are needed to further clarify the role of PGOs in epileptic brain. PMID:23105174

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

PubMed

Vogt, Viola Lara; Äikiä, Marja; Del Barrio, Antonio; Boon, Paul; Borbély, Csaba; Bran, Ema; Braun, Kees; Carette, Evelien; Clark, Maria; Cross, Judith Helen; Dimova, Petia; Fabo, Daniel; Foroglou, Nikolaos; Francione, Stefano; Gersamia, Anna; Gil-Nagel, Antonio; Guekht, Alla; Harrison, Sue; Hecimovic, Hrvoje; Heminghyt, Einar; Hirsch, Edouard; Javurkova, Alena; Kälviäinen, Reetta; Kavan, Nicole; Kelemen, Anna; Kimiskidis, Vasilios K; Kirschner, Margarita; Kleitz, Catherine; Kobulashvili, Teia; Kosmidis, Mary H; Kurtish, Selin Yagci; Lesourd, Mathieu; Ljunggren, Sofia; Lossius, Morten Ingvar; Malmgren, Kristina; Mameniskiené, Ruta; Martin-Sanfilippo, Patricia; Marusic, Petr; Miatton, Marijke; Özkara, Çiğdem; Pelle, Federica; Rubboli, Guido; Rudebeck, Sarah; Ryvlin, Philippe; van Schooneveld, Monique; Schmid, Elisabeth; Schmidt, Pia-Magdalena; Seeck, Margitta; Steinhoff, Bernhard J; Shavel-Jessop, Sara; Tarta-Arsene, Oana; Trinka, Eugen; Viggedal, Gerd; Wendling, Anne-Sophie; Witt, Juri-Alexander; Helmstaedter, Christoph

2017-03-01

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Epilepsy After Resolution of Presumed Childhood Encephalitis.

PubMed

Rismanchi, Neggy; Gold, Jeffrey J; Sattar, Shifteh; Glaser, Carol A; Sheriff, Heather; Proudfoot, James; Mower, Andrew; Crawford, John R; Nespeca, Mark; Wang, Sonya G

2015-07-01

To evaluate factors associated with the development of epilepsy after resolution of presumed childhood encephalitis. A total of 217 patients with suspected encephalitis who met criteria for the California Encephalitis Project were identified. Evaluable outcome information was available for 99 patients (40 girls, 59 boys, ages 2 months to 17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans. We identified factors correlated with the development of epilepsy after resolution of the acute illness. Development of epilepsy was correlated with the initial presenting sign of seizure (P < 0.001). With each additional antiepileptic drug used to control seizures, the odds ratio of developing epilepsy was increased twofold (P < 0.001). An abnormal electroencephalograph (P < 0.05) and longer hospital duration (median of 8 versus 21 days) also correlated with development of epilepsy (P < 0.01). The need for medically induced coma was associated with epilepsy (P < 0.001). Seizures in those patients were particularly refractory, often requiring longer than 24 hours to obtain seizure control. Individuals who required antiepileptic drugs at discharge (P < 0.001) or were readmitted after their acute illness (P < 0.001) were more likely to develop epilepsy. Of our patients who were able to wean antiepileptic drugs after being started during hospitalization, 42% were successfully tapered off within 6 months. Limited data are available on the risk of developing epilepsy after childhood encephalitis. This is the first study that not only identifies risk factors for the development of epilepsy, but also provides data regarding the success rate of discontinuing antiepileptic medication after resolution of encephalitis. Copyright © 2015 Elsevier Inc. All rights reserved.

Ketogenic Diet in Refractory Childhood Epilepsy: Starting With a Liquid Formulation in an Outpatient Setting.

PubMed

Weijenberg, Amerins; van Rijn, Margreet; Callenbach, Petra M C; de Koning, Tom J; Brouwer, Oebele F

2018-01-01

Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

Novel approaches to anticonvulsant drug discovery.

PubMed

Miziak, Barbara; Chrościńska-Krawczyk, Magdalena; Błaszczyk, Barbara; Radzik, Iwona; Czuczwar, Stanisław J

2013-11-01

The history of epilepsy dates back to 2000 BC. Yet, it was not until 1912 that the activity of the first antiepileptic, phenobarbital was discovered by accident. After this discovery, the next antiepileptic drugs to be discovered (phenytoin and primidone) were based on the phenobarbital's structure. Then, in 1960, carbamazepine was developed empirically, while in 1962, valproate demonstrated anticonvulsant activity against experimental seizures. The next antiepileptic drugs synthesized were either modifications of the existing drugs (such as oxcarbazepine and pregabalin) or completely novel chemical structures (lacosamide, perampanel and retigabine). The present paper briefly refers to the history of epilepsy and development of antiepileptic drugs. Further, the paper provides a discussion on the antiepileptogenic effects of antiepileptic drugs in terms of the constant percentage of epileptic patients with refractory seizures. The authors also review the likely factors involved in the false refractoriness (such as through the use of caffeine-containing beverages and smoking). Finally, the authors consider future directions in the search of novel antiepileptic drugs. In spite of the considerable number of newer antiepileptic drugs, the number of drug-resistant epileptic patients remains unchanged. This may be rather an indication of the suitability of the currently available discovery procedures for effective antiepileptic drugs in the whole population of epileptic patients. The authors, however, believe that it is likely that models of mimic chronic epilepsy will help bridge the gaps and aid in the discovery of novel antiepileptic drugs - ones that can effectively modify the course of the disease.

Polyunsaturated fatty acid supplementation for drug-resistant epilepsy.

PubMed

Sarmento Vasconcelos, Vivian; Macedo, Cristiane R; de Souza Pedrosa, Alexsandra; Pereira Gomes Morais, Edna; Porfírio, Gustavo J M; Torloni, Maria R

2016-08-17

An estimated 1% to 3% of all individuals will receive a diagnosis of epilepsy during their lives, which corresponds to approximately 50 million affected people worldwide. The real prevalence is possibly higher because epilepsy is underreported in developing countries. Although most will achieve adequate control of their disease though the use of medication, approximately 25% to 30% of all those with epilepsy are refractory to pharmacological treatment and will continue to have seizures despite the use of two or more agents in adequate dosages. Over the last decade, researchers have tested the use of polyunsaturated fatty acid (PUFA) supplements for the treatment of refractory epilepsy, with inconsistent results. There have also been some concerns about the use of omega-3 PUFA compounds because they reduce platelet aggregation and could, in theory, cause bleeding. To assess the effectiveness and tolerability of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid-EPA and docosahexanoic acid-DHA) in the control of seizures in people with refractory epilepsy. We searched the Cochrane Epilepsy Group Specialised Register (from inception up to November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, issue 11), MEDLINE (1948 to November 2015), EMBASE (1980 to November 2015), SCOPUS (1823 to November 2015); LILACS (Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde) (1982 to November 2015); ClinicalTrials.gov; World Health Organization (WHO) International Clinical Trials Registry Platform (November 2015). No language restrictions were imposed. We contacted study authors for additional and unpublished information and screened the reference lists of retrieved citations for potentially eligible studies not identified through the electronic search. All randomised and quasi-randomised studies using PUFAs for the treatment of drug-resistant epilepsy. Two review authors were involved in study selection, data extraction and quality assessment of the included trials. The following outcomes were assessed: seizure freedom, seizure reduction, improvement in quality of life, potential adverse effects, gastrointestinal effects, drop-out rates and changes in plasma lipid profile. Primary analyses were by intention to treat. Eight studies were identified as potentially relevant; three fulfilled the selection criteria and were included in the review. Two placebo-controlled, double blind trials involving adult participants were conducted in developed countries, while one placebo-controlled, single blind trial involving children was conducted in a developing country (Egypt). Bromfield 2008 randomised 27 American adults to receive 2.2 g/day of omega-3 PUFAs (EPA:DHA in a 3:2 ratio) or placebo. Yuen 2005 randomised 58 people in the UK to approximately 1.7 g/day omega-3 PUFAs (1g EPA and 0.7g DHA) or placebo. Reda 2015 randomised 70 Egyptian children to receive 3 ml/day of 1200 mg fish oil (providing 0.24 g DHA and 0.36 g EPA) or placebo. The three studies recruited a total of 155 subjects (85 adults and 70 children); 78 of them (43 adults and 35 children) were randomised to PUFAs and 77 (42 adults and 35 children) to placebo. All participants were followed for up to 12 weeks. Seizure freedom was reported by only one study, with a high risk of bias, involving exclusively children. The risk estimate for this outcome was significantly higher in the children receiving PUFA compared to the control group (risk ratio (RR) 20.00, 95% confidence interval (CI) 2.84 to 140.99, 1 study, 70 children). Similarly, PUFA supplementation was associated with a significant difference in the proportion of children with at least 50% reduction in seizure frequency (RR 33.00 95% CI 4.77 to 228.15, 1 study with a high risk of bias, 70 children). However, this effect was not observed when the data from two studies including adult participants were pooled (RR 0.57, 95% CI 0.19 to 1.75, I² 0%, 2 studies, 78 participants, low-quality evidence). One of our three primary outcomes (adverse effects related to bleeding) was not assessed in any of the studies included in this review. There were no significant differences between the PUFA and control groups in relation to gastrointestinal effects (RR 0.78, 95% CI 0.32 to 1.89, 2 studies, 85 participants, low-quality evidence).Supplementation with PUFA did not produce significant differences in mean frequency of seizures, quality of life or other side effects. In view of the limited number of studies and small sample sizes, there is not enough evidence to support the use of PUFA supplementation in people with refractory epilepsy. More trials are needed to assess the benefits of PUFA supplementation in the treatment of drug-resistant epilepsy.

The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

ERIC Educational Resources Information Center

Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.; Duncan, John S.

2010-01-01

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

Absence of simple partial seizure in temporal lobe epilepsy: its diagnostic and prognostic significance.

PubMed

Inoue, Y; Mihara, T; Matsuda, K; Tottori, T; Otsubo, T; Yagi, K

2000-02-01

The diagnostic and prognostic significance of the absence of simple partial seizures (SPS) immediately preceding complex partial seizures (CPS) was examined in patients with temporal lobe epilepsy. The status of self-reported SPS in 193 patients with temporal lobe epilepsy who had surgical therapy more than 2 years ago was reviewed. Before surgery, 37 patients never experienced SPS before CPS (Group A), 156 patients either always or occasionally had SPS before CPS (Group B). The frequency of mesial temporal sclerosis (MTS) was lower and the age at onset of epilepsy was higher in Group A. The seizure focus was in the language-dominant temporal lobe in 73% of the cases in Group A, compared with 40% in Group B. The surgical outcome did not differ between the two groups. The findings suggest that temporal lobe seizures without preceding SPS tend to originate in the language-dominant temporal lobe that contains a pathologic etiology other than MTS, especially in the lateral temporal lobe. The surgical outcome in patients without SPS is similar to that in patients with SPS.

Cognitive and psychosocial effects of oxcarbazepine monotherapy in newly diagnosed partial epilepsy.

PubMed

Kim, Daeyoung; Seo, Ji-Hye; Joo, Eun Yeon; Lee, Hyang Woon; Shin, Won Chul; Hong, Seung Bong

2014-01-01

The aim of this study was to assess the effects of oxcarbazepine (OXC) on cognition and psychosocial difficulties in patients with new-onset partial epilepsy. Cognitive and psychosocial assessments were performed before and after 6 to 12 months of OXC monotherapy in 52 drug-naive patients (25 women; mean age, 31.1 years; SD, 12.1 years). Cognitive functions were evaluated with well-structured and validated tools. Mood, psychological distress, subjective handicap, and quality of life were also evaluated. Differences between baseline and after-treatment evaluation were compared and adjusted for possible confounders such as age, sex, seizure control, duration of epilepsy, assessment interval, and epileptogenic region. Mean assessment interval was 231.8 (range, 182-348) days, and mean (SD) OXC dose at retest was 693.8 (208.9) mg. The OXC was found to have no significant adverse effect on cognition. Furthermore, OXC monotherapy was not found to affect psychosocial difficulties, including psychological distress and subjective handicap. The results suggest that OXC monotherapy could be used to treat newly diagnosed partial epilepsy without adversely affecting cognitive and psychosocial functions.

Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy.

PubMed

von Schoen-Angerer, Tido; Madeleyn, René; Kienle, Gunver; Kiene, Helmut; Vagedes, Jan

2015-07-01

Viscum album (European mistletoe) extracts have known immunomodulatory effects but little data exist on anticonvulsant activity despite its usefulness having been reported for centuries. A 4½-year-old girl with childhood absence epilepsy and global developmental delay was treated with different antiepileptic drugs and ketogenic diet but failed to become seizure free over a 2-year period. She also received different herbal remedies as part of an integrative medicine approach. Initial improvement occurred on valproate-ethosuximide, a further improvement was seen after adding clobazam to valproate. Final cessation of absence activity occurred after a dose increase of V album. She was still seizure free at the 12-month follow-up. V album appears to have been a necessary adjunct treatment for this child to become seizure free. We call on physicians to report their experiences of V album in epilepsy and suggest further study. © The Author(s) 2014.

Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder.

PubMed

Ananth, Amitha L; Robichaux-Viehoever, Amy; Kim, Young-Min; Hanson-Kahn, Andrea; Cox, Rachel; Enns, Gregory M; Strober, Jonathan; Willing, Marcia; Schlaggar, Bradley L; Wu, Yvonne W; Bernstein, Jonathan A

2016-06-01

Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novoGNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy. Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients. All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age four years in all but one patient, who developed chorea at 14 years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients. Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of Psychopathology in Childhood Epilepsy: Categorical and Dimensional Measures

ERIC Educational Resources Information Center

Dunn, David W.; Austin, Joan K.; Perkins, Susan M.

2009-01-01

Few studies have utilized both categorical and dimensional measures of psychopathology in children with epilepsy. We evaluated 173 children (88 males, 85 females; mean age 11.7y [SD 1.8]; range 9-14y) who had epilepsy (generalized 36%, partial 61%) for at least 6 months. The primary caregiver completed a dimensional measure, the Child Behavior…

Automated T2 relaxometry of the hippocampus for temporal lobe epilepsy.

PubMed

Winston, Gavin P; Vos, Sjoerd B; Burdett, Jane L; Cardoso, M Jorge; Ourselin, Sebastien; Duncan, John S

2017-09-01

Hippocampal sclerosis (HS), the most common cause of refractory temporal lobe epilepsy, is associated with hippocampal volume loss and increased T2 signal. These can be identified on quantitative imaging with hippocampal volumetry and T2 relaxometry. Although hippocampal segmentation for volumetry has been automated, T2 relaxometry currently involves subjective and time-consuming manual delineation of regions of interest. In this work, we develop and validate an automated technique for hippocampal T2 relaxometry. Fifty patients with unilateral or bilateral HS and 50 healthy controls underwent T 1 -weighted and dual-echo fast recovery fast spin echo scans. Hippocampi were automatically segmented using a multi-atlas-based segmentation algorithm (STEPS) and a template database. Voxelwise T2 maps were determined using a monoexponential fit. The hippocampal segmentations were registered to the T2 maps and eroded to reduce partial volume effect. Voxels with T2 >170 msec excluded to minimize cerebrospinal fluid (CSF) contamination. Manual determination of T2 values was performed twice in each subject. Twenty controls underwent repeat scans to assess interscan reproducibility. Hippocampal T2 values were reliably determined using the automated method. There was a significant ipsilateral increase in T2 values in HS (p < 0.001), and a smaller but significant contralateral increase. The combination of hippocampal volumes and T2 values separated the groups well. There was a strong correlation between automated and manual methods for hippocampal T2 measurement (0.917 left, 0.896 right, both p < 0.001). Interscan reproducibility was superior for automated compared to manual measurements. Automated hippocampal segmentation can be reliably extended to the determination of hippocampal T2 values, and a combination of hippocampal volumes and T2 values can separate subjects with HS from healthy controls. There is good agreement with manual measurements, and the technique is more reproducible on repeat scans than manual measurement. This protocol can be readily introduced into a clinical workflow for the assessment of patients with focal epilepsy. © 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy.

PubMed

Schraegle, William A; Titus, Jeffrey B

2017-03-01

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age=11.34, SD=3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

Relationship between social competence and neurocognitive performance in children with epilepsy.

PubMed

Raud, Triin; Kaldoja, Mari-Liis; Kolk, Anneli

2015-11-01

Epilepsy may affect a child's social skills and social cognition. The purpose of the study was to examine associations between sociocognitive skills and neurocognitive performance in children with epilepsy. Thirty-five children with epilepsy between the ages of 7 and 12 years (25 with partial and 10 with generalized epilepsy) and 30 controls participated. Theory of Mind (ToM) tasks, Social Cognition Questionnaire proposed by Saltzman-Benaiah and Lalonde (2007), and Social Skills Rating System were used to assess social competence and sociocognitive skills. Neurocognitive performance was assessed using the NEPSY battery. Children with epilepsy demonstrated more difficulties in understanding false belief (p<.001) and intentional lying (p<.05) and exhibited more behavioral problems (p<.05). Notably, their social skills were at the same level as typically developing peers. Children with epilepsy performed significantly worse in attention, executive, verbal, and fine motor tasks (p<.05). We found positive correlations between the understanding of false belief and in executive (r=.6, p<.05), verbal (r=.45-.49, p<.05), and visuospatial skills (r=.34-.48, p<0.01). Children with generalized epilepsy had more problems in memory tasks (p<.05) and understanding of sarcasm (p<.05) compared with children with partial epilepsy. An age of onset over 9.1 years was positively associated with ToM skills (r=.42, p<.05). In conclusion, better ToM in children with better executive functions, and language and visuospatial skills was revealed. The type of epilepsy and age of onset significantly affected ToM skills. Copyright © 2015 Elsevier Inc. All rights reserved.

