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Sample records for partial onset seizures

  1. Lacosamide: in partial-onset seizures.

    PubMed

    Cross, Sarah A; Curran, Monique P

    2009-01-01

    Lacosamide is a functionalized amino acid, the antiepileptic effects of which appear to be due to a novel mode of action, namely the selective enhancement of slow inactivation of voltage-gated sodium channels. Lacosamide is available as oral or intravenous formulations. Bioequivalence between the oral tablet and the oral syrup of lacosamide has been established. The bioavailability of the oral lacosamide tablet was similar to that of a 30- or 60-minute intravenous infusion of lacosamide administered at the same dosage. Oral lacosamide when added concomitantly with between one and three antiepileptic drugs was effective in adult patients with uncontrolled partial-onset seizures with or without secondary generalization, according to pooled data (n = 1308) from three phase II/III studies that had a 12-week maintenance phase. The percentage of patients with a >or=50% reduction from baseline to the maintenance phase in seizure frequency was significantly greater with oral lacosamide 200 or 400 mg/day (34% and 40%) than with placebo (23%). The median percentage reduction in seizure frequency per 28 days from baseline to the maintenance phase was significantly greater with lacosamide 400 mg/day than with placebo in each of the three phase II/III studies. Lacosamide was generally well tolerated in adult patients with partial-onset seizures, with most treatment-emergent adverse events being of mild or moderate severity. Dizziness was the most common treatment-related adverse event. When used as short-term replacement for oral lacosamide, intravenous lacosamide was well tolerated when administered as a 15-, 30- or 60-minute infusion.

  2. Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

    PubMed Central

    Jouny, Christophe C.; Bergey, Gregory K.

    2011-01-01

    Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

  3. Characterization of early partial seizure onset: frequency, complexity and entropy.

    PubMed

    Jouny, Christophe C; Bergey, Gregory K

    2012-04-01

    A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Eighteen different measures including power in frequency bands up to 300 Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from 45 patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures.

    PubMed

    Nolan, Sarah J; Marson, Anthony G; Pulman, Jennifer; Tudur Smith, Catrin

    2013-08-23

    This is an updated version of the previously published Cochrane review (Issue 4, 2009)Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that valproate is more effective for generalised onset tonic-clonic seizures with or without other generalised seizure types. To review the best evidence comparing phenytoin and valproate when used as monotherapy in individuals with partial onset seizures or generalised onset tonic-clonic seizures with or without other generalised seizure types. We searched the Cochrane Epilepsy Group's Specialised Register (19 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, The Cochrane Library, January 2013), MEDLINE (1946 to 18 February 2013), SCOPUS (19 February 2013), ClinicalTrials.gov (19 February 2013), and WHO International Clinical Trials Registry Platform ICTRP (19 February 2013). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of valproate monotherapy versus phenytoin monotherapy. This was an individual patient data review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. Cox proportional hazards regression models were used to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) with the generic inverse variance method used to obtain the overall pooled HR and 95% CI. Individual patient data were available for 669 individuals out of 1119 eligible individuals from five out of 11 trials, 60% of the potential data. Results apply to generalised tonic-clonic seizures, but not absence or myoclonus seizure types. For remission outcomes, HR > 1 indicates an

  5. Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalised onset tonic-clonic seizures.

    PubMed

    Nolan, Sarah J; Tudur Smith, Catrin; Pulman, Jennifer; Marson, Anthony G

    2013-01-31

    This is an updated version of the original Cochrane review published in The Cochrane Library 2001, Issue 4.Worldwide, particularly in the developing world, phenytoin and phenobarbitone are commonly used antiepileptic drugs, primarily because they are inexpensive. The aim of this review is to summarise data from existing trials comparing phenytoin and phenobarbitone. To review the best evidence comparing phenobarbitone and phenytoin when used as monotherapy in participants with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types. We searched the Cochrane Epilepsy Group trials register (31 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 5 of 12, The Cochrane Library 2012) and MEDLINE (1946 to May week 4, 2012). We hand-searched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field.   Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of phenobarbitone monotherapy with phenytoin monotherapy. This was an individual participant data (IPD) review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. Cox proportional hazards regression models were used to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) with the generic inverse variance method used to obtain the overall pooled estimate of HRs and 95% CIs. Data have been obtained for four of eight studies meeting the inclusion criteria, amounting to 599 individuals, or approximately 63% of the potential data.The main overall results (pooled HR, 95% CI) were (a) time to treatment withdrawal 1.62 (1.23 to 2.14); (b) time to 12-month remission 0.90 (0.69 to 1.18) (c) time to six-month remission 0.92 (0.73 to 1.16) and (d) time to first seizure 0.85 (0.68 to 1.05). These results

  6. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

    PubMed

    Handforth, A; DeGiorgio, C M; Schachter, S C; Uthman, B M; Naritoku, D K; Tecoma, E S; Henry, T R; Collins, S D; Vaughn, B V; Gilmartin, R C; Labar, D R; Morris, G L; Salinsky, M C; Osorio, I; Ristanovic, R K; Labiner, D M; Jones, J C; Murphy, J V; Ney, G C; Wheless, J W

    1998-07-01

    The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

  7. Lacosamide adjunctive therapy for partial-onset seizures: a meta-analysis.

    PubMed

    Sawh, Sonja C; Newman, Jennifer J; Deshpande, Santosh; Jones, Philip M

    2013-01-01

    Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established. Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures. Data Sources. A systematic review of the medical literature using Medline (1946-Week 4, 2012), EMBASE (1980-Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied. Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included. Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data. Data Synthesis. All pooled analyses used the random effects model. Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I(2) = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I(2) = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group. Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs. Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to

  8. 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. ...

  9. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures.

    PubMed

    Gidal, Barry E; Ferry, Jim; Majid, Oneeb; Hussein, Ziad

    2013-08-01

    Although there is a general paucity of published pharmacokinetic (PK) data for new antiepileptic drugs (AEDs), PK analyses of pooled data from clinical studies of perampanel have recently been presented. We present PK/pharmacodynamic (PD) analyses of pooled data from phase III studies of perampanel describing efficacy and safety as a function of exposure, in order to determine whether a predictable concentration-effect relationship exists for perampanel efficacy and/or adverse events (AEs). The effects of concomitant enzyme-inducing AEDs (EIAEDs) and non-enzyme-inducing AEDs on the exposure, efficacy, and safety of perampanel are also considered. Three multicenter, randomized, double-blind, placebo-controlled phase III studies investigated the efficacy and safety of perampanel 2-12 mg in patients with uncontrolled partial-onset seizures despite prior therapy with two or more AEDs. From baseline onward, patients also received ongoing treatment with stable doses of one to three approved concomitant AEDs. AEs were monitored throughout the studies. Changes from baseline in seizure frequency and 50% responder rates were evaluated. Exposure to perampanel was predicted based on the actual (last) dose using a previously established PK model. A population PK/PD model for the relationship between perampanel exposure and seizure frequency was estimated using nonlinear mixed-effect modeling with first-order conditional estimation, whereas logistic analyses for responder rate and AEs were performed using SAS analysis software. The PK/PD population included 1,109 patients. Seizure frequency decreased linearly as predicted perampanel average steady-state plasma concentrations increased. Concomitant EIAEDs (carbamazepine, oxcarbazepine, and phenytoin) reduced exposure to perampanel but had no effect on the slope of the PD model-predicted relationship between exposure and reduction in seizure frequency. The probability of patients achieving a response was predicted to increase as

  10. Development of lacosamide for the treatment of partial-onset seizures.

    PubMed

    Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

    2013-07-01

    Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.

  11. Ezogabine: an evaluation of its efficacy and safety as adjunctive therapy for partial-onset seizures in adults.

    PubMed

    Yamada, Mikiko; Welty, Timothy E

    2012-10-01

    To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamic properties, and clinical application of ezogabine (retigabine, INN), an antiepileptic drug approved in 2011. Published data from in vitro, animal, and clinical studies were obtained from PubMed and CINAHL searches, from January 1980 to March 31, 2012. Other relevant data regarding the safety and efficacy of ezogabine were obtained from the Food and Drug Administration and the European Medication Agency Web sites. Selected articles were prospective in vitro, animal, and controlled clinical studies of ezogabine. Non-English-language articles were excluded. In vitro and animal studies show that ezogabine activates voltagegated potassium channels, leading to reduction of seizure frequency by inhibiting hyperexcitability activity in the central nervous system. Additionally, ezogabine enhances γ-aminobutyric acid (GABA) activity and de novo GABA synthesis. Eight clinical studies of ezogabine have been published, 5 being Phase 1 clinical trials in healthy subjects and 3 being Phase 3 clinical trials in patients with pharmaco-resistant partial-onset seizures. Phase 3 clinical trials demonstrated the safety and efficacy of ezogabine in patients with partial-onset seizures. Clinical trials have shown that ezogabine is efficacious as an adjunctive agent in patients with pharmacoresistant partial seizures. Careful monitoring of drug interactions and adverse reactions is necessary. While ezogabine is efficacious for partial seizures, its precise role in the management of patients with epilepsy is yet to be determined.

  12. Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

    PubMed

    Simoens, Steven

    2011-01-01

    This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

  13. Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

    PubMed Central

    Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

    2014-01-01

    Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

  14. Lacosamide: a review of its use as adjunctive therapy in the management of partial-onset seizures.

    PubMed

    Hoy, Sheridan M

    2013-12-01

    Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet) and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in several countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures; however, prescribing regulations differ between countries. This article reviews the use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where it is approved in this patient population as an adjunctive therapy to other AEDs in the treatment of partial-onset seizures, with or without secondary generalization. In three randomized, double-blind, placebo-controlled, multicentre studies in adults and adolescents (aged 16-18 years) with partial-onset seizures, adjunctive therapy with oral lacosamide (administered for an initial titration period followed by 12 weeks' maintenance therapy) generally reduced the frequency of seizures to a significantly greater extent than placebo, with antiepileptic efficacy sustained following longer-term treatment (up to 8 years) in this patient population. Oral and intravenous lacosamide were generally well tolerated in clinical studies, with the majority of adverse events being mild or moderate in severity. Very common adverse reactions following adjunctive therapy with oral lacosamide included diplopia, dizziness, headache and nausea; the tolerability profile of intravenous lacosamide appeared consistent with that of oral lacosamide, although intravenous administration was associated with local adverse events, such as injection site discomfort or pain, irritation and erythema. Thus, oral and intravenous lacosamide as an adjunctive therapy to other AEDs provides a useful option in the treatment of patients with partial-onset seizures.

  15. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies

    PubMed Central

    Mameniškienė, Rūta; Quarato, Pier Paolo; Klein, Pavel; Gamage, Jessica; Schiemann, Jimmy; Johnson, Martin E.; Whitesides, John; McDonough, Belinda; Eckhardt, Klaus

    2016-01-01

    Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures. PMID:27335114

  16. Safety and efficacy of levetiracetam for the treatment of partial onset seizures in children from one month of age

    PubMed Central

    Cormier, Justine; Chu, Catherine J

    2013-01-01

    Epilepsy is a common neurological disorder in the pediatric population, affecting up to one percent of children, and for which the mainstay of treatment is anticonvulsant medication. Despite the frequent use of anticonvulsant drugs, remarkably little is known about the safety and efficacy of most of these medications in the pediatric epilepsy population. Of 34 anticonvulsants currently approved for use by the US Food and Drug Administration (FDA), only 13 have been approved for use in children. Although infants and young children are disproportionately affected by epilepsy, there are currently only three anticonvulsant medications that have been specifically evaluated and approved for use in children younger than 2 years of age. In 2012, the FDA approved levetiracetam as an adjunctive treatment for partial onset seizures in infants and children from one month of age. Here we review the available data on levetiracetam in the pediatric epilepsy population. We first discuss the pharmacological profile of levetiracetam, including its mechanism of action, formulations and dosing, and pharmacokinetics in children. We then review the available efficacy, safety, and tolerability data in children from one month of age with partial onset seizures. We conclude that the current data leading to the approval of levetiracetam for use in infants and children with partial onset seizures is encouraging, although more work needs to be done before definitive conclusions can be drawn about the efficacy of levetiracetam across different pediatric age groups. PMID:23458993

  17. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

    PubMed Central

    Heck, Christianne N; King-Stephens, David; Massey, Andrew D; Nair, Dileep R; Jobst, Barbara C; Barkley, Gregory L; Salanova, Vicenta; Cole, Andrew J; Smith, Michael C; Gwinn, Ryder P; Skidmore, Christopher; Van Ness, Paul C; Bergey, Gregory K; Park, Yong D; Miller, Ian; Geller, Eric; Rutecki, Paul A; Zimmerman, Richard; Spencer, David C; Goldman, Alica; Edwards, Jonathan C; Leiphart, James W; Wharen, Robert E; Fessler, James; Fountain, Nathan B; Worrell, Gregory A; Gross, Robert E; Eisenschenk, Stephan; Duckrow, Robert B; Hirsch, Lawrence J; Bazil, Carl; O'Donovan, Cormac A; Sun, Felice T; Courtney, Tracy A; Seale, Cairn G; Morrell, Martha J

    2014-01-01

    Objective To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Methods Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. Results All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Significance Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures. PMID:24621228

  18. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

    PubMed

    Heck, Christianne N; King-Stephens, David; Massey, Andrew D; Nair, Dileep R; Jobst, Barbara C; Barkley, Gregory L; Salanova, Vicenta; Cole, Andrew J; Smith, Michael C; Gwinn, Ryder P; Skidmore, Christopher; Van Ness, Paul C; Bergey, Gregory K; Park, Yong D; Miller, Ian; Geller, Eric; Rutecki, Paul A; Zimmerman, Richard; Spencer, David C; Goldman, Alica; Edwards, Jonathan C; Leiphart, James W; Wharen, Robert E; Fessler, James; Fountain, Nathan B; Worrell, Gregory A; Gross, Robert E; Eisenschenk, Stephan; Duckrow, Robert B; Hirsch, Lawrence J; Bazil, Carl; O'Donovan, Cormac A; Sun, Felice T; Courtney, Tracy A; Seale, Cairn G; Morrell, Martha J

    2014-03-01

    To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

  19. Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

    PubMed

    Toledano, Rafael; Jovel, Camilo Espinosa; Jiménez-Huete, Adolfo; Bayarri, Pau Giner; Campos, Dulce; Gomariz, Elena López; Giráldez, Beatriz González; García-Morales, Irene; Falip, Mercé; Agredano, Paula Martínez; Palao, Susana; Prior, María José Aguilar Amat; Pascual, María Rosa Querol; Navacerrada, Francisco José; González, Francisco Javier López; Ojeda, Joaquín; Sáez, Aránzazu Alfaro; Bermejo, Pedro Emilio; Gil-Nagel, Antonio

    2017-08-01

    Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    PubMed Central

    Ulloa, Carol M; Towfigh, Allen; Safdieh, Joseph

    2009-01-01

    Levetiracetam is a second-generation antiepileptic drug (AED) with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma) was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A). Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is <10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures. PMID:19777068

  1. A randomized, double-blind, placebo-controlled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures.

    PubMed

    Biton, Victor; Krauss, Gregory; Vasquez-Santana, Blanca; Bibbiani, Francesco; Mann, Allison; Perdomo, Carlos; Narurkar, Milind

    2011-02-01

    Efficacy and safety of adjunctive rufinamide (3,200 mg/day) was assessed in adolescents and adults with inadequately controlled partial-onset seizures receiving maintenance therapy with up to three antiepileptic drugs (AEDs). This randomized, double-blind, placebo-controlled, parallel-group, multicenter study comprised a 56-day baseline phase (BP), 12-day titration phase, and 84-day maintenance phase (MP). The primary efficacy variable was percentage change in total partial seizure frequency per 28 days (MP vs. BP). Secondary efficacy outcome measures included ≥50% responder rate and reduction in mean total partial seizure frequency during the MP. Safety and tolerability evaluation included adverse events (AEs), physical and neurologic examinations, and laboratory values. Pharmacokinetic and pharmacodynamic assessments were conducted. Three hundred fifty-seven patients were randomized: 176 to rufinamide and 181 to placebo. Patients had a median of 13.3 seizures per 28 days during BP; 86% were receiving ≥2 AEDs. For the intent-to-treat population, the median percentage reduction in total partial seizure frequency per 28 days was 23.25 for rufinamide versus 9.80 for placebo (p = 0.007). Rufinamide-treated patients were more than twice as likely to have had a ≥50% reduction in partial seizure frequency (32.5% vs. 14.3%; p < 0.001) and had a greater reduction in median total partial seizure rate per 28 days during the MP (13.2 vs. 5.2; p < 0.001). Treatment-emergent AEs occurring at ≥5% higher incidence in the rufinamide group compared with placebo were dizziness, fatigue, nausea, somnolence, and diplopia. Adjunctive treatment with rufinamide reduced total partial seizures in refractory patients. AEs reported were consistent with the known tolerability profile of rufinamide. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  2. The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

    PubMed

    Jung, Julien; Bouet, Romain; Delpuech, Claude; Ryvlin, Philippe; Isnard, Jean; Guenot, Marc; Bertrand, Olivier; Hammers, Alexander; Mauguière, François

    2013-10-01

    Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure

  3. [Post traumatic partial seizures].

    PubMed

    Carvajal, P; Almárcegui, C; Pablo, M J; Peralta, P; Bernal, M; Valdizán, J R

    Post traumatic epilepsy represents 4% of the prevalence of the disorder and is one of the sequelas which is most difficult to prevent. Risk factors have been described to predict the appearance of seizures. A seven year old boy with a severe head injury was admitted to the Intensive Care Unit. On neuroimaging studies there were multiple foci of contusion, mainly in the left hemisphere, and blood in the III and IV ventricles and frontal horn of the left lateral ventricle. The patient had severe sequelae of head injury with a right spastic hemiplegia and hemiparesia with hypertony of the left side, together with complete blindness of both eyes due to bilateral atrophy of the optic nerve. Serial EEG were done, in which a recording showed alternating periods of hypervoltage grapho elements superimposed on a trace of very low voltage, with continuous activity of low voltage and low frequency. There were no grapho elements with acute morphology. However, the patient had a first partial seizure a year and a half after his head injury. On the EEG an epileptogenic focus was identified in the left hemisphere. Within two years of his head injury he had seven seizures. He had not received prophylactic antiepileptic treatment after the head injury. We report a case of epilepsy secondary to a head injury, in which the first seizure occurred one and a half years after injury. In view of the risk factors, we discuss whether prophylactic anti epileptic treatment might have been beneficial.

  4. Partial Seizures Are Associated with Early Increases in Signal Complexity

    PubMed Central

    Jouny, Christophe C; Bergey, Gregory K; Franaszczuk, Piotr J

    2009-01-01

    Objectives Partial seizures are often believed to be associated with EEG signals of low complexity because seizures are associated with increased neural network synchrony. The investigations reported here provide an assessment of the signal complexity of epileptic seizure onsets using newly developed quantitative measures. Methods Using the Gabor atom density (GAD) measure of signal complexity, 339 partial seizures in 45 patients with intracranial electrode arrays were analyzed. Segmentation procedures were applied to determine the timing and amplitude of GAD changes relative to the electrographic onset of the seizure. Results 330 out of 339 seizures have significant complexity level changes, with 319 (97%) having an increase in complexity. GAD increases occur within seconds of the onset of the partial seizure but are not observed in channels remote from the focus. The complexity increase is similar for seizures from mesial temporal origin, neocortical temporal and extra-temporal origin. Conclusions Partial onset seizures are associated with early increases in signal complexity as measured by GAD. This increase is independent of the location of the seizure focus. Significance Despite the often predominant rhythmic activity that characterizes onset and early evolution of epileptic seizures, partial seizure onset is associated with an early increase in complexity. These changes are common to partial seizures originating from different brain regions, indicating a similar seizure dynamic. PMID:19910249

  5. Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

    PubMed

    Biton, Victor; Gil-Nagel, Antonio; Brodie, Martin J; Derossett, Sarah E; Nohria, Virinder

    2013-11-01

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

  6. 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

  7. Initiation, Propagation, and Termination of Partial (Focal) Seizures

    PubMed Central

    de Curtis, Marco; Avoli, Massimo

    2015-01-01

    The neurophysiological patterns that correlate with partial (focal) seizures are well defined in humans by standard electroencephalogram (EEG) and presurgical depth electrode recordings. Seizure patterns with similar features are reproduced in animal models of partial seizures and epilepsy. However, the network determinants that support interictal spikes, as well as the initiation, progression, and termination of seizures, are still elusive. Recent findings show that inhibitory networks are prominently involved at the onset of these seizures, and that extracellular changes in potassium contribute to initiate and sustain seizure progression. The end of a partial seizure correlates with an increase in network synchronization, which possibly involves both excitatory and inhibitory mechanisms. PMID:26134843

  8. Value and limitations of seizure semiology in localizing seizure onset.

    PubMed

    So, Elson L

    2006-08-01

    Seizure semiology has been the foundation of clinical diagnosis of seizure disorders. This article discusses the value and the limitations of behavioral features of seizure episodes in localizing seizure onset. Studies have shown that some semiologic features of seizures are highly accurate in the hemispheric lateralization and lobar localization of seizures. There is good agreement between blinded reviewers in lateralizing video-recorded seizures in temporal lobe and extratemporal lobe epilepsies. However, seizure semiology alone should not be used to determine the site of seizure onset. Each semiologic feature may falsely localize seizure onset. Seizure semiology in some patients may signify the site of seizure propagation rather than origination. Moreover, seizure semiology may not be as reliable in multifocal epilepsies as it is in unifocal epilepsies. Many semiologic features of seizures of adults are often missing in seizures of children. Seizure semiology should be analyzed and integrated with EEG and neuroimaging data to localize the seizure focus. A sample of the recorded seizures should be shown to the patient's relatives or friends to verify that it is representative of habitual seizures.

  9. Retention, dosing, tolerability and patient reported seizure outcome of Zonisamide as only add-on treatment under real-life conditions in adult patients with partial onset seizures: Results of the observational study ZOOM.

    PubMed

    Hamer, Hajo; Baulac, Michel; McMurray, Rob; Kockelmann, Edgar

    2016-01-01

    Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures. This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated. After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months. Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions. Copyright © 2015. Published by Elsevier Ltd.

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

    PubMed Central

    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

    2015-01-01

    Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods 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. Results 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. Significance 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

  11. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures

    PubMed Central

    Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

    2015-01-01

    Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10–30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca2+ channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%–11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

  12. Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

    PubMed

    Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

    2014-12-01

    Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.

  13. Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial.

    PubMed

    Zadeh, Wendy Waldman; Escartin, Antonio; Byrnes, William; Tennigkeit, Frank; Borghs, Simon; Li, Ting; Dedeken, Peter; De Backer, Marc

    2015-09-01

    To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after ≥ 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase. 456 patients received ≥ 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 ± 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 ± 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Termination Patterns of Complex Partial Seizures: An Intracranial EEG Study

    PubMed Central

    Afra, Pegah; Jouny, Christopher C.; Bergey, Gregory K.

    2015-01-01

    Purpose While seizure onset patterns have been the subject of many reports, there have been few studies of seizure termination. In this study we report the incidence of synchronous and asynchronous termination patterns of partial seizures recorded with intracranial arrays. Methods Data were collected from patients with intractable complex partial seizures undergoing presurgical evaluations with intracranial electrodes. Patients with seizures originating from mesial temporal and neocortical regions were grouped into three groups based on patterns of seizure termination: synchronous only (So), asynchronous only (Ao), or mixed (S/A, with both synchronous and asynchronous termination patterns). Results 88% of the patients in the MT group had seizures with a synchronous pattern of termination exclusively (38%) or mixed (50%). 82% of the NC group had seizures with synchronous pattern of termination exclusively (52%) or mixed (30%). In the NC group, there was a significant difference of the range of seizure durations between So and Ao groups, with Ao exhibiting higher variability. Seizures with synchronous termination had low variability in both groups. Conclusions Synchronous seizure termination is a common pattern for complex partial seizures of both mesial temporal or neocortical onset. This may reflect stereotyped network behavior or dynamics at the seizure focus. PMID:26552555

  15. Termination patterns of complex partial seizures: An intracranial EEG study.

    PubMed

    Afra, Pegah; Jouny, Christopher C; Bergey, Gregory K

    2015-11-01

    While seizure onset patterns have been the subject of many reports, there have been few studies of seizure termination. In this study we report the incidence of synchronous and asynchronous termination patterns of partial seizures recorded with intracranial arrays. Data were collected from patients with intractable complex partial seizures undergoing presurgical evaluations with intracranial electrodes. Patients with seizures originating from mesial temporal and neocortical regions were grouped into three groups based on patterns of seizure termination: synchronous only (So), asynchronous only (Ao), or mixed (S/A, with both synchronous and asynchronous termination patterns). 88% of the patients in the MT group had seizures with a synchronous pattern of termination exclusively (38%) or mixed (50%). 82% of the NC group had seizures with synchronous pattern of termination exclusively (52%) or mixed (30%). In the NC group, there was a significant difference of the range of seizure durations between So and Ao groups, with Ao exhibiting higher variability. Seizures with synchronous termination had low variability in both groups. Synchronous seizure termination is a common pattern for complex partials seizures of both mesial temporal or neocortical onset. This may reflect stereotyped network behavior or dynamics at the seizure focus. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. Localizing epileptic seizure onsets with Granger causality

    NASA Astrophysics Data System (ADS)

    Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh

    2013-09-01

    Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for successful surgery, which usually depends on the information obtained from intracranial electroencephalography (IEEG) recordings. The visual criteria and univariate methods of analyzing IEEG recordings have not always produced clarity on the SOZs for resection and ultimate seizure freedom for patients. Here, to contribute to improving the localization of the SOZs and to understanding the mechanism of seizure propagation over the brain, we applied spectral interdependency methods to IEEG time series recorded from patients during seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs before the onset of any visible ictal activity and causal relationships involve the recording electrodes where clinically identifiable seizures later develop. These results suggest that high-frequency oscillatory network activities precede and underlie epileptic seizures, and that GC spectral measures derived from IEEG can assist in precise delineation of seizure onset times and SOZs.

  17. Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures.

    PubMed

    Villanueva, Vicente; Holtkamp, Martin; Delanty, Norman; Rodriguez-Uranga, Juan; McMurray, Rob; Santagueda, Patricia

    2017-09-18

    The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assessed after 3, 6, and 12 months of ESL treatment, and at the final visit. Safety and tolerability were assessed throughout ESL treatment by evaluating adverse events (AEs) and ESL discontinuation due to AEs. Data from 2058 patients (52.1% male; mean age 44.0 years) were included. All 2058 patients were assessed for safety and 1975 (96.0%) patients were assessed for effectiveness. After 12 months, retention, responder (≥50% seizure frequency reduction), and seizure freedom rates were 73.4, 75.6, and 41.3%, respectively. AEs were reported for 34.0% of patients and led to discontinuation in 13.6% of patients. The most frequently reported AEs were dizziness (6.7% of patients), fatigue (5.4%), and somnolence (5.1%). No unexpected safety signals emerged over a median duration of follow-up of >5 years. Subgroup analyses revealed that ESL was significantly more effective in patients aged ≥65 versus <65 years, in patients who were not receiving treatment with other sodium channel blockers versus those who were receiving treatment with other sodium channel blockers, and in patients who were receiving <2 versus ≥2 concomitant antiepileptic drugs at baseline. Euro-Esli is the largest ESL clinical practice study conducted to date. This study provides strong and reassuring evidence of ESL's safety profile, and complements the data from clinical trials.

  18. The adult seizure and social outcomes of children with partial complex seizures.

    PubMed

    Camfield, Carol S; Camfield, Peter R

    2013-02-01

    Most intellectually normal children with focal epilepsy have partial complex or focal with secondary generalization seizures without a precise epilepsy syndrome. Their long-term outcome is largely unknown. Cases were identified from the population-based Nova Scotia Childhood Epilepsy cohort. Those eligible had seizure onset at 1 month to 16 years between 1977 and 1985, normal intelligence, ≥10 years of follow-up, only focal seizures and no benign epilepsy syndromes. There were 108 patients with partial complex with or without secondary generalization as the only seizure type(s) throughout (partial complex group) and 80 with secondary generalization as the only seizure type (secondary generalization group). Average age ± standard deviation at onset was 7.3 ± 4.5 years and follow-up was 27.9 ± 5.4 years. At follow-up, 57% of the partial complex group were in remission versus 81% of the secondary generalization group (P = 0.001). The partial complex group was more likely to be intractable or have undergone epilepsy surgery (36% versus 5%, P = 0.000). In the partial complex group, 28% had <5 years seizure free versus 5% in the secondary generalized group (P = 0.000). More patients in the partial complex group had undergone mental health assessments (59% versus 32%, P = 0.000), and 33% had a psychiatric diagnosis versus 15% in the secondary generalized group (P = 0.004). More patients with partial complex seizures had specific learning disorders (63% versus 45%, P = 0.03). Seven markers of poor social outcome were more common in patients with partial complex seizures (>2 markers: 34% versus 10%, P = 0.000). During 25-30 years of follow-up, >50% of intellectually normal patients with childhood-onset partial complex seizures had difficult-to-control seizures and learning and psychiatric/social problems. Most with secondary generalized seizures only had remission and better academic and psychiatric/social outcomes.

  19. A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures.

    PubMed

    Steinhoff, Bernhard J; Eckhardt, Klaus; Doty, Pamela; De Backer, Marc; Brunnert, Marcus; Schulze-Bonhage, Andreas

    2016-05-01

    This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were

  20. Duration of complex partial seizures: an intracranial EEG study.

    PubMed

    Afra, Pegah; Jouny, Christophe C; Bergey, Gregory K

    2008-04-01

    The dynamics of partial seizures originating from neocortical and mesial temporal regions are thought to differ, yet there are no quantitative comparative studies. The studies reported here investigate the duration of complex partial seizures in these populations using analyses of seizures recorded from intracranial arrays. Data were collected from patients undergoing presurgical evaluation with intracranial electrodes. Seizure duration was defined as the time of earliest sustained ictal activity until the termination either in all electrodes (global duration, GD), or at the onset area (focal duration, FD). Patients were divided into three groups: mesial temporal lobe epilepsy (MTLE), neocortical temporal lobe epilepsy (NCTLE), and neocortical extratemporal lobe epilepsy (NCXTLE). Complex partial seizure durations were significantly longer in the MTLE group compared to the NCXTLE group. Median GD for MTLE was 106 s, and for NCXTLE was 78 s. There were no significant differences between seizure durations when comparing MTLE group to NCTLE group, or comparing NCTLE group to NCXTLE group. In the MTLE group, patients with bilateral recording arrays had significantly longer median seizure durations (GD and FD) than those sampled with unilateral arrays. In this select group of patients there is a significant difference between the duration of complex partial seizures of mesial temporal and neocortical extratemporal origin with mesial temporal complex partial seizures being longer. This may result from a number of possibilities including the bilateral propagation of some mesial temporal seizures and differences in ictal generators of the underlying networks.

  1. Targeted treatment of migrating partial seizures of infancy with quinidine.

    PubMed

    Bearden, David; Strong, Alanna; Ehnot, Jessica; DiGiovine, Marissa; Dlugos, Dennis; Goldberg, Ethan M

    2014-09-01

    Migrating partial seizures of infancy is an early onset epileptic encephalopathy syndrome that is typically resistant to treatment. The most common cause is a gain of function mutation in the potassium channel KCNT1. The antiarrhythmic drug quinidine is a partial antagonist of KCNT1 and hence may be a candidate drug for treatment of this condition. We report the case of a child with migrating partial seizures of infancy secondary to an activating mutation in KCNT1 treated with quinidine. Treatment with quinidine was correlated with a marked reduction in seizure frequency and improved psychomotor development.

  2. Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: the current evidence base

    PubMed Central

    Brandt, Christian; May, Theodor W.; Bien, Christian G.

    2016-01-01

    Brivaracetam (BRV) is a novel antiepileptic drug recently licensed for the treatment of partial epilepsy in adults and adolescents over 16 years old. Like levetiracetam (LEV), it is a ligand of the synaptic vesicle protein SV2A. BRV has been shown in animal models and in studies using human brain slices to have a higher SV2A affinity and faster penetration into the brain. Its efficacy and safety have been shown in several randomized, controlled studies. The recommended initial dose is 50–100 mg, divided into two daily doses. Up-titration to a 200 mg daily dose is possible. Dizziness and somnolence are frequent side effects. There are some hints that BRV may be less frequently associated with behavioural adverse events than LEV. Long-term efficacy and safety and BRV use in special patient groups have to be assessed in the future. PMID:27800023

  3. A long-term open-label extension study assessing cognition and behavior, tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4 to 16 years with partial-onset seizures.

    PubMed

    Schiemann-Delgado, Jimmy; Yang, Haichen; Loge, Christine de la; Stalvey, Tracy J; Jones, John; Legoff, Daniel; Mintz, Mark

    2012-01-01

    The objective of this study was to assess cognition and behavior in children (4-16 years; n = 103) with partial-onset seizures using the Leiter-R International Performance Scale and Achenbach Child Behavior Checklist. The study was a multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD] change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome scores improved from baseline at weeks 24 and 48 (total problems mean [SD] change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well tolerated (most frequently reported central nervous system-related treatment-emergent adverse events: headache [24.3%], aggression [7.8%], irritability [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse events. Levetiracetam provided good and sustained seizure control (median percentage reduction from baseline in partial-onset seizure frequency/wk during maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all seizure types for ≥40 weeks. In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.

  4. Management of Adult Onset Seizures.

    PubMed

    Crepeau, Amy Z; Sirven, Joseph I

    2017-02-01

    Epilepsy is a common yet heterogeneous disease. As a result, management often requires complex decision making. The ultimate goal of seizure management is for the patient to have no seizures and no considerable adverse effects from the treatment. Antiepileptic drugs are the mainstay of therapy, with more than 20 medications currently approved in the United States. Antiepileptic drug selection requires an understanding of the patient's epilepsy, along with consideration of comorbidities and potential for adverse events. After a patient has failed at least 2 appropriate antiepileptic drugs, they are determined to be medically refractory. At this time, additional therapy, including dietary, device, or surgical treatments, need to be considered, typically at a certified epilepsy center. All these treatments require consideration of the potential for seizure freedom, balanced against potential adverse effects, and can have a positive effect on seizure control and quality of life. This review article discussed the treatment options available for adults with epilepsy, including medical, surgical, dietary, and device therapies. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  5. Triggers and techniques in termination of partial seizures.

    PubMed

    Dionisio, Jenna; Tatum, William O

    2010-02-01

    Growing interest in seizure prediction exists as a means to deliver newer antiepileptic therapies, though patient self-termination of seizures has received little attention. Two hundred twenty-three patients able to recognize seizure onset were surveyed in an outpatient epilepsy clinic. A seven-question survey administered prospectively assessed self-reported seizure prediction and clinical techniques used for self-termination. Survey responses targeted percentage predictability of seizures, timing of clinical prediction, likelihood/timing of termination, frequency and effectiveness of methods used, and perspectives of patient and physician belief in self-termination. Two hundred twenty-three patients (89 males) with a mean age of 42.7 years, average duration of epilepsy of 20.8 years and monthly mean seizure frequency of 4.1 comprised the study group. Thirty-eight percent completed >75% of the survey. Prior treatment included a mean of 6.0 AEDs (40/192 had surgery); 65% had ongoing seizures. Sixty percent of 223 patients reported a history of an aura, and 39% consistently noted auras for >75% of their current seizures. Of the patients with auras, seizure triggers were reported in 74%, with worry and stress (N=69), sleep deprivation (N=60), and missed medication (N=56) most frequently cited. Seventeen percent were positive/somewhat sure they could predict onset, with approximately 20% noting rapid onset in <15 seconds. Twenty-two of 82 noted that they had some ability to self-terminate their seizures, and 9% were positive that they could do so. Methods to self-terminate were effective (>75% certainty) in 35% (26/75). The primary methods were lying down/resting and taking extra medication. The majority of patients with partial seizures recognize triggers of seizure onset. In addition, more than one-third believe they can effectively self-terminate their partial-onset seizures. Lying down, resting, and taking extra medication were the most common techniques

  6. [Efficacy and safety of levetiracetam as adjunctive therapy in Japanese children with uncontrolled partial-onset seizures: multicenter and open-label study (N01223), short term evaluation].

    PubMed

    Nakamura, Hidefumi; Osawa, Makiko; Yokoyama, Terumichi; Yoshida, Katsumi; Suzuki, Atsushi

    2013-09-01

    A multicenter, open-label, single-armed study (N01223) was conducted to evaluate efficacy and safety of levetiracetam (LEV) as an add-on therapy in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). A total of 73 children aged 4-15 years (mean±SD=10.1±3.4 years) were enrolled in the study, which consisted of an 8-week baseline period and a 14-week treatment period, including a 4-week titration period. A historical placebo control from a pivotal overseas pediatric study in POS add-on therapy was used. A 16.3% median percent reduction from the baseline in POS was observed in this placebo control. Therefore, in the present study, this value (16.3%) was chosen as the predefined threshold for the lower limit of the 95% confident interval (95% CI) of the median percent reduction from the baseline for LEV. In the present study, the percentage reduction (95% CI) in POS during the treatment period was 43.21% (26.19-52.14%), indicating a beneficial impact of LEV. The incidences of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 82.2% (60/73 cases) and 56.2% (41/73 cases), respectively. The most common TEAEs were somnolence, nasopharyngitis, upper respiratory tract infection, and pyrexia. Frequent ADRs (more than 3%) were somnolence and feeling jittery. No serious TEAE or death was reported during the study. Our results suggested that adjunctive therapy with LEV is clinically efficacious and well tolerated in Japanese children with uncontrolled POS.

  7. Treatment of partial seizures and seizure-like activity with felbamate in six dogs.

    PubMed

    Ruehlmann, D; Podell, M; March, P

    2001-08-01

    Six dogs with partial seizures or partial seizure-like activity were treated with the antiepileptic drug felbamate between 1993 and 1998. All dogs had a history and results of diagnostic testing suggestive of either primary (idiopathic) or occult secondary epilepsy. Dogs ranged between four months and eight years of age at the onset of seizure activity. The median time period between onset of the first seizure and the start of felbamate therapy was 3.8 months (range 0.75 to 36 months). Median duration of therapy was nine months (range two to 22 months). All dogs experienced a reduction in seizure frequency after felbamate administration. Median total number of seizures post-treatment was two (range 0 to 9). Two dogs had an immediate and prolonged cessation of seizure activity. Steady-state trough serum felbamate concentrations measured at two weeks, and one, 12 and 22 months after the commencement of therapy in four dogs ranged between 13 and 55 mg/litre (median 35 mg/litre). Reversible haematological adverse effects were detected in two dogs, with one dog developing concurrent keratoconjunctivitis sicca. These results suggest that felbamate can be an effective antiepileptic drug without life-threatening complications when used as monotherapy for partial seizures in the dog.

  8. Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures.

    PubMed

    Theodore, W H; Bhatia, S; Hatta, J; Fazilat, S; DeCarli, C; Bookheimer, S Y; Gaillard, W D

    1999-01-01

    Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. To determine whether epilepsy duration is related to HF atrophy. We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.

  9. Pyramidal cells accumulate chloride at seizure onset

    PubMed Central

    Lillis, Kyle P; Kramer, Mark A; Mertz, Jerome; Staley, Kevin J

    2012-01-01

    Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABAA receptors or by hyperpolarizing the GABAA reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABAA receptor-mediated chloride influx shifts EGABA to produce a positive feedback loop that contributes to the initiation of seizure activity. PMID:22677032

  10. Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy

    NASA Technical Reports Server (NTRS)

    Blum, A. S.; Ives, J. R.; Goldberger, A. L.; Al-Aweel, I. C.; Krishnamurthy, K. B.; Drislane, F. W.; Schomer, D. L.

    2000-01-01

    PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

  11. The temporal relation between seizure onset and arousal-awakening in temporal lobe seizures.

    PubMed

    Gumusyayla, Sadiye; Erdal, Abidin; Tezer, F Irsel; Saygi, Serap

    2016-07-01

    Our main aim was to determine the time interval between the seizure onsets and arousal-awakening related to these seizures in patients with temporal lobe epilepsy (TLE) and to discuss the role of lateralization on arousal-awakening mechanisms. Thirty-three TLE patients who underwent video-EEG monitoring with simultaneous polysomnography (PSG) and had recorded nocturnal seizures were retrospectively examined. These TLE patients had 64 seizures during sleep. The onsets of seizures and arousal-awakening related to these seizures were marked according to clinical and electrophysiological features. The time interval between the seizure onset and arousal-awakening related to the seizure was compared in patients with right- or left-sided temporal lobe seizures. In our TLE patients nocturnal seizures mostly followed arousal-awakening (64%). The time interval between the seizure onset and arousal-awakening related to the seizure was significantly shorter in patients with left-sided temporal lobe seizures (p=0.01). Video-EEG monitoring and PSG with scalp electrodes in our TLE patients showed that nocturnal seizures mostly followed arousal-awakening, and it was more pronounced in those with left-sided seizures. Arousal-awakening might be a signal for subsequent seizures in patients with TLE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Ictal onset zone and seizure propagation delineated on ictal F-18 fluorodeoxyglucose positron emission tomography/computed tomography.

    PubMed

    Tripathi, Madhavi; Tripathi, Manjari; Garg, Ajay; Damle, Nishikant; Bal, Chandrasekhar

    2016-01-01

    The present case highlights the utility of ictal F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in delineating the seizure onset zone in a child with complex partial seizures. Although F-18 FDG PET has been successfully used to delineate interictal hypometabolism, planned ictal FDG PET, in cases with prolonged seizure activity, can provide better spatial resolution than single-photon emission CT by delineating the seizure onset zone and propagation pathway.

  13. Ictal flatulence: seizure onset in the nondominant hemisphere.

    PubMed

    Vittal, Nandakumar Bangalore; Singh, Pradumna; Azar, Nabil J

    2009-12-01

    We describe the case of a 45-year-old woman with frequent simple partial seizures consisting mainly of autonomic manifestations including flatulence. The ictal onset and interictal EEG epileptiform abnormalities were localized to the right frontotemporal region. This localization was supported by structural brain imaging showing recurrence of a right frontotemporal oligodendroglioma with involvement of the insula. We therefore suggest that ictal flatulence is one of several autonomic and gastrointestinal symptoms and signs that may be used clinically in lateralizing to the nondominant hemisphere.

  14. Risk factors of recurrent seizure, co-morbidities, and mortality in new onset seizure in elderly.

    PubMed

    Phabphal, Kanitpong; Geater, Alan; Limapichat, Kitti; Sathirapanya, Pornchai; Setthawatcharawanich, Suwanna

    2013-09-01

    To determine the risk factors of seizure recurrence and the most common comorbidities in elderly patients with epilepsy. We did a retrospective study of 278 patients older than 65 years with first seizure. We evaluated electrolytes, blood glucose, urea and creatinine levels, and performed electrocardiography (ECG), and routine electroencephalogram (EEG) on all patients. We evaluated seizure recurrence and comorbidities at 2 years. Univariate analysis found that significant (P<0.05) factors affecting seizure recurrence were etiology of seizure, EEG, and status epilepticus at first presentation. In multivariate regression analysis, etiology of seizure and EEG were significant statistical factors in seizure recurrence at 2 years follow up. Age, sex, duration of time between first seizure and diagnosis of seizure, seizure type, misdiagnosis of non-epileptic seizure, and use of antiepileptic drugs were not significant factors for predicting seizure recurrence. Depression and anxiety were the most common comorbidities in our study, followed by sleep-related disorders and stroke. There were no statistically significantly differences in comorbidities between patients who remained seizure free and patients who had recurrent seizure. Most of the new onset seizures in our elderly patients were focal onset. Acute symptomatic etiology, remote symptomatic etiology, progressive symptomatic etiology and abnormal EEG features were powerful predictors of seizure recurrence, and mood disorder, sleep disorder and stroke were the common comorbidities. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. Network dynamics of the brain and influence of the epileptic seizure onset zone.