Methods and apparatus for reducing corrosion in refractory linings

DOEpatents

Poeppel, Roger B.; Greenberg, Sherman; Diercks, Dwight R.

1987-01-01

Methods and apparatus are provided for reducing corrosion in a refractory lining of a liquid-containing vessel used in direct steelmaking processes. The vessel operates at between about 1600.degree. C. and about 1800.degree. C. and an oxygen partial pressure of about 10.sup.-12 atmospheres, creating slag which is rich in FeO. The refractory lining includes a significant level of chromium oxide (Cr.sub.2 O.sub.3), and has small interconnected pores which may be filled with a gas mixture having a higher total pressure and oxygen partial pressure than the total pressure and oxygen partial pressure associted with the liquid against the lining of the vessel. The gas mixture is forced through the pores of the lining so that the pores are continuously filled with the mixture. In this manner, the gas mixture creates a blanket which increases the oxygen partial pressure at the lining enough to maintain the chromium in the lining in a selected valence state in which the chromium has decreased solubility in the FeO slag, thereby reducing corrosion by the FeO and increasing the useful life of the refractory lining.

Charles Bonnet syndrome in hemianopia, following antero-mesial temporal lobectomy for drug-resistant epilepsy.

PubMed

Contardi, Sara; Rubboli, Guido; Giulioni, Marco; Michelucci, Roberto; Pizza, Fabio; Gardella, Elena; Pinardi, Federica; Bartolomei, Ilaria; Tassinari, Carlo Alberto

2007-09-01

Charles Bonnet syndrome (CBS) is a disorder characterized by the occurrence of complex visual hallucinations in patients with acquired impairment of vision and without psychiatric disorders. In spite of the high incidence of visual field defects following antero-mesial temporal lobectomy for refractory temporal lobe epilepsy, reports of CBS in patients who underwent this surgical procedure are surprisingly rare. We describe a patient operated on for drug-resistant epilepsy. As a result of left antero-mesial temporal resection, she presented right homonymous hemianopia. A few days after surgery, she started complaining of visual hallucinations, such as static or moving "Lilliputian" human figures, or countryside scenes, restricted to the hemianopic field. The patient was fully aware of their fictitious nature. These disturbances disappeared progressively over a few weeks. The incidence of CBS associated with visual field defects following epilepsy surgery might be underestimated. Patients with post-surgical CBS should be reassured that it is not an epileptic phenomenon, and that it has a benign, self-limiting, course which does not usually require treatment.

Cannabidiol: promise and pitfalls.

PubMed

Welty, Timothy E; Luebke, Adrienne; Gidal, Barry E

2014-09-01

Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has related to the treatment of refractory epilepsy-especially in children with Dravet syndrome-using cannabidiol (CBD). Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products. Cannabidiol is the major nonpsychoactive component of Cannabis sativa. Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever. These preparations were widely employed as analgesics by Western medical practitioners in the 19(th) century (1). More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis (1).

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.

PubMed

Crippa, José A S; Crippa, Ana C S; Hallak, Jaime E C; Martín-Santos, Rocio; Zuardi, Antonio W

2016-01-01

Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract. The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.

Chronic sorrow and coping in families of children with epilepsy.

PubMed

Hobdell, Elizabeth F; Grant, Mitzie L; Valencia, Ignacio; Mare, Jane; Kothare, Sanjeev V; Legido, Agustin; Khurana, Divya S

2007-04-01

Epilepsy, a common problem in child neurology, affects the entire family. There is a potential for such psychosocial consequences as parental chronic sorrow and alterations in coping. In this study, 67 parents completed brief questionnaires about their sorrow and coping styles. Results demonstrated chronic sorrow as measured by the Adapted Burke Questionnaire (10.45 +/- 7.9). Interestingly, the total score was not significantly different between parents of children with refractory and nonrefractory epilepsy or parents of children with comorbid or without comorbid conditions. Selection of the individual item disbelief, however, was significantly increased in parents of children with nonrefractory epilepsy, and selection of the item anger was significantly increased in parents of children with comorbid conditions. Parental coping styles were similar to those reported in the normative data for the instrument used, the Coping Health Inventory for Parents (CHIP). The correlation between chronic sorrow and coping was significant between the grief component of sorrow and Coping Pattern II of the CHIP. Implications for practice include earlier identification of parental feelings of sorrow and coping styles, which may contribute to a positive outcome.

Alterations in the contents of consciousness in partial epileptic seizures.

PubMed

Johanson, Mirja; Valli, Katja; Revonsuo, Antti; Chaplin, John E; Wedlund, Jan-Eric

2008-08-01

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.

The influence of endophenotypic, disease-specific, and environmental variables on the expression of anxiety in pediatric epilepsy.

PubMed

Schraegle, William A; Titus, Jeffrey B

2017-10-01

Children and adolescents with epilepsy often show higher rates of anxiety, which carries an increased risk for reduced health-related quality of life (HRQOL). The current study assessed the role of parental psychiatric history (i.e., anxiety, depression, and/or bipolar disorder) on the rate of anxiety features in youth seen in a tertiary epilepsy clinic. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 180 children and adolescents (mean age=11.40, SD=3.98). Our results identified clinically elevated anxiety ratings in nearly half the sample (47%) with previous psychiatric history endorsed by 48% of parents. The effect of parental psychiatric history on youth anxiety was found to be significant and associated with a threefold increase in the rate of youth anxiety features. This risk increased to fourfold in refractory epilepsy, and the impact of family psychiatric history is greater in adolescent females and in families that report higher levels of stress. In those families who reported no psychiatric history, anxiety was best predicted by epilepsy-specific factors above and beyond sociodemographic factors. Parental psychiatric history was also identified as a significant risk factor for diminished patient HRQOL, even after accounting for seizure control. These findings highlight the impact of family and epilepsy factors on psychological functioning and offer further support for the strong relationship between parental adjustment and child outcome in pediatric epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Urinary urge seizure semiology localization by intracranial monitoring.

PubMed

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature.

Temporal lobe neoplasm and seizures: how deep does the story go?

PubMed

Jehi, Lara E; Lüders, Hans O; Naugle, Richard; Ruggieri, Paul; Morris, Harold; Foldvary, Nancy; Wyllie, Elaine; Kotagal, Prakash; Bingaman, Bill; Dinner, Dudley; Prayson, Richard; Diehl, Beate; Alexopoulos, Andreas; Bautista, Jocelyn; Busch, Robyn

2008-03-01

[March 2008-Cleveland Case Report]. There is a well-described association between the occurrence of developmental tumors and the presence of cortical dysplasia in the neighboring brain tissue. The main surgical approaches in the treatment of medically refractory epilepsy related to such developmental tumors include a lesionectomy versus a tailored cortical resection, often guided by an invasive evaluation. This case report describes the surgical management of a 26-year-old female with olfactory auras evolving into automotor seizures and convulsions, occurring in the context of a right temporo-parietal developmental lesion. It illustrates the pros and cons of various surgical approaches, and discusses some pathophysiological aspects of developmental tumors, dysplasia and epilepsy. [Published with video sequences].

Urinary urge seizure semiology localization by intracranial monitoring

PubMed Central

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

ABSTRACT Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature. PMID:29686574

Reforming of fuel inside fuel cell generator

DOEpatents

Grimble, Ralph E.

1988-01-01

Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream I and spent fuel stream II. Spent fuel stream I is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream I and exhaust stream II, and exhaust stream I is vented. Exhaust stream II is mixed with spent fuel stream II to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells.

Reforming of fuel inside fuel cell generator

DOEpatents

Grimble, R.E.

1988-03-08

Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream 1 and spent fuel stream 2. Spent fuel stream 1 is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream 1 and exhaust stream 2, and exhaust stream 1 is vented. Exhaust stream 2 is mixed with spent fuel stream 2 to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells. 1 fig.

Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

PubMed

Press, Craig A; Knupp, Kelly G; Chapman, Kevin E

2015-04-01

Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center. A retrospective chart review of children and adolescents who were given OCE for treatment of their epilepsy was performed. Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders). If the family had moved to CO for OCE treatment, the responder rate was 47% vs. 22% for children who already were in CO. The responder rate varied based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available was not improved. Additional benefits reported included: improved behavior/alertness (33%), improved language (10%), and improved motor skills (10%). Adverse events (AEs) occurred in 44% of patients including increased seizures (13%) and somnolence/fatigue (12%). Rare adverse events included developmental regression, abnormal movements, status epilepticus requiring intubation, and death. Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment; however, we also found a variety of challenges and possible confounding factors in studying OCE retrospectively in an open-labeled fashion. We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker. This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.

PubMed

Ribierre, Théo; Deleuze, Charlotte; Bacq, Alexandre; Baldassari, Sara; Marsan, Elise; Chipaux, Mathilde; Muraca, Giuseppe; Roussel, Delphine; Navarro, Vincent; Leguern, Eric; Miles, Richard; Baulac, Stéphanie

2018-04-30

DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia. Here, using postoperative human tissue, we provide the proof of concept that a biallelic 2-hit - brain somatic and germline - mutational mechanism in DEPDC5 causes focal epilepsy with FCD. We discovered a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone. Furthermore, we demonstrate the causality of a Depdc5 brain mosaic inactivation using CRISPR-Cas9 editing and in utero electroporation in a mouse model recapitulating focal epilepsy with FCD and SUDEP-like events. We further unveil a key role of Depdc5 in shaping dendrite and spine morphology of excitatory neurons. This study reveals promising therapeutic avenues for treating drug-resistant focal epilepsies with mTORC1-targeting molecules.

Reliable change indices and regression-based measures for the Rey-Osterreith Complex Figure test in partial epilepsy patients.

PubMed

Nakhutina, L; Pramataris, P; Morrison, C; Devinsky, O; Barr, W B

2010-01-01

The Rey-Osterreith Complex Figure (ROCF) is commonly used in evaluations of patients undergoing epilepsy surgery. We assessed test-retest performance on ROCF in 30 partial epilepsy patients (mean interval = 33.7 months) to derive reliable change indices (RCIs) and regression-based measures for change. ROCF reproductions were rescored by three raters (IRR Copy: 0.963; Delayed Recall: 0.986). The derived adjusted RC (90% CI) cutoff values for the ROCF Copy were (or=8.4) and were (or=10.0) for the Delayed Recall. Results from regression-based analyses were negative, using age, education, seizure duration, and age of onset, whereas a baseline score was a significant predictor of a follow-up score. The results provide a means to evaluate long-term outcome in epilepsy patients using the ROCF.

Protective Effect of Resveratrol on the Brain in a Rat Model of Epilepsy.

PubMed

Li, Zhen; You, Zhuyan; Li, Min; Pang, Liang; Cheng, Juan; Wang, Liecheng

2017-06-01

Accumulating evidence has suggested resveratrol as a promising drug candidate for the treatment of epilepsy. To validate this, we tested the protective effect of resveratrol on a kainic acid (KA)-induced epilepsy model in rats and investigated the underlying mechanism. We found that acute resveratrol application partially inhibited evoked epileptiform discharges in the hippocampal CA1 region. During acute, silent and chronic phases of epilepsy, the expression of hippocampal kainate glutamate receptor (GluK2) and the GABA A receptor alpha1 subunit (GABA A R-alpha1) was up-regulated and down-regulated, respectively. Resveratrol reversed these effects and induced an antiepileptic effect. Furthermore, in the chronic phase, resveratrol treatment inhibited the KA-induced increased glutamate/GABA ratio in the hippocampus. The antiepileptic effects of resveratrol may be partially attributed to the reduction of glutamate-induced excitotoxicity and the enhancement in GABAergic inhibition.

The role of executive functioning in memory performance in pediatric focal epilepsy

PubMed Central

Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

2016-01-01

Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. PMID:28111742

Seizures and Teens: Surgery for Seizures--What's It All About?

ERIC Educational Resources Information Center

Duchowny, Michael S.; Dean, Patricia

2006-01-01

Nearly 1 out of 2 children and teens with seizures may need to take medications throughout their lives. At least 25% will develop a condition called refractory epilepsy--meaning that their seizures do not respond to medical therapy. For these children and teens, non-drug therapies such as brain surgery are available that may offer a chance to…

Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy.

PubMed Central

Gillham, R A; Blacklaw, J; McKee, P J; Brodie, M J

1993-01-01

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation. PMID:8270925

Gamma knife treatment for refractory epilepsy in seizure focus localized by positron emission tomography/CT★

PubMed Central

Bai, Xia; Wang, Xuemei; Wang, Hongwei; Zhao, Shigang; Han, Xiaodong; Hao, Linjun; Wang, Xiangcheng

2012-01-01

A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The foci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser’s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser’s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser’s classification score was significantly higher in the single-focus group as compared with the multiple-foci group. PMID:25317147

Classification Preictal and Interictal Stages via Integrating Interchannel and Time-Domain Analysis of EEG Features.

PubMed

Lin, Lung-Chang; Chen, Sharon Chia-Ju; Chiang, Ching-Tai; Wu, Hui-Chuan; Yang, Rei-Cheng; Ouyang, Chen-Sen

2017-03-01

The life quality of patients with refractory epilepsy is extremely affected by abrupt and unpredictable seizures. A reliable method for predicting seizures is important in the management of refractory epilepsy. A critical factor in seizure prediction involves the classification of the preictal and interictal stages. This study aimed to develop an efficient, automatic, quantitative, and individualized approach for preictal/interictal stage identification. Five epileptic children, who had experienced at least 2 episodes of seizures during a 24-hour video EEG recording, were included. Artifact-free preictal and interictal EEG epochs were acquired, respectively, and characterized with 216 global feature descriptors. The best subset of 5 discriminative descriptors was identified. The best subsets showed differences among the patients. Statistical analysis revealed most of the 5 descriptors in each subset were significantly different between the preictal and interictal stages for each patient. The proposed approach yielded weighted averages of 97.50% correctness, 96.92% sensitivity, 97.78% specificity, and 95.45% precision on classifying test epochs. Although the case number was limited, this study successfully integrated a new EEG analytical method to classify preictal and interictal EEG segments and might be used further in predicting the occurrence of seizures.

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.

PubMed

Walker, Melissa A; Mohler, Kyle P; Hopkins, Kyle W; Oakley, Derek H; Sweetser, David A; Ibba, Michael; Frosch, Matthew P; Thibert, Ronald L

2016-08-01

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins. © The Author(s) 2016.

[Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis].

PubMed

Olivares-Granados, Gonzalo; Ríos-Pelegrina, Rosa María; Ruiz-Giménez, Jesús; Galdón-Castillo, Alberto; Escobar-Delgado, Teresa; García Del Moral, Raimundo

Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

PubMed Central

Zhu, Fei; Lang, Sen-Yang; Wang, Xiang-Qing; Shi, Xiao-Bing; Ma, Yun-Feng; Zhang, Xu; Chen, Ya-Nan; Zhang, Jia-Tang

2015-01-01

Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64–44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate. PMID:26608980

Status Epilepticus and Refractory Status Epilepticus Management

PubMed Central

Abend, Nicholas S.; Bearden, David; Helbig, Ingo; McGuire, Jennifer; Narula, Sona; Panzer, Jessica A.; Topjian, Alexis; Dlugos, Dennis J.

2014-01-01

Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status, and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician’s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other anti-seizure medications. If seizures persist then refractory SE is diagnosed and management options include additional anti-seizure medications or infusions of midazolam or pentobarbital. This paper reviews the management of pediatric SE and RSE. PMID:25727508

Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

Objective: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. Methods: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. Results: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ∼7% from 1 to 5 years postimplantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. Recommendations: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. PMID:23986299

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PubMed

Van Paesschen, W; King, M D; Duncan, J S; Connelly, A

2001-07-01

To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

A predictive risk model for medical intractability in epilepsy.

PubMed

Huang, Lisu; Li, Shi; He, Dake; Bao, Weiqun; Li, Ling

2014-08-01

This study aimed to investigate early predictors (6 months after diagnosis) of medical intractability in epilepsy. All children <12 years of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital between 1992 and 2006 were included. Medical intractability was defined as failure, due to lack of seizure control, of more than 2 antiepileptic drugs at maximum tolerated doses, with an average of more than 1 seizure per month for 24 months and no more than 3 consecutive months of seizure freedom during this interval. Univariate and multivariate logistic regression models were performed to determine the risk factors for developing medical intractability. Receiver operating characteristic curve was applied to fit the best compounded predictive model. A total of 649 patients were identified, out of which 119 (18%) met the study definition of intractable epilepsy at 2 years after diagnosis, and the rate of intractable epilepsy in patients with idiopathic syndromes was 12%. Multivariate logistic regression analysis revealed that neurodevelopmental delay, symptomatic etiology, partial seizures, and more than 10 seizures before diagnosis were significant and independent risk factors for intractable epilepsy. The best model to predict medical intractability in epilepsy comprised neurological physical abnormality, age at onset of epilepsy under 1 year, more than 10 seizures before diagnosis, and partial epilepsy, and the area under receiver operating characteristic curve was 0.7797. This model also fitted best in patients with idiopathic syndromes. A predictive model of medically intractable epilepsy composed of only four characteristics is established. This model is comparatively accurate and simple to apply clinically. Copyright © 2014 Elsevier Inc. All rights reserved.

A retrospective diagnosis of epilepsy in three historical figures: St Paul, Joan of Arc and Socrates.