    PubMed

    Burns, Samuel P; Santaniello, Sabato; Yaffe, Robert B; Jouny, Christophe C; Crone, Nathan E; Bergey, Gregory K; Anderson, William S; Sarma, Sridevi V

    2014-12-09

    The human brain is a dynamic networked system. Patients with partial epileptic seizures have focal regions that periodically diverge from normal brain network dynamics during seizures. We studied the evolution of brain connectivity before, during, and after seizures with graph-theoretic techniques on continuous electrocorticographic (ECoG) recordings (5.4 ± 1.7 d per patient, mean ± SD) from 12 patients with temporal, occipital, or frontal lobe partial onset seizures. Each electrode was considered a node in a graph, and edges between pairs of nodes were weighted by their coherence within a frequency band. The leading eigenvector of the connectivity matrix, which captures network structure, was tracked over time and clustered to uncover a finite set of brain network states. Across patients, we found that (i) the network connectivity is structured and defines a finite set of brain states, (ii) seizures are characterized by a consistent sequence of states, (iii) a subset of nodes is isolated from the network at seizure onset and becomes more connected with the network toward seizure termination, and (iv) the isolated nodes may identify the seizure onset zone with high specificity and sensitivity. To localize a seizure, clinicians visually inspect seizures recorded from multiple intracranial electrode contacts, a time-consuming process that may not always result in definitive localization. We show that network metrics computed from all ECoG channels capture the dynamics of the seizure onset zone as it diverges from normal overall network structure. This suggests that a state space model can be used to help localize the seizure onset zone in ECoG recordings.

  16. Network dynamics of the brain and influence of the epileptic seizure onset zone

    PubMed Central

    Burns, Samuel P.; Santaniello, Sabato; Yaffe, Robert B.; Jouny, Christophe C.; Crone, Nathan E.; Bergey, Gregory K.; Anderson, William S.; Sarma, Sridevi V.

    2014-01-01

    The human brain is a dynamic networked system. Patients with partial epileptic seizures have focal regions that periodically diverge from normal brain network dynamics during seizures. We studied the evolution of brain connectivity before, during, and after seizures with graph-theoretic techniques on continuous electrocorticographic (ECoG) recordings (5.4 ± 1.7 d per patient, mean ± SD) from 12 patients with temporal, occipital, or frontal lobe partial onset seizures. Each electrode was considered a node in a graph, and edges between pairs of nodes were weighted by their coherence within a frequency band. The leading eigenvector of the connectivity matrix, which captures network structure, was tracked over time and clustered to uncover a finite set of brain network states. Across patients, we found that (i) the network connectivity is structured and defines a finite set of brain states, (ii) seizures are characterized by a consistent sequence of states, (iii) a subset of nodes is isolated from the network at seizure onset and becomes more connected with the network toward seizure termination, and (iv) the isolated nodes may identify the seizure onset zone with high specificity and sensitivity. To localize a seizure, clinicians visually inspect seizures recorded from multiple intracranial electrode contacts, a time-consuming process that may not always result in definitive localization. We show that network metrics computed from all ECoG channels capture the dynamics of the seizure onset zone as it diverges from normal overall network structure. This suggests that a state space model can be used to help localize the seizure onset zone in ECoG recordings. PMID:25404339

  17. A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

    PubMed Central

    Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

    2015-01-01

    Objective The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70 – 110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. Approach We used 7 complex partial seizures recorded from 4 patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a directed transfer function measure. Main results We showed that a directed transfer function can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical seizure onset zone and the time from seizure onset, ictal propagation changed in directional characteristics over a 2 to 10 seconds time scale, with gross directionality limited to spatial dimensions of approximately 9mm2. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined seizure onset zone than inside. Significance This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices. PMID:26061006

  18. Local cerebral metabolism during partial seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-04-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

  19. Mechanisms underlying different onset patterns of focal seizures

    PubMed Central

    Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

    2017-01-01

    Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

  20. A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

    NASA Astrophysics Data System (ADS)

    Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

    2015-08-01

    Objective. The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70-110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. Approach. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. Main results. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately 9 m{{m}2}. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. Significance. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

  1. A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone.

    PubMed

    Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J; Anderson, William S

    2015-08-01

    The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the [Formula: see text] Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately [Formula: see text]. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

  2. Vagus nerve stimulation for partial seizures.

    PubMed

    Panebianco, Mariangela; Rigby, Alexandra; Weston, Jennifer; Marson, Anthony G

    2015-04-03

    Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. VNS consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. The majority of people given a diagnosis of epilepsy have a good prognosis, and their seizures will be controlled by treatment with a single antiepileptic drug (AED), but up to 20%-30% of patients will develop drug-resistant epilepsy, often requiring treatment with combinations of AEDs. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of vagus nerve stimulation when used as an adjunctive treatment for people with drug-resistant partial epilepsy. This is an updated version of a Cochrane review published in Issue 7, 2010. To determine:(1) The effects on seizures of VNS compared to controls e.g. high-level stimulation compared to low-level stimulation (presumed sub-therapeutic dose); and(2) The adverse effect profile of VNS compared to controls e.g. high-level stimulation compared to low-level stimulation. We searched the Cochrane Epilepsy Group's Specialised Register (23 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 23 February 2015), MEDLINE (1946 to 23 February 2015), SCOPUS (1823 to 23 February 2015), ClinicalTrials.gov (23 February 2015) and ICTRP (23 February 2015). No language restrictions were imposed. The following study designs were eligible for inclusion: randomised, double-blind, parallel or crossover studies, controlled trials of VNS as add-on treatment comparing high and low stimulation paradigms (including three different stimulation paradigms - duty cycle: rapid, mid and slow) and VNS stimulation versus no stimulation or a different intervention. Eligible participants were adults or children with drug-resistant partial seizures not eligible for surgery or who failed

  3. Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report.

    PubMed

    Saade, Dimah; Joshi, Charuta

    2015-05-01

    Malignant migrating partial seizures in infancy is a devastating pharmacoresistent epileptic encephalopathy of unknown etiology characterized by onset in the first 6 months of life, continuous migrating focal seizures with corresponding multifocal electroencephalographic discharges, developmental deterioration, and early mortality. Recent widespread interest in the nonpsychoactive component of the cannabis plant, cannabidiol, as a potential treatment for refractory devastating epilepsies has led to individual trials initiated by families or physicians in states that have legalized medical marijuana with anecdotal success. We describe a now 10-month-old boy with malignant migrating partial seizures in infancy who made developmental gains and demonstrated sustained seizure reduction with the addition of cannabidiol to his antiepileptic regimen. This report supports a role for cannabidiol in the treatment of malignant migrating partial seizures in infancy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Levetiracetam extended release and levetiracetam immediate release as adjunctive treatment for partial-onset seizures: an indirect comparison of treatment-emergent adverse events using meta-analytic techniques.

    PubMed

    Richy, Florent F; Banerjee, Soutrik; Brabant, Yves; Helmers, Sandra

    2009-10-01

    The safety profiles of once-daily adjunctive levetiracetam (LEV) extended release (XR) (1000mg/day) and adjunctive LEV immediate release (IR) (500mg twice daily) were compared using data from three randomized, placebo (PBO)-controlled phase III clinical trials in patients with partial-onset seizures. MedDRA 9.0 treatment-emergent adverse events (TEAEs) were indirectly compared using meta-analytic techniques, including calculation of risk difference (RD) and mixed-effects analysis. Statistical significance was set at 10% alpha risk, the normative value for these analyses. Data from 555 patients older than 16 (204 LEV IR, 70 LEV XR, 281 PBO) were analyzed. Following adjustment for incidence of placebo TEAEs, LEV XR showed statistically significantly lower rates of TEAEs than LEV IR across nervous system disorders (RD=-18%, P=0.03), psychiatric disorders (RD=-11%, P=0.08), and metabolism and nutrition disorders (RD=-3%, P=0.08). Among nervous system disorders, the RD for headache favored LEV XR (RD=-11%, P=0.08). These results suggest that adjunctive LEV XR may be associated with a lower incidence of nervous system, psychiatric, and nutritional and metabolic TEAEs as compared with LEV IR. However, this difference was observed at a broad scale and not at a specific TEAE level except for headache.

  5. Lateralizing value of the auditory aura in partial seizures.

    PubMed

    Florindo, Irene; Bisulli, Francesca; Pittau, Francesca; Naldi, Ilaria; Striano, Pasquale; Striano, Salvatore; Michelucci, Roberto; Testoni, Stefania; Baruzzi, Agostino; Tinuper, Paolo

    2006-01-01

    To describe the semiological features of auditory aura and to assess their possible lateralizing value in partial epilepsy. Out of a series of 8,000 patients with epilepsy, we investigated 121 cases with partial seizures in whom auditory features were the first ictal symptom. According to the dominant type of aura, patients were divided into four subgroups-1A (67 cases), 1B (22 cases), 2A (14 cases), and 2B (18 cases)-corresponding to the presence of simple or complex hallucinations and positive or negative illusions, respectively. The side of the epileptic zone (EZ) was defined based on available data: surgical/presurgical study or presence of a neuroradiological lesion, corresponding interictal epileptiform EEG and ictal semiology (level 1); a left EZ was also hypothesized in right-handed patients with ictal aphasia plus a left neuroradiological lesion or a left interictal EEG focus (level 2). Forty-five patients (37%) described the aura as unilateral. The side of epileptogenic zone (EZ) was definable in 36 patients (level 1: 24; level 2: 12). Overall, a unilateral auditory aura was contralateral to the EZ in half of the cases (8/16), but always contralateral in patients studied for presurgical evaluation (4/4). Simple hallucinations lateralized seizure onset on the right side in nine cases, on the left in 12. Among 1B patients (either musical and verbal contents), the EZ was on the left side in all cases (5/5). Positive illusions were associated with right foci in two cases, and left foci in two. Negative illusions always lateralized seizure onset to the dominant hemisphere (6/6). Auditory aura is a rare symptom in partial epilepsy. The perception of the auditory sensation referred to one ear is not a unique lateralizing sign for the contralateral temporal neocortex. Complex hallucinations with verbal content and negative illusion may lateralize seizure onset in the dominant hemisphere. The role of laterality for musical hallucinations remains unclear as it

  6. Generalized versus partial reflex seizures: a review.

    PubMed

    Italiano, Domenico; Ferlazzo, Edoardo; Gasparini, Sara; Spina, Edoardo; Mondello, Stefania; Labate, Angelo; Gambardella, Antonio; Aguglia, Umberto

    2014-08-01

    In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm. We discuss in particular evidence from animal, clinical, neurophysiological and neuroimaging studies supporting the concept that "generalized" reflex seizures, usually occurring in the setting of IGE, should be considered as focal seizures with quick secondary generalization. We also review recent advances in genetic and therapeutic approach of reflex seizures. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  8. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

    PubMed

    Bergey, Gregory K; Morrell, Martha J; Mizrahi, Eli M; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E; Shields, Donald C; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B; Hirsch, Lawrence J; Courtney, Tracy; Sun, Felice T; Seale, Cairn G

    2015-02-24

    The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. © 2015 American Academy of Neurology.

  9. New onset seizures in HIV--seizure semiology, CD4 counts, and viral loads.

    PubMed

    Modi, Mala; Mochan, Andre; Modi, Girish

    2009-05-01

    Thirty-seven HIV-positive patients with new-onset seizures (NOS) were prospectively identified during a 1-year study period. The patients were categorized according to the different mechanisms causing NOS in HIV, namely focal brain lesion (FBL) in 21 patients (57%), meningitis in 6 patients (16%), metabolic derangement (no patient), and no identified cause (NIC) other than HIV itself (10 patients, 27%). Seizure semiology, CD4 counts, and blood and cerebral spinal fluid (CSF) viral loads were studied to identify any special characteristics of the different categories. With respect to seizure semiology, all NIC patients had generalized seizures. Two-thirds of the meningitis patients had generalized seizures with one-third having focal seizures. Half of the patients with FBL had generalized seizures and one-third had focal seizures. Status epilepticus was strongly associated with FBL. No significant difference could be detected between the subgroups with respect to CD4 counts and serum and CSF viral loads. The median CD4 count in all patients was 108 cells/ml, indicating advanced immunosuppression. In the FBL group this was 104 cells/ml. In the meningitis group the median CD4 count was 298 cells/ml, and in the NIC group this was 213 cells/ml. Similarly, no differences were noted in the NOS categories with respect to serum and CSF viral loads. Seizures in HIV are a nonspecific manifestation of the seizure mechanism.

  10. 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 ...

  11. Content analysis of subjective experiences in partial epileptic seizures.

    PubMed

    Johanson, Mirja; Valli, Katja; Revonsuo, Antti; Wedlund, Jan-Eric

    2008-01-01

    A new content analysis method for systematically describing the phenomenology of subjective experiences in connection with partial epileptic seizures is described. Forty patients provided 262 descriptions of subjective experience relative to their partial epileptic seizures. The results revealed that subjective experiences during seizures consist mostly of sensory and bodily sensations, hallucinatory experiences, and thinking. The majority of subjective experiences during seizures are bizarre and distorted; nevertheless, the patients are able to engage in adequate behavior. To the best of our knowledge, this is the first study for which detailed subjective seizure descriptions were collected immediately after each seizure and the first study in which the content of verbal reports of subjective experiences during seizures, including both the ictal and postictal experiences, has been analyzed in detail.

  12. Detection of recurrent activation patterns across focal seizures: Application to seizure onset zone identification.

    PubMed

    Vila-Vidal, Manel; Principe, Alessandro; Ley, Miguel; Deco, Gustavo; Tauste Campo, Adrià; Rocamora, Rodrigo

    2017-06-01

    We introduce a method that quantifies the consistent involvement of intracranially monitored regions in recurrent focal seizures. We evaluated the consistency of two ictal spectral activation patterns (mean power change and power change onset time) in intracranial recordings across focal seizures from seven patients with clinically marked seizure onset zone (SOZ). We examined SOZ discrimination using both patterns in different frequency bands and periods of interest. Activation patterns were proved to be consistent across more than 80% of recurrent ictal epochs. In all patients, whole-seizure mean activations were significantly higher for SOZ than non-SOZ regions (P<0.05) while activation onset times were significantly lower for SOZ than for non-SOZ regions (P<0.001) in six patients. Alpha-beta bands (8-20Hz) achieved the highest patient-average effect size on the whole-seizure period while gamma band (20-70Hz) achieved the highest discrimination values between SOZ and non-SOZ sites near seizure onset (0-5s). Consistent spectral activation patterns in focal epilepsies discriminate the SOZ with high effect sizes upon appropriate selection of frequency bands and activation periods. The present method may be used to improve epileptogenic identification as well as pinpoint additional regions that are functionally altered during ictal events. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Prolactin and gonadotrophin changes following generalised and partial seizures.

    PubMed Central

    Dana-Haeri, J; Trimble, M r; Oxley, J

    1983-01-01

    Postictal values of prolactin, LH and FSH have been recorded in patients with both generalised tonic-clonic and partial seizures. Elevations of prolactin and LH were seen immediately and at 20 minutes in males and females with generalised attacks. At sixty minutes values for prolactin had fallen to baseline levels, but LH remained elevated. FSH values were increased in females only, at twenty and sixty minutes. Following partial seizures prolactin was elevated, especially with complex partial seizures, at twenty minutes. These results are discussed in the light of known electrophysiological mechanisms relating to partial seizures, and clinical guidelines for the use of neurohormonal tests in the evaluation of seizures are suggested. PMID:6405014

  15. Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate.

    PubMed

    Velez, Fulton F; Bond, T Christopher; Anastassopoulos, Kathryn P; Wang, Xuezhe; Sousa, Rui; Blum, David; Cramer, Joyce A

    2017-03-01

    Subjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N=842) using the validated Quality of Life in Epilepsy Inventory-31 (QOLIE-31). QOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (≥50% and ≥75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs). Mean changes were greater among responders for TS (5.2 versus 1.4 for ≥50% SFR; 7.5 versus 1.9 for ≥75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for ≥50% SFR; 56.9% versus 35.8% for ≥75% SFR) and all subscales. Responders had significantly higher final scores for TS (LSM difference=4.0 for ≥50% SFR; LSM difference=5.7 for ≥75% SFR) and all subscales except emotional well-being at ≥50% SFR. LSM differences exceeded MCIDs at ≥75% SFR for TS and five of seven subscales, and two subscales at ≥50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall. In clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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

  18. Consciousness and epilepsy: why are complex-partial seizures complex?

    PubMed Central

    Englot, Dario J.; Blumenfeld, Hal

    2010-01-01

    Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral

  19. Juvenile and adult-onset psychogenic non-epileptic seizures.

    PubMed

    Asadi-Pooya, Ali A; Emami, Mehrdad

    2013-09-01

    Psychogenic non-epileptic seizures (PNES) tend to begin in adolescence and young adulthood, although the seizures can occur in a wide range of ages. In the current study, we investigated the age of onset in patients with PNES and tried to determine the correlation between the age of onset and the demographic and clinical characteristics and factors potentially predisposing to PNES. In this cross-sectional study, all patients with a clinical diagnosis of PNES were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2012. We dichotomized the patients into two groups; those with age of onset below 18 years (juvenile), and those with age of onset at 18-55 years (adult-onset). We studied the demographic and clinical characteristics and factors potentially predisposing to PNES between these two groups. Statistical analyses were performed using Chi square and Fisher's Exact tests and Mann-Whitney U test. Fifty-seven patients with juvenile and 129 people with adult-onset PNES were studied. Demographic characteristics of these two groups were not different significantly. Seizure characteristics and semiology in these two groups were not significantly different either. However, factors potentially predisposing to PNES were significantly different between these two groups. History of being abused, academic failure, epilepsy or family history of epilepsy were more frequently observed in juvenile PNES, while medical comorbidities were more frequent among patients with adult-onset PNES. Age of onset of PNES is not correlated with the clinical manifestations; however, factors potentially predisposing to PNES are significantly different in patients with juvenile compared to those with adult-onset PNES. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. An algorithm for seizure onset detection using intracranial EEG.

    PubMed

    Kharbouch, Alaa; Shoeb, Ali; Guttag, John; Cash, Sydney S

    2011-12-01

    This article addresses the problem of real-time seizure detection from intracranial EEG (IEEG). One difficulty in creating an approach that can be used for many patients is the heterogeneity of seizure IEEG patterns across different patients and even within a patient. In addition, simultaneously maximizing sensitivity and minimizing latency and false detection rates has been challenging as these are competing objectives. Automated machine learning systems provide a mechanism for dealing with these hurdles. Here we present and evaluate an algorithm for real-time seizure onset detection from IEEG using a machine-learning approach that permits a patient-specific solution. We extract temporal and spectral features across all intracranial EEG channels. A pattern recognition component is trained using these feature vectors and tested against unseen continuous data from the same patient. When tested on more than 875 hours of IEEG data from 10 patients, the algorithm detected 97% of 67 test seizures of several types with a median detection delay of 5 seconds and a median false alarm rate of 0.6 false alarms per 24-hour period. The sensitivity was 100% for 8 of 10 patients. These results indicate that a sensitive, specific, and relatively short-latency detection system based on machine learning can be employed for seizure detection from EEG using a full set of intracranial electrodes to individual patients. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.

  1. Epileptic fast intracerebral EEG activity: evidence for spatial decorrelation at seizure onset

    PubMed Central

    Wendling, Fabrice; Bartolomei, Fabrice; Bellanger, Jean-Jacques; Bourien, Jérôme; Chauvel, Patrick

    2003-01-01

    Low-voltage rapid discharges (or fast EEG ictal activity) constitute a characteristic electrophysiological pattern in focal seizures of human epilepsy. They are characterized by a decrease of signal voltage with a marked increase of signal frequency (typically beyond 25 Hz). They have long been observed in stereoelectroencephalographic (SEEG) signals recorded with intra-cerebral electrodes, generally occurring at seizure onset and simultaneously involving distinct brain regions. Spectral properties of rapid ictal discharges as well as spatial correlations measured between SEEG signals generated from distant sites before, during and after these discharges were studied. Cross-correlation estimates within typical EEG sub-bands and statistical tests performed in ten patients suffering from partial epilepsy (frontal, temporal or fronto-temporal) reveal that SEEG signals are significantly de-correlated during the discharge period compared to periods that precede and follow this discharge. These results can be interpreted as a functional decoupling of distant brain sites at seizure onset followed by an abnormally high re-coupling when the seizure develops. They lead to the concept of “disruption” that is complementary of that of “activation” (revealed by significantly high correlations between signals recorded during seizures), both giving insights into our understanding of pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology. PMID:12764064

  2. Seizure Clustering during Drug Treatment Affects Seizure Outcome and Mortality of Childhood-Onset Epilepsy

    ERIC Educational Resources Information Center

    Sillanpaa, Matti; Schmidt, Dieter

    2008-01-01

    To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases)…

  3. Seizure Clustering during Drug Treatment Affects Seizure Outcome and Mortality of Childhood-Onset Epilepsy

    ERIC Educational Resources Information Center

    Sillanpaa, Matti; Schmidt, Dieter

    2008-01-01

    To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases)…

  4. Pediatric-onset gelastic seizures: clinical data and outcome.

    PubMed

    Shahar, Eli; Kramer, Uri; Mahajnah, Muhammad; Lerman-Sagie, Tallie; Goez, Rachel; Gross, Varda; Kutai, Miriam; Genizi, Jacob

    2007-07-01

    Gelastic seizures are an extremely rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. The objective was to survey all Israeli children found to develop recurrent gelastic seizures and report presenting symptoms, electroencephalographic and radiologic data, and response to either antiepileptic drugs or surgery. Ten children who developed gelastic seizures at the age of 1 week to 6.5 years (mean, 25 months) at a frequency from 3 bouts per week to >10 prolonged bouts per day were followed for a period of 1.3-12 years (mean, 6 years). Seven cases were defined as symptomatic: cortical magnetic resonance imaging revealed a hypothalamic hamartoma in four patients and cortical abnormalities in three others. Seizure control was achieved in four patients, including a neonate with status gelasticus and hypothalamic hamartoma, and partial control in one more. Five children remained resistant to polytherapy, including three with hypothalamic hamartoma even after two of them underwent hemartoma excision. Thus, children with gelastic seizures may respond relatively well to drug therapy. Four of the 10 patients became seizure free with drug therapy; in three intractable symptomatic cases, surgery was tried but failed in two of the three.

  5. Neologistic speech automatisms during complex partial seizures.

    PubMed

    Bell, W L; Horner, J; Logue, P; Radtke, R A

    1990-01-01

    There are no documented cases of seizures causing reiterative neologistic speech automatisms. We report an 18-year-old right-handed woman with stereotypic ictal speech automatisms characterized by phonemic jargon and reiterative neologisms. Video-EEG during the reiterative neologisms demonstrated rhythmic delta activity, which was most prominent in the left posterior temporal region. At surgery, there was an arteriovenous malformation impinging on the left supramarginal gyrus and the posterior portion of the superior temporal gyrus. Though intelligible speech automatisms can result from seizure foci in either hemisphere, neologistic speech automatisms may implicate a focus in the language-dominant hemisphere.