PubMed

Muhammed, Louwai

2013-11-01

It has been suggested that undiagnosed epilepsy profoundly influenced the lives of several key figures in history. Historical sources recounting strange voices and visions may in fact have been describing manifestations of epileptic seizures rather than more supernatural phenomena. Well-documented accounts of such experiences exist for three individuals in particular: Socrates, St Paul and Joan of Arc. The great philosopher Socrates described a 'daimonion' that would visit him throughout his life. This daimonion may have represented recurrent simple partial seizures, while the peculiar periods of motionlessness for which Socrates was well known may have been the result of co-existing complex partial seizures. St Paul's religious conversion on the Road to Damascus may have followed a temporal lobe seizure which would account for the lights, voices, blindness and even the religious ecstasy he described. Finally, Joan of Arc gave a detailed narrative on the voices she heard from childhood during her Trial of Condemnation. Her auditory hallucinations appear to follow sudden acoustic stimuli in a way reminiscent of idiopathic partial epilepsy with auditory features. By analysing passages from historical texts, it is possible to argue that Socrates, St Paul and Joan of Arc each had epilepsy.

Schizophrenia and epilepsy: is there a shared susceptibility?

PubMed

Cascella, Nicola G; Schretlen, David J; Sawa, Akira

2009-04-01

Individuals with epilepsy are at increased risk of having psychotic symptoms that resemble those of schizophrenia. More controversial and less searched is if schizophrenia is a risk factor for epilepsy. Here we review overlapping epidemiological, clinical, neuropathological and neuroimaging features of these two diseases. We discuss the role of temporal and other brain areas in the development of schizophrenia-like psychosis of epilepsy. We underline the importance of ventricular enlargement in both conditions as a phenotypic manifestation of a shared biologic liability that might relate to abnormalities in neurodevelopment. We suggest that genes implicated in neurodevelopment may play a common role in both conditions and speculate that recently identified causative genes for partial complex seizures with auditory features might help explain the pathophysiology of schizophrenia. These particularly include the leucine-rich glioma inactivated (LGI) family gene loci overlap with genes of interest for psychiatric diseases like schizophrenia. Finally, we conclude that LGI genes associated with partial epilepsy with auditory features might also represent genes of interest for schizophrenia, especially among patients with prominent auditory hallucinations and formal thought disorder.

Self-concept and gender effects in Korean adolescents with epilepsy.

PubMed

Lee, Sang-Ahm; Choi, Eun-Ju; Kwon, Soonhak; Eom, Soyong

2016-08-01

We aimed to determine whether adolescents with epilepsy (AWE) have a compromised self-concept, whether a lower self-concept is related to mental health, and whether there are sex differences in self-concept in AWE. A total of 179 AWE and 259 control adolescents without epilepsy participated in this cross-sectional, multicenter study. Self-concept was measured using the Harter's Self-Perception Profile for Children. Depressive symptoms and anxiety were assessed by the Hospital Anxiety Depression Scale (HADS). A group-by-sex interaction was evaluated using an analysis of covariance controlling for age. Adolescents with epilepsy had a lower level of self-concept, especially in domains of behavioral conduct (partial eta(2): 0.257) and social acceptance (partial eta(2): 0.116), than controls (p<0.05). The level of self-concept did not differ by sex in the group with epilepsy. A group-by-sex interaction effect was found on social acceptance (p=0.042). Unlike the control group, age was not correlated with self-concept in AWE. Physical appearance was negatively correlated with HADS-anxiety scores (r=-0.291, p<0.01) but only in girls with epilepsy. Epilepsy duration was correlated with social acceptance in boys (r=0.211, p<0.05) and physical appearance in girls (r=-0.249, p<0.05). Adolescents with epilepsy had a lower level of self-concept, especially in the domains of behavioral conduct and social acceptance, than controls. Sex differences in self-concept were identified in the control group but not in the group with epilepsy. Physical appearance was negatively correlated with anxiety in girls with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Global Health: Epilepsy.

PubMed

Ali, Amza

2018-04-01

Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone-related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

MRI-negative temporal lobe epilepsy-What do we know?

PubMed

Muhlhofer, Wolfgang; Tan, Yee-Leng; Mueller, Susanne G; Knowlton, Robert

2017-05-01

Temporal lobe epilepsy (TLE) is the most common focal epilepsy in adults. TLE has a high chance of becoming medically refractory, and as such, is frequently considered for further evaluation and surgical intervention. Up to 30% of TLE cases, however, can have normal ("nonlesional" or negative) magnetic resonance imaging (MRI) results, which complicates the presurgical workup and has been associated with worse surgical outcomes. Helped by contributions from advanced imaging techniques and electrical source localization, the number of surgeries performed on MRI-negative TLE has increased over the last decade. Thereby new epidemiologic, clinical, electrophysiologic, neuropathologic, and surgical data of MRI-negative TLE has emerged, showing characteristics that are distinct from those of lesional TLE. This review article summarizes what we know today about MRI-negative TLE, and discusses the comprehensive assessment of patients with MRI-negative TLE in a structured and systematic approach. It also includes a concise description of the most recent developments in structural and functional imaging, and highlights postprocessing imaging techniques that have been shown to add localization value in MRI-negative epilepsies. We evaluate surgical outcomes of MRI-negative TLE, identify prognostic makers of postoperative seizure freedom, and discuss strategies for optimizing the selection of surgical candidates in this group. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Seizure outcomes in children with epilepsy after resective brain surgery.

PubMed

Nagarajan, Lakshmi; Lee, Michael; Palumbo, Linda; Lee, Sharon; Shah, Snehal; Walsh, Peter; Cannell, Patricia; Ghosh, Soumya

2015-09-01

To assess the role of resective brain surgery in childhood epilepsy. We retrospectively analysed the seizure outcomes in 55 children with epilepsy who had resective brain surgery between 1997 and 2012, at our centre. The children were 1.5-18 years at the time of surgery; their seizure onset was between 0.2 andto 15 years of age. 48 had refractory epilepsy. One child died of tumour progression. Follow-up duration in the survivors ranged from 2 to -16 years (mean: 9).Presurgical evaluation included clinical profiles, non-invasive V-EEG monitoring, neuroimaging with MRIs in all; SPECT and PET in selected patients. 54 had intraoperative ECoG. An Engel Class 1 outcome was seen in 78% of the cohort, with 67% being off all AEDs at the most recent follow-up. Children with tumours constituted the majority (56%), with 87% of this group showing a Class 1 outcome and 84% being off AEDs. Children with cortical dysplasia had a Class 1 outcome in 56%. Resective brain surgery is an efficacious option in some children with epilepsy. We found ECoG useful to tailor the cortical resection and in our opinion ECoG contributed to the good seizure outcomes. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The role of executive functioning in memory performance in pediatric focal epilepsy.

PubMed

Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

2017-02-01

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Treatment of pediatric epilepsy in Poland.

PubMed

Dunin-Wąsowicz, Dorota; Mazurkiewicz-Bełdzińska, Maria; Steinborn, Barbara; Wheless, James; Jóźwiak, Sergiusz

2015-05-01

The many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. To provide an overview of current practice in Poland and compare results with European and US clinical guidelines. Polish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). Fifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. Polish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians. Copyright © 2015. Published by Elsevier Ltd.

The Role of Skull Modeling in EEG Source Imaging for Patients with Refractory Temporal Lobe Epilepsy.

PubMed

Montes-Restrepo, Victoria; Carrette, Evelien; Strobbe, Gregor; Gadeyne, Stefanie; Vandenberghe, Stefaan; Boon, Paul; Vonck, Kristl; Mierlo, Pieter van

2016-07-01

We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2012-06-13

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug and usually require treatment with a combination of two or more antiepileptic drugs. In recent years, many newer antiepileptic drugs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (1 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library, 2012) and MEDLINE (1 May 2012). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. There were no language restrictions. Randomized controlled add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RR) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients were eligible for inclusion. Both trials assessed losigamone 1200 or 1500 mg/d as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodologic quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/d) is associated with a greater reduction in seizure frequency than lower doses, but is also associated with more dropouts due to adverse events. The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed.

Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

PubMed

Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

2012-06-01

Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical outcomes

PubMed Central

Bonilha, Leonardo

2015-01-01

Medically intractable temporal lobe epilepsy (TLE) remains a serious health problem. Across treatment centers, up to 40% of patients with TLE will continue to experience persistent postoperative seizures at 2-year follow-up. It is unknown why such a large number of patients continue to experience seizures despite being suitable candidates for resective surgery. Preoperative quantitative MRI techniques may provide useful information on why some patients continue to experience disabling seizures, and may have the potential to develop prognostic markers of surgical outcome. In this article, we provide an overview of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have improved the understanding of brain structural alterations in patients with refractory TLE. We subsequently review the studies that have applied quantitative structural imaging techniques to identify the neuroanatomical factors that are most strongly related to a poor postoperative prognosis. In summary, quantitative imaging studies strongly suggest that TLE is a disorder affecting a network of neurobiological systems, characterized by multiple and inter-related limbic and extra-limbic network abnormalities. The relationship between brain alterations and postoperative outcome are less consistent, but there is emerging evidence suggesting that seizures are less likely to remit with surgery when presurgical abnormalities are observed in the connectivity supporting brain regions serving as network nodes located outside the resected temporal lobe. Future work, possibly harnessing the potential from multimodal imaging approaches, may further elucidate the etiology of persistent postoperative seizures in patients with refractory TLE. Furthermore, quantitative imaging techniques may be explored to provide individualized measures of postoperative seizure freedom outcome. PMID:25853080

Partial monosomy Xq(Xq23 --> qter) and trisomy 4p(4p15.33 --> pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features.

PubMed

Bartocci, Arnaldo; Striano, Pasquale; Mancardi, Maria Margherita; Fichera, Marco; Castiglia, Lucia; Galesi, Ornella; Michelucci, Roberto; Elia, Maurizio

2008-06-01

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

Epilepsy genetics: clinical beginnings and social consequences.

PubMed

Johnston, J A; Rees, M I; Smith, P E M

2009-07-01

The approach to epilepsy care has transformed in the last 30 years, with more and better anti-epileptic medications, improved cerebral imaging and increased surgical options. Alongside this, developments in neuroscience and molecular genetics have furthered the understanding of epileptogenesis. Future developments in pharmacogenomics hold the promise of antiepileptic drugs matched to specific genotypes. Despite this rapid progress, one-third of epilepsy patients remain refractory to medication, with their seizures impacting upon day-to-day activity, social well-being, independence, economic output and quality of life. International genome collaborations, such as HapMap and the Welcome Trust Case-Control Consortium single nucleotide polymorphism (SNP) mapping project have identified common genetic variations in diseases of major public health importance. Such genetic signposts should help to identify at-risk populations with a view to producing more effective pharmaceutical treatments. Neurological disorders, despite comprising one-fifth of UK acute medical hospital admissions, are surprisingly under-represented in these projects. Epilepsy is the commonest serious neurological disorder worldwide. Although physically, psychologically, socially and financially disabling, it rarely receives deserved attention from physicians, scientists and governmental bodies. As outlined in this article, research into epilepsy genetics presents unique challenges. These help to explain why the identification of its complex genetic traits has lagged well behind other disciplines, particularly the efforts made in neuropsychiatric disorders. Clinical beginnings must underpin any genetic understanding in epilepsy. Success in identifying genetic traits in other disorders does not make the automatic case for genome-wide screening in epilepsy, but such is a desired goal. The essential clinical approach of accurately phenotyping, diagnosing and interpreting the dynamic nature of epilepsy remains fundamental to harvesting its potential translational outcomes.

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

PubMed

Kobulashvili, Teia; Höfler, Julia; Dobesberger, Judith; Ernst, Florian; Ryvlin, Philippe; Cross, J Helen; Braun, Kees; Dimova, Petia; Francione, Stefano; Hecimovic, Hrvoje; Helmstaedter, Christoph; Kimiskidis, Vasilios K; Lossius, Morten Ingvar; Malmgren, Kristina; Marusic, Petr; Steinhoff, Bernhard J; Boon, Paul; Craiu, Dana; Delanty, Norman; Fabo, Daniel; Gil-Nagel, Antonio; Guekht, Alla; Hirsch, Edouard; Kalviainen, Reetta; Mameniskiené, Ruta; Özkara, Çiğdem; Seeck, Margitta; Rubboli, Guido; Krsek, Pavel; Rheims, Sylvain; Trinka, Eugen

2016-05-01

The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A multicentre study of vigabarin for drug-resistant epilepsy

PubMed Central

Browne, T. R.; Mattson, R. H.; Penry, J. K.; Smith, D. B.; Treiman, D. M.; Wilder, B. J.; Ben-Menachem, E.; Miketta, R. M.; Sherry, K. M.; Szabo, G. K.

1989-01-01

1 Vigabatrin (GVG) was given in a single-blind fashion to 89 patients with complex partial seizures (CPS) refractory to conventional drugs. 2 The median number of CPS per month decreased from 11.0 to 5.0 after addition of GVG, and 51% of patients had a 50% or greater decrease in CPS frequency (P < 0.001). 3 Side effects (principally drowsiness, ataxia, headache) occurred mainly during the initiation of therapy and decreased during therapy. After 12 weeks on GVG side effects significantly interfered with functioning in only 13% of patients, and the efficacy: toxicity ratio warranted continued administration in 74% of patients. 4 Co-administration of GVG resulted in a mean decrease of 20% in phenytoin serum concentration (P < 0.001). 5 Sixty-six patients having a favourable response to GVG during the single-blind study have been followed for 6-54 (median 33) months on GVG. Only 17 patients have dropped out of long-term follow-up due to break through seizures and/or side effects. No serious systemic or neurological toxicity has been detected. PMID:2667606

Tuberous Sclerosis with Epilepsy

DTIC Science & Technology

2009-02-01

seizures. She uses a vagal nerve stimulator (VNS) set at maximum level, and she is maintained on a modified ketogenic diet to help control seizure...refractory to medical treatment include ketogenic diet or VNS. The anticonvulsant effects of the ketogenic diet are a result of the persistent state of...patient’s situation improved seizure control was achieved with a combination of a modified ketogenic diet , VNS, and depot medroxyprogesterone acetate

Infraslow status epilepticus: A new form of subclinical status epilepticus recorded in a child with Sturge-Weber syndrome.

PubMed

Bello-Espinosa, Luis E

2015-08-01

Analysis of infraslow EEG activity (ISA) has shown potential in the evaluation of patients with epilepsy and in the differentiation between focal and generalized epilepsies. Infraslow EEG activity analysis may also provide insights into the pathophysiology of refractory clinical and subclinical status epilepticus. The purpose of this report is to describe a girl with Sturge-Weber syndrome (SWS) who presented with a 96-h refractory encephalopathy and nonischemic hemiparesis and who was identified to have infraslow status epilepticus (ISSE), which successfully resolved after midazolam administration. The continuous EEG recording of a 5-year-old girl with known structural epilepsy due to Sturge-Weber syndrome is presented. The patient presented to the ED with acute confusion, eye deviation, and right hemiparesis similar to two previous admissions. Despite administration of lorazepam, fosphenytoin, phenobarbital, and valproic loads, the patient showed no improvement in the clinical condition after 48 h. The continuous video-EEG monitoring (VEM) showed continuous severe diffuse nonrhythmic asymmetric slowing but no apparent ictal activity on continuous conventional EEG recording settings. As brain CT, CTA, CTV, and complete MRI scans including DWI obtained within 72 h of presentation failed to demonstrate any ischemic changes, analysis of the EEG infraslow (ISA) activity was undertaken using LFF: 0.01 Hz and HFF: of 0.1 Hz, respectively. Continuous subclinical unilateral rhythmic ictal ISA was identified. This was only evident on the left hemisphere which correlated with the structural changes due to SWS. A trial of continuous 120 to 240 μg/kg/h of IV midazolam resulted in immediate resolution of the contralateral hemiparesis and encephalopathy. Continuous prolonged rhythmic ictal infraslow activity (ISA) can cause super-refractory subclinical focal status epilepticus. This has not been previously reported, and we propose that this be called infraslow status epilepticus (ISSE). Infraslow EEG activity analysis should be performed in all patients with unexplained subclinical status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Developing from child to adult: Risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy.

PubMed

Geerlings, R P J; Aldenkamp, A P; Gottmer-Welschen, L M C; de With, P H N; Zinger, S; van Staa, A L; de Louw, A J A

2015-10-01

Childhood-onset epilepsy during the years of transition to adulthood may affect normal social, physical, and mental development, frequently leading to psychosocial and health-related problems in the long term. This study aimed to describe the main characteristics of patients in transition and to identify risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy. Patients with epilepsy, 15-25years of age, who visited the Kempenhaeghe Epilepsy Transition Clinic from March 2012 to December 2014 were included (n=138). Predefined risk scores for medical, educational/occupational status, and independence/separation/identity were obtained, along with individual risk profile scores for poor psychosocial outcome. Multivariate linear regression analysis and discriminant analysis were used to identify variables associated with an increased risk of poor long-term psychosocial outcome. Demographic, epilepsy-related, and psychosocial variables associated with a high risk of poor long-term outcome were lower intelligence, higher seizure frequency, ongoing seizures, and an unsupportive and unstable family environment. Using the aforementioned factors in combination, we were able to correctly classify the majority (55.1%) of the patients regarding their risk of poor psychosocial outcome. Our analysis may allow early identification of patients at high risk of prevention, preferably at pretransition age. The combination of a chronic refractory epilepsy and an unstable family environment constitutes a higher risk of transition problems and poor outcome in adulthood. As a consequence, early interventions should be put into place to protect youth at risk of poor transition outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

PubMed

Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

2016-11-01

Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence-Based Guideline Update: Vagus Nerve Stimulation for the Treatment of Epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ~7% from 1 to 5 years postim-plantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. Neurology® 2013;81:1–7 PMID:24348133

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients.

PubMed

Doucet, Gaelle E; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients

PubMed Central

Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates. PMID:26594628

Automated seizure detection systems and their effectiveness for each type of seizure.

PubMed

Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

2016-08-01

Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. Copyright © 2016. Published by Elsevier Ltd.

Vertical parasagittal hemispherotomy for Sturge-Weber syndrome in early infancy: case report and literature review.

PubMed

Liu, Xiangyu; Otsuki, Taisuke; Takahashi, Akio; Kaido, Takanobu

2016-01-01

The authors here present a rare case of a 3-month-old infant with unilateral Sturge-Weber syndrome (SWS) who had excellent seizure control and no aggravation of previous existed neurological deficits after vertical parasagittal hemispherotomy (VPH). To our knowledge, this patient with SWS was the youngest one who received VPH. The use of VPH results in a successful treatment of intractable epilepsy in a patient with seizure onset in early infancy. At follow-up, the patient's neurodevelopmental status has been improved since the surgery. It is generally accepted that early-onset seizures in children with SWS are associated with worse neurological and developmental outcomes. However, when surgical treatment should be considered and how it should be performed remain a longstanding controversy. We promote early surgery in children with SWS and early-onset epilepsy. We suggest that VPH may be a useful adjuvant in the management of SWS with refractory epilepsy in early infancy and this procedure carries low neurological risk.

Neuroprotection trek--the next generation: neuromodulation II. Applications--epilepsy, nerve regeneration, neurotrophins

NASA Technical Reports Server (NTRS)

Andrews, Russell J.

2003-01-01

Three examples of neuroprotective applications of electrical stimulation-neuromodulation-are considered: (1) the diagnosis and treatment of epilepsy, (2) the augmentation of peripheral nerve regeneration after transection, and (3) the interaction between electrical stimulation and neurotrophins (notably brain derived neurotrophic factor [BDNF]) in various neuroprotective situations. The research cited demonstrates clear benefit from appropriate electrical stimulation in the treatment of (1) certain patients with medication-refractory epilepsy, and (2) the functional regeneration of peripheral nerves after transection and surgical repair. Furthermore, neuromodulation of peripheral nerve regeneration has been associated with an increase in the neurotrophin BDNF. The roles of BDNF and other neurotrophins in several disorders of the nervous system are discussed in the context of neuromodulation and its augmentation of neurotrophins. Neuromodulation-at least in part through its effect on BDNF and other neurotrophins-will likely play a major role in the treatment (and possibly prevention) of disorders of the nervous system for which neuroproteive pharmacologic agents have traditionally been sought.

Absence of gender effect on amygdala volume in temporal lobe epilepsy.

PubMed

Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

2010-11-01

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.

Self-injury and incontinence in psychogenic seizures.

PubMed

Peguero, E; Abou-Khalil, B; Fakhoury, T; Mathews, G

1995-06-01

Two patients who incurred significant injuries during psychogenic seizures prompted us to do a telephone survey of self-injury and incontinence in 102 consecutive patients diagnosed with psychogenic seizures by EEG-closed-circuit TV (EEG-CCTV) monitoring. Seventy-three patients (or a close family member or friend) were reached by telephone and responded to our survey. During typical attacks of psychogenic seizures, 40% reported injuries, 44% reporting tongue biting, and 44% reported urinary incontinence. Suicide attempts were reported by 32% and were more common in those with self-injury and urinary incontinence. We compared the results of patients with psychogenic seizures with those of 30 patients with refractory epilepsy documented by ictal recordings, using a similar telephone survey. Injuries of all types were more commonly reported by epilepsy patients. Burn injuries were reported only by patients with epilepsy. Suicide attempts were more commonly reported by the psychogenic seizure group. Self-injury and incontinence are commonly reported by psychogenic seizure patients. In view of their significant association with suicide attempts, they may indicate an underlying depression.

Neuroprotection trek--the next generation: neuromodulation II. Applications--epilepsy, nerve regeneration, neurotrophins.

PubMed

Andrews, Russell J

2003-05-01

Three examples of neuroprotective applications of electrical stimulation-neuromodulation-are considered: (1) the diagnosis and treatment of epilepsy, (2) the augmentation of peripheral nerve regeneration after transection, and (3) the interaction between electrical stimulation and neurotrophins (notably brain derived neurotrophic factor [BDNF]) in various neuroprotective situations. The research cited demonstrates clear benefit from appropriate electrical stimulation in the treatment of (1) certain patients with medication-refractory epilepsy, and (2) the functional regeneration of peripheral nerves after transection and surgical repair. Furthermore, neuromodulation of peripheral nerve regeneration has been associated with an increase in the neurotrophin BDNF. The roles of BDNF and other neurotrophins in several disorders of the nervous system are discussed in the context of neuromodulation and its augmentation of neurotrophins. Neuromodulation-at least in part through its effect on BDNF and other neurotrophins-will likely play a major role in the treatment (and possibly prevention) of disorders of the nervous system for which neuroproteive pharmacologic agents have traditionally been sought.

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis.

PubMed

Pascoal, Tharick; Paglioli, Eliseu; Palmini, André; Menezes, Rafael; Staudt, Martin

2013-08-01

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17-year-old boy with congenital hemiparesis and therapy-refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Spotlight on perampanel in the management of seizures: design, development and an update on place in therapy.

PubMed

Faulkner, Michele A

2017-01-01

Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic-clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors. Efficacy in refractory seizures has been established, and ongoing efficacy demonstrated by post-marketing data. The drug is completely absorbed, and exhibits a half-life that allows for once-daily administration in doses up to 12 mg/day. Drug interactions are minimal, but increased doses may be necessary when given with strong inducers of cytochrome P450 enzymes, including when perampanel is co-administered with other antiepileptics that exhibit this property. The most common adverse effects noted in both clinical trials and post-marketing are dizziness and somnolence. Psychiatric and behavioral adverse events have been documented in both adult and pediatric patients, including those with no corresponding diagnostic history. Perampanel is a novel adjunctive antiepileptic medication that is an effective option for adolescents and adults with partial seizures, and primarily generalized tonic-clonic seizures uncontrolled with other medications.

Spotlight on perampanel in the management of seizures: design, development and an update on place in therapy

PubMed Central

Faulkner, Michele A

2017-01-01

Purpose Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic–clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. Summary Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors. Efficacy in refractory seizures has been established, and ongoing efficacy demonstrated by post-marketing data. The drug is completely absorbed, and exhibits a half-life that allows for once-daily administration in doses up to 12 mg/day. Drug interactions are minimal, but increased doses may be necessary when given with strong inducers of cytochrome P450 enzymes, including when perampanel is co-administered with other antiepileptics that exhibit this property. The most common adverse effects noted in both clinical trials and post-marketing are dizziness and somnolence. Psychiatric and behavioral adverse events have been documented in both adult and pediatric patients, including those with no corresponding diagnostic history. Conclusion Perampanel is a novel adjunctive antiepileptic medication that is an effective option for adolescents and adults with partial seizures, and primarily generalized tonic–clonic seizures uncontrolled with other medications. PMID:29042752

Ketogenic diet in adolescents and adults with epilepsy.

PubMed

Nei, Maromi; Ngo, Ly; Sirven, Joseph I; Sperling, Michael R

2014-06-01

The ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. Twenty-nine adult and adolescent patients (mean age 32 years, range 11-51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. Fifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13-35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. The ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Region-specific connectivity in patients with periventricular nodular heterotopia and epilepsy: A study combining diffusion tensor imaging and functional MRI.

PubMed

Liu, Wenyu; An, Dongmei; Tong, Xin; Niu, Running; Gong, Qiyong; Zhou, Dong

2017-10-01

Periventricular nodular heterotopia (PNH) is an important cause of chronic epilepsy. The purpose of this study was to evaluate region-specific connectivity in PNH patients with epilepsy and assess correlation between connectivity strength and clinical factors including duration and prognosis. Diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) were performed in 28 subjects (mean age 27.4years; range 9-56years). The structural connectivity of fiber bundles passing through the manually-selected segmented nodules and other brain regions were analyzed by tractography. Cortical lobes showing functional correlations to nodules were also determined. For all heterotopic gray matter nodules, including at least one in each subject, the most frequent segments to which nodular heterotopia showed structural (132/151) and functional (146/151) connectivity were discrete regions of the ipsilateral overlying cortex. Agreement between diffusion tensor tractography and functional connectivity analyses was conserved in 81% of all nodules (122/151). In patients with longer duration or refractory epilepsy, the connectivity was significantly stronger, particularly to the frontal and temporal lobes (P<0.05). Nodules in PNH were structurally and functionally connected to the cortex. The extent is stronger in patients with longstanding or intractable epilepsy. These findings suggest the region-specific interactions may help better evaluate prognosis and seek medical or surgical interventions of PNH-related epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy.

PubMed

Zhao, Junli; Wang, Yi; Xu, Cenglin; Liu, Keyue; Wang, Ying; Chen, Liying; Wu, Xiaohua; Gao, Feng; Guo, Yi; Zhu, Junming; Wang, Shuang; Nishibori, Masahiro; Chen, Zhong

2017-08-01

Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients. The mAb showed an anti-seizure effect with a long-term manner and appeared to be minimal side effects at even very high dose (no disrupted physical EEG rhythm and no impaired basic physical functions, such as body growth rate and thermoregulation). This anti-seizure effect of mAb results from its inhibition of translocated HMGB1 from nuclei following seizures, and the anti-seizure effect was absent in toll-like receptor 4 knockout (TLR4 -/- ) mice. Interestingly, the anti-HMGB1 mAb also showed a disease-modifying anti-epileptogenetic effect on epileptogenesis after status epileptics, which is indicated by reducing seizure frequency and improving the impaired cognitive function. These results indicate that the anti-HMGB1 mAb should be viewed as a very promising approach for the development of novel therapies to treat refractory epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

Optogenetic approaches to treat epilepsy.

PubMed

Wykes, Robert C; Kullmann, Dimitri M; Pavlov, Ivan; Magloire, Vincent

2016-02-15

Novel treatments for drug-resistant epilepsy are required. Optogenetics is a combination of optical and genetic methods used to control the activity of specific populations of excitable cells using light with high temporal and spatial resolution. Derived from microbial organisms, 'opsin' genes encode light-activated ion channels and pumps. Opsins can be genetically targeted to well-defined neuronal populations in mammalian brains using viral vectors. When exposed to light of an appropriate wavelength, the excitability of neurons can be increased or decreased optically on a millisecond timescale. Alternative treatments for drug-resistant epilepsy such as vagal, cortical or subcortical stimulation, focal cooling, callosotomy, or ketogenic diet have met with limited success, whereas optogenetic approaches have shown considerable pre-clinical promise. Several groups have reported that optogenetic approaches successfully attenuated epileptiform activity in different rodent models of epilepsy, providing proof of the principle that this approach may translate to an effective treatment for epilepsy patients. However, further studies are required to determine the optimal opsin, in which types (or subtypes) of neurons it should be expressed, and what are the most efficient temporal profiles of photostimulation. Although invasive due to the need to inject a viral vector into the brain and implant a device to deliver light to opsin-transduced neurons, this approach has the potential to be effective in suppressing spontaneous seizures while avoiding the side-effects of anti-epileptic drugs (AEDs) or the need to permanently excise regions of the brain. Optogenetic approaches may treat drug-refractory epilepsies. Copyright © 2015 Elsevier B.V. All rights reserved.

Strategic hospital partnerships: improved access to care and increased epilepsy surgical volume.

PubMed

Vadera, Sumeet; Chan, Alvin Y; Mnatsankanyan, Lilit; Sazgar, Mona; Sen-Gupta, Indranil; Lin, Jack; Hsu, Frank P K

2018-05-01

OBJECTIVE Surgical treatment of patients with medically refractory focal epilepsy is underutilized. Patients may lack access to surgically proficient centers. The University of California, Irvine (UCI) entered strategic partnerships with 2 epilepsy centers with limited surgical capabilities. A formal memorandum of understanding (MOU) was created to provide epilepsy surgery to patients from these centers. METHODS The authors analyzed UCI surgical and financial data associated with patients undergoing epilepsy surgery between September 2012 and June 2016, before and after institution of the MOU. Variables collected included the length of stay, patient age, seizure semiology, use of invasive monitoring, and site of surgery as well as the monthly number of single-surgery cases, complex cases (i.e., staged surgeries), and overall number of surgery cases. RESULTS Over the 46 months of the study, a total of 104 patients underwent a total of 200 operations; 71 operations were performed in 39 patients during the pre-MOU period (28 months) and 129 operations were performed in 200 patients during the post-MOU period (18 months). There was a significant difference in the use of invasive monitoring, the site of surgery, the final therapy, and the type of insurance. The number of single-surgery cases, complex-surgery cases, and the overall number of cases increased significantly. CONCLUSIONS Partnerships with outside epilepsy centers are a means to increase access to surgical care. These partnerships are likely reproducible, can be mutually beneficial to all centers involved, and ultimately improve patient access to care.

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.

PubMed

Germanò, Eva; Gagliano, Antonella; Magazù, Angela; Sferro, Caterina; Calarese, Tiziana; Mannarino, Erminia; Calamoneri, Filippo

2005-05-01

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.

The changes of HRV in refractory epilepsy: The potential index to predict the onset of epilepsy in children.

PubMed

Gong, Xuehao; Mao, Xuhua; Chen, Yan; Huang, Leidan; Liu, Weizong; Huang, Xian; Tan, Zheng; Wang, Xianming; Wu, Wanqing; Chen, Qian; Li, Rong

2016-01-01

In this study, we examine the potential of heart rate variability (HRV) as an efficient tool for predicting the onset of epilepsy in children. We totally collected 53 seizures EEG and ECG data using Video - EEG - ECG monitoring system. We then separated the ECG data into three segments: ten-minute before onset of each seizure, five-minute before onset of each seizure, and five-minute from the onset of each seizure. After the HRV parameters in all segments were calculated, we compared the differences between pre-ictal period and ictal period. We found that the values of meanHR, LF and LF/HF were greater in onset period. And the values of meanRR and the HF were less in ictal period. And it presented the similar changes when seizures occurred in the daytime and seizures occurred in the nighttime. In brief, we found that the sympathetic nervous system was under a more active status during onset period. We speculated that the HRV parameters such as the LF, HF or LF/HF could have potential to predict the seizures in children with epilepsy.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

PubMed

Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

2017-02-01

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol

PubMed Central

Crippa, José A. S.; Crippa, Ana C. S.; Hallak, Jaime E. C.; Martín-Santos, Rocio; Zuardi, Antonio W.

2016-01-01

Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract. The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines. PMID:27746737

Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

PubMed

Amlerova, Jana; Laczo, Jan; Vlcek, Kamil; Javurkova, Alena; Andel, Ross; Marusic, Petr

2013-01-01

At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

How do we make models that are useful in understanding partial epilepsies?

PubMed

Prince, David A

2014-01-01

The goals of constructing epilepsy models are (1) to develop approaches to prophylaxis of epileptogenesis following cortical injury; (2) to devise selective treatments for established epilepsies based on underlying pathophysiological mechanisms; and (3) use of a disease (epilepsy) model to explore brain molecular, cellular and circuit properties. Modeling a particular epilepsy syndrome requires detailed knowledge of key clinical phenomenology and results of human experiments that can be addressed in critically designed laboratory protocols. Contributions to understanding mechanisms and treatment of neurological disorders has often come from research not focused on a specific disease-relevant issue. Much of the foundation for current research in epilepsy falls into this category. Too strict a definition of the relevance of an experimental model to progress in preventing or curing epilepsy may, in the long run, slow progress. Inadequate exploration of the experimental target and basic laboratory results in a given model can lead to a failed effort and false negative or positive results. Models should be chosen based on the specific issues to be addressed rather than on convenience of use. Multiple variables including maturational age, species and strain, lesion type, severity and location, latency from injury to experiment and genetic background will affect results. A number of key issues in clinical and basic research in partial epilepsies remain to be addressed including the mechanisms active during the latent period following injury, susceptibility factors that predispose to epileptogenesis, injury - induced adaptive versus maladaptive changes, mechanisms of pharmaco-resistance and strategies to deal with multiple pathophysiological processes occurring in parallel.

Theories of Impaired Consciousness in Epilepsy

PubMed Central

Yu, Lissa; Blumenfeld, Hal

2015-01-01

Although the precise mechanisms for control of consciousness are not fully understood, emerging data show that conscious information processing depends on the activation of certain networks in the brain and that the impairment of consciousness is related to abnormal activity in these systems. Epilepsy can lead to transient impairment of consciousness, providing a window into the mechanisms necessary for normal consciousness. Thus, despite differences in behavioral manifestations, cause, and electrophysiology, generalized tonic–clonic, absence, and partial seizures engage similar anatomical structures and pathways. We review prior concepts of impaired consciousness in epilepsy, focusing especially on temporal lobe complex partial seizures, which are a common and debilitating form of epileptic unconsciousness. We discuss a “network inhibition hypothesis” in which focal temporal lobe seizure activity disrupts normal cortical–subcortical interactions, leading to depressed neocortical function and impaired consciousness. This review of the major prior theories of impaired consciousness in epilepsy allows us to put more recent data into context and to reach a better understanding of the mechanisms important for normal consciousness. PMID:19351355

Illness perception in Chinese adults with epilepsy.