  6. Synchrony in Normal and Focal Epileptic Brain: The Seizure Onset Zone is Functionally Disconnected

    PubMed Central

    Warren, Christopher P.; Hu, Sanqing; Stead, Matt; Brinkmann, Benjamin H.; Bower, Mark R.

    2010-01-01

    Synchronization of local and distributed neuronal assemblies is thought to underlie fundamental brain processes such as perception, learning, and cognition. In neurological disease, neuronal synchrony can be altered and in epilepsy may play an important role in the generation of seizures. Linear cross-correlation and mean phase coherence of local field potentials (LFPs) are commonly used measures of neuronal synchrony and have been studied extensively in epileptic brain. Multiple studies have reported that epileptic brain is characterized by increased neuronal synchrony except possibly prior to seizure onset when synchrony may decrease. Previous studies using intracranial electroencephalography (EEG), however, have been limited to patients with epilepsy. Here we investigate neuronal synchrony in epileptic and control brain using intracranial EEG recordings from patients with medically resistant partial epilepsy and control subjects with intractable facial pain. For both epilepsy and control patients, average LFP synchrony decreases with increasing interelectrode distance. Results in epilepsy patients show lower LFP synchrony between seizure-generating brain and other brain regions. This relative isolation of seizure-generating brain underlies the paradoxical finding that control patients without epilepsy have greater average LFP synchrony than patients with epilepsy. In conclusion, we show that in patients with focal epilepsy, the region of epileptic brain generating seizures is functionally isolated from surrounding brain regions. We further speculate that this functional isolation may contribute to spontaneous seizure generation and may represent a clinically useful electrophysiological signature for mapping epileptic brain. PMID:20926610

  7. Features and futures: seizure detection in partial epilepsies.

    PubMed

    Han, Yu; Hsin, Yue-Loong; Harnod, Tomor; Liu, Wentai

    2011-10-01

    Many factors underlying basic epileptic conditions determine the characteristics of epileptic seizures and the therapeutic outcome. Diagnosis and treatment rely on the clinical manifestations as well as electroencephalographic (EEG) epileptic activities. This article briefly reviews the fundamentals of the EEG, interictal, and ictal electrical activities of both extracranial and intracranial EEG of partial epilepsies, based on the information obtained from epilepsy patients who have undergone epilepsy surgery. The authors also present the status of their current research, focusing on decomposed seizure sources and the rendered spatial-temporal transitions in focal seizure.

  8. Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.

    PubMed

    Linane, Avriel; Lagrange, Andre H; Fu, Cary; Abou-Khalil, Bassel

    2016-01-01

    We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification. The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology. Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency. Generalized onset seizures may occasionally have focal evolution with semiology

  9. Modeling early-onset post-ischemic seizures in aging mice.

    PubMed

    Wu, Chiping; Wang, Justin; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2015-09-01

    Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals.

  10. Complex partial seizures and aphasia as initial manifestations of non-ketotic hyperglycemia. Case report.

    PubMed

    Batista, M S; Silva, D F; Ferraz, H B; de Andrade, L A

    1998-06-01

    We describe a case of non-ketotic hyperglycemia (NKH), heralded by complex partial seizures and aphasia of epileptic origin, besides versive and partial motor seizures. This clinical picture was accompanied by left fronto-temporal spikes in the EEG. The seizures were controlled by carbamazepine only after the control of the diabetes. A month later, carbamazepine was discontinued. The patient remained without seizures, with normal language, using only glybenclamide. Complex partial seizures, opposed to simple partial seizures, are rarely described in association to NKH. Epileptic activity localized over language regions can manifest as aphasia.

  11. Gelastic epilepsy and dysprosodia in a case of late-onset right frontal seizures.

    PubMed

    Cercy, Steven P; Kuluva, Joshua E

    2009-10-01

    Gelastic epilepsy (GE) is an uncommon type of seizure disorder characterized by stereotyped, unprovoked, inappropriate ictal laughter. GE is most frequently associated with hypothalamic hamartoma, with onset almost invariably occurring during childhood. GE also occurs occasionally with temporal and frontal cortical seizure foci. We describe an unusual case of senescent-onset GE with a right frontal seizure focus. In addition to laughter, dysprosodia was a clinical feature. Clinical and electroencephalographic evidence of seizure activity ceased on levetiracetam, and the patient showed concurrent improvement in cognitive function. We review the evidence for the cerebral representation of laughter and prosody, and discuss issues bearing on the differential diagnosis and management of GE.

  12. Perampanel: a new agent for adjunctive treatment of partial seizures.

    PubMed

    Faulkner, Michele A

    2014-02-01

    The pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of perampanel are reviewed. Perampanel, a first-in-class antiepileptic agent, was recently approved for use as adjunctive therapy for the treatment of resistant partial seizures in patients 12 years of age and older. It acts as a selective, noncompetitive antagonist at postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors. Perampanel exhibits linear pharmacokinetics and has a half-life of approximately 105 hours. The drug is rapidly and nearly completely absorbed after oral administration, achieving its maximum serum concentration in approximately 1 hour. Its bioavailability is nearly complete. Several efficacy studies have consistently demonstrated the utility of perampanel as adjunctive therapy for the treatment of refractory partial seizures with or without secondary generalization. Drug interactions have been noted with agents that induce cytochrome P-450 hepatic enzymes, including other antiepileptics, and alterations in perampanel dosing may be necessary when these medications are used concurrently. Adverse effects associated with perampanel use are primarily related to the central nervous system, and slow dosage adjustment and bedtime administration are recommended to maximize patient tolerance. The drug's labeling includes a boxed warning about the possible induction of serious adverse psychiatric and behavioral reactions that necessitate close monitoring. Perampanel is not recommended for individuals with severe liver disease or severely compromised kidney function, including those undergoing hemodialysis. Perampanel is a novel antiepileptic agent specifically designed to exhibit selective noncompetitive antagonist activity at AMPA receptors. Perampanel has consistently demonstrated the ability to control treatment-refractory partial seizures in many patients.

  13. A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

    PubMed

    Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P

    2013-04-01

    Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA.

  14. Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

    PubMed Central

    Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

    2015-01-01

    Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent

  15. Diagnostic value of lumbar puncture in afebrile infants with suspected new-onset seizures.

    PubMed

    Lateef, Tarannum M; Tsuchida, Tammy N; Chang, Taeun; Johnson, Jami; Gaillard, William D; Nelson, Karin B

    2008-07-01

    No established guidelines address the need for lumbar puncture in fever-free infants younger than 6 months of age with a first seizure. We analyzed cerebrospinal fluid results in infants and found that lumbar puncture adds little diagnostic value to the evaluation of young, well-appearing infants presenting with possible new-onset seizures.

  16. Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

    SciTech Connect

    Gozukirmizi, E.; Meyer, J.S.; Okabe, T.; Amano, T.; Mortel, K.; Karacan, I.

    1982-01-01

    Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significance was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements.

  17. The causes of new-onset epilepsy and seizures in the elderly

    PubMed Central

    Liu, Shasha; Yu, Weihua; Lü, Yang

    2016-01-01

    With increasing age, the prevalence and incidence of epilepsy and seizures increases correspondingly. New-onset epilepsy in elderly people often has underlying etiology, including cerebrovascular diseases, primary neuron degenerative disorders, intracerebral tumors, and traumatic head injury. In addition, an acute symptomatic seizure cannot be called epilepsy, which manifests usually as a common symptom secondary to metabolic or toxicity factors in older people. In this review, we have mainly focused on the causes of new-onset epilepsy and seizures in elderly people. This knowledge will certainly help us to understand the reasons for high incidences of epilepsy and seizures in elderly people. We look forward to controlling epileptic seizures via the treatment of primary diseases in the future. PMID:27382285

  18. The causes of new-onset epilepsy and seizures in the elderly.

    PubMed

    Liu, Shasha; Yu, Weihua; Lü, Yang

    2016-01-01

    With increasing age, the prevalence and incidence of epilepsy and seizures increases correspondingly. New-onset epilepsy in elderly people often has underlying etiology, including cerebrovascular diseases, primary neuron degenerative disorders, intracerebral tumors, and traumatic head injury. In addition, an acute symptomatic seizure cannot be called epilepsy, which manifests usually as a common symptom secondary to metabolic or toxicity factors in older people. In this review, we have mainly focused on the causes of new-onset epilepsy and seizures in elderly people. This knowledge will certainly help us to understand the reasons for high incidences of epilepsy and seizures in elderly people. We look forward to controlling epileptic seizures via the treatment of primary diseases in the future.

  19. Correlation of electrocorticographic to clinical seizure onset and interhemispheric propagation times in temporal lobe epilepsy.

    PubMed

    Weinand, Martin E; Hussain, Namath; Labiner, David M; Ahern, Geoffrey L

    2006-12-01

    This study was performed to test the hypothesis that, in human temporal lobe epilepsy, electrocorticographic time factors involved in the ictal EEG to clinical ictal transition (electrocorticographic to clinical seizure onset time, ECOT) and the interhemispheric propagation of epileptic activity (interhemispheric propagation time, IHPT), which are independently correlated with temporal lobe epileptogenicity and predictive of seizure-free outcome following temporal lobectomy, are correlated with one another in a quantitative fashion. A series of 37 patients with medically intractable temporal lobe seizures was studied with long-term subdural videoelectroencephalographic monitoring. Temporal lobe seizure interhemispheric propagation time (IHPT) was found to be a negative, exponential function of electrocorticographic to clinical seizure onset time (ECOT) (f(x)=8.201x10(-0.016x), r=0.347, d.f.=35, t=2.19, p<0.05, where f(x)=IHPT and x=ECOT). A small increase in ECOT was associated with a substantial decrease in IHPT and vice versa. The results suggest the electrophysiological time factor, ECOT, involved in the transition from ictal EEG seizure onset to clinical seizure onset, may determine the speed of interhemispheric propagation of established epileptic activity. The results suggest the interesting hypothesis that, in human temporal lobe epilepsy and, perhaps, under non-pathological circumstances, the human temporal lobe might possess a "time-labeling" function amenable to quantitative analysis.

  20. Line Length: An Efficient Feature for Seizure Onset Detection

    DTIC Science & Technology

    2007-11-02

    feature was evaluated over a total of 1,215 hours of intracranial EEG signal from 10 patients. Results confirmed this feature as being useful for...of 111 seizures analyzed of which 23 were subclinical. Keywords – seizure detection, fractal dimension . I. INTRODUCTION There is a lot of...Olsen [4], and later referred to as curve length in [3]. This feature can be derived from the fractal dimension by Katz [5] studied in [6]-[7]; however

  1. A prospective observational longitudinal study of new-onset seizures and newly diagnosed epilepsy in dogs.

    PubMed

    Fredsø, N; Toft, N; Sabers, A; Berendt, M

    2017-02-16

    Seizures are common in dogs and can be caused by non-epileptic conditions or epilepsy. The clinical course of newly diagnosed epilepsy is sparsely documented. The objective of this study was to prospectively investigate causes for seizures (epileptic and non-epileptic) in a cohort of dogs with new-onset untreated seizures, and for those dogs with newly diagnosed epilepsy to investigate epilepsy type, seizure type and the course of disease over time, including the risk of seizure recurrence. Untreated client-owned dogs experiencing new-onset seizures were prospectively enrolled in a longitudinal observational study including clinical investigations and long-term monitoring at the Copenhagen University Hospital for Companion Animals. A baseline clinical assessment was followed by investigator/owner contact every eight weeks from inclusion to death or end of study. Inclusion of dogs was conducted from November 2010 to September 2012, and the study terminated in June 2014. One hundred and six dogs were included in the study. Seventy-nine dogs (74.5%) were diagnosed with epilepsy: 61 dogs (77.2%) with idiopathic epilepsy, 13 dogs (16.5%) with structural epilepsy and five dogs (6.3%) with suspected structural epilepsy. A non-epileptic cause for seizures was identified in 13 dogs and suspected in 10 dogs. Four dogs in which no cause for seizures was identified experienced only one seizure during the study. In dogs with idiopathic epilepsy 60% had their second epileptic seizure within three months of seizure onset. Twenty-six dogs with idiopathic epilepsy (43%) completed the study without receiving antiepileptic treatment. The natural course of idiopathic epilepsy (uninfluenced by drugs) was illustrated by highly individual and fluctuating seizure patterns, including long periods of remission. Cluster seizures motivated early treatment. In a few dogs with a high seizure frequency owners declined treatment against the investigators advice. Epilepsy is the most likely

  2. Identification of seizure onset zone and preictal state based on characteristics of high frequency oscillations.

    PubMed

    Malinowska, Urszula; Bergey, Gregory K; Harezlak, Jaroslaw; Jouny, Christophe C

    2015-08-01

    We investigate the relevance of high frequency oscillations (HFO) for biomarkers of epileptogenic tissue and indicators of preictal state before complex partial seizures in humans. We introduce a novel automated HFO detection method based on the amplitude and features of the HFO events. We examined intracranial recordings from 33 patients and compared HFO rates and characteristics between channels within and outside the seizure onset zone (SOZ). We analyzed changes of HFO activity from interictal to preictal and to ictal periods. The average HFO rate is higher for SOZ channels compared to non-SOZ channels during all periods. Amplitudes and durations of HFO are higher for events within the SOZ in all periods compared to non-SOZ events, while their frequency is lower. All analyzed HFO features increase for the ictal period. HFO may occur in all channels but their rate is significantly higher within SOZ and HFO characteristics differ from HFO outside the SOZ, but the effect size of difference is small. The present results show that based on accumulated dataset it is possible to distinguish HFO features different for SOZ and non-SOZ channels, and to show changes in HFO characteristics during the transition from interictal to preictal and to ictal periods. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Hippocampal body changes in pure partial onset sleep and pure partial onset waking epileptic patients.

    PubMed

    Motamedi, Mahmood; Zandieh, Ali; Hajimirzabeigi, Alireza; Tahsini, Majid; Vakhshiteh, Fatemeh; Rahimian, Elham

    2013-09-01

    The aim of the current study was to evaluate for the first time the hippocampal changes in patients with pure sleep and pure waking epilepsy. A total of 35 patients with pure partial onset sleep epilepsy and 35 patients with pure partial onset waking epilepsy matched for age and sex ratio were enrolled. MR images were analyzed to determine hippocampal body changes. Rounding ratio of hippocampal body was defined as short axis divided by long axis and hippocampal bodies with ratios ≥ 0.70 were considered rounded. Hippocampal sclerosis and atrophy were found in nine (25.7 %) and seven (20.0 %) patients with pure sleep epilepsy, and in 12 (34.3 %) and 11 (31.4 %) patients with pure waking epilepsy, respectively (P > 0.05 for the comparison between sleep and waking epilepsy). However, proportion of subjects with rounded hippocampal bodies (15, 42.9 % vs. 3, 8.6 % for patients with sleep and waking epilepsy, respectively) and rounding ratios of both left and right hippocampal bodies (0.66 ± 0.13 and 0.61 ± 0.12, respectively for left and right hippocampal bodies in sleep epileptic patients vs. 0.57 ± 0.11 and 0.55 ± 0.11, respectively for left and right hippocampal bodies in waking epileptic patients) were increased in patients with sleep epilepsy (P < 0.05). Further, in sleep epileptic patients with left sided hippocampal body rounding, epileptiform discharges were more readily lateralized to the left temporal lobe (P < 0.05). In conclusion, hippocampal sclerosis and atrophy are not different between pure partial onset sleep and waking epileptic patients. However, rounding ratio and frequency of hippocampal body rounding are increased in sleep epileptic patients.

  4. Acute EEG findings in HIV-infected Zambian adults with new-onset seizure

    PubMed Central

    Elafros, Melissa A.; Sikazwe, Izukanji; Birbeck, Gretchen L.; Kalungwana, Lisa; Potchen, Michael J.; Bositis, Christopher M.; Koralnik, Igor J.; Theodore, William H.

    2015-01-01

    Objective: To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure. Methods: Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome. Results: Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103–560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051). Conclusions: EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis. PMID:25740861

  5. Comparison of fractal dimension estimation algorithms for epileptic seizure onset detection

    NASA Astrophysics Data System (ADS)

    Polychronaki, G. E.; Ktonas, P. Y.; Gatzonis, S.; Siatouni, A.; Asvestas, P. A.; Tsekou, H.; Sakas, D.; Nikita, K. S.

    2010-08-01

    Fractal dimension (FD) is a natural measure of the irregularity of a curve. In this study the performances of three waveform FD estimation algorithms (i.e. Katz's, Higuchi's and the k-nearest neighbour (k-NN) algorithm) were compared in terms of their ability to detect the onset of epileptic seizures in scalp electroencephalogram (EEG). The selection of parameters involved in FD estimation, evaluation of the accuracy of the different algorithms and assessment of their robustness in the presence of noise were performed based on synthetic signals of known FD. When applied to scalp EEG data, Katz's and Higuchi's algorithms were found to be incapable of producing consistent changes of a single type (either a drop or an increase) during seizures. On the other hand, the k-NN algorithm produced a drop, starting close to the seizure onset, in most seizures of all patients. The k-NN algorithm outperformed both Katz's and Higuchi's algorithms in terms of robustness in the presence of noise and seizure onset detection ability. The seizure detection methodology, based on the k-NN algorithm, yielded in the training data set a sensitivity of 100% with 10.10 s mean detection delay and a false positive rate of 0.27 h-1, while the corresponding values in the testing data set were 100%, 8.82 s and 0.42 h-1, respectively. The above detection results compare favourably to those of other seizure onset detection methodologies applied to scalp EEG in the literature. The methodology described, based on the k-NN algorithm, appears to be promising for the detection of the onset of epileptic seizures based on scalp EEG.

  6. Comparison of fractal dimension estimation algorithms for epileptic seizure onset detection.

    PubMed

    Polychronaki, G E; Ktonas, P Y; Gatzonis, S; Siatouni, A; Asvestas, P A; Tsekou, H; Sakas, D; Nikita, K S

    2010-08-01

    Fractal dimension (FD) is a natural measure of the irregularity of a curve. In this study the performances of three waveform FD estimation algorithms (i.e. Katz's, Higuchi's and the k-nearest neighbour (k-NN) algorithm) were compared in terms of their ability to detect the onset of epileptic seizures in scalp electroencephalogram (EEG). The selection of parameters involved in FD estimation, evaluation of the accuracy of the different algorithms and assessment of their robustness in the presence of noise were performed based on synthetic signals of known FD. When applied to scalp EEG data, Katz's and Higuchi's algorithms were found to be incapable of producing consistent changes of a single type (either a drop or an increase) during seizures. On the other hand, the k-NN algorithm produced a drop, starting close to the seizure onset, in most seizures of all patients. The k-NN algorithm outperformed both Katz's and Higuchi's algorithms in terms of robustness in the presence of noise and seizure onset detection ability. The seizure detection methodology, based on the k-NN algorithm, yielded in the training data set a sensitivity of 100% with 10.10 s mean detection delay and a false positive rate of 0.27 h(-1), while the corresponding values in the testing data set were 100%, 8.82 s and 0.42 h(-1), respectively. The above detection results compare favourably to those of other seizure onset detection methodologies applied to scalp EEG in the literature. The methodology described, based on the k-NN algorithm, appears to be promising for the detection of the onset of epileptic seizures based on scalp EEG.

  7. Prognostic value of intracranial seizure onset patterns for surgical outcome of the treatment of epilepsy.

    PubMed

    Jiménez-Jiménez, Diego; Nekkare, Ramesh; Flores, Lorena; Chatzidimou, Katerina; Bodi, Istvan; Honavar, Mrinalini; Mullatti, Nandini; Elwes, Robert D C; Selway, Richard P; Valentín, Antonio; Alarcón, Gonzalo

    2015-02-01

    To investigate if intracranial EEG patterns at seizure onset can predict surgical outcome. Ictal onset patterns from intracranial EEG were analysed in 373 electro-clinical seizures and subclinical seizures from 69 patients. Seizure onset patterns were classified as: (a) Diffuse electrodecremental (DEE); (b) Focal fast activity (FA); (c) Simultaneous onset of fast activity and diffuse electrodecremental event (FA-DEE); (d) Spikes; (e) Spike-wave activity; (f) Sharp waves; (g) Alpha activity; (h) Delta activity. Presence of preceding epileptiform discharge (PED) was also studied. Engel and ILAE surgical outcome scales were used. The mean follow-up period was 42.1 months (SD=30.1). Fast activity was the most common seizure onset pattern seen (33%), followed by (FA-DEE) (20%), DEE (19%), spike-wave activity (12%), sharp-waves (6%), alpha activity (6%), delta activity (3%) and spikes (1%). Preceding epileptiform discharges were present in 75% of patients. FA was associated with favourable outcome (p=0.0083) whereas DEE was associated with poor outcome (p=0.0025). A widespread PED was not associated with poor outcome (p=0.9559). There was no clear association between seizure onset pattern and specific pathology, except possibly between sharp/spike waves and mesial temporal sclerosis. FA activity is associated with favourable outcome. DEE at onset was associated with poor surgical outcome. Widespread/bilateral PEDs were not associated with poor or good outcome. FA appears to be the best marker for the epileptogenic zone. Surgery should be contemplated with caution if DEE is the first ictal change. However, a widespread/bilateral PED at onset is common and should not discourage surgery. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors.

    PubMed

    Senf, Philine; Schmitz, Bettina; Holtkamp, Martin; Janz, Dieter

    2013-12-10

    Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy. However, little is known about the long-term medical evolution of this clinical entity. The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome. In this retrospective cohort study, we analyzed seizure outcome in 66 patients who had JME, were treated at the Department of Neurology, Charité-Universitätsmedizin Berlin, and were initially diagnosed by a single senior epileptologist. After a mean follow-up time of 44.6 years (20-69 years), 59.1% of patients remained free of seizures for at least 5 years before the last contact. Among the seizure-free patients, 28 (71.8%) were still taking antiepileptic drugs and 11 (28.2%) were off medication for at least the last 5 years. We identified manifestation of additional absence seizures at onset of JME as an independent predictor of an unfavorable outcome regarding seizure freedom. A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome.

  9. Clinical analysis of leucine-rich glioma inactivated-1 protein antibody associated with limbic encephalitis onset with seizures

    PubMed Central

    Li, Zhimei; Cui, Tao; Shi, Weixiong; Wang, Qun

    2016-01-01

    Abstract We summarized the clinical characteristics of patients presenting with seizures and limbic encephalitis (LE) associated with leucine-rich glioma inactivated-1 protein antibody (LGI1) in order help recognize and treat this condition at its onset. We analyzed clinical, video electroencephalogram (VEEG), magnetic resonance imaging (MRI), and laboratory data of 10 patients who presented with LGI1-LE and followed up their outcomes from 2 to 16 (9.4 ± 4.2) months. All patients presented with seizures onset, including faciobrachial dystonic seizure (FBDS), partial seizure (PS), and generalized tonic-clonic seizure (GTCS). Four patients (Cases 3, 5, 7, and 8) had mild cognitive deficits. Interictal VEEG showed normal patterns, focal slowing, or sharp waves in the temporal or frontotemporal lobes. Ictal VEEG of Cases 4, 5, and 7 showed diffuse voltage depression preceding FBDS, a left frontal/temporal origin, and a bilateral temporal origin, respectively. Ictal foci could not be localized in other cases. MRI scan revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity and evidence of edema in the right medial temporal lobe in Case 3, left hippocampal atrophy in Case 5, hyperintensities in the bilateral medial temporal lobes in Case 7, and hyperintensities in the basal ganglia and frontal cortex in Case 10. All 10 serum samples were positive for LGI1 antibody, but it was only detected in the cerebrospinal fluid (CSF) of 7 patients. Five patients (Cases 2, 4, 6, 7, and 8) presented with hyponatremia. One patient (Case 2) was diagnosed with small cell lung cancer. While responses to antiepileptic drugs (AEDs) were poor, most patients (except Case 2) responded favorably to immunotherapy. LGI1-LE may initially manifest with various types of seizures, particularly FBDS and complex partial seizures (CPS) of mesial temporal origin, and slowly progressive cognitive involvement. Clinical follow-up, VEEG monitoring, and MRI scan are helpful in early

  10. Seizures

    MedlinePlus

    ... Your 1- to 2-Year-Old First Aid: Seizures KidsHealth > For Parents > First Aid: Seizures Print A A A en español Folleto de instructiones: Convulsiones (Seizures) Although seizures can be frightening, many last only ...

  11. Evolution of genuine cross-correlation strength of focal onset seizures.

    PubMed

    Müller, Markus F; Baier, Gerold; Jiménez, Yurytzy López; Marín García, Arlex O; Rummel, Christian; Schindler, Kaspar

    2011-10-01

    To quantify the evolution of genuine zero-lag cross-correlations of focal onset seizures, we apply a recently introduced multivariate measure to broad band and to narrow-band EEG data. For frequency components below 12.5 Hz, the strength of genuine cross-correlations decreases significantly during the seizure and the immediate postseizure period, while higher frequency bands show a tendency of elevated cross-correlations during the same period. We conclude that in terms of genuine zero-lag cross-correlations, the electrical brain activity as assessed by scalp electrodes shows a significant spatial fragmentation, which might promote seizure offset.

  12. Intelligence and cortical thickness in children with complex partial seizures.

    PubMed

    Tosun, Duygu; Caplan, Rochelle; Siddarth, Prabha; Seidenberg, Michael; Gurbani, Suresh; Toga, Arthur W; Hermann, Bruce

    2011-07-15

    Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Microwave oven injuries in patients with complex partial seizures.

    PubMed

    DeToledo, John C; Lowe, Merredith R

    2004-10-01

    Microwave ovens are often recommended as a safe cooking alternative for persons with epilepsy. We report four patients who suffered serious burns to their hands while handling microwave-heated liquids during a complex partial seizure (CPS). Injuries were due to the contact of the skin with a very hot container. The fact that all patients held on to the hot containers despite being burned and that they did not remember experiencing any pain at the time of the accident indicates that neither high temperatures nor pain will prevent patients who are having a CPS from suffering this type of injury. Unfortunately, there is no foolproof way to prevent the individual from opening the oven and removing its contents during a CPS. The only solution for this problem is "prevention"-individuals with poorly controlled CPS should be cautioned about these risks. The use of microwave settings that permit the heating but not boiling of liquids and the use of gloves while heating food and liquids to scalding temperatures may minimize the risk of this type of injury.

  14. Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    PubMed

    Lim, Byung Chan; Hwang, Hee; Kim, Hunmin; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Yum, Mi-Sun; Ko, Tae-Sung

    2015-01-01

    The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated. We presented five new cases with a chromosome 2q24.3 deletion involving SCN1A and investigated their epilepsy phenotype in relation to the extent of the deletion. Three cases with deletion of the whole sodium channel gene cluster (SCN3A, SCN2A, SCN1A, SCN9A, and SCN7A) exhibited a complex epilepsy phenotype that was atypical for Dravet syndrome and suggestive of migrating partial seizures of infancy: early seizure onset (before 2 months of age), severe developmental delay from seizure onset, multifocal interictal spikes, polymorphous focal seizures, and acquired microcephaly. Two cases with partial deletion of SCN1A and SCN9A and whole SCN1A deletion had an epilepsy phenotype of Dravet syndrome. A literature review of cases with chromosome 2q24.3 deletion revealed that, in most Dravet syndrome cases, it does not involve SCN2A and SCN3A, whereas a complex epilepsy phenotype that is shared with migrating partial seizures of infancy was associated with cases of deletion of the whole sodium channel gene cluster. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Yield of Emergent Neuroimaging in Children with New-Onset Seizure and Status Epilepticus

    PubMed Central

    Lyons, Todd W.; Johnson, Kara B.; Michelson, Kenneth A.; Nigrovic, Lise E.; Loddenkemper, Tobias; Prabhu, Sanjay P.; Kimia MD, Amir A.

    2017-01-01

    PURPOSE To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. PMID:26773658

  16. Yield of emergent neuroimaging in children with new-onset seizure and status epilepticus.

    PubMed

    Lyons, Todd W; Johnson, Kara B; Michelson, Kenneth A; Nigrovic, Lise E; Loddenkemper, Tobias; Prabhu, Sanjay P; Kimia, Amir A

    2016-02-01

    To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. We performed a cross-sectional study of children seen at a single ED between 1995 and 2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 min or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29-43%) children with 15 (8.5%, 95% confidence interval 5.2-14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Giant Intradural Mucocele in a Patient with Adult Onset Seizures

    PubMed Central

    Kechagias, E.; Georgakoulias, N.; Ioakimidou, C.; Kyriazi, S.; Kontogeorgos, G.; Seretis, A.

    2009-01-01

    A rare case of mucopyocele in a patient who presented with epileptic seizures is reported. The computed tomography scan (CT) and the magnetic resonance (MR) imaging revealed an intradural extension of a giant fronto-ethmoidal mucopyocele, eroding the cribriform plate and compressing both frontal lobes. The lesion was removed by craniotomy with elimination of the mass effect and reconstruction of the anterior skull base. An intracranial-intradural mucopyocele is an extremely rare cause of generalized convulsion as a presenting symptom, with only 6 cases reported in the literature. The total removal of the lesion associated with anterior fossa reconstruction is the treatment of choice. PMID:20847833

  18. Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

    PubMed Central

    Inceoglu, Bora; Zolkowska, Dorota; Yoo, Hyun Ju; Wagner, Karen M.; Yang, Jun; Hackett, Edward; Hwang, Sung Hee; Lee, Kin Sing Stephen; Rogawski, Michael A.; Morisseau, Christophe; Hammock, Bruce D.

    2013-01-01

    In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders. PMID:24349022

  19. Partial complex seizures in children: an analysis of 69 seizures in 24 patients using EEG FM radiotelemetry and videotape recording.

    PubMed

    Holmes, G L

    1984-01-01

    The electroencephalographic and clinical manifestations of 69 partial complex seizures in 24 pediatric patients recorded during EEG-FM radiotelemetry and videotape monitoring were reviewed. The seizure could be divided into 3 electro-clinical types. Type I attacks were characterized by an initial motionless stare often followed by automatisms and associated with initial lateralized EEG changes. Type II attacks began with automatic behavior and had bilateral, diffuse changes on the EEG initially. Type II attacks began with a loss of body tone followed by automatisms and with bilateral EEG changes initially. This study demonstrates that both the clinical and electroencephalographic aspects of partial complex seizures in children are similar to those reported in adults. This similarity may be secondary to the early maturation of the limbic structures.

  20. Emerging drugs for partial-onset epilepsy: a review of brivaracetam

    PubMed Central

    Gao, Lan; Li, Shuchuen

    2016-01-01

    There are more than 12 new antiepileptic drugs approved in the last 2 decades. Even with these newer agents, seizure remission is still unachievable in around 30% of patients with partial-onset seizures (POS). Brivaracetam (BRV) is chemically related to levetiracetam (LEV) and possesses a strong binding affinity for the synaptic vesicle protein 2A tenfold above that of LEV, and other possible modes of antiepileptic actions. BRV is now under Phase III development for POS, but data from one Phase III trial also suggested its potential efficacy for primary generalized seizures. The purpose of this review is to provide updated information on the mechanisms of action of the available antiepileptic drugs, with a focus on BRV to assess its pharmacology, pharmacokinetics, clinical efficacy, safety, and tolerability in patients with uncontrolled POS. To date, six Phase IIb and III clinical trials have been performed to investigate the efficacy, safety, and tolerability of BRV as an adjunctive treatment for patients with POS. Generally, BRV was well tolerated and did not show significant difference in safety profile, compared to placebo. The efficacy outcomes of BRV, although not consistent across trials, did indicate that BRV was a promising add-on therapy for patients with POS. In conclusion, the many favorable attributes of BRV, like its high oral efficacy, good tolerability, dosing regimen, and minimal drug interaction, make it a promising antiepileptic therapy for patients with uncontrolled partial-onset epilepsy. PMID:27217762

  1. Abnormal interictal gamma activity may manifest a seizure onset zone in temporal lobe epilepsy.

    PubMed

    Medvedev, Andrei V; Murro, Anthony M; Meador, Kimford J

    2011-04-01

    Even though recent studies have suggested that seizures do not occur suddenly and that before a seizure there is a period with an increased probability of seizure occurrence, neurophysiological mechanisms of interictal and pre-seizure states are unknown. The ability of mathematical methods to provide much more sensitive tools for the detection of subtle changes in the electrical activity of the brain gives promise that electrophysiological markers of enhanced seizure susceptibility can be found even during interictal periods when EEG of epilepsy patients often looks 'normal'. Previously, we demonstrated in animals that hippocampal and neocortical gamma-band rhythms (30-100 Hz) intensify long before seizures caused by systemic infusion of kainic acid. Other studies in recent years have also drawn attention to the fast activity (>30 Hz) as a possible marker of epileptogenic tissue. The current study quantified gamma-band activity during interictal periods and seizures in intracranial EEG (iEEG) in 5 patients implanted with subdural grids/intracranial electrodes during their pre-surgical evaluation. In all our patients, we found distinctive (abnormal) bursts of gamma activity with a 3 to 100 fold increase in power at gamma frequencies with respect to selected by clinicians, quiescent, artifact-free, 7-20 min "normal" background (interictal) iEEG epochs 1 to 14 hours prior to seizures. Increases in gamma activity were largest in those channels which later displayed the most intensive electrographic seizure discharges. Moreover, location of gamma-band bursts correlated (with high specificity, 96.4% and sensitivity, 83.8%) with seizure onset zone (SOZ) determined by clinicians. Spatial localization of interictal gamma rhythms within SOZ suggests that the persistent presence of abnormally intensified gamma rhythms in the EEG may be an important tool for focus localization and possibly a determinant of epileptogenesis.

  2. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

    PubMed

    Jones, Nicholas A; Glyn, Sarah E; Akiyama, Satoshi; Hill, Thomas D M; Hill, Andrew J; Weston, Samantha E; Burnett, Matthew D A; Yamasaki, Yuki; Stephens, Gary J; Whalley, Benjamin J; Williams, Claire M

    2012-06-01

    Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥ 10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

  3. Homozygous PLCB1 Deletion Associated with Malignant Migrating Partial Seizures in Infancy

    PubMed Central

    Poduri, Annapurna; Chopra, Sameer S.; Neilan, Edward G.; Elhosary, P. Christina; Kurian, Manju A.; Meyer, Esther; Barry, Brenda J.; Khwaja, Omar S.; Salih, Mustafa A. M.; Sci, Dr Med; Stödberg, Tommy; Scheffer, Ingrid E.; Maher, Eamonn R.; Sahin, Mustafa; Wu, Bai-Lin; Med, M; Berry, Gerard T.; Walsh, Christopher A.; Picker, Jonathan; Kothare, Sanjeev V.

    2013-01-01

    Summary Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants (CNVs) genome-wide and long-range PCR to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes. PMID:22690784

  4. Vagal stimulation for control of complex partial seizures in medically refractory epileptic patients.

    PubMed

    Wilder, B J; Uthman, B M; Hammond, E J

    1991-01-01

    Chronic intermittent stimulation of the vagus nerve is a new method currently being tested for the treatment of medically intractable complex partial seizures (CPS). We have studied the effects of vagal stimulation in nine patients with CPS for 4-16 months to determine its safety and efficacy. With the patients maintained on constant dosages of antiepileptic drugs, we recorded the electroencephalogram and electrocardiogram, and performed clinical laboratory tests and gastric analysis over a 6-week baseline period. The neurocybernetic prosthesis (NCP) was then implanted and connected to two spiral electrodes wound around the left vagus nerve. After a 4-week placebo period, vagal stimulation was started. Stimulation parameters were increased stepwise at monthly intervals until patients were being stimulated for 30-second periods at 20-50 Hz with 1-2 mA of current at 250-500 microseconds pulses. A second 4-week placebo period was added 3 months after the implantation. Thereafter, vagal stimulation was resumed and self-stimulation with magnetic activation was allowed for a 1-minute period at the onset of an aura. Six patients had a significant reduction in the frequency, intensity, or duration of seizures. All patients tolerated the implantation and stimulation well and none reported pain, discomfort, or important changes in their daily activities, sleep habits, eating, swallowing, or breathing. There were no remarkable changes in blood pressure or heart rate.

  5. Ruptured intracranial dermoid cyst manifesting as new onset seizure: a case report

    PubMed Central

    Kucera, Jennifer Neville; Roy, Pinakpani; Murtagh, Ryan

    2011-01-01

    Intracranial dermoid cysts are rare tumors derived from ectopic epithelial cells. They are slow-growing benign entities, but can cause significant morbidity through compression of neurovascular structures and, rarely, rupture into the subarachnoid space. We present a rare case of a spontaneously ruptured intracranial dermoid cyst presenting as new onset seizures due to chemical meningitis caused by dissemination of fat droplets. PMID:22470786

  6. Ruptured intracranial dermoid cyst manifesting as new onset seizure: a case report.

    PubMed

    Kucera, Jennifer Neville; Roy, Pinakpani; Murtagh, Ryan

    2011-01-01

    Intracranial dermoid cysts are rare tumors derived from ectopic epithelial cells. They are slow-growing benign entities, but can cause significant morbidity through compression of neurovascular structures and, rarely, rupture into the subarachnoid space. We present a rare case of a spontaneously ruptured intracranial dermoid cyst presenting as new onset seizures due to chemical meningitis caused by dissemination of fat droplets.

  7. Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy

    PubMed Central

    Lévesque, Maxime; Salami, Pariya; Gotman, Jean; Avoli, Massimo

    2016-01-01

    High-frequency oscillations(HFOs; 80–500 Hz ) are thought to mirror the pathophysiological changes occurring in epileptic brains. However, the distribution of HFOs during seizures remains undefined. Here, we recorded from the hippocampal CA3 subfield, subiculum, entorhinal cortex, and dentate gyrus to quantify the occurrence of ripples (80–200 Hz) and fast ripples (250–500 Hz) during low-voltage fast-onset (LVF) and hypersynchronous-onset (HYP) seizures in the rat pilocarpine model of temporal lobe epilepsy. We discovered in LVF seizures that (1) progression from preictal to ictal activity was characterized in seizure-onset zones by an increase of ripple rates that were higher when compared with fast ripple rates and (2) ripple rates during the ictal period were higher compared with fast ripple rates in seizure-onset zones and later in regions of secondary spread. In contrast, we found in HYP seizures that (1) fast ripple rates increased during the preictal period and were higher compared with ripple rates in both seizure-onset zones and in regions of secondary spread and (2) they were still higher compared with ripple rates in both seizure-onset zones and regions of secondary spread during the ictal period. Our findings demonstrate that ripples and fast ripples show distinct time- and region-specific patterns during LVF and HYP seizures, thus suggesting that they play specific roles in ictogenesis. PMID:22993442

  8. Treatment approach in a child with hysterical seizures superimposed on partial complex seizures.

    PubMed

    Parraga, H C; Kashani, J H

    1981-03-01

    This article reports the case of a 9 1/2 year old child with a history of psychomotor epilepsy which was uncontrolled by multiple anticonvulsant medications. When admitted to the psychiatric inpatient service, he was treated with a combination of pharmacological, behavioural and psychodynamically oriented approaches. A period of intensive family counseling was conducted to clarify the parents' concerns about causality of the seizures and methods for dealing with them. This combined approach led to a complete cessation of reported seizures and a decreased number and dosage of anticonvulsant medications. The authors discuss the reluctance of some physicians to accept the co-existence of neurogenic and psychogenic seizures in a given patient. Patients with pharmacologically uncontrolled seizures must be identified and accurately diagnosed (neurogenic and/or psychogenic) to prevent complication such as over-medication and to administer appropriate treatment. Multiple disciplinary therapy including psychodynamic, pharmacological, behavioural and educational approaches should be implemented.

  9. Management of refractory complex partial seizures: current state of the art

    PubMed Central

    Treiman, David M

    2010-01-01

    Diagnosis of complex partial epilepsy is based on the clinical history, and laboratory tests, including EEG and neuroimaging studies, corroborate the diagnosis. The goal of epilepsy management is to make the patient completely seizure-free without drug-induced side effects, even in the patient with refractory complex partial seizures. Frequently this can be accomplished by choice of the optimal antiepileptic drug (AED) or a combination of drugs, the use of strategies to maximize the effectiveness of drug treatment, or by surgical removal of the seizure focus. Currently there are five “classical” first-line AEDs and 11 new AEDs available in the US and in many other countries for the treatment of localization-related epilepsy. The current state of the evidence is that no AED is clearly superior to other AEDs in the management of refractory complex partial seizures. Therefore the choice of which drug to use in an individual patient has to be based on other considerations, including the potential adverse reactions that may occur in that patient. There are a number of strategies for optimal use of AEDs in the management of refractory complex partial seizures. These include verification of the diagnosis of epilepsy and classification of specific seizure types, use of monotherapy if possible but polytherapy if necessary, starting with a low dose and raising it slowly but, until complete seizure control is achieved, pushing to the maximum tolerated dose, changing timing of dosing to reduce toxicity, using pharmacokinetic principles to fine-tune AED doses, adjusting dose for drug–drug interactions, and never giving up in the pursuit of better seizure control. Resection of the seizure focus can be curative in the majority of patients with seizures localized to one mesial temporal lobe. Success rates for resection of extratemporal seizure foci are lower. Vagus nerve stimulation (VNS) devices result in a significant reduction of seizure frequency in many patients, but

  10. A signal processing based analysis and prediction of seizure onset in patients with epilepsy

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.

    2016-01-01

    One of the main areas of behavioural neuroscience is forecasting the human behaviour. Epilepsy is a central nervous system disorder in which nerve cell activity in the brain becomes disrupted, causing seizures or periods of unusual behaviour, sensations and sometimes loss of consciousness. An estimated 5% of the world population has epileptic seizure but there is not any method to cure it. More than 30% of people with epilepsy cannot control seizure. Epileptic seizure prediction, refers to forecasting the occurrence of epileptic seizures, is one of the most important but challenging problems in biomedical sciences, across the world. In this research we propose a new methodology which is based on studying the EEG signals using two measures, the Hurst exponent and fractal dimension. In order to validate the proposed method, it is applied to epileptic EEG signals of patients by computing the Hurst exponent and fractal dimension, and then the results are validated versus the reference data. The results of these analyses show that we are able to forecast the onset of a seizure on average of 25.76 seconds before the time of occurrence. PMID:26586477

  11. A signal processing based analysis and prediction of seizure onset in patients with epilepsy.

    PubMed

    Namazi, Hamidreza; Kulish, Vladimir V; Hussaini, Jamal; Hussaini, Jalal; Delaviz, Ali; Delaviz, Fatemeh; Habibi, Shaghayegh; Ramezanpoor, Sara

    2016-01-05

    One of the main areas of behavioural neuroscience is forecasting the human behaviour. Epilepsy is a central nervous system disorder in which nerve cell activity in the brain becomes disrupted, causing seizures or periods of unusual behaviour, sensations and sometimes loss of consciousness. An estimated 5% of the world population has epileptic seizure but there is not any method to cure it. More than 30% of people with epilepsy cannot control seizure. Epileptic seizure prediction, refers to forecasting the occurrence of epileptic seizures, is one of the most important but challenging problems in biomedical sciences, across the world. In this research we propose a new methodology which is based on studying the EEG signals using two measures, the Hurst exponent and fractal dimension. In order to validate the proposed method, it is applied to epileptic EEG signals of patients by computing the Hurst exponent and fractal dimension, and then the results are validated versus the reference data. The results of these analyses show that we are able to forecast the onset of a seizure on average of 25.76 seconds before the time of occurrence.

  12. Identifying seizure onset zone from electrocorticographic recordings: A machine learning approach based on phase locking value.

    PubMed

    Elahian, Bahareh; Yeasin, Mohammed; Mudigoudar, Basanagoud; Wheless, James W; Babajani-Feremi, Abbas

    2017-10-01

    Using a novel technique based on phase locking value (PLV), we investigated the potential for features extracted from electrocorticographic (ECoG) recordings to serve as biomarkers to identify the seizure onset zone (SOZ). We computed the PLV between the phase of the amplitude of high gamma activity (80-150Hz) and the phase of lower frequency rhythms (4-30Hz) from ECoG recordings obtained from 10 patients with epilepsy (21 seizures). We extracted five features from the PLV and used a machine learning approach based on logistic regression to build a model that classifies electrodes as SOZ or non-SOZ. More than 96% of electrodes identified as the SOZ by our algorithm were within the resected area in six seizure-free patients. In four non-seizure-free patients, more than 31% of the identified SOZ electrodes by our algorithm were outside the resected area. In addition, we observed that the seizure outcome in non-seizure-free patients correlated with the number of non-resected SOZ electrodes identified by our algorithm. This machine learning approach, based on features extracted from the PLV, effectively identified electrodes within the SOZ. The approach has the potential to assist clinicians in surgical decision-making when pre-surgical intracranial recordings are utilized. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Intracranial EEG seizure onset-patterns correlate with high-frequency oscillations in patients with drug-resistant epilepsy.