PubMed

Ji, Haixia; Zhang, Lei; Li, Lunlan; Gong, Guiping; Cao, Zhaolun; Zhang, Jianfeng; Zhou, Nong; Wang, Yu; Tu, Houmian; Wang, Kai

2016-12-01

Epilepsy is among the most common neurological disorders worldwide. Understanding the patient's subjective experience plays an important role in the treatment and rehabilitation of the patient. However, few studies are concerned about the illness perception of Chinese adults with epilepsy. 117 Chinese adults with epilepsy and 87 Chinese adults with chronic liver disease completed the Chinese version of the Revised Illness Perception Questionnaire (CIPQ-R). The Chinese epilepsy patients also completed the Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). A comparison about CIPQ-R score between the epilepsy group and chronic liver group was conducted using the independent sample t test. Partial correlation coefficients were calculated among the eight subscales of the CIPQ-R and its associated factors. Results for the CIPQ-R indicated that both the epilepsy patients and the chronic liver disease patients had a moderate belief in their personal control and treatment control over their disorder. Consistent with our hypothesis, patients with epilepsy and those with chronic liver disease perceived their respective disease similarly in terms of timeline and illness coherence. However, epilepsy patients had a higher negative emotional representations level than that we expected when compared to those of the patients suffering from chronic liver disease. Partial correlation analysis in Chinese epilepsy patients showed that the timeline acute/chronic dimension and emotional representations dimension were closely related to the other dimensions of illness perception. Moreover, the illness perception of the patients was significantly associated with social support, coping style, duration of epilepsy, seizure frequency, and the number of antiepileptic drugs. Chinese patients with epilepsy had limited understanding of the illness, and poor belief in personal control and treatment control. They had a negative emotional response to their illness, and feared of the effects on the patient or patient's family. Social support, coping style, duration of epilepsy, seizure frequency, and the number of antiepileptic drugs could affect the illness perception of these patients. Further studies should focus on how to improve patients' attitudes towards their disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report.

PubMed

Song, Haa-Na; Kang, Min Gyu; Park, Jeong Rang; Hwang, Jin-Yong; Kang, Jung Hun; Lee, Won Seop; Lee, Gyeong-Won

2018-01-22

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death ligand receptor-1 (PD-L1) antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

Partial epilepsy and 47,XXX karyotype: report of four cases.

PubMed

Roubertie, Agathe; Humbertclaude, Véronique; Leydet, Julie; Lefort, Geneviève; Echenne, Bernard

2006-07-01

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation.

Reflex epilepsy and reflex seizures of the visual system: a clinical review.

PubMed

Zifkin, B G; Kasteleijn-Nolst Trenité, D

2000-09-01

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

Tantrums, Emotion Reactions and Their EEG Correlates in Childhood Benign Rolandic Epilepsy vs. Complex Partial Seizures: Exploratory Observations.

PubMed

Potegal, Michael; Drewel, Elena H; MacDonald, John T

2018-01-01

We explored associations between EEG pathophysiology and emotional/behavioral (E/B) problems of children with two types of epilepsy using standard parent questionnaires and two new indicators: tantrums recorded by parents at home and brief, emotion-eliciting situations in the laboratory. Children with Benign Rolandic epilepsy (BRE, N = 6) reportedly had shorter, more angry tantrums from which they recovered quickly. Children with Complex Partial Seizures (CPS, N = 13) had longer, sadder tantrums often followed by bad moods. More generally, BRE correlated with anger and aggression; CPS with sadness and withdrawal. Scores of a composite group of siblings ( N = 11) were generally intermediate between the BRE and CPS groups. Across all children, high voltage theta and/or interictal epileptiform discharges (IEDs) correlated with negative emotional reactions. Such EEG abnormalities in left hemisphere correlated with greater social fear, right hemisphere EEG abnormalities with greater anger. Right hemisphere localization in CPS was also associated with parent-reported problems at home. If epilepsy alters neural circuitry thereby increasing negative emotions, additional assessment of anti-epileptic drug treatment of epilepsy-related E/B problems would be warranted.

Impaired consciousness in partial seizures is bimodally distributed

PubMed Central

Cunningham, Courtney; Chen, William C.; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P.; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T.

2014-01-01

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale–Revised (n = 552 test administrations, 184 patients). Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. PMID:24727311

Impaired consciousness in partial seizures is bimodally distributed.

PubMed

Cunningham, Courtney; Chen, William C; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T; Blumenfeld, Hal

2014-05-13

To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients). Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

Scott Fitzgerald: famous writer, alcoholism and probable epilepsy.

PubMed

Wolski, Mariana M; Paola, Luciano de; Teive, Hélio A G

2017-01-01

Scott Fitzgerald, a world-renowned American writer, suffered from various health problems, particularly alcohol dependence, and died suddenly at the age of 44. According to descriptions in A Moveable Feast, by Ernest Hemingway, Fitzgerald had episodes resembling complex partial seizures, raising the possibility of temporal lobe epilepsy.

Effects of Temperature, Oxygen Partial Pressure, and Materials Selection on Slag Infiltration into Porous Refractories for Entrained-Flow Gasifiers

NASA Astrophysics Data System (ADS)

Kaneko, Tetsuya Kenneth

The penetration rate of molten mineral contents (slag) from spent carbonaceous feedstock into porous ceramic-oxide refractory linings is a critical parameter in determining the lifecycle of integrated gasification combined cycle energy production plants. Refractory linings that withstand longer operation without interruption are desirable because they can mitigate consumable and maintenance costs. Although refractory degradation has been extensively studied for many other high-temperature industrial processes, this work focuses on the mechanisms that are unique to entrained-flow gasification systems. The use of unique feedstock mixtures, temperatures from 1450 °C to 1600 °C, and oxygen partial pressures from 10-7 atm to 10-9 atm pose engineering challenges in designing an optimal refractory material. Experimentation, characterization, and modeling show that gasifier slag infiltration into porous refractory is determined by interactions between the slag and the refractory that either form a physical barrier that impedes fluid flow or induce an increased fluid viscosity that decelerates the velocity of the fluid body. The viscosity of the slag is modified by the thermal profile of the refractory along the penetration direction as well as reactions between the slag and refractory that alter the chemistry, and thereby the thermo-physical properties of the fluid. Infiltration experiments reveal that the temperature gradient inherently present along the refractory lining limits penetration. A refractory in near-isothermal conditions demonstrates deeper slag penetration as compared to one that experiences a steeper thermal profile. The decrease in the local temperatures of the slag as it travels deeper into the refractory increases the viscosity of the fluid, which in turn slows the infiltration velocity of fluid body into the pores of the refractory microstructure. With feedstock mixtures that exhibit high iron-oxide concentrations, a transition-metal-oxide, the oxygen partial pressure of the operating atmosphere regulates the penetration of slag into refractory. The viscosity of the slag, which dictates its penetration rate, is influenced by the oxidation state of the Fe cation. Slag penetrations are shallower in oxidizing conditions than they are in reducing conditions because the iron-oxide from the slag solutions into the corundum-structured refractory and the slag is depleted of iron-oxide, increasing the viscosity of slags. Equally, the chemistries of both the refractory and slag materials dictate the course of penetration. Cr2O3-Al2O3 refractory limits mixed feedstock slag penetration through formation of a chromium spinel layer that functions as a physical obstacle against fluid flow. Al2O 3-SiO2 refractory limits eastern coal feedstock slag penetration as a result of refractory dissolution of SiO2, which increases the viscosity of slags. A physical model, which considers unidirectional fluid flow of slag through each pore of the porous microstructure of the refractory, sufficiently approximates the penetration depth of the slag into the refractory. Agreement between experiments and the physical model demonstrates that the slag is driven into the refractory by capillary pressure. Since the viscosity of the slag continuously changes as the slag travels through the inherent temperature gradient of the refractory lining, the model incorporates dynamic viscosities that are dependent on both temperature and composition to project depths that are unique to the experimental parameters. The significantly different length scales of the radial and penetration directions of the pores allows for the application of a lubrication approximation onto the momentum equation. This process produces an analytical solution that effectively envelopes the variable viscosity into a single term.

Efficacy of Pregabalin in Childhood Refractory Partial Seizure

PubMed Central

Zamani, Gholamreza; Tavasoli, Alireza; Zare-Shahabadi, Ameneh; Rezaei, Nima; Ahmadvand, Alireza

2014-01-01

Objective: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. Methods: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. Conclusion: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures. PMID:25793053

Vagus nerve stimulation for 6- to 12-year-old children with refractory epilepsy: Impact on seizure frequency and parenting stress index.

PubMed

Fan, Hueng-Chuen; Hsu, Ting-Rong; Chang, Kai-Ping; Chen, Shyi-Jou; Tsai, Jeng-Dau

2018-06-01

Refractory epilepsy (RE) is frequently associated with neuropsychological impairment in children and may disrupt their social development. Vagus nerve stimulation (VNS) had been reported to have beneficial effects on behavioral outcomes. The aim of this study was to compare Parenting Stress Index (PSI) scores before and after VNS device implantation in children with RE, especially those who experienced seizure frequency reduction. We conducted a one-group pretest-posttest study in school age children with RE. Seizure frequency and PSI were recorded at 12months after VNS device implantation. Treatment with VNS was significantly associated with reduced seizure frequency and parental stress as measured by PSI. Factors contributing to seizure frequency included idiopathic/cryptogenic etiology and neurobehavioral comorbidities. In children with reduced seizure frequency, statistically significant improvements in the child domain of the PSI on the subscales of mood and reinforces parent were found. In the parent domain, the scores for social isolation were reduced. Treatment with VNS was significantly associated with reduced seizure frequency and improved PSI scores, especially within the child domain on the mood and reinforces parent subscales. These findings suggest that VNS reduced not only seizure frequency but also the psychological burden on children with RE. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

PubMed

Leon, Amanda; Saito, Erin K; Mehta, Bijal; McMurtray, Aaron M

2015-02-01

This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population. Published by Elsevier Inc.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

PubMed

Spritzer, Scott D; Hoerth, Matthew T; Zimmerman, Richard S; Shmookler, Aaron; Hoffman-Snyder, Charlene R; Wellik, Kay E; Demaerschalk, Bart M; Wingerchuk, Dean M

2012-09-01

Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

Epileptic auras and their role in driving safety in people with epilepsy.

PubMed

Punia, Vineet; Farooque, Pue; Chen, William; Hirsch, Lawrence J; Berg, Anne T; Blumenfeld, Hal

2015-11-01

The aim of our study was to evaluate the role of auras in preventing motor vehicle accidents (MVAs) among patients with medically refractory epilepsy. The Multicenter Study of Epilepsy Surgery database was used to perform a case-control study by identifying patients who had seizures while driving that led to MVAs (cases) and those who had seizures while driving without MVAs (controls). We compared presence of reliable auras and other aura-related features between the two groups. Two hundred fifteen of 553 patients reported having seizure(s) while driving; 74 were identified as "controls" and 141 as "cases." The two groups had similar demographic and clinical features. The presence of reliable auras was not different between the two groups (67% in cases vs. 65% in controls; odds ratio [OR] 0.89, 95% confidence interval [CI] 0.49-1.61, p = 0.76). In addition, the groups did not differ in the proportion of patients who reported longer (>1 min) auras (OR 0.7, 95% CI 0.28-1.76, p = 0.47), or who thought that their auras were of sufficient duration to be protective (OR 1.19, 95% CI 0.62-2.00, p = 0.77). Our study questions the long-held belief of a protective role of reliable auras against MVAs in people with epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Toll-like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE-induced epilepsy in mice.

PubMed

Gross, Adi; Benninger, Felix; Madar, Ravit; Illouz, Tomer; Griffioen, Kathleen; Steiner, Israel; Offen, Daniel; Okun, Eitan

2017-04-01

Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE). To test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls. In this model, a single SE event leads to spontaneous recurrent seizures (SRS). Two weeks after SE, mice were implanted with wireless electroencephalography (EEG) transmitters for up to 1 month. The impact of TLR3 deficiency on SE was assessed using separate cohorts of mice regarding EEG activity, seizure progression, hippocampal microglial distribution, and expression of the proinflammatory cytokines tumor necrosis factor (TNF)α and interferon (IFN)β. Our data indicate that TLR3 deficiency reduced SRS, microglial activation, and the levels of the proinflammatory cytokines TNFα and IFNβ, and increased survival following SE. This study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

PubMed

Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

2014-05-01

Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Fewer specialists support using medical marijuana and CBD in treating epilepsy patients compared with other medical professionals and patients: result of Epilepsia's survey.

PubMed

Mathern, Gary W; Beninsig, Laurie; Nehlig, Astrid

2015-01-01

From May 20 to September 1 2014, Epilepsia conducted an online survey seeking opinions about the use of medical marijuana and cannabidiol (CBD) for people with epilepsy. This study reports the findings of that poll. The survey consisted of eight questions. Four questions asked if there were sufficient safety and efficacy data, whether responders would advise trying medical marijuana in cases of severe refractory epilepsy, and if pharmacologic grade compounds containing CBD should be available. Four questions addressed occupation, geographic region of residence, if responders had read the paper, and if they were International League Against Epilepsy/International Bureau for Epilepsy (ILAE/IBE) members. Of 776 who started or completed the survey, 58% were patients from North America, and 22% were epileptologists and general neurologists from Europe and North America. A minority of epileptologists and general neurologists said that there were sufficient safety (34%) and efficacy (28%) data, and 48% would advise using medical marijuana in severe cases of epilepsy. By comparison, nearly all patients and the public said there were sufficient safety (96%) and efficacy (95%) data, and 98% would recommend medical marijuana in cases of severe epilepsy. General physicians, basic researchers, nurses, and allied health professions sided more with patients, saying that there were sufficient safety (70%) and efficacy (71%) data, and 83% would advise using marijuana in severe cases. A majority (78%) said there should be pharmacologic grade compounds containing CBD, and there were no differences between specialists, general medical personal, and patients and the public. This survey indicates that there is a wide disparity in opinion on the use of medical marijuana and CBD in the treatment of people with epilepsy, which varied substantially, with fewer medical specialists supporting its use compared with general medical personal, and patients and the public. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Ketogenic diet for treatment of intractable epilepsy in adults: A meta-analysis of observational studies.

PubMed

Liu, Hongyan; Yang, Yi; Wang, Yunbing; Tang, Hong; Zhang, Fan; Zhang, Yong; Zhao, Yong

2018-03-01

The ketogenic diet (KD) is an effective treatment for children with drug-resistant epilepsy and has been widely used in young children. Adult patients with intractable epilepsy would also benefit from this dietary treatment. However, only a few studies have been published, and the use of the KD in intractable epilepsy in adults has been limited. This meta-analysis summarized the findings of the relevant published studies to identify the efficacy of the KD for the treatment of intractable epilepsy in adults. In this meta-analysis, PubMed, Embase, and Cochrane Library were used for searching studies concerning the effects of the KD and its major subtypes with intractable epilepsy in adults published up to January 10, 2017. The primary outcomes were seizure freedom, seizure reduction by 50% or more, and seizure reduction by <50%. The quality of the methodology of the observational studies was reviewed by using the Newcastle-Ottawa Scale. We identified 402 articles, of which, 16 studies including 338 patients met the inclusion criteria. The results of the meta-analysis showed that the combined efficacy rates of all the symptoms of seizure freedom, seizure reduction by 50% or more, and seizure reduction below 50% in adults with intractable epilepsy were 13%, 53%, and 27%, respectively. The adverse reactions of the KD were mild, whereas low glycemic index diet (LGID) and low-dose fish oil diet (LFOD) may have fewer side effects. Weight loss, high level of low-density lipoprotein, and elevated total cholesterol were most frequent. The meta-analysis indicates that the KD for refractory epilepsy in adults is a well-tolerated treatment and that its side effects are acceptable, which show that the KD is a promising treatment in adult intractable epilepsy. Further research is needed to assess which type of diet or ratio is more effective in the KD treatment.

Decreased ghrelin and des-acyl ghrelin plasma levels in patients affected by pharmacoresistant epilepsy and maintained on the ketogenic diet.

PubMed

Marchiò, Maddalena; Roli, Laura; Giordano, Carmela; Trenti, Tommaso; Guerra, Azzurra; Biagini, Giuseppe

2018-03-23

The gastric hormones ghrelin and des-acyl ghrelin have been found to be altered in patients treated with antiepileptic drugs. However, it is unknown if these hormones could be modified by other antiepileptic treatments, such as the ketogenic diet. Especially, a reduction in ghrelin levels could be relevant in view of the growth retardation observed under ketogenic diet treatment. For this reason we aimed to determine the changes in ghrelin and des-acyl ghrelin plasma levels in children affected by refractory epilepsy and treated with the ketogenic diet up to 90 days. Both peptides were measured by immunoassays in plasma obtained from 16 children. Ghrelin plasma levels were progressively reduced by the ketogenic diet, reaching a minimum corresponding to 42% of basal levels after 90 days of ketogenic diet (P < 0.05, Duncan's test). Des-acyl ghrelin plasma levels were similarly affected, reaching minimal levels at 30 days (65% of basal levels), and maintaining a significant reduction until 90 days after the onset of ketogenic diet (P < 0.01 for both time intervals). No significant changes in growth were observed during the monitored period of ketogenic diet administration. Ghrelin and des-acyl ghrelin are downregulated by the ketogenic diet in children affected by refractory epilepsy. Although no significant changes in growth were observed during the short time period of our investigation, the reduction in ghrelin availability may explain the reported growth retardation found in children treated with the ketogenic diet in the long-term. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Tuberous sclerosis: clinical characteristics and their relationship to genotype/phenotype].