    PubMed

    Ferrari-Marinho, Taissa; Perucca, Piero; Dubeau, Francois; Gotman, Jean

    2016-11-01

    High-frequency oscillations (80-500Hz; HFOs) have been shown to be a specific biomarker of the seizure-onset zone. The relationship of HFOs with seizures having different intracranial electroencephalography (iEEG) morphological onsets, however, has shown significant relationships in experimental animals but has not been studied in humans. We investigated how interictal and ictal HFOs relate to different seizure-onset morphological patterns. We analyzed the most representative seizure type of 37 patients with drug-resistant focal epilepsy who underwent iEEG for diagnostic evaluation. According to the morphology, 211 seizure-onset zone channels were classified in six patterns (low-voltage fast activity; sharp activity at ≤13Hz; low-frequency high-amplitude periodic spikes; burst of high-amplitude polyspikes; spike-and-wave activity; and delta brush). Interictal and ictal HFOs were compared between the six seizure-onset patterns. Interictal ripple and fast ripple rates differed significantly across seizure-onset patterns (p<0.001). Significant differences were also found for ictal HFOs density across the different seizure-onset patterns (p<0.001). Sharp activity at ≤13Hz was associated with the lowest interictal HFO rate suggesting either that the mechanism that generates this type of EEG morphology do not generate HFOs or possibly that this pattern is more likely to be generated in a region of seizure spread. Regarding the difference in HFO density between pre-ictal baseline and seizure-onset section across the six patterns, burst of high-amplitude polyspikes and delta brushes had the highest densities of both ripples and fast ripples (p<0.001). We demonstrated that distinct seizure-onset patterns correlate specific interictal and ictal HFO profiles confirming that seizures with different morphological patterns likely have different mechanisms of generation. This study emphazises that, in clinical practice, seizure-onset patterns should be distinguished and

  14. Controlling Seizures

    ERIC Educational Resources Information Center

    Henderson, Nancy

    2008-01-01

    This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

  15. Controlling Seizures

    ERIC Educational Resources Information Center

    Henderson, Nancy

    2008-01-01

    This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

  16. Case report of a patient with complex partial frontal lobe seizures as a complication of bifrontal lobotomy.

    PubMed

    Engelborghs, S; Borggreve, F; Pickut, B A; Michiels, K; Van de Mosselaer, W; De Deyn, P P

    1998-06-01

    This case report describes an 85 year-old woman who underwent a bilateral frontal lobotomy for presumed schizophrenia 50 years ago. The patient presented with sudden alterations of consciousness accompanied by motionless staring and speech and movement arrest. After 5 to 10 seconds, contact recovered briskly. As there was electrophysiological evidence for a frontal epileptic focus, these fits were classified as complex partial frontal lobe seizures with impairment of consciousness at onset. An aetiological link with the bifrontal lobotomy is probable. At the occasion of this case report, complications of frontal lobotomy are reviewed.

  17. Rapid eye movement sleep and hippocampal theta oscillations precede seizure onset in the tetanus toxin model of temporal lobe epilepsy.

    PubMed

    Sedigh-Sarvestani, Madineh; Thuku, Godfrey I; Sunderam, Sridhar; Parkar, Anjum; Weinstein, Steven L; Schiff, Steven J; Gluckman, Bruce J

    2014-01-22

    Improved understanding of the interaction between state of vigilance (SOV) and seizure onset has therapeutic potential. Six rats received injections of tetanus toxin (TeTX) in the ventral hippocampus that resulted in chronic spontaneous seizures. The distribution of SOV before 486 seizures was analyzed for a total of 19 d of recording. Rapid eye movement sleep (REM) and exploratory wake, both of which express prominent hippocampal theta rhythm, preceded 47 and 34%, for a total of 81%, of all seizures. Nonrapid eye movement sleep (NREM) and nonexploratory wake, neither of which expresses prominent theta, preceded 6.8 and 13% of seizures. We demonstrate that identification of SOV yields significant differentiation of seizure susceptibilities, with the instantaneous seizure rate during REM nearly 10 times higher than baseline and the rate for NREM less than half of baseline. Survival analysis indicated a shorter duration of preseizure REM bouts, with a maximum transition to seizure at ∼90 s after the onset of REM. This study provides the first analysis of a correlation between SOV and seizure onset in the TeTX model of temporal lobe epilepsy, as well as the first demonstration that hippocampal theta rhythms associated with natural behavioral states can serve a seizure-promoting role. Our findings are in contrast with previous studies suggesting that the correlations between SOV and seizures are primarily governed by circadian oscillations and the notion that hippocampal theta rhythms inhibit seizures. The documentation of significant SOV-dependent seizure susceptibilities indicates the potential utility of SOV and its time course in seizure prediction and control.

  18. Seizure-Onset Mapping Based on Time-Variant Multivariate Functional Connectivity Analysis of High-Dimensional Intracranial EEG: A Kalman Filter Approach.

    PubMed

    Lie, Octavian V; van Mierlo, Pieter

    2017-01-01

    The visual interpretation of intracranial EEG (iEEG) is the standard method used in complex epilepsy surgery cases to map the regions of seizure onset targeted for resection. Still, visual iEEG analysis is labor-intensive and biased due to interpreter dependency. Multivariate parametric functional connectivity measures using adaptive autoregressive (AR) modeling of the iEEG signals based on the Kalman filter algorithm have been used successfully to localize the electrographic seizure onsets. Due to their high computational cost, these methods have been applied to a limited number of iEEG time-series (<60). The aim of this study was to test two Kalman filter implementations, a well-known multivariate adaptive AR model (Arnold et al. 1998) and a simplified, computationally efficient derivation of it, for their potential application to connectivity analysis of high-dimensional (up to 192 channels) iEEG data. When used on simulated seizures together with a multivariate connectivity estimator, the partial directed coherence, the two AR models were compared for their ability to reconstitute the designed seizure signal connections from noisy data. Next, focal seizures from iEEG recordings (73-113 channels) in three patients rendered seizure-free after surgery were mapped with the outdegree, a graph-theory index of outward directed connectivity. Simulation results indicated high levels of mapping accuracy for the two models in the presence of low-to-moderate noise cross-correlation. Accordingly, both AR models correctly mapped the real seizure onset to the resection volume. This study supports the possibility of conducting fully data-driven multivariate connectivity estimations on high-dimensional iEEG datasets using the Kalman filter approach.

  19. A new algorithm for epilepsy seizure onset detection and spread estimation from EEG signals

    NASA Astrophysics Data System (ADS)

    Quintero-Rincón, Antonio; Pereyra, Marcelo; D'Giano, Carlos; Batatia, Hadj; Risk, Marcelo

    2016-04-01

    Appropriate diagnosis and treatment of epilepsy is a main public health issue. Patients suffering from this disease often exhibit different physical characterizations, which result from the synchronous and excessive discharge of a group of neurons in the cerebral cortex. Extracting this information using EEG signals is an important problem in biomedical signal processing. In this work we propose a new algorithm for seizure onset detection and spread estimation in epilepsy patients. The algorithm is based on a multilevel 1-D wavelet decomposition that captures the physiological brain frequency signals coupled with a generalized gaussian model. Preliminary experiments with signals from 30 epilepsy crisis and 11 subjects, suggest that the proposed methodology is a powerful tool for detecting the onset of epilepsy seizures with his spread across the brain.

  20. Seizures

    MedlinePlus

    ... often with a loss of or change in consciousness. Seizures can be frightening, but most last only ... unusual sensations, uncontrollable muscle spasms, and loss of consciousness. Some seizures may be due to another medical ...

  1. Emergency centre investigation of first-onset seizures in adults in the Western Cape, South Africa.

    PubMed

    Smith, A B; Van Hoving, D J; Wallis, L A

    2013-08-21

    Patients with first-onset seizures commonly present to emergency centres (ECs). The differential diagnosis is broad, potentially life-threatening conditions need to be excluded, and these patients need to be correctly diagnosed and appropriately referred. There are currently no data on adults presenting with first-onset seizures to ECs in South Africa. To review which investigations were performed on adults presenting with first-onset seizures to six ECs in the Western Cape Province. A prospective, cross-sectional study was conducted from 1 July 2011 to 31 December 2011. All adults with first-onset seizures were included; children and trauma patients were excluded. Subgroup analyses were conducted regarding HIV status and inter-facility variation. A total of 309 patients were included. Computed tomography (CT) scans were planned in 218 (70.6%) patients, but only performed in 169; 96 (56.8%) showed abnormalities judged to be causative (infarction, intracerebral haemorrhage and atrophy being the most common). At least 80% of patients (n=247) received a full renal and electrolyte screen, blood glucose testing and a full haematological screen. Lumbar puncture (LP) was performed in 67 (21.7%) patients, with normal cerebrospinal fluid findings in 51 (76.1%). Only 27 (8%) patients had an electroencephalogram, of which 5 (18%) were abnormal. There was a statistically significant difference in the number of CT scans (p=0.002) and LPs (p<0.001) performed in the HIV-positive group (n=49). This study demonstrated inconsistency and wide local variance for all types of investigations done. It emphasises the need for a local guideline to direct doctors to appropriate investigations, ensuring better quality patient care and potential cost-saving.

  2. Acute encephalitis with refractory, repetitive partial seizures: Pathological findings and a new therapeutic approach using tacrolimus.

    PubMed

    Sato, Yuko; Numata-Uematsu, Yurika; Uematsu, Mitsugu; Kikuchi, Atsuo; Nakayama, Tojo; Kakisaka, Yosuke; Kobayashi, Tomoko; Hino-Fukuyo, Naomi; Suzuki, Hiroyoshi; Takahashi, Yukitoshi; Saito, Yoshiaki; Tanuma, Naoyuki; Hayashi, Masaharu; Iwasaki, Masaki; Haginoya, Kazuhiro; Kure, Shigeo

    2016-09-01

    Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by prolonged severe seizures and a high-grade fever. We experienced a boy with severe AERRPS with frequent partial seizures that exhibited right-side predominance. The patient required the continuous intravenous administration of many antiepileptic drugs and respirator management for several months. Methylprednisolone pulse therapy and intravenous immunoglobulin administration were only temporarily effective. The MRI and EEG showed the abnormality in the left occipital lobe. Although occipital lobectomy was performed, his seizures continued. His cerebrospinal fluid exhibited elevated protein and proinflammatory cytokine levels, and was positive for anti-glutamate receptor ε2 antibodies. Pathological examination showed infiltration of many neutrophilic leukocytes, T cells, and microglia in the area exhibiting severe spongiosis. We thought that the exaggerated microglia and T-cell responses were related to the pathogenesis of the patient's seizures, and we therefore initiated treatment with tacrolimus. As a result, many of the daily seizure clusters were ameliorated, and the patient was discharged. We attempted to discontinue the tacrolimus twice, but the patient's seizure clusters recurred each time. This is the first case report of the pathological findings of AERRPS and showing an effective therapeutic approach using tacrolimus. Tacrolimus may be an effective immunosuppressant, especially for patients with severe AERRPS. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Seizures

    MedlinePlus

    ... because of sudden, abnormal electrical activity in the brain. When people think of seizures, they often think of convulsions in which a person's body shakes rapidly and uncontrollably. Not all seizures ... part of the brain. Generalized seizures are a result of abnormal activity ...

  4. Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

    PubMed

    Duncan, R; Patterson, J; Roberts, R; Hadley, D M; Bone, I

    1993-02-01

    Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.

  5. Right hemispheric reversible cerebral vasoconstriction syndrome in a patient with left hemispheric partial seizures

    PubMed Central

    Perez, Gina S.; McCaslin, Justin

    2017-01-01

    We report a right-handed 19-year-old girl who developed reversible cerebral vasoconstriction syndrome (RCVS) lateralized to the right hemisphere with simultaneous new-onset left hemispheric seizures. RCVS, typically more diffuse, was lateralized to one of the cerebral hemispheres. PMID:28405089

  6. Menkes disease – An important cause of early onset refractory seizures

    PubMed Central

    Jain, Puneet; Kannan, Lakshminarayanan; Chakrabarty, Biswaroop; Kumar, Atin; Gupta, Neerja; Kabra, Madhulika; Gulati, Sheffali

    2014-01-01

    Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures (1). The electroencephalographic abnormalities included hypsarrythmia (2) and multifocal epileptiform discharges (3). The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis. PMID:24891895

  7. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  8. Pharmacological therapies against soman-induced seizures in rats 30 min following onset and anticonvulsant impact.

    PubMed

    Myhrer, Trond; Enger, Siri; Aas, Pål

    2006-10-24

    Systemic administration does not allow a clear differentiation between the anticonvulsant properties of GABAA (gamma-aminobutyric acid) modulators. For this reason, various GABAA modulators have previously been micro-infused into seizure controlling substrates (area tempestas, substantia nigra) in the rat brain as a screening method for potential systemic administration. The purpose of the present study was to examine the anticonvulsant impact of the GABAergic modulators muscimol, ethanol, and propofol (screened by micro-infusions) when each drug was combined with procyclidine and administered systemically. The results showed that all 3 combinations could effectively terminate soman-induced (100 microg/kg s.c.) seizures when administered 30-35 min after onset. Procyclidine and propofol were considered as the most relevant double regimen to replace a previous triple regimen (procyclidine, diazepam, pentobarbital) against soman-induced seizures. Additionally, it was shown that unilateral implantation of hippocampal electrodes resulted in increased resistance to aphagia/adipsia and neuropathology, but not to lethality following soman. Efficient pharmacological treatment of soman-induced seizures at an early stage (< 20 min) is crucial to avoid neuropathology and cognitive deficits.

  9. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    PubMed

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.

  10. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum.

    PubMed

    McTague, Amy; Appleton, Richard; Avula, Shivaram; Cross, J Helen; King, Mary D; Jacques, Thomas S; Bhate, Sanjay; Cronin, Anthony; Curran, Andrew; Desurkar, Archana; Farrell, Michael A; Hughes, Elaine; Jefferson, Rosalind; Lascelles, Karine; Livingston, John; Meyer, Esther; McLellan, Ailsa; Poduri, Annapurna; Scheffer, Ingrid E; Spinty, Stefan; Kurian, Manju A; Kneen, Rachel

    2013-05-01

    Migrating partial seizures of infancy, also known as epilepsy of infancy with migrating focal seizures, is a rare early infantile epileptic encephalopathy with poor prognosis, presenting with focal seizures in the first year of life. A national surveillance study was undertaken in conjunction with the British Paediatric Neurology Surveillance Unit to further define the clinical, pathological and molecular genetic features of this disorder. Fourteen children with migrating partial seizures of infancy were reported during the 2 year study period (estimated prevalence 0.11 per 100,000 children). The study has revealed that migrating partial seizures of infancy is associated with an expanded spectrum of clinical features (including severe gut dysmotility and a movement disorder) and electrographic features including hypsarrhythmia (associated with infantile spasms) and burst suppression. We also report novel brain imaging findings including delayed myelination with white matter hyperintensity on brain magnetic resonance imaging in one-third of the cohort, and decreased N-acetyl aspartate on magnetic resonance spectroscopy. Putaminal atrophy (on both magnetic resonance imaging and at post-mortem) was evident in one patient. Additional neuropathological findings included bilateral hippocampal gliosis and neuronal loss in two patients who had post-mortem examinations. Within this cohort, we identified two patients with mutations in the newly discovered KCNT1 gene. Comparative genomic hybridization array, SCN1A testing and genetic testing for other currently known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was non-informative for the rest of the cohort.

  11. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum

    PubMed Central

    McTague, Amy; Appleton, Richard; Avula, Shivaram; Cross, J. Helen; King, Mary D.; Jacques, Thomas S.; Bhate, Sanjay; Cronin, Anthony; Curran, Andrew; Desurkar, Archana; Farrell, Michael A.; Hughes, Elaine; Jefferson, Rosalind; Lascelles, Karine; Livingston, John; Meyer, Esther; McLellan, Ailsa; Poduri, Annapurna; Scheffer, Ingrid E.; Spinty, Stefan; Kurian, Manju A.

    2013-01-01

    Migrating partial seizures of infancy, also known as epilepsy of infancy with migrating focal seizures, is a rare early infantile epileptic encephalopathy with poor prognosis, presenting with focal seizures in the first year of life. A national surveillance study was undertaken in conjunction with the British Paediatric Neurology Surveillance Unit to further define the clinical, pathological and molecular genetic features of this disorder. Fourteen children with migrating partial seizures of infancy were reported during the 2 year study period (estimated prevalence 0.11 per 100 000 children). The study has revealed that migrating partial seizures of infancy is associated with an expanded spectrum of clinical features (including severe gut dysmotility and a movement disorder) and electrographic features including hypsarrhythmia (associated with infantile spasms) and burst suppression. We also report novel brain imaging findings including delayed myelination with white matter hyperintensity on brain magnetic resonance imaging in one-third of the cohort, and decreased N-acetyl aspartate on magnetic resonance spectroscopy. Putaminal atrophy (on both magnetic resonance imaging and at post-mortem) was evident in one patient. Additional neuropathological findings included bilateral hippocampal gliosis and neuronal loss in two patients who had post-mortem examinations. Within this cohort, we identified two patients with mutations in the newly discovered KCNT1 gene. Comparative genomic hybridization array, SCN1A testing and genetic testing for other currently known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was non-informative for the rest of the cohort. PMID:23599387

  12. Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy.

    PubMed

    Iwasaki, Masaki; Uematsu, Mitsugu; Nakayama, Tojo; Hino-Fukuyo, Naomi; Sato, Yuko; Kobayashi, Tomoko; Haginoya, Kazuhiro; Osawa, Shin-Ichiro; Jin, Kazutaka; Nakasato, Nobukazu; Tominaga, Teiji

    2013-05-01

    To elucidate the benefit of corpus callosotmy in terms of parental satisfaction and seizure outcome. This study included 16 consecutive patients with infantile or early childhood onset epilepsy who underwent total corpus callosotomy for alleviation of seizures. Questionnaires were sent anonymously to the parents asking about relative changes in seizures and about parental satisfaction for the post-operative outcome. The improvements in frequency, intensity, and duration of seizures were correlated with the level of satisfaction (Spearman's rank-order correlation coefficient, ρ=0.87, 0.93, and 0.75, respectively). The highest level of satisfaction was only seen in patients who achieved freedom from all seizures or drop attacks. Complete seizure freedom and freedom from drop attacks are important goals of corpus callosotomy for parental satisfaction. These factors should be considered in assessing post-operative outcome after corpus callosotomy. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures.

    PubMed

    Veerapandiyan, Aravindhan; Singh, Piyush; Mikati, Mohamad A

    2012-03-01

    Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

  14. Source localization of the seizure onset zone from ictal EEG/MEG data.

    PubMed

    Pellegrino, Giovanni; Hedrich, Tanguy; Chowdhury, Rasheda; Hall, Jeffery A; Lina, Jean-Marc; Dubeau, Francois; Kobayashi, Eliane; Grova, Christophe

    2016-07-01

    Surgical treatment of drug-resistant epilepsy relies on the identification of the seizure onset zone (SOZ) and often requires intracranial EEG (iEEG). We have developed a new approach for non-invasive magnetic and electric source imaging of the SOZ (MSI-SOZ and ESI-SOZ) from ictal magnetoencephalography (MEG) and EEG recordings, using wavelet-based Maximum Entropy on the Mean (wMEM) method. We compared the performance of MSI-SOZ and ESI-SOZ with interictal spike source localization (MSI-spikes and ESI-spikes) and clinical localization of the SOZ (i.e., based on iEEG or lesion topography, denoted as clinical-SOZ). A total of 46 MEG or EEG seizures from 13 patients were analyzed. wMEM was applied around seizure onset, centered on the frequency band showing the strongest power change. Principal component analysis applied to spatiotemporal reconstructed wMEM sources (0.4-1 s around seizure onset) identified the main spatial pattern of ictal oscillations. Qualitative sublobar concordance and quantitative measures of distance and spatial overlaps were estimated to compare MSI/ESI-SOZ with MSI/ESI-Spikes and clinical-SOZ. MSI/ESI-SOZ were concordant with clinical-SOZ in 81% of seizures (MSI 90%, ESI 64%). MSI-SOZ was more accurate and identified sources closer to the clinical-SOZ (P = 0.012) and to MSI-Spikes (P = 0.040) as compared with ESI-SOZ. MSI/ESI-SOZ and MSI/ESI-Spikes did not differ in terms of concordance and distance from the clinical-SOZ. wMEM allows non-invasive localization of the SOZ from ictal MEG and EEG. MSI-SOZ performs better than ESI-SOZ. MSI/ESI-SOZ can provide important additional information to MSI/ESI-Spikes during presurgical evaluation. Hum Brain Mapp 37:2528-2546, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Efficacy and Safety of Levetiracetam and Carbamazepine as Monotherapy in Partial Seizures

    PubMed Central

    Suresh, Swaroop Hassan; Chakraborty, Ananya; Virupakshaiah, Akash; Kumar, Nithin

    2015-01-01

    Introduction. Levetiracetam (LEV) is a newer antiepileptic drug with better pharmacokinetic profile. Currently, it is frequently used for the treatment of partial seizures. The present study was undertaken to compare the efficacy and safety of LEV and Carbamazepine (CBZ) in partial epilepsy. Methods. This was a prospective, open labeled, randomized study. It was conducted in participants suffering from partial seizures after the approval of ethics committee and written informed consent. The first group received Tab LEV (500 to 3000 mg/day) and the second group received Tab CBZ (300 to 600 mg/day). The primary outcomes were efficacy and safety. The secondary outcome was the Quality of Life (QOL). Efficacy was assessed by comparing the seizure freedom rates at the end of 6 months. Safety profile was evaluated by comparing the adverse effects. QOL was assessed by QOLIE-10 scale. Results. The overall seizure freedom rate at the end of 6 months was 71.42% in CBZ group compared to 78.57% in LEV group (p = 0.2529). Both LEV and CBZ reported a similar incidence of adverse reactions. LEV group reported more behavioral changes like increased aggression and anxiety. Also, it showed better QOL compared to the CBZ group. Conclusion. LEV monotherapy and CBZ monotherapy demonstrated similar efficacy for treatment of partial epilepsy and were found to be well tolerated. PMID:26798511

  16. SCOPE-mTL: A non-invasive tool for identifying and lateralizing mesial temporal lobe seizures prior to scalp EEG ictal onset.

    PubMed

    Lam, Alice D; Maus, Douglas; Zafar, Sahar F; Cole, Andrew J; Cash, Sydney S

    2017-09-01

    In mesial temporal lobe (mTL) epilepsy, seizure onset can precede the appearance of a scalp EEG ictal pattern by many seconds. The ability to identify this early, occult mTL seizure activity could improve lateralization and localization of mTL seizures on scalp EEG. Using scalp EEG spectral features and machine learning approaches on a dataset of combined scalp EEG and foramen ovale electrode recordings in patients with mTL epilepsy, we developed an algorithm, SCOPE-mTL, to detect and lateralize early, occult mTL seizure activity, prior to the appearance of a scalp EEG ictal pattern. Using SCOPE-mTL, 73% of seizures with occult mTL onset were identified as such, and no seizures that lacked an occult mTL onset were identified as having one. Predicted mTL seizure onset times were highly correlated with actual mTL seizure onset times (r=0.69). 50% of seizures with early mTL onset were lateralizable prior to scalp ictal onset, with 94% accuracy. SCOPE-mTL can identify and lateralize mTL seizures prior to scalp EEG ictal onset, with high sensitivity, specificity, and accuracy. Quantitative analysis of scalp EEG can provide important information about mTL seizures, even in the absence of a visible scalp EEG ictal correlate. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  17. Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.

    PubMed

    Gupta, Lalit; Janssens, Rick; Vlooswijk, Mariëlle C G; Rouhl, Rob P W; de Louw, Anton; Aldenkamp, Albert P; Ulman, Shrutin; Besseling, René M H; Hofman, Paul A M; van Kranen-Mastenbroek, Vivianne H; Hilkman, Danny M; Jansen, Jacobus F A; Backes, Walter H

    2017-03-01

    The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure. We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs). We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences. The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  18. Characterization of two de novoKCNT1 mutations in children with malignant migrating partial seizures in infancy.

    PubMed

    Rizzo, Francesca; Ambrosino, Paolo; Guacci, Anna; Chetta, Massimiliano; Marchese, Giovanna; Rocco, Teresa; Soldovieri, Maria Virginia; Manocchio, Laura; Mosca, Ilaria; Casara, Gianluca; Vecchi, Marilena; Taglialatela, Maurizio; Coppola, Giangennaro; Weisz, Alessandro

    2016-04-01

    The KCNT1 gene encodes for subunits contributing to the Na(+)-activated K(+) current (KNa), expressed in many cell types. Mutations in KCNT1 have been found in patients affected with a wide spectrum of early-onset epilepsies, including Malignant Migrating Partial Seizures in Infancy (MMPSI), a severe early-onset epileptic encephalopathy characterized by pharmacoresistant focal seizures migrating from one brain region or hemisphere to another and neurodevelopment arrest or regression, resulting in profound disability. In the present study we report identification by whole exome sequencing (WES) of two de novo, heterozygous KCNT1 mutations (G288S and, not previously reported, M516V) in two unrelated MMPSI probands. Functional studies in a heterologous expression system revealed that channels formed by mutant KCNT1 subunits carried larger currents when compared to wild-type KCNT1 channels, both as homo- and heteromers with these last. Both mutations induced a marked leftward shift in homomeric channel activation gating. Interestingly, the KCNT1 blockers quinidine (3-1000μM) and bepridil (0.03-10μM) inhibited both wild-type and mutant KCNT1 currents in a concentration-dependent manner, with mutant channels showing higher sensitivity to blockade. This latter result suggests two genotype-tailored pharmacological strategies to specifically counteract the dysfunction of KCNT1 activating mutations in MMPSI patients.

  19. A Fuzzy Logic System for Seizure Onset Detection in Intracranial EEG

    PubMed Central

    Rabbi, Ahmed Fazle; Fazel-Rezai, Reza

    2012-01-01

    We present a multistage fuzzy rule-based algorithm for epileptic seizure onset detection. Amplitude, frequency, and entropy-based features were extracted from intracranial electroencephalogram (iEEG) recordings and considered as the inputs for a fuzzy system. These features extracted from multichannel iEEG signals were combined using fuzzy algorithms both in feature domain and in spatial domain. Fuzzy rules were derived based on experts' knowledge and reasoning. An adaptive fuzzy subsystem was used for combining characteristics features extracted from iEEG. For the spatial combination, three channels from epileptogenic zone and one from remote zone were considered into another fuzzy subsystem. Finally, a threshold procedure was applied to the fuzzy output derived from the final fuzzy subsystem. The method was evaluated on iEEG datasets selected from Freiburg Seizure Prediction EEG (FSPEEG) database. A total of 112.45 hours of intracranial EEG recordings was selected from 20 patients having 56 seizures was used for the system performance evaluation. The overall sensitivity of 95.8% with false detection rate of 0.26 per hour and average detection latency of 15.8 seconds was achieved. PMID:22577370

  20. A fuzzy logic system for seizure onset detection in intracranial EEG.

    PubMed

    Rabbi, Ahmed Fazle; Fazel-Rezai, Reza

    2012-01-01

    We present a multistage fuzzy rule-based algorithm for epileptic seizure onset detection. Amplitude, frequency, and entropy-based features were extracted from intracranial electroencephalogram (iEEG) recordings and considered as the inputs for a fuzzy system. These features extracted from multichannel iEEG signals were combined using fuzzy algorithms both in feature domain and in spatial domain. Fuzzy rules were derived based on experts' knowledge and reasoning. An adaptive fuzzy subsystem was used for combining characteristics features extracted from iEEG. For the spatial combination, three channels from epileptogenic zone and one from remote zone were considered into another fuzzy subsystem. Finally, a threshold procedure was applied to the fuzzy output derived from the final fuzzy subsystem. The method was evaluated on iEEG datasets selected from Freiburg Seizure Prediction EEG (FSPEEG) database. A total of 112.45 hours of intracranial EEG recordings was selected from 20 patients having 56 seizures was used for the system performance evaluation. The overall sensitivity of 95.8% with false detection rate of 0.26 per hour and average detection latency of 15.8 seconds was achieved.

  1. Seizures

    MedlinePlus

    ... entire body Sudden falling Tasting a bitter or metallic flavor Teeth clenching Temporary stop in breathing Uncontrollable ... Causes of seizures can include: Abnormal levels of sodium or glucose in the blood Brain infection, including ...

  2. Children with new onset seizures: A prospective study of parent variables, child behavior problems, and seizure occurrence.

    PubMed

    Austin, Joan K; Haber, Linda C; Dunn, David W; Shore, Cheryl P; Johnson, Cynthia S; Perkins, Susan M

    2015-12-01

    Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures; however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4-14 years) and their parents over a 24-month period (with data collected at baseline and 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizure group. Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Secondary generalization of focal-onset seizures: examining the relationship between seizure propagation and epilepsy surgery outcome.

    PubMed

    Tomlinson, Samuel B; Venkataraman, Arun

    2017-04-01

    Surgical intervention often fails to achieve seizure-free results in patients with intractable epilepsy. Identifying features of the epileptic brain that dispose certain patients to unfavorable outcomes is critical for improving surgical candidacy assessments. Recent research by Martinet, Ahmad, Lepage, Cash, and Kramer (J Neurosci 35: 9477-9490, 2015) suggests that pathways of secondary seizure generalization distinguish patients with favorable (i.e., seizure free) vs. unfavorable (i.e., seizure persistent) surgical outcomes, lending insights into the network mechanisms of epilepsy surgery failure. Copyright © 2017 the American Physiological Society.

  4. Factors associated with academic achievement in children with recent-onset seizures.

    PubMed

    McNelis, Angela M; Johnson, Cynthia S; Huberty, Thomas J; Austin, Joan K

    2005-07-01

    Children with chronic epilepsy are more at risk for achievement problems than either children without seizures or children with other chronic disorders. Factors that lead to such problems in children with epilepsy, however, are not well understood. Exploring these factors is important because academic underachievement can lead to poor social outcomes and contribute to underemployment or unemployment in adulthood. This descriptive, cross-sectional study investigated a group of children who had been diagnosed with seizures approximately 12 months previously, providing the opportunity to describe relationships among family and child characteristics; parent, child, and teacher responses; and child academic achievement at the same point in time across the sample. Seventy-two children had standardized test total battery scores, 101 had a teacher's rating of performance, and 67 had scores for both. Data were analyzed using multivariable regression. Child adaptive competency and seizure severity were associated with higher teacher ratings of academic performance (beta=0.73, p<0.0001 and beta=2.38, p=0.0182, respectively). Child adaptive competency was associated with higher total battery scores (beta=0.73, p<0.0001). Contrary to findings in studies of children with chronic epilepsy, mean academic achievement in this sample of children with recent-onset seizures was in the average range; however, 25% of the children were at or below one standard deviation below the mean on the teacher's rating of performance and 10% on the total battery. It is therefore important for health professionals and educators to regularly assess the child's academic functioning and school performance to identify those at risk for problems. Health professionals and educators need to collaborate on assessment and interventions to help maximize child academic success.

  5. Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

    PubMed

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

    2015-01-01

    Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

  6. Localisation value of ictal arterial spin-labelled sequences in partial seizures.

    PubMed

    Toledo, Manuel; Munuera, Josep; Salas-Puig, Xavier; Santamarina, Estevo; Lacuey, Nuria; Rovira, Alex

    2011-09-01

    Perfusion-based magnetic resonance imaging (MRI) using pulsed arterial spin-labelled (ASL) sequences is becoming a more commonly used tool for the diagnosis of patients with focal epilepsy. We report a patient with post-traumatic epilepsy and cortical haemorrhage who had a complex partial seizure characterised mainly by ictal speech (verbalisation) during MRI acquisition. Ictal ASL showed focal hyperperfusion over the right temporal region which had resolved on follow-up MRI, two weeks later. Seizure semiology and interictal EEG suggested seizure origin in the non-dominant temporal lobe, which matched the increased ictal blood flow observed by ASL. The patient had language dominance in the left hemisphere, as observed by functional MRI. Our findings suggest that focal hyperperfusion, as observed by ASL, may have localising value in temporal epilepsies when performed in the ictal period.

  7. Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

    PubMed

    Itakura, Ayako; Saito, Yoshiaki; Nishimura, Yoko; Okazaki, Tetsuya; Ohno, Koyo; Sejima, Hitoshi; Yamamoto, Toshiyuki; Maegaki, Yoshihiro

    2016-08-01

    A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  8. 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

  9. 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

  10. Relationship of clinical and quality of life trajectories following the onset of seizures: findings from the UK MESS Study.

    PubMed

    Jacoby, Ann; Lane, Steven; Marson, Anthony; Baker, Gus A

    2011-05-01

    We defined a series of clinical trajectories represented among adult patients with new-onset seizures across a 4-year follow-up period; and linked these clinical trajectories to the quality of life (QOL) profiles and trajectories of those experiencing them. We examined both between- and within-group differences. Analyses were based on 253 individuals completing QOL questionnaires at baseline and 2 and 4 years subsequently. Based on patient self-report, we defined five "clinical trajectory" groups: individuals experiencing a single seizure only; individuals entering early remission; individuals experiencing late remission; individuals initially becoming seizure-free but subsequently relapsing; individuals with seizures persisting throughout follow-up. QOL profiles at each time point were compared using a validated QOL battery, NEWQOL. Even at baseline, there were significant between-group differences, with patients experiencing a single seizure only reporting the best QOL profile and those with seizures subsequently persisting across all time points reporting the worst. By 2 years, the QOL profiles of individuals experiencing early remission were similar to those of single seizure patients, as were those for late remission and relapse patients. A consistent pattern was seen, with "single seizure" individuals doing best and individuals with persistent seizures doing worst. Of particular concern is that even at baseline, individuals whose seizures persisted were doing poorly for QOL, suggesting the possibility that underlying neurobiologic mechanisms were operating. In contrast, our findings support previous reports of only short-lived and small QOL decrements for individuals experiencing a single or few seizures. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  11. Mutational scanning of potassium, sodium and chloride ion channels in malignant migrating partial seizures in infancy.

    PubMed

    Coppola, Giangennaro; Veggiotti, Pierangelo; Del Giudice, Emanuele Miraglia; Bellini, Giulia; Longaretti, Francesca; Taglialatela, Maurizio; Pascotto, Antonio

    2006-03-01

    The mutational analysis of potassium (KCNQ2, KCNQ3), sodium (SCN1A, SCN2A), and chloride (CLCN2) ion channels was performed in three children with typical features of the recently described syndrome of migrating partial seizures in infancy. Mutational analysis was performed by PCR and automatic sequencing. The coding regions, including the exon-intron boundaries, were amplified in the patients using appropriate primers sets. No mutations associated to migrating partial seizures have been found. Mutational screening of CLCN2 gene, revealed a homozygous mutation G2003C (exon 17), leading to a Ser/Thr substitution at the codon 668, in two of the three patients. The same variation has been found in 38 out of 100 control alleles. The identification of the genetic basis of this new epileptic encephalopathy requires further studies that might be enforced by familial cases.

  12. Novel mutation in SLC6A19 causing late-onset seizures in Hartnup disorder.

    PubMed

    Cheon, Chong Kun; Lee, Beom Hee; Ko, Jung Min; Kim, Hyun-Ji; Yoo, Han-Wook

    2010-05-01

    Hartnup disorder is caused by an inborn error of neutral amino acid transport in the kidneys and intestines. It is characterized by pellagra-like rash, ataxia, and psychotic behavior. Elevated urinary neutral amino acids are the first indicator of the disorder. SLC6A19 was identified as the causative gene in autosomal-recessive Hartnup disorder, which encodes the amino acid transporter B(0)AT1, mediating neutral amino acid transport from the luminal compartment to the intracellular space. Here, we report on a Korean boy aged 8 years and 5 months with Hartnup disorder, as confirmed by SLC6A19 gene analysis. He manifested seizures, attention-deficit hyperactivity disorder, and mental retardation without pellagra or ataxia. Multiple neutral amino acids were increased in his urine, and genetic analysis of SLC6A19 revealed compound heterozygous mutations, c.908C>T (p.Ser303Leu) and c.1787_1788insG (p.Thr596fsX73), both of which are novel. A novel SLC6A19 gene mutation was associated with late-onset seizures in a Korean patient with Hartnup disorder. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Biventricular noncompaction cardiomyopathy in a patient presenting with new onset seizure: case report.

    PubMed

    Odiete, Oghenerukevwe; Nagendra, Ramanna; Lawson, Mark A; Okafor, Henry

    2012-01-01

    Ventricular noncompaction (VNC) of the myocardium is a rare genetic cardiomyopathy caused by a disorder during endocardial morphogenesis and could be accompanied by life-threatening complications. The major clinical manifestations of VNC are heart failure, arrhythmias, and embolic events. The left ventricle is the most commonly reported affected site, but a few cases of right ventricular involvement have also been reported. We report a case of biventricular noncompaction cardiomyopathy in a 31-year-old woman presenting with a new onset seizure. On the second day of her telemetry-monitored hospitalization, she suffered a witnessed ventricular fibrillation arrest requiring emergency direct-current cardioversion and induced hypothermia. Transthoracic echocardiography (TTE) showed isolated left ventricular (LV) noncompaction and depressed LV systolic function. Subsequent cardiac magnetic resonance imaging (MRI) revealed both left and right ventricular noncompaction. This unusual presentation highlights the importance of a complete and thorough evaluation of patients even when presenting with apparently noncardiac symptom(s).

  14. Epilepsy and weather: A significant correlation between the onset of epileptic seizures and specific atmospherics — a pilot study

    NASA Astrophysics Data System (ADS)

    Ruhenstroth-Bauer, G.; Baumer, H.; Kugler, J.; Spatz, R.; Sönning, W.; Filipiak, B.

    1984-12-01

    The possibility of connections between weather and the onset of epileptic seizures has long been suggested (see, for example, the Hammurabi Codex 1600 BC). Work in the 20th Century points to a probability that the onset of both local and generalised epilepsy is significantly influenced by an interaction between genetic and extrinsic factors. In an attempt to clarify the situation a detailed study of the history of 315 attacks from 1 Jan. to 31 July 1981 suffered by a small number of patients in Munich has been undertaken. Although linkages between “classical” meteorological parameters and the onset of seizures are very weak, links with more generalised indexes (e.g. passage of fronts and disturbances) are more promising. However, the correlation between onsets and “atmospherics” of 28 KHz (positive) and 10 KHz (negative) impulses, are significant and call for urgent study.

  15. Permittivity coupling across brain regions determines seizure recruitment in partial epilepsy.

    PubMed

    Proix, Timothée; Bartolomei, Fabrice; Chauvel, Patrick; Bernard, Christophe; Jirsa, Viktor K

    2014-11-05

    Brain regions generating seizures in patients with refractory partial epilepsy are referred to as the epileptogenic zone (EZ). During a seizure, paroxysmal activity is not restricted to the EZ, but may recruit other brain regions and propagate activity through large brain networks, which comprise brain regions that are not necessarily epileptogenic. The identification of the EZ is crucial for candidates for neurosurgery and requires unambiguous criteria that evaluate the degree of epileptogenicity of brain regions. To obtain such criteria and investigate the mechanisms of seizure recruitment and propagation, we develop a mathematical framework of coupled neural populations, which can interact via signaling through a slow permittivity variable. The permittivity variable captures effects evolving on slow timescales, including extracellular ionic concentrations and energy metabolism, with time delays of up to seconds as observed clinically. Our analyses provide a set of indices quantifying the degree of epileptogenicity and predict conditions, under which seizures propagate to nonepileptogenic brain regions, explaining the responses to intracerebral electric stimulation in epileptogenic and nonepileptogenic areas. In conjunction, our results provide guidance in the presurgical evaluation of epileptogenicity based on electrographic signatures in intracerebral electroencephalograms. Copyright © 2014 the authors 0270-6474/14/3415009-13$15.00/0.

  16. A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.

    PubMed

    Ishii, Atsushi; Shioda, Mutsuki; Okumura, Akihisa; Kidokoro, Hiroyuki; Sakauchi, Masako; Shimada, Shino; Shimizu, Toshiaki; Osawa, Makiko; Hirose, Shinichi; Yamamoto, Toshiyuki

    2013-12-01

    We performed analysis of KCNT1 in two unrelated patients with malignant migrating partial seizures in infancy. Both patients had intractable focal seizures since two months of age. Their seizures were characterized by a shift of epileptic focus during a single seizure and were resistant to most antiepileptic drugs but responded to vagus nerve stimulation in one and clorazepate in the other. Bidirectional sequencing for KCNT1 was analyzed by standard Sanger sequencing method. A de novo c.862G>A (p.Gly288Ser) missense mutation was identified at the pore region of KCNT1 channel in both patients, whereas all KCNT1 mutations in the previous reports were identified mostly in the intracellular C-terminal region. Computational analysis suggested possible changes in the molecular structure and the ion channel property induced by the Gly288Ser mutation. Because the G-to-A transition was located at CG dinucleotide sequences as previously reported for KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated the hot spots of these locations.

  17. New developments in the management of partial-onset epilepsy: role of brivaracetam

    PubMed Central

    Coppola, Giangennaro; Iapadre, Giulia; Operto, Francesca Felicia; Verrotti, Alberto

    2017-01-01

    Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children. Among the newest anticonvulsant drugs, brivaracetam, a high-affinity synaptic vesicle protein 2A ligand, reported to be 10- to 30-fold more potent than levetiracetam, is highly effective in a broad range of experimental models of focal and generalized seizures. Unlike levetiracetam, brivaracetam does not inhibit high-voltage Ca2+ channels and AMPA receptors and appears to inhibit neuronal voltage-gated sodium channels playing a role as a partial antagonist. Brivaracetam has a linear pharmacokinetic profile, is extensively metabolized and is excreted by urine (only 8%–11% unchanged). It does not seem to influence the pharmacokinetics of other antiepileptic drugs. It was approved in the European Union in January 2016 and in the US in February 2016 as an adjunctive therapy for the treatment of POS in patients older than 16 years of age. To date, its clinical efficacy as adjunctive antiepileptic treatment in adults with refractory POS at doses between 50 and 200 mg daily has been extensively assessed in two Phase IIb and four Phase III randomized controlled studies. Long-term extension studies show sustained efficacy of brivaracetam. Overall, the drug is generally well tolerated with only mild-to-moderate side effects. This is true also by intravenous route

  18. New developments in the management of partial-onset epilepsy: role of brivaracetam.

    PubMed

    Coppola, Giangennaro; Iapadre, Giulia; Operto, Francesca Felicia; Verrotti, Alberto

    2017-01-01

    Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children. Among the newest anticonvulsant drugs, brivaracetam, a high-affinity synaptic vesicle protein 2A ligand, reported to be 10- to 30-fold more potent than levetiracetam, is highly effective in a broad range of experimental models of focal and generalized seizures. Unlike levetiracetam, brivaracetam does not inhibit high-voltage Ca(2+) channels and AMPA receptors and appears to inhibit neuronal voltage-gated sodium channels playing a role as a partial antagonist. Brivaracetam has a linear pharmacokinetic profile, is extensively metabolized and is excreted by urine (only 8%-11% unchanged). It does not seem to influence the pharmacokinetics of other antiepileptic drugs. It was approved in the European Union in January 2016 and in the US in February 2016 as an adjunctive therapy for the treatment of POS in patients older than 16 years of age. To date, its clinical efficacy as adjunctive antiepileptic treatment in adults with refractory POS at doses between 50 and 200 mg daily has been extensively assessed in two Phase IIb and four Phase III randomized controlled studies. Long-term extension studies show sustained efficacy of brivaracetam. Overall, the drug is generally well tolerated with only mild-to-moderate side effects. This is true also by intravenous route

  19. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial.