PubMed

Monteiro, T; Garrido, C; Pina, S; Chorão, R; Carrilho, I; Figueiroa, S; Santos, M; Temudo, T

2014-11-01

Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. Our goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Retrospective analysis of patients with TS, including review of medical records and available MRI imaging. We studied 35 cases with a median age at diagnosis of ten months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioral disorders. A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and5 of them had refractory epilepsy. In our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Gender differences in prevalence of psychiatric disorders, levels of alexithymia, and coping strategies in patients with refractory mesial temporal epilepsy and comorbid psychogenic nonepileptic seizures.

PubMed

de Barros, Amanda Cristian Serafim; Furlan, Ana Eliza Romano; Marques, Lucia Helena Neves; de Araújo Filho, Gerardo Maria

2018-05-01

The objective of this study was to investigate the psychological aspects and psychiatric disorders (PDs) in patients dually diagnosed with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) with psychogenic nonepileptic seizures (PNES) treated in a tertiary center in order to find any gender differences in psychiatric, clinical, and sociodemographic characteristics. Psychiatric assessment was performed through the Diagnostic and Statistical Manual for Psychiatric Disorders - 5th edition (DSM-5). The Brazilian versions of the Medical Outcomes Study 36 (SF-36), Toronto Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Ways of Coping Checklist (WCC) were applied. Of the 47 patients enrolled (25 females; 53.2%), females were significantly more likely to have a history of previous psychiatric treatment (P=0.02), family history of epilepsy (P=0.01), and family history of PD (P=0.03). They also presented earlier onset of PNES (P=0.01) and higher PNES duration (P=0.02) compared with males. Major depressive disorder (MDD) was the most frequent PD (24; 51.0%). Females presented more psychiatric diagnoses (P<0.001), more diagnoses of MDD (P<0.001), and posttraumatic stress disorder (PTSD) (P<0.001). Several differences regarding quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies were observed between groups. There are significant gender differences in psychiatric, clinical, and sociodemographic aspects in a group of patients with TLE-MTS and PNES, as well as in quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies. These gender differences suggest that specific approaches might be adopted depending on the patient's gender and, consequently, their distinct psychological/psychiatric profile. Copyright © 2018 Elsevier Inc. All rights reserved.

Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood.

PubMed

Hallböök, Tove; Lundgren, Johan; Stjernqvist, Karin; Blennow, Gösta; Strömblad, Lars-Göran; Rosén, Ingmar

2005-10-01

Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with refractory epilepsy. There is growing evidence of additional quality of life (QOL) benefits of VNS. We report the effects of VNS on seizure frequency and severity and how these changes are related to cognitive abilities, QOL, behaviour and mood in 15 children with medically refractory and for surgery not eligible epilepsy. Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with Bayley Scales of Infant Development (BSID), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R), Wechlser Intelligence Scales for Children (WISC-III) depending on the child's level of functioning, a Visual Analogue Scale for validating QOL, Child Behaviour Checklist (CBCL) for quantifying behaviour problems, Dodrill Mood Analogue Scale and Birleson Depression Self-Rating Scale, and the National Hospital Seizure Severity Scale (NHS3). A diary of seizure frequency was collected. Six of 15 children showed a 50% or more reduction in seizure frequency; one of these became seizure-free. Two children had a 25-50% seizure reduction. Two children showed increased seizure frequency. In 13 of 15 children there was an improvement in NHS3. The parents reported shorter duration of seizure and recovery phase. There were no changes in cognitive functioning. Twelve children showed an improvement in QOL. Eleven of these also improved in seizure severity and mood and five also in depressive parameters. This study has shown a good anti-seizure effect of VNS, an improvement in seizure severity and in QOL and a tendency to improvement over time regarding behaviour, mood and depressive parameters. The improvement in seizure severity, QOL, behaviour, mood and depressive parameters was not related to the anti-seizure effect.

[A novel mutation in KCNB1 gene in a child with neuropsychiatric comorbidities with both intellectual disability and epilepsy and review of literature].

PubMed

Miao, P; Peng, J; Chen, C; Gai, N; Yin, F

2017-02-02

Objective: To explore the association between the phenotype and KCNB1 gene mutation. Method: Clinical information including physical features, laboratory and genetic data of one patient of mental retardation with refractory epilepsy from Department of Pediatrics, Xiangya Hospital in January 2016 was analyzed. This patient was discovered to have KCNB1 gene mutations through whole exome sequencing. Relevant information about KCNB1 gene mutation was searched and collected from Pubmed, CNKI, Human Gene Mutation Database(HGMD) and Online Mendelian Inheritance in Man(OMIM). Searching was done using "KCNB1" as a keyword. Result: A 3.5 years old boy who visited our hospital firstly at the age of 2 years because of development delay came for follow up as he developed seizures.The forms included tonic, clonic seizures and spasm. The condition became more severe 10 months later. Electroencephalogram(EEG) showed high frequency discharge (>85%). He had poor response to multiple anti-epileptic drugs, methylprednisolone and ketogenic diet. At the age of 3, he started to have mental regression. Whole exome-sequencing study (trios) identified a novel heterozygous mutation c. G1136T (p.G379V) in KCNB1, which is not available in the databases mentioned above. This is the first case report of KCNB1 gene mutation in China. Eight cases have been reported so far worldwide and all of them were diagnosed with refractory epilepsy. Those 8 reported cases of encephalopathy were all due to de novo mutation. Conclusion: The main clinical features of patients with KCNB1 mutations include severe to profound intellectual disability, intractable seizures, hypotonia and regression of cognition and motor activity which lead to poor prognosis.

Affective temperament profiles and clinical correlates in patients with epilepsy: a link from mood disorders.

PubMed

Erdoğan Taycan, Serap; Taycan, Okan

2014-08-01

The current study sought to investigate the affective temperaments of patients with epilepsy and possible relationships between disease characteristics and temperament profiles. A total of 70 adults with epilepsy and 70 healthy volunteers completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A). Patients with epilepsy had higher scores on these three scales than healthy controls. With respect to temperaments, irritable temperament alone was significantly higher in patients than controls. Irritable temperament also had a significant positive correlation with psychiatric history, whereas depressive temperament had a significant positive correlation with illness and treatment duration. Patients who had suffered simple partial and complex partial seizures had higher anxious temperament scores than patients with generalized epilepsy. Because the study group was recruited through consecutive patients seen in a single neurology clinic, our findings may not be representative of PWE in general. Because irritability is one of the key symptoms of interictal dysphoric disorder and because TEMPS-A irritable temperament and BDI scores were found to be significantly related, the high rate of irritable temperament in our patient sample may be associated with depressive mood. We may suggest that at least some of the affective symptoms in patients with epilepsy and the historical concept of "epileptic personality" may be explained by affective temperaments. Copyright © 2014 Elsevier B.V. All rights reserved.

Teaching the Student with Epilepsy: A Dilemma or an Opportunity.

ERIC Educational Resources Information Center

Walton, Ann Viva

The paper looks at epilepsy, with emphasis on student problems and the role of the teacher. Initial sections describe characteristics of absence seizures, generalized tonic-clonic (grand mal) seizures, and complex partial seizures. The educator's role is considered relating to three areas: medical problems, social problems, and psychological…

Status epilepticus in the elderly: Prognostic implications of rhythmic and periodic patterns in electroencephalography and hyperintensities on diffusion-weighted imaging.

PubMed

Yoshimura, Hajime; Matsumoto, Riki; Ueda, Hiroyuki; Ariyoshi, Koichi; Kawamoto, Michi; Ishii, Junko; Ikeda, Akio; Takahashi, Ryosuke; Kohara, Nobuo

2016-11-15

To delineate the clinical characteristics and functional outcome of status epilepticus (SE) in elderly people, and elucidate prognostic implications of SE-associated rhythmic and periodic patterns (RPPs) in electroencephalography and hyperintensities on diffusion-weighted imaging. We retrospectively investigated 107 consecutive patients with SE aged≥65years in a comprehensive community hospital. RPPs were classified using the 2012 American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. Poor outcome was defined as an increase in modified Rankin Scale (mRS) score at discharge compared with that at baseline, including death. Median age of patients was 80.0years. Median mRS score at baseline was 3. Thirty-four patients (31.8%) had a previous diagnosis of epilepsy. Cerebrovascular disease and dementia were major etiologies. Poor outcome occurred in 41 (38.3%). In electroencephalography, periodic discharges (PDs) were present in 21.0% (22/105), rhythmic delta activity (RDA) in 10.5% (11/105), and conventional seizure patterns in 9.5% (10/105). Diffusion-weighted hyperintensities associated with SE were observed in 28.0% (26/93). With univariate analysis, poor outcome was significantly associated with no previous diagnosis of epilepsy, etiology, refractory SE, specific electroencephalographic patterns (PDs and conventional seizure patterns, but not RDA), and diffusion-weighted hyperintensities. With multivariate logistic regression analysis, diffusion-weighted hyperintensities (OR 6.13 [95% CI 1.72-21.9]) and refractory SE (OR 5.36 [95% CI 1.28-22.4]) were independently associated with poor outcome. SE often occurred as the first seizure in already disabled elderly people, further worsening their functional disabilities. Diffusion-weighted hyperintensities and refractory SE, but not RPPs in electroencephalography, were independent functional prognostic factors. Copyright © 2016 Elsevier B.V. All rights reserved.

Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior.

PubMed

Benedetti-Isaac, Juan C; Torres-Zambrano, Martin; Vargas-Toscano, Andres; Perea-Castro, Esther; Alcalá-Cerra, Gabriel; Furlanetti, Luciano L; Reithmeier, Thomas; Tierney, Travis S; Anastasopoulos, Constantin; Fonoff, Erich T; Contreras Lopez, William Omar

2015-07-01

The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

The role of histopathologic subtype in the setting of hippocampal sclerosis-associated mesial temporal lobe epilepsy.

PubMed

Gales, Jordan M; Jehi, Lara; Nowacki, Amy; Prayson, Richard A

2017-05-01

Hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) are among the most common neuropathological findings in those undergoing surgery for refractory mesial temporal lobe epilepsy. Existing data regarding differences among the most recent International League Against Epilepsy (ILAE) HS subtypes remain limited. This study sought to characterize the roles of HS subtype and coexistent FCD. Epilepsy surgery pathologic specimens in 307 cases of temporal lobe epilepsy with HS were reviewed (mean age±SD, 37±15years; 56% women). HS and coexistent FCD were classified according to ILAE guidelines. Medical records were reviewed for data on seizure recurrence and seizure burden (clinical follow-up mean duration ± SD, 5±4years). Cases of typical HS (ILAE type I) predominated (ILAE type Ia: 41%, Ib: 47%, II: 11%, and III: 0.7%]. The HS subtypes shared similar demographic and etiologic characteristics, as well as associated pathology and postoperative seizure outcomes. Individuals with type Ib HS were more likely to remain seizure free at long-term follow-up when compared with other subtypes, and they had a later age of seizure onset. Two hundred forty-three cases (79%) demonstrated FCD within the adjacent temporal lobe. Its presence was associated with a significantly decreased risk of seizure recurrence (P=.02). When present, FCD was predominantly type I (98%). HS subtype does not appear to affect epilepsy surgery outcomes despite some clinical differences between the subgroups. FCD is often observed in association with HS in mesial temporal lobe epilepsy; the finding of FCD was associated with better postoperative outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies.

PubMed

Santos, Kleber; Palmini, Andre; Radziuk, Ana L; Rotert, Rosana; Bastos, Fernanda; Booij, Linda; Fernandes, Brisa S

2013-07-01

Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Clinical neurofeedback: case studies, proposed mechanism, and implications for pediatric neurology practice.

PubMed

Legarda, Stella B; McMahon, Doreen; Othmer, Siegfried; Othmer, Sue

2011-08-01

Trends in alternative medicine use by American health care consumers are rising substantially. Extensive literature exists reporting on the effectiveness of neurofeedback in the treatment of autism, closed head injury, insomnia, migraine, depression, attention deficit hyperactivity disorder, epilepsy, and posttraumatic stress disorder. We speculated that neurofeedback might serve as a therapeutic modality for patients with medically refractory neurological disorders and have begun referring patients to train with clinical neurofeedback practitioners. The modality is not always covered by insurance. Confident their child's medical and neurological needs would continue to be met, the parents of 3 children with epilepsy spectrum disorder decided to have their child train in the modality. The children's individual progress following neurofeedback are each presented here. A proposed mechanism and practice implications are discussed.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

PubMed

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report

PubMed Central

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10–15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events. PMID:29479337

New onset paediatric epilepsy in 1-5 years age group children--approach to management in a tertiary care centre with newer anti-epileptic levetiracetam.

PubMed

Barik, Kanai Lal; Paul, Uttam Kumar; Bhattacharyya, Anup Kumar; Adhikary, Amit; Agarwal, Gajanand; Rana, Kriti Sundar

2014-02-01

Epilepsy is a common paediatric neurologic disorder that is difficult to manage in a substantial portion of children, highlighting the continued need for more effective and better tolerated drugs. A multicentric study was conducted from August, 2011 to July, 2013 using levetiracetam (LEV) in newely diagnosed epilepsy in 122 young children of 1-5 years age group to find its role in practical scenario depending upon the knowledge from prior literature available. It has been demonstrated effective as adjunctive therapy as well as monotherapy for new-onset partial seizures and generalised tonic-clonic seizures (GTCS) but it acts better as adjunctive therapy than the monotherapy. When LEV was used as adjunctive therapy 15.4% children with partial seizure were seizure-free as compared to 11.12% in GTCS and when LEV was used as monotherapy 16.17% children with partial seizure were seizure-free as compared to 15.38% in GTCS. When LEV was used as add on therapy 16.67% children < 2 years were seizure-free as compared to 17.85% in > 2 years. When LEV was used as monotherapy 25.00% children < 2 years were seizure-free as compared to 18.18% > 2 years. So, it was found more efficacious in partial group of seizures than the GTCS variety. It also shows more efficacy in older age group (> 2 years) than the younger ones (< 2 years). Somnolence and behavioural changes were noted as ad- verse effects in a few cases. So, LEV is an important addition to the treatment of paediatric epilepsy.

A novel regimen for relapsed/refractory adult acute myeloid leukemia using a KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI 8485.

PubMed

Mims, Alice S; Mishra, Anjali; Orwick, Shelley; Blachly, James; Klisovic, Rebecca B; Garzon, Ramiro; Walker, Alison R; Devine, Steven M; Walsh, Katherine J; Vasu, Sumithira; Whitman, Susan; Marcucci, Guido; Jones, Daniel; Heerema, Nyla A; Lozanski, Gerard; Caligiuri, Michael A; Bloomfield, Clara D; Byrd, John C; Piekarz, Richard; Grever, Michael R; Blum, William

2018-06-01

KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro , sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemoresponse. We developed a regimen for this unique molecular subset, but due to relatively low frequency of KMT2A partial tandem duplication, this dose finding study was conducted in relapsed/refractory disease regardless of molecular subtype. Seventeen adults (< age 60) with relapsed/refractory acute myeloid leukemia were treated on study. Patients received decitabine 20 milligrams/meter 2 daily on days 1-10 and vorinostat 400 milligrams daily on days 5-10. Cytarabine was dose-escalated from 1.5 grams/meter 2 every 12 hours to 3 grams/meter 2 every 12 hours on days 12, 14 and 16. Two patients experienced dose limiting toxicities at dose level 1 due to prolonged myelosuppression. However, as both patients achieved complete remission after Day 42, the protocol was amended to adjust the definition of hematologic dose limiting toxicity. No further dose limiting toxicities were found. Six of 17 patients achieved complete remission including 2 of 4 patients with KMT2A partial tandem duplication. Combination therapy with decitabine, vorinostat and cytarabine was tolerated in younger relapsed/refractory acute myeloid leukemia and should be explored further focusing on the KMT2A partial tandem duplication subset. ( clinicaltrials.gov identifier 01130506 ). Copyright © 2018 Ferrata Storti Foundation.

Posterior cortex epilepsy surgery in childhood and adolescence: Predictors of long-term seizure outcome.

PubMed

Ramantani, Georgia; Stathi, Angeliki; Brandt, Armin; Strobl, Karl; Schubert-Bast, Susanne; Wiegand, Gert; Korinthenberg, Rudolf; van Velthoven, Vera; Zentner, Josef; Schulze-Bonhage, Andreas; Bast, Thomas

2017-03-01

We aimed to investigate the long-term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors. We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)-visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri- or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases. At last follow-up (mean 8 years, range 1.5-18 years), 60% patients remained seizure-free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left-sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence. Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Evaluation of Posterior Hippocampal Epileptogenicity During Epilepsy Surgery For Temporal Lobe Cavernoma by the Occipital Approach.

PubMed

Akiyama, Yukinori; Suzuki, Kengo; Ochi, Satoko; Miyamoto, Susumu; Mikuni, Nobuhiro

2015-11-01

Cavernomas frequently are associated with intractable epilepsy. When cavernomas located in the temporal lobe are associated with intractable epilepsy, the hippocampus also may have an epileptic focus. The objective in the present study was to clarify the importance of evaluation of the posterior hippocampal epileptogenicity during epilepsy surgery for posteromedial temporal lobe cavernoma. In this study, we describe 2 rare cases of medically intractable epilepsy in patients with posteromedial temporal lobe cavernomas who underwent surgery via the occipital approach. Using longitudinal insertion of depth electrodes into the hippocampus, we evaluated epileptogenicity in both patients from the cavernoma cavity and its surrounding hemosiderin, as well as from the posterior hippocampus near the cavernoma. We show that the transoccipital approach to the posteromedial temporal lobe is compatible with depth electrode insertion and subdural electrode placement on the temporal lobe, enabling an accurate evaluation of potential epileptogenic zones in the posterior part of the hippocampus. Both patients did not experience any seizures and had no postoperative neurologic deficits, and their cognitive functions were intact. The transoccipital approach enables the optimization of the extent of posterior hippocampectomy while avoiding unnecessary resection for seizure control. We suggest resecting the posterior part of the hippocampus in addition to the cavernoma and surrounding areas in patients with medically refractory epilepsy due to a posteromedial temporal cavernoma. Tailored systematic resection guided by intraoperative electrocorticography and electroencephalography with a depth electrode was important and necessary in the present cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Emotion recognition and social cognition in temporal lobe epilepsy and the effect of epilepsy surgery.

PubMed

Amlerova, Jana; Cavanna, Andrea E; Bradac, Ondrej; Javurkova, Alena; Raudenska, Jaroslava; Marusic, Petr

2014-07-01

The abilities to identify facial expression from another person's face and to attribute mental states to others refer to preserved function of the temporal lobes. In the present study, we set out to evaluate emotion recognition and social cognition in presurgical and postsurgical patients with unilateral refractory temporal lobe epilepsy (TLE). The aim of our study was to investigate the effects of TLE surgery and to identify the main risk factors for impairment in these functions. We recruited 30 patients with TLE for longitudinal data analysis (14 with right-sided and 16 with left-sided TLE) and 74 patients for cross-sectional data analysis (37 with right-sided and 37 with left-sided TLE) plus 20 healthy controls. Besides standard neuropsychological assessment, we administered an analog of the Ekman and Friesen test and the Faux Pas Test to assess emotion recognition and social cognition, respectively. Both emotion recognition and social cognition were impaired in the group of patients with TLE, irrespective of the focus side, compared with healthy controls. The performance in both tests was strongly dependent on the intelligence level. Beyond intelligence level, earlier age at epilepsy onset, longer disease duration, and history of early childhood brain injury predicted social cognition problems in patients with TLE. Epilepsy surgery within the temporal lobe seems to have neutral effect on patients' performances in both domains. However, there are a few individual patients who appear to be at risk of postoperative decline, even when seizure freedom is achieved following epilepsy surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Targeted Upregulation of FMRP Expression as an Approach to the Treatment of Fragile X Syndrome

DTIC Science & Technology

2015-08-01

form of autism, and a relatively common cause of epilepsy . The syndrome is caused by partial or complete silencing of the fragile X (FMR1) gene when...potential to correct ALL of the clinical domains of fragile X syndrome, including epilepsy -like activity observed for both those with FXS and carriers of...the FMR1 gene. 15. SUBJECT TERMS Fragile X, autism, FMR1, FXTAS, CGG repeat, epilepsy , seizures, FMRP, PTSD, premutation, iPSC, progenitor, calcium

Less Common Etiologies of Status Epilepticus

PubMed Central

Bleck, Thomas P

2010-01-01

Status epilepticus is treated as a neurologic emergency and only later are the potential etiologies assessed. While sometimes the cause for status epilepticus is apparent (e.g., antiepileptic drug withdrawal), all too often it is not identified, even after extensive diagnostic testing has been performed. With emphasis on the less-common etiologies, this review will cover various probable and known causes of status epilepticus among adults, children, and those patients with refractory epilepsy. PMID:20231917

Baseline Cognition, Behavior, and Motor Skills in Children with New-Onset, Idiopathic Epilepsy

ERIC Educational Resources Information Center

Bhise, Vikram V.; Burack, Gail D.; Mandelbaum, David E.

2010-01-01

Aim: Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized…

Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females

PubMed Central

Depienne, Christel; Trouillard, Oriane; Bouteiller, Delphine; Gourfinkel-An, Isabelle; Poirier, Karine; Rivier, François; Berquin, Patrick; Nabbout, Rima; Chaigne, Denys; Steschenko, Dominique; Gautier, Agnès; Hoffman-Zacharska, Dorota; Lannuzel, Annie; Lackmy-Port-Lis, Marilyn; Maurey, Hélène; Dusser, Anne; Bru, Marie; Gilbert-Dussardier, Brigitte; Roubertie, Agathe; Kaminska, Anna; Whalen, Sandra; Mignot, Cyril; Baulac, Stéphanie; Lesca, Gaetan; Arzimanoglou, Alexis; LeGuern, Eric

2011-01-01

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc. PMID:21053371

Epileptic auras and their role in driving safety in people with epilepsy

PubMed Central

Punia, Vineet; Farooque, Pue; Chen, William; Hirsch, Lawrence J.; Berg, Anne T.; Blumenfeld, Hal

2015-01-01

Summary The aim of our study was to evaluate the role of auras in preventing motor vehicle accidents (MVA) among medically-refractory epilepsy patients. The Multicenter Study of Epilepsy Surgery database was used to perform a case-control study by identifying patients who had seizures while driving that led to MVAs (Cases) and those who had seizures while driving without MVAs (Controls). We compared presence of reliable auras and other aura-related features between the two groups. 215 out of 553 patients reported having seizure(s) while driving; 74 were identified as ‘Controls’ and 141 as ‘Cases’. The two groups had similar demographic and clinical features. The presence of reliable auras was not different between the two groups (67% in Cases vs 65% in Controls; OR = 0.89, 95% CI 0.49 – 1.61, p = 0.76). In addition, the groups did not differ in the proportion of patients who reported longer (>1 minute) auras (OR 0.7; 95% CI 0.28 – 1.76; p = 0.47), or who thought that their auras were sufficiently long to protect themselves (OR 1.19; 95% CI 0.62 – 2.00; p = 0.77). Our study questions the long-held belief of a protective role of reliable auras against MVAs in people with epilepsy. PMID:26391317

SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model.

PubMed

Lösing, Pascal; Niturad, Cristina Elena; Harrer, Merle; Reckendorf, Christopher Meyer Zu; Schatz, Theresa; Sinske, Daniela; Lerche, Holger; Maljevic, Snezana; Knöll, Bernd

2017-07-17

A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance. Adult conditional SRF deficient mice (Srf CaMKCreERT2 ) were more refractory to initial status epilepticus (SE) acquisition. Further, SRF deficient mice developed more spontaneous recurrent seizures (SRS). Genome-wide transcriptomic analysis uncovered a requirement of SRF for SE and SRS induced IEG induction (e.g. Fos, Egr1, Arc, Npas4, Btg2, Atf3). SRF was required for epilepsy associated neurodegeneration, mossy fiber sprouting and inflammation. We uncovered MAP kinase signaling as SRF target during epilepsy. Upon SRF ablation, seizure evoked induction of dual specific phosphatases (Dusp5 and Dusp6) was reduced. Lower expression of these negative ERK kinase regulators correlated with altered P-ERK levels in epileptic Srf mutant animals.Overall, this study uncovered an SRF contribution to several processes of epileptogenesis in the pilocarpine model.

Morphometric MRI features are associated with surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Sandim, Gabriel Barbosa; Assunção Leme, Idaiane Batista; Carrete, Henrique; Centeno, Ricardo Silva; Sato, João Ricardo; Yacubian, Elza Márcia Targas

2017-05-01

Corticoamygdalohippocampectomy (CAH) improves seizure control, quality of life, and decreases mortality for refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). One-third of patients continue having seizures, and it is pivotal to determine structural abnormalities that might influence the postoperative outcome. Studies indicate that nonhippocampal regions may play a role in the epileptogenic network in MTLE-HS and could generate seizures postoperatively. The aim of this study is to analyze areas of atrophy, not always detected on routine MRI, comparing patients who became seizure free (SF) with those non seizure free (NSF) after CAH, in an attempt to establish possible predictors of surgical outcome. 105 patients with refractory MTLE-HS submitted to CAH (59 left MTLE; 46 males) and 47 controls were enrolled. FreeSurfer was performed for cortical thickness and volume estimation comparing patients to controls and SF versus NSF patients. The final sample after post processing procedures resulted in 99 patients. Cortical thickness analyses showed reductions in left insula in NSF patients compared to those SF. Significant volume reductions in SF patients were present in bilateral thalami, hippocampi and pars opercularis, left parahippocampal gyrus and right temporal pole. In NSF patients reductions were present bilaterally in thalami, hippocampi, entorhinal cortices, superior frontal and supramarginal gyri; on the left: superior and middle temporal gyri, temporal pole, parahippocampal gyrus, pars opercularis and middle frontal gyrus; and on the right: precentral, superior, middle and inferior temporal gyri. Comparison between SF and NSF patients showed ipsilateral gray matter reductions in the right entorhinal cortex (p=0.003) and contralateral parahippocampal gyrus (p=0.05) in right MTLE-HS. Patients NSF had a longer duration of epilepsy than those SF (p=0.028). NSF patients exhibited more extensive areas of atrophy than SF ones. As entorhinal cortex and parahippocampal gyrus are reduced in NSF patients compared to those SF these structures might be implicated in the network responsible for the maintenance of postoperative seizures. Duration of epilepsy is a predictor of seizure outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2015-12-10

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug (AED) and usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6). To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (16 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 16 February 2015) and MEDLINE (Ovid, 1946 to 16 February 2015). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review.

"A journey around the world": Parent narratives of the journey to pediatric resective epilepsy surgery and beyond.

PubMed

Baca, Christine B; Pieters, Huibrie C; Iwaki, Tomoko J; Mathern, Gary W; Vickrey, Barbara G

2015-06-01

Although shorter time to pediatric resective epilepsy surgery is strongly associated with greater disease severity, other nonclinical diagnostic and sociodemographic factors also play a role. We aimed to examine parent-reported barriers to timely receipt of pediatric epilepsy surgery. We conducted 37 interviews of parents of children who previously had resective epilepsy surgery at University of California Los Angeles (UCLA; 2006-2011). Interviews were audio-recorded, transcribed, and systematically coded using thematic analysis by two independent coders, and subsequently checked for agreement. Clinical data, including "time to surgery" (age of epilepsy onset to surgery) were abstracted from medical records. The mean time to surgery was 5.3 years (standard deviation [SD] 3.8); surgery types included 32% hemispherectomy, 43% lobar/focal, and 24% multilobar. At surgery, parents were on average 38.4 years (SD 6.6) and children were on average 8.2 years (SD 4.7). The more arduous and longer aspect of the journey to surgery was perceived by parents to be experienced prior to presurgical referral. The time from second antiepileptic drug failure to presurgical referral was ≥ 1 year in 64% of children. Thematic analysis revealed four themes (with subthemes) along the journey to surgery and beyond: (1) recognition--"something is wrong" (unfamiliarity with epilepsy, identification of medical emergency); (2) searching and finding--"a circuitous journey" (information seeking, finding the right doctors, multiple medications, insurance obstacles, parental stress); (3) surgery is a viable option--"the right spot" (surgery as last resort, surgery as best option, hoping for candidacy); and (4) life now--"we took the steps we needed to" (a new life, giving back). Multipronged interventions targeting parent-, provider-, and system-based barriers should focus on the critical presurgical referral period; such interventions are needed to remediate delays and improve access to subspecialty care for children with medically refractory epilepsy and potentially eligible for surgery. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

The utility score of epilepsy with partial seizure measured by TTO, VAS, and EQ-5D in the general Korean population.

PubMed

Kang, Hee-Jin; Kang, Eunjeong; Jo, Min-Woo; Park, Eun-Ja; Yoon, Seonyoung; Lee, Eui-Kyung

2014-07-01

This study aimed to measure utilities, which are quantitative terms incorporating preferences, for various health states of epilepsy with partial seizure in the general population in South Korea. It also aimed to find socio-demographic characteristics associated with the utility scores. Utility scores using Time Trade-Off (TTO), Visual Analog Scale (VAS), and EuroQol five Dimension (EQ-5D) were obtained from 300 people aged 16 and over by face-to-face interviews. We measured utilities for three hypothetical health states of epilepsy for which scenarios were defined based on the frequency of partial seizure: seizure-free, seizure reduction, and withdrawal. We compared utilities with varying seizure frequency using a repeated-measures ANOVA, and analyzed the association between utilities and socio-demographic characteristics using a generalized estimating equation (GEE). The mean utility scores for withdrawal state, seizure reduction state, and seizure-free state were 0.303, 0.493, and 0.899, respectively, when measured by TTO. VAS yielded the mean utility scores of 0.211, 0.424, and 0.752 for respective health states, and corresponding scores with EQ-5D were 0.261, 0.645, and 0.959. The utility scores for the three health states were statistically different in TTO, VAS, and EQ-5D. The withdrawal state had the lowest utility scores. There were differences in mean utilities for the three health states across the three methods. Utilities by EQ-5D tended to have higher values than those by TTO and VAS. Utilities by VAS had the lowest values. In GEE analysis, the severity of epilepsy and household income were significantly related to utility scores. The withdrawal state of epilepsy had the lowest utility value and the seizure-free state had the highest by all three techniques of utility measurement used. There were significant differences in utilities between one severity level of epilepsy and another. Utility was associated with household income and the severity of disease. Utility scores for distinct epilepsy states obtained in this study could facilitate health economic analyses of epilepsy treatments and thus help decision making in resource allocation. Copyright © 2014 Elsevier B.V. All rights reserved.

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

PubMed Central

Sanz-García, Ancor; Vega-Zelaya, Lorena; Pastor, Jesús; Torres, Cristina V.; Sola, Rafael G.; Ortega, Guillermo J.

2016-01-01

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area. PMID:28060326

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review.

PubMed

AlQassmi, Amal; Burneo, Jorge G; McLachlan, Richard S; Mirsattari, Seyed M

2016-12-01

We present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014. Hospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24months with or without an AED. Twenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15-80years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5-8years), but all had seizure recurrence within 2 to 4weeks. Not all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated. Copyright © 2016 Elsevier Inc. All rights reserved.

Emission computed tomography of /sup 18/F-fluorodeoxyglucose and /sup 13/N-ammonia in stroke and epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.; Phelps, M.E.; Engel, J. Jr.

1980-01-01

The ECAT Positron Tomograph was used to scan normal control subjects, stroke patients at various times during recovery, and patients with partial epilepsy during EEG monitoring. /sup 18/F-fluorodeoxyglucose (/sup 18/FDG) and /sup 13/N-Ammonia (/sup 13/NH/sub 3/) were used as indicators of abnormalities in local cerebral glucose utilization (LCMR/sub glc/) and relative perfusion, respectively. Hypometabolism, due to deactivation or minimal damage, was demonstrated with the /sup 18/FDG scan in deep structures and broad zones of cerebral cortex which appeared normal on x-ray CT (XCT) and /sup 99m/Tc pertechnetate scans. In patients with partial epilepsy, who had unilateral or focal electrical abnormalities,more » interictal /sup 18/FDG scan patterns clearly showed localized regions of decreased (20 to 50%) LCMR/sub glc/, which correlated anatomically with the eventual EEG localization.« less

Focus on desynchronization rather than excitability: a new strategy for intraencephalic electrical stimulation.

PubMed

Medeiros, Daniel de Castro; Moraes, Márcio Flávio Dutra

2014-09-01

Epilepsy is a severely debilitating brain disease, often associated with premature death, which has an urgent need for alternative methods of treatment. In fact, roughly 25% of patients with epilepsy do not have seizures satisfactorily controlled by pharmacological treatment, and 30% of these patients with treatment-refractory seizures are not even eligible for ablative surgery. Epilepsy is most readily identifiable by its seizures and/or paroxysmal events, mostly viewed as spontaneously recurrent and unpredictable, which are caused by stereotyped changes in neurological function associated with hyperexcitability and hypersynchronicity of the underlying neural networks. Treatment has strongly been based on the fixed goal of depressing neuronal activity, working under the veiled assumption that hyperexcitability would lead to synchronous neuronal activity and, therefore, to seizure. Over the last 20-30 years, the emergence of electrical (ES) of deep brain structures, a practicable option for treating patients with otherwise untreatable seizures, has broadened our understanding of anticonvulsant mechanisms that conceptually differ from those of pharmacological treatment. Conversely, the research on ES therapy applied to epilepsy is contributing significantly to untwine the phenomena of excitation from that of synchronization as potential target mechanisms for abolishing seizures and predicting paroxysmal events. This paper is, thus, an addendum to other reviews on the subject of ES therapy in epilepsy which focuses on the desynchronization effect ES has on epileptogenic neural networks rather than its effect on overall brain excitability. Copyright © 2014 Elsevier Inc. All rights reserved.

Declarative long-term memory and the mesial temporal lobe: Insights from a 5-year postsurgery follow-up study on refractory temporal lobe epilepsy.

PubMed

Salvato, Gerardo; Scarpa, Pina; Francione, Stefano; Mai, Roberto; Tassi, Laura; Scarano, Elisa; Lo Russo, Giorgio; Bottini, Gabriella

2016-11-01

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

[Monitoring time of interictal epileptiform discharges by long-term video EEG in patients with epilepsy].

PubMed

Wu, Han; Wang, Zhongjin; Ming, Wenjie; Wang, Shuang; Ding, Meiping

2017-01-25

Objective: To optimize the monitoring time of interictal epileptiform discharges (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG). Methods: The cumulative percentages of IED detected by VEEG in 346 epilepsy patients (349 times) with different purposes, different waking sleep states and different MRI findings were retrospectively analyzed. According to the purposes, there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124 times) for preoperative evaluation and 58 patients (60 times) for adjustment of medications. According to MRI results, there were responsible lesions in 98 patients (98 times) and no responsible lesions in 173 patients (174 times). Results: Among 346 patients (349 times), IED was detected within 24 h in 231 patients (times). The percentage of detection in patients with purpose of preoperative evaluation was higher than those with purpose of diagnosis and medication adjustment. The detection of LED was gradually increased in first 8 h with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time, particularly in the second stage of sleep. The cumulative percentage of IED in patients with abnormal MRI findings was higher in all periods. It reached 83.7% within 8 h, and then tended to be stable. Conclusion: The study shows that LED should be monitored by VEEG at least 8 hours and should include the second stage of sleep in patients with epilepsy. Patients with refractory epilepsy and with abnormal lesions on MRI should record IED more frequently.

The current status of artisanal cannabis for the treatment of epilepsy in the United States.

PubMed

Sulak, Dustin; Saneto, Russell; Goldstein, Bonni

2017-05-01

The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, including potential risks and benefits, challenges related to artisanal preparations, and cannabinoid dosing, are discussed. Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy.

PubMed

Elliott, Cameron A; Broad, Andrew; Narvacan, Karl; Steve, Trevor A; Snyder, Thomas; Urlacher, Jordan; Wheatley, B Matt; Sinclair, D Barry

2018-06-22

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the initial operation was significantly more likely following ATL (47/61, 77%) than SelAH (8/18, 44%; p = 0.017, Fisher's exact test). There was no statistically significant difference in the proportion of patients with postoperative neuropsychological deficits following SelAH (8/18, 44%) or ATL (21/61, 34%). However, reoperation was significantly more likely following SelAH (8/18, 44%) than after ATL (7/61, 11%; p = 0.004) and was more likely to result in Engel I outcome for ATL after failed SelAH (7/8, 88%) than for posterior extension after failed ATL (1/7, 14%; p = 0.01). Reoperation was well tolerated without significant neuropsychological deterioration. Ultimately, including 15 reoperations, 58 of 79 (73%) patients were free from disabling seizures at the most recent follow-up. CONCLUSIONS SelAH among pediatric patients with medically refractory unilateral TLE yields significantly worse rates of seizure control compared with ATL. Reoperation is significantly more likely following SelAH, is not associated with incremental neuropsychological deterioration, and frequently results in freedom from disabling seizures. These results are significant in that they argue against using SelAH for pediatric TLE surgery.

A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia.

PubMed

Rowland, Nathan C; Englot, Dario J; Cage, Tene A; Sughrue, Michael E; Barbaro, Nicholas M; Chang, Edward F

2012-05-01

Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.

The Teacher's Role: Children and Epilepsy. A Guide for School Personnel. Revised Edition.

ERIC Educational Resources Information Center

Epilepsy Foundation of America, Landover, MD.

The brief guide offers information on epilepsy to teachers and other school personnel. Types of seizures are defined (e.g., simple and complex partial seizures, generalized tonic clonic seizures), and management practices in the classroom setting for each type of seizure are described. Signs indicating that a seizure requires immediate medical…

Perampanel. Just another anticonvulsant for partial epilepsy: no progress.

PubMed

2014-07-01

Nearly a dozen antiepileptic drugs have been shown to prevent attacks in patients with partial epilepsy, whether used alone, or in combination when successive single-agent well-conducted treatments have failed. Perampanel (Fycompa, Eisai) an AMPA glutamate receptor antagonist, has been granted marketing authorisation in the European Union and United States, for use in combination with other antiepileptic drugs in patients aged 12 years or older with partial epilepsy. Perampanel has not been compared with other antiepileptic drugs in clinical trials. Its evaluation is based on three comparative, double-blind, placebo-controlled trials, in which perampanel was added to other antiepileptic drugs considered to be inadequately effective. In these trials, after 19 weeks of treatment, its efficacy was only modest: the response rate was at best only about 20% higher than with placebo. Indirect comparison, albeit inherently unreliable, suggests that perampanel is no better than other antiepileptic drugs. Perampanel has frequent and often dose-dependent adverse effects; they mainly include irritability, aggression, impaired alertness and coordination, and weight gain. Cardiac disorders were observed during a long-term trial of perampanel. This possible adverse effect requires further study. Perampanel led to stunted growth in experimental animals. It is not known whether adolescents are also at risk. Perampanel does not appear to be a potent inducer or inhibitor of the cytochrome P450 enzyme system, but its drug interaction profile requires further evaluation. In animal studies, perampanel exposure resulted in increased perinatal mortality. In practice, there is no evidence that perampanel represents a therapeutic advance for patients with partial epilepsy. In addition to its known adverse effects, there are concerns over possible long-term cardiac toxicity and a deleterious effect on growth. Other acceptable solutions, based on better-known drugs, should be discussed with epileptic patients.

Evaluation of Hospitalized Intractable Epileptic Children with SPECT Scan in Ahvaz, South West of Iran

PubMed Central

Ahmadi, Faramarz; Malekian, Arash; Davoodzadeh, Hannaneh; Kabirinia, Hossein

2016-01-01

Introduction Seizures are the most frequent neurologic disorder seen in childhood. Epilepsy is a group of disorders that includes an abnormally increased susceptibility to seizures. Aim To examine the effectiveness of SPECT (Single Photon Emission Computerized Tomography) in detecting seizure foci in 21 Iranian children who had medically refractory epilepsy. Materials and Methods Children between 2 to 15 years of age with uncontrolled seizures were investigated using SPECT scan as a standardized protocol. Results In 16 cases (76.2%), likely seizure foci were evident, as were seen in the form of decreased regional blood flow, while in 5 cases (23.8%), SPECT scan results were normal. Left temporal lobe was the most common area which had decreased regional blood flow. Conclusion SPECT scan can potentially be used to investigate children with uncontrolled seizures. PMID:27891419

[Ivermectin as an adjunct in the treatment of refractory epilepsy].

PubMed

Diazgranados-Sanchez, J A; Mejia-Fernandez, J L; Chan-Guevara, L S; Valencia-Artunduaga, M H; Costa, J L

2017-10-01

Ivermectin, a 22'23 dihydro derivative of avermectins beta-1a, is a highly effective veterinary and human anti parasitic, used to treat endoparasites of difficult control such as filariasis and onchocerciasis, with a median plasma life of at least of 16 hours. The recommended therapeutic doses range from 0.05 to 0.40 mg/kg, without undesirable effects or risk to human life. It went from being a great success in animal health to its application in humans, where it has had great impact. Studies in basic sciences have shown that ivermectin has anticonvulsive effects in different epileptic animal models, where five different mechanisms of action have been described. Descriptive, prospective observational study, performed between 2013 and 2015, with 32 refractory epileptic patients, who received ivermectin as an a dose of adjunctive treatment of 10 mg/day three or seven times a week, controlled every three months, followed by 12-24 months, without withdrawal of anticonvulsant medications that they received previously. Progressively, patients entered into crisis control, at the end of the programmed follow-up period, the total percentage of crisis reduction was 97%, of which 57% did not return to crisis from the beginning of treatment, all patients being free of crisis according to International League Against Epilepsy criteria. Ivermectin has been useful as an adjuvant, achieving a significant decrease in seizures in this group of drug resistant patients.

Photogenic partial seizures.

PubMed

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

Predictors of spontaneous transient seizure remission in patients of medically refractory epilepsy due to mesial temporal sclerosis (MTS).

PubMed

Dhiman, Vikas; Sinha, Sanjib; Arimappamagan, Arivazhagan; Mahadevan, Anita; Bharath, Rose Dawn; Saini, Jitender; Rajeswaran, Jamuna; Rao, Malla Bhaskar; Shankar, Susrala K; Satishchandra, Parathasarthy

2015-02-01

To analyze the predictors of spontaneous transient seizure remission for ≥1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal sclerosis (MTS). This analysis included 38 patients with DRE (M:F = 20:18, age: 31.7 ± 10.9 years) diagnosed with unilateral MTS (right:left = 16:22). Group I ('remission' group) comprised of patients with seizure remission (M:F = 10:8, age: 32.8 ± 12.3 years, mean seizure free period: 2.2 ± 1.1 years; median: 2.1 years). Group II ('non-remission' group) comprised of age and gender matched 20 patients (M:F = 10:10, age: 30.7 ± 9.7 years) with unilateral MTS who never had seizure remission and subsequently underwent epilepsy surgery. Groups I and II were compared to find the predictors associated with transient seizure remission. The age at onset of seizures in group I was 13.2 ± 11.8 years and in group II was 12.0 ± 7.6 years. The duration of seizure was: group I - 19.7 ± 12.5 years and group II - 19.3 ± 7.7 years. Past history of seizure remissions (p < 0.001), frequent periods of remissions (p < 0.001), first remission within a year of onset of seizures (p = 0.04) and normal EEG (p = 0.04) were the important clinical predictors associated with seizure remission in this cohort. Fifteen patients in group I (83.3%) experienced remission following either change in AED (p ≤ 0.001) or increase in AED dosages (p < 0.001). There was no difference between the two groups regarding the type of semiology (partial vs. secondarily generalized) (p = 0.50), family history of seizures (p = 1.0), side of the lesion (p = 0.34), history of febrile seizures (p = 1.0) and the number of AEDs used (p = 0.53). The present study unfolds, some of the clinically relevant predictors associated with transient seizure remission in patients with DRE and MTS. Future molecular and network studies are required to understand its mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Epilepsy Care in Zambia: A Study of Traditional Healers

PubMed Central

Baskind, Roy; Birbeck, Gretchen

2005-01-01

Summary Purpose Most people with epilepsy (PWE) reside in developing countries with limited access to medical care. In sub-Saharan Africa (SSA), traditional healers (THs) play a prominent role in caring for PWE, yet little is known about epilepsy care by THs. We conducted a multimethod, qualitative study to better understand the epilepsy care delivered by THs in Zambia. Methods We conducted focus-group discussions with THs, in-depth semistructured interviews with a well-recognized TH at his place of work, and multiple informal interviews with health-care providers in rural Zambia. Results THs recognize the same symptoms that a neurologist elicits to characterize seizure onset (e.g., olfactory hallucinations, jacksonian march, automatisms). Although THs acknowledge a familial propensity for some seizures and endorse causes of symptomatic epilepsy, they believe witchcraft plays a central, provocative role in most seizures. Treatment is initiated after the first seizure and usually incorporates certain plant and animal products. Patients who do not experience further seizures are considered cured. Those who do not respond to therapy may be referred to other healers. Signs of concomitant systemic illness are the most common reason for referral to a hospital. As a consequence of this work, our local Epilepsy Care Team has developed a more collaborative relationship with THs in the region. Conclusions THs obtain detailed event histories, are treatment focused, and may refer patients who have refractory seizures to therapy to other healers. Under some circumstances, they recognize a role for modern health care and refer patients to the hospital. Given their predominance as care providers for PWE, further understanding of their approach to care is important. Collaborative relationships between physicians and THs are needed if we hope to bridge the treatment gap in SSA. PMID:16026565

Diurnal patterns and relationships between physiological and self-reported stress in patients with epilepsy and psychogenic non-epileptic seizures.

PubMed

Novakova, Barbora; Harris, Peter R; Reuber, Markus

2017-05-01

Patients with epilepsy and those with psychogenic non-epileptic seizures (PNES) experience high levels of stress and stress is one of the most frequently self-identified seizure precipitants. Although stress is a multifaceted phenomenon, few studies have systematically examined its different components in patients with seizures. The aim of this study was therefore to describe diurnal patterns of psychological and physiological measures of stress in patients with epilepsy and patients with PNES, and explore their relationships to each other in order to improve our understanding of the mechanisms underlying stress and seizure occurrence in these patients. A range of stress markers including self-reported stress, salivary cortisol, and heart rate variability (HRV) were explored in adult patients with refractory epilepsy (N=22) and those with PNES (N=23) undergoing three- to five-day video-telemetry. A diurnal pattern was observed in the physiological measures, characterized by higher levels of physiological arousal in the mornings and lower levels at night in both patients with epilepsy and PNES. The physiological measures (cortisol and HRV) were associated with each other in patients with epilepsy; no close relationship was found with self-reported stress in either of the two patient groups. The findings contribute to and expand on previous studies of the patterns of stress in patients with seizures. The results also indicate a discrepancy between patients' physiological responses and their subjective stress perceptions, suggesting that simple self-reports cannot be used as a proxy of physiological arousal in patients with seizures and stress. Stress in these patient groups should be studied using a combination of complementary measures. Copyright © 2017 Elsevier Inc. All rights reserved.

CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

PubMed

Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

2009-11-01

Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: evidence of clinical benefit.

PubMed

Fosi, Tangunu; Lax-Pericall, Maria T; Scott, Rod C; Neville, Brian G; Aylett, Sarah E

2013-12-01

To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6–18 years). With use of a combination of a behavioral management program and MPH 0.3–1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69–0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed.

H.M. never again! An analysis of H.M.'s epilepsy and treatment.

PubMed

Mauguière, F; Corkin, S

2015-03-01

On August 25, 1953, the patient H.M., aged 27, underwent a bilateral surgical destruction of the inner aspect of his temporal lobes performed by William Beecher Scoville with the aim to control H.M.'s drug refractory epileptic seizures and alleviate their impact on his quality of life. Postoperatively, H.M. presented for 55 years a "striking and totally unexpected grave loss of recent memories". This paper reports what we know about H.M.'s epilepsy before and after surgery and puts forward arguments supporting the syndromic classification of his epilepsy. We attempted to elucidate what could have been the rationale, in 1953, of Scoville's decision to carry out a bilateral ablation of H.M.'s medial temporal lobe structures, and we examined whether there was any convincing argument published before 1953 suggesting that bilateral hippocampal ablation could result in a permanent and severe amnesia. Our a posteriori analysis of H.M.'s medical history suggested that he was most probably suffering from idiopathic generalized epilepsy with absences and generalized convulsive seizures worsened by high dosage phenytoin treatment, or less probably from cryptogenic frontal lobe epilepsy. Importantly, he did not have temporal lobe epilepsy. Scoville based his proposal of bilateral mesial temporal lobe ablation on his experience as a psychosurgeon and on the assumption that the threshold of generalized epileptic activity could be lowered by some kind of hippocampal dysfunction potentially epileptic in nature. Given the scanty information on the link between amnesia and medial temporal lobe lesions that was available in humans in 1953, one can understand why Scoville was so surprised by the "striking and totally unexpected" memory loss he observed in H.M. after the bilateral ablation of his mesial temporal lobe structures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Association between ABCB1 genotype and seizure outcome in Collies with epilepsy.

PubMed

Muñana, K R; Nettifee-Osborne, J A; Bergman, R L; Mealey, K L

2012-01-01

Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy. Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy. Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs). Prospective and retrospective cohort study. Dogs were classified as having a good outcome (≤ 1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects. Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1∆ mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014). ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Why do seizures occur when they do? Situations perceived to be associated with increased or decreased seizure likelihood in people with epilepsy and intellectual disability

PubMed Central

Illingworth, Josephine L.; Watson, Peter; Ring, Howard

2014-01-01

Seizure precipitants are commonly reported in the general population of people with epilepsy. However, there has been little research in this area in people with epilepsy and intellectual disability (ID). We conducted a survey of the situations associated with increased or decreased seizure likelihood in this population. The aim of the research was to identify situations of increased seizure likelihood (SISLs) and situations of decreased seizure likelihood (SDSLs) reported by carers of people with an ID and epilepsy. Three study groups were investigated: two groups comprising individuals with ID associated with a specific genetic diagnosis – Rett syndrome or fragile X syndrome – and one group consisting of individuals with a range of other etiologies. Responses relating to 100 people were received: 44 relating to people with Rett syndrome, 25 to people with fragile X syndrome, and 31 to people whose ID had some other etiologies. Ninety-eight percent of the respondents reported at least one SISL, and 60% reported at least one SDSL. Having more seizure types and greater seizure frequency were associated with a higher number of SISLs reported. The most commonly reported SISLs and SDSLs for each of the three groups are presented. The most common SISL overall was illness, which was reported as an SISL by 71% of the respondents. There was less consensus with regard to SDSLs. These findings provide a greater understanding of when seizures occur in those with ID and epilepsy, with possible implications for adjunctive behavioral management of seizures in those with treatment-refractory epilepsy. PMID:25218091

Why do seizures occur when they do? Situations perceived to be associated with increased or decreased seizure likelihood in people with epilepsy and intellectual disability.

PubMed

Illingworth, Josephine L; Watson, Peter; Ring, Howard

2014-10-01

Seizure precipitants are commonly reported in the general population of people with epilepsy. However, there has been little research in this area in people with epilepsy and intellectual disability (ID). We conducted a survey of the situations associated with increased or decreased seizure likelihood in this population. The aim of the research was to identify situations of increased seizure likelihood (SISLs) and situations of decreased seizure likelihood (SDSLs) reported by carers of people with an ID and epilepsy. Three study groups were investigated: two groups comprising individuals with ID associated with a specific genetic diagnosis - Rett syndrome or fragile X syndrome - and one group consisting of individuals with a range of other etiologies. Responses relating to 100 people were received: 44 relating to people with Rett syndrome, 25 to people with fragile X syndrome, and 31 to people whose ID had some other etiologies. Ninety-eight percent of the respondents reported at least one SISL, and 60% reported at least one SDSL. Having more seizure types and greater seizure frequency were associated with a higher number of SISLs reported. The most commonly reported SISLs and SDSLs for each of the three groups are presented. The most common SISL overall was illness, which was reported as an SISL by 71% of the respondents. There was less consensus with regard to SDSLs. These findings provide a greater understanding of when seizures occur in those with ID and epilepsy, with possible implications for adjunctive behavioral management of seizures in those with treatment-refractory epilepsy. Copyright © 2014. Published by Elsevier Inc.

Music and epilepsy: a critical review.

PubMed

Maguire, Melissa Jane

2012-06-01

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl's gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native-born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

PubMed Central

Wolfart, Jakob; Laker, Debora

2015-01-01

Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723