    PubMed

    Brodie, Martin J; Rosenfeld, William E; Vazquez, Blanca; Sachdeo, Rajesh; Perdomo, Carlos; Mann, Allison; Arroyo, Santiago

    2009-08-01

    To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged > or = 16 years with refractory partial seizures. This double-blind, placebo-controlled, randomized, parallel-group, multicenter trial included an 8-week baseline phase and a 13-week double-blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a >/=50% reduction in partial seizure frequency. Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide-treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo-treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide-treated subjects, 28.2% experienced a > or = 50% decrease in partial seizure frequency versus 18.6% of placebo-treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase. Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.

  20. [An unusual case of status epilepticus of simple partial seizure with an occipital lobe focus].

    PubMed

    Yokoyama, E; Hirata, Y; Nagata, K

    1994-08-01

    A 45-year-old man developed generalized convulsion and consciousness disturbance at age 43. An X-ray CT revealed hemorrhagic infarction in the left fronto-parieto-temporal area. A conventional angiography disclosed complete occlusion of the left cortical vein. In the chronic stage of the stroke, he had incomplete right quadrantopsia, a mild right hemiparesis and sensory aphasia. The patient has had partial somatosensory seizures since February 1990. Ictal EEG recordings showed epileptogenic discharges in the left parietal region. The seizures were adequately controlled with clonazepam. Since July 27, 1993, he has become aware of blurred vision in both eyes accompanied with headache and dizziness. On August 6, he was admitted to the hospital with right homonymons hemianopsia, sensory aphsia and tonic seizures in the right hand. Ictal EEG recordings demonstrated theta waves of the left parieto-occipital region and epileptogenic discharges in the left occipital region which consisted of spikes, sharp waves and spike-wave complexes. Single photon emission computed tomography (SEPCT) images obtained during seizures showed considerable hyperperfusion in the left occipital temporal lobes, while there was hypoperfusion in the left temporo-parietal area corresponding to the lesion of the old cerebral infarction. A T2-weighted MRI scan showed an abnormal high-intensity area in the left occipital lobe that suggested brain edema. After the admission, the patient was treated with additional anticonvulsant drugs. The tonic seizures in the right hand disappeared and right homonymous hemianopsia and sensory aphasia showed gradual improvement in the next four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Design and Implementation of an On-Chip Patient-Specific Closed-Loop Seizure Onset and Termination Detection System.

    PubMed

    Zhang, Chen; Bin Altaf, Muhammad Awais; Yoo, Jerald

    2016-07-01

    This paper presents the design of an area- and energy-efficient closed-loop machine learning-based patient-specific seizure onset and termination detection algorithm, and its on-chip hardware implementation. Application- and scenario-based tradeoffs are compared and reviewed for seizure detection and suppression algorithm and system which comprises electroencephalography (EEG) data acquisition, feature extraction, classification, and stimulation. Support vector machine achieves a good tradeoff among power, area, patient specificity, latency, and classification accuracy for long-term monitoring of patients with limited training seizure patterns. Design challenges of EEG data acquisition on a multichannel wearable environment for a patch-type sensor are also discussed in detail. Dual-detector architecture incorporates two area-efficient linear support vector machine classifiers along with a weight-and-average algorithm to target high sensitivity and good specificity at once. On-chip implementation issues for a patient-specific transcranial electrical stimulation are also discussed. The system design is verified using CHB-MIT EEG database [1] with a comprehensive measurement criteria which achieves high sensitivity and specificity of 95.1% and 96.2%, respectively, with a small latency of 1 s. It also achieves seizure onset and termination detection delay of 2.98 and 3.82 s, respectively, with seizure length estimation error of 4.07 s.

  2. Seizure Onset Zone Localization from Ictal High-Density EEG in Refractory Focal Epilepsy.

    PubMed

    Staljanssens, Willeke; Strobbe, Gregor; Holen, Roel Van; Birot, Gwénaël; Gschwind, Markus; Seeck, Margitta; Vandenberghe, Stefaan; Vulliémoz, Serge; van Mierlo, Pieter

    2017-03-01

    Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.

  3. Optimizing SPECT SISCOM analysis to localize seizure-onset zone by using varying z scores.

    PubMed

    Newey, Christopher R; Wong, Chong; Wang, Z Irene; Chen, Xin; Wu, Guiyun; Alexopoulos, Andreas V

    2013-05-01

    Subtraction ictal single photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure-free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score. Twenty-six patients were identified as having ictal-interictal SPECT images, preoperative and postoperative MRI studies, and having remained seizure free for at least 6 months after temporal or extratemporal surgical resection. SISCOM analysis was performed using preoperative MRI studies, and then blindly reviewed for localization of hyperperfused regions. With the added information from postoperative, coregistered MRI, perfusion patterns were determined. Using pair-wise comparisons, we found that the optimal z score for SPECT-SISCOM localization of the epileptogenic zone was 1.5, not the commonly used z score of 2. The z score of 1.5 was 84.8% sensitive and 93.8% specific. The z score of 1.5 had a moderate interrater agreement (0.70). When an hourglass configuration hyperperfusion pattern was present, a trend toward correctly localizing the seizure onset region was suggested (100% of the 11 observed occurrences). Nonetheless this trend was not statistically significant, possibly reflecting the small number of occurrences in our study. SISCOM is a useful modality in evaluating patients for epilepsy surgery. This study shows that the z score of 1.5 represents a highly sensitive and

  4. The Cause of the Imbalance in the Neuronal Network Leading to Seizure Activity Can Be Predicted by the Electrographic Pattern of the Seizure Onset

    PubMed Central

    Bragin, Anatol; Azizyan, Avetis; Almajano, Joyel; Engel, Jerome

    2009-01-01

    This study investigates the temporal dynamics of ictal electrical activity induced by injection of the GABAA receptor antagonist bicuculline, and the glutamate agonist kainic acid, into the CA3 area of hippocampus. Experiments were conducted in freely moving adult Wistar rats implanted with microelectrodes in multiple brain areas. Wide-band electrical activity (0.1–3000 Hz) was recorded, and the latency of seizure onset as well as the pattern of electrical activity were investigated for each drug. The latencies between injection and the occurrence of first epileptiform events were 3.93 ± 2.76 (±STD) min for bicuculline and 6.37 ± 7.66 min for kainic acid, suggesting the existence of powerful seizure-suppressive mechanisms in the brain. Bicuculline evoked high-amplitude rhythmic epileptiform events at the site of injection which resembled interictal EEG spikes and rapidly propagated to adjacent and remote brain areas. Kainic acid evoked a completely different pattern with a gradual increase in the amplitude of 30–80 Hz activity. Whereas there was strong temporal correlation between EEG events at the site of bicuculline injection and discharges in distant areas, much less correlation was seen with kainic acid injection. Both patterns were followed by generalized ictal EEG discharges and behavioral seizures. Our results illustrate that the same area of the brain can trigger seizures with different electrographic patterns. The knowledge of the network mechanisms underlying these two distinct electrographic patterns might be helpful in designing differential strategies for preventing seizure occurrence. PMID:19295168

  5. Efficacy and safety of adjunctive zonisamide in adult patients with refractory partial-onset epilepsy: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Lu, Yang; Xiao, Zhanqin; Yu, Weihua; Xiao, Fei; Xiao, Zheng; Hu, Yida; Chen, Yangmei; Wang, Xuefeng

    2011-01-01

    Clinical studies have reported that zonisamide is effective for a wide range of seizure types, including refractory partial-onset seizures. However, there have been no reported studies of the efficacy of zonisamide in the Chinese population to date. The aim of the present study was to evaluate the efficacy and safety of zonisamide in the treatment of adult Chinese patients with refractory partial-onset epilepsy. This was a randomized, double-blind, placebo-controlled trial conducted over a 16-week period. 104 patients with refractory partial-onset epilepsy were enrolled. Participants were randomly assigned to receive add-on zonisamide or placebo. Zonisamide was titrated to a target dosage of 300 or 400 mg/day. Seizure frequency and adverse effects were documented. 102 patients completed the trial. Zonisamide showed significantly greater efficacy compared with placebo (responder rate 55.8% vs 36.0%, p<0.05), including 55.2% (16 of 29 patients) in the zonisamide 300 mg/day arm and 56.5% (13 of 23 patients) in the zonisamide 400 mg/day arm. Zonisamide 300 and 400 mg/day showed similar efficacy (p>0.05). Moreover, similar efficacy of zonisamide was found in the control of complex partial seizures, simple partial seizures and secondary generalized seizures. There was no difference in the incidence of adverse effects between zonisamide and placebo. Reported adverse effects in the zonisamide group involved the digestive system (32.5% of total adverse effects in the group) [including transient increases in liver enzymes (27.8%)], weight changes (30.2%), the haematological system (15.1%), neurological/psychiatric effects (10.3%), the urinary system (7.9%) and the cardiovascular system (4.0%). Only digestive system adverse effects constituted a significantly higher proportion of adverse effects in the zonisamide group than in the placebo group (32.5% vs 30.2%, p<0.05). Zonisamide 300-400 mg/day is effective and well tolerated as an adjunctive drug in adult Chinese

  6. Comparison of precipitating factors for mania and partial seizures: Indicative of shared pathophysiology?

    PubMed

    Bostock, Emmanuelle C S; Kirkby, Kenneth C; Garry, Michael I; Taylor, Bruce V M

    2015-09-01

    Mania in bipolar disorder (BD) and partial (focal) seizures (PS) arising from the temporal lobes, have a number of similarities. Typically, a chronic course of the disorders is punctuated by acute illness episodes. Common features of episodes may include sensory, perceptual, cognitive and affective changes. Both respond to anticonvulsant treatment. Common mechanisms imputed include neurotransmitters and kindling processes. Further investigation may improve understanding of the occurrence of both mania and PS, casting light on the relevance of temporal lobe mediated processes and pathology. One avenue of investigation is to compare aetiological factors and determine the extent of overlap which may indicate shared brain localization or pathophysiology. Aetiology includes predisposing, precipitating or perpetuating factors. This paper examines the literature on precipitating factors of mania, first or subsequent episode, and of PS in diagnosed epilepsy, which is the second or subsequent seizure, to identify the extent and nature of their overlap. Narrative review based on a literature search of PubMed and Google Scholar. Precipitating factors for both mania and PS were stress, sleep deprivation, antidepressant medication and, tentatively, emotion. For mania alone, goal-attainment events, spring and summer season, postpartum, and drugs include steroids and stimulants. For PS alone, winter season, menstruation and specific triggers in complex reflex epilepsies. Those not substantiated include lunar phase and menopause. A wide range of chemicals may provoke isolated seizures but by definition epilepsy requires at least two seizures. The overlap of precipitating factors in mania and PS imply that common brain processes may contribute to both, consistent with findings from neuroscience research. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Vagus nerve stimulation for complex partial seizures: surgical technique, safety, and efficacy.

    PubMed

    Landy, H J; Ramsay, R E; Slater, J; Casiano, R R; Morgan, R

    1993-01-01

    Electrical stimulation of the vagus nerve has shown efficacy in controlling seizures in experimental models, and early clinical trials have suggested possible benefit in humans. Eleven patients with complex partial seizures were subjected to implantation of vagus nerve stimulators. Electrode contacts embedded in silicone rubber spirals were placed on the left vagus nerve in the low cervical area. A transcutaneously programmable stimulator module was placed in an infraclavicular subcutaneous pocket and connected to the electrode. One patient required replacement of the system due to electrode fracture. Another patient developed delayed ipsilateral vocal-cord paralysis; the technique was then modified to allow more tolerance for postoperative nerve edema. A third patient showed asymptomatic vocal-cord paresis on immediate postoperative laryngoscopy. Vagus nerve stimulation produces transient vocal-cord dysfunction while the current is on. Nine patients were randomly assigned to receive either high- or low-current stimulation, and seizure frequency was recorded. The high-current stimulation group showed a median reduction in seizure frequency of 27.7% compared to the preimplantation baseline, while the low-current stimulation group showed a median increase of 6.3%. This difference approached statistical significance. The entire population then received maximally tolerable stimulation. The high-current stimulation group showed a further 14.3% reduction, while the low-current stimulation group showed a 25.4% reduction compared to the blinded period. The efficacy of vagus nerve stimulation seemed to depend on stimulus parameters, and a cumulative effect was evident. These results are encouraging, and further study of this modality as an adjunct treatment for epilepsy is warranted.

  8. Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors.

    PubMed

    Uzbay, Tayfun I; Kayir, Hakan; Ceyhan, Mert

    2007-02-01

    Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.

  9. The NAB shape learning subtest as a predictor of lateralized seizure onset.

    PubMed

    Hill, Stacy W; Strutt, Adriana M; Uber-Zak, Lori; Fogel, Travis G; Ropacki, Michael T

    2012-05-01

    This study presents the first empirical evaluation of the predictive value of the Neuropsychological Assessment Battery Shape Learning (NAB-SL) subtest in a sample of patients with unilateral temporal lobe epilepsy. Stimulus characteristics of the NAB-SL may improve predictive ability over other commonly used visual memory tests. Forty-nine patients with unilateral temporal lobe epilepsy were compared on measures of non-verbal and verbal memory (NAB-SL and Wechsler Memory Scale-III subtests). Univariate and forward conditional logistic regressions identified predictive values for each memory test individually and in combination. The NAB-SL delayed memory demonstrated consistently stronger predictive power over visual reproduction at the univariate and multivariate levels. The NAB-SL was a good predictor (80% range) of lateralized seizure onset when combined with a verbal memory measure. These preliminary results provide support for the use of the NAB-SL in preoperative epilepsy evaluations as a predictor of non-dominant temporal lobe dysfunction. Potential benefits of this test are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Identifying Seizure Onset Zone From the Causal Connectivity Inferred Using Directed Information

    NASA Astrophysics Data System (ADS)

    Malladi, Rakesh; Kalamangalam, Giridhar; Tandon, Nitin; Aazhang, Behnaam

    2016-10-01

    In this paper, we developed a model-based and a data-driven estimator for directed information (DI) to infer the causal connectivity graph between electrocorticographic (ECoG) signals recorded from brain and to identify the seizure onset zone (SOZ) in epileptic patients. Directed information, an information theoretic quantity, is a general metric to infer causal connectivity between time-series and is not restricted to a particular class of models unlike the popular metrics based on Granger causality or transfer entropy. The proposed estimators are shown to be almost surely convergent. Causal connectivity between ECoG electrodes in five epileptic patients is inferred using the proposed DI estimators, after validating their performance on simulated data. We then proposed a model-based and a data-driven SOZ identification algorithm to identify SOZ from the causal connectivity inferred using model-based and data-driven DI estimators respectively. The data-driven SOZ identification outperforms the model-based SOZ identification algorithm when benchmarked against visual analysis by neurologist, the current clinical gold standard. The causal connectivity analysis presented here is the first step towards developing novel non-surgical treatments for epilepsy.

  11. Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide

    PubMed Central

    Saneto, Russell P; Anderson, Gail D

    2009-01-01

    Lennox-Gaustaut syndrome is an electroclinical epilepsy syndrome characterized by the triad of electroencephalogram showing diffuse slow spike-and-wave discharges and paroxysmal fast activity, multiple intractable seizure types, and cognitive impairment. The intractability to seizure medications and cognitive impairment gives rise to eventual institutionalized patient care. Only a small subset of seizure medications has been shown to be helpful in seizure control. Most patients take up to 3 medications at high therapeutic dosing and are susceptible to medication-induced side effects. The lack of medication efficacy in seizure control has led one meta-analysis to conclude that there is no single medication that is highly efficacious in controlling seizures in this syndrome. On this background, a new and structurally novel seizure medication, rufinamide, has been found to be beneficial in the treatment of seizures in this syndrome. In a multicenter, double-blinded, randomized, placebo-controlled study, rufinamide was found to reduce seizures by over 30%. More importantly, it reduced the frequency of the seizure type that induces most of the morbidity of this syndrome, the drop seizure, by over 40%. There were few side effects, the medication was well tolerated, and in the open labeled extension study, tolerance was not found. In this review, we describe the main electroclinical features of Lennox-Gaustaut syndrome and summarize the few controlled studies that have contributed to its rational treatment. Currently, there is no single agent or combination of agents that effectively treat the multiple seizure types and co-morbidities in this syndrome. Our focus will be on the role of the new medication rufinamide in seizure reduction in patients with Lennox-Gaustaut syndrome. PMID:19536315

  12. Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide.

    PubMed

    Saneto, Russell P; Anderson, Gail D

    2009-04-01

    Lennox-Gaustaut syndrome is an electroclinical epilepsy syndrome characterized by the triad of electroencephalogram showing diffuse slow spike-and-wave discharges and paroxysmal fast activity, multiple intractable seizure types, and cognitive impairment. The intractability to seizure medications and cognitive impairment gives rise to eventual institutionalized patient care. Only a small subset of seizure medications has been shown to be helpful in seizure control. Most patients take up to 3 medications at high therapeutic dosing and are susceptible to medication-induced side effects. The lack of medication efficacy in seizure control has led one meta-analysis to conclude that there is no single medication that is highly efficacious in controlling seizures in this syndrome. On this background, a new and structurally novel seizure medication, rufinamide, has been found to be beneficial in the treatment of seizures in this syndrome. In a multicenter, double-blinded, randomized, placebo-controlled study, rufinamide was found to reduce seizures by over 30%. More importantly, it reduced the frequency of the seizure type that induces most of the morbidity of this syndrome, the drop seizure, by over 40%. There were few side effects, the medication was well tolerated, and in the open labeled extension study, tolerance was not found. In this review, we describe the main electroclinical features of Lennox-Gaustaut syndrome and summarize the few controlled studies that have contributed to its rational treatment. Currently, there is no single agent or combination of agents that effectively treat the multiple seizure types and co-morbidities in this syndrome. Our focus will be on the role of the new medication rufinamide in seizure reduction in patients with Lennox-Gaustaut syndrome.

  13. 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.

  14. Early Seizure Frequency and Aetiology Predict Long-Term Medical Outcome in Childhood-Onset Epilepsy

    ERIC Educational Resources Information Center

    Sillanpaa, Matti; Schmidt, Dieter

    2009-01-01

    In clinical practice, it is important to predict as soon as possible after diagnosis and starting treatment, which children are destined to develop medically intractable seizures and be at risk of increased mortality. In this study, we determined factors predictive of long-term seizure and mortality outcome in a population-based cohort of 102…

  15. Early Seizure Frequency and Aetiology Predict Long-Term Medical Outcome in Childhood-Onset Epilepsy

    ERIC Educational Resources Information Center

    Sillanpaa, Matti; Schmidt, Dieter

    2009-01-01

    In clinical practice, it is important to predict as soon as possible after diagnosis and starting treatment, which children are destined to develop medically intractable seizures and be at risk of increased mortality. In this study, we determined factors predictive of long-term seizure and mortality outcome in a population-based cohort of 102…

  16. Characterization of epileptic seizure dynamics using Gabor atom density.

    PubMed

    Jouny, Christophe C; Franaszczuk, Piotr J; Bergey, Gregory K

    2003-03-01

    The study of epileptic electroencephalograph (EEG) dynamics can potentially provide insights into seizure onset, evolution and termination. We propose a new synthetic measure based on time-frequency decomposition to provide detailed characterization of these dynamic changes. The matching pursuit (MP) method allows for continuous time-frequency decomposition. We have developed a derivative of the MP method, the Gabor atom density method (GAD) that facilitates interpretation during the dynamic ictal period. The GAD analysis was applied to intracranial recordings of complex partial seizures (n = 43) of mesial temporal origin in 7 patients. Complex partial seizure occurrence is systematically associated with a GAD increase of 400 +/- 150%. The GAD increase coincides with the electrographical evidence of seizure onset. The similarity between seizures in a given patient is very high with uniform onset slope, maximum level and termination pattern. Global GAD responses over all channels can reveal detailed seizure propagation patterns including secondary independent foci and secondary generalization. The GAD measure based on the MP decomposition is a reliable tool to detect seizure occurrence in long-term recordings, to differentiate seizures from artifacts on a multi-channel basis and to examine patterns of seizure propagation. The reproducible GAD pattern suggests consistent changes in signal inner structure and may provide new clues about seizure dynamics and evolution. The GAD method can provide information about seizure dynamics that can contribute to methods of seizure detection. These analyses may lead to better understanding of seizure termination and help facilitate application of responsive seizure control devices in humans.

  17. Interictal high-frequency oscillations generated by seizure onset and eloquent areas may be differentially coupled with different slow waves.

    PubMed

    Nonoda, Yutaka; Miyakoshi, Makoto; Ojeda, Alejandro; Makeig, Scott; Juhász, Csaba; Sood, Sandeep; Asano, Eishi

    2016-06-01

    High-frequency oscillations (HFOs) can be spontaneously generated by seizure-onset and functionally-important areas. We determined if consideration of the spectral frequency bands of coupled slow-waves could distinguish between epileptogenic and physiological HFOs. We studied a consecutive series of 13 children with focal epilepsy who underwent extraoperative electrocorticography. We measured the occurrence rate of HFOs during slow-wave sleep at each electrode site. We subsequently determined the performance of HFO rate for localization of seizure-onset sites and undesirable detection of nonepileptic sensorimotor-visual sites defined by neurostimulation. We likewise determined the predictive performance of modulation index: MI(XHz)&(YHz), reflecting the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. The predictive accuracy was quantified using the area under the curve (AUC) on receiver-operating characteristics analysis. Increase in HFO rate localized seizure-onset sites (AUC⩾0.72; p<0.001), but also undesirably detected nonepileptic sensorimotor-visual sites (AUC⩾0.58; p<0.001). Increase in MI(HFOs)&(3-4Hz) also detected both seizure-onset (AUC⩾0.74; p<0.001) and nonepileptic sensorimotor-visual sites (AUC⩾0.59; p<0.001). Increase in subtraction-MIHFOs [defined as subtraction of MI(HFOs)&(0.5-1Hz) from MI(HFOs)&(3-4Hz)] localized seizure-onset sites (AUC⩾0.71; p<0.001), but rather avoided detection of nonepileptic sensorimotor-visual sites (AUC⩽0.42; p<0.001). Our data suggest that epileptogenic HFOs may be coupled with slow-wave3-4Hz more preferentially than slow-wave0.5-1Hz, whereas physiologic HFOs with slow-wave0.5-1Hz more preferentially than slow-wave3-4Hz during slow-wave sleep. Further studies in larger samples are warranted to determine if consideration of the spectral frequency bands of slow-waves coupled with HFOs can positively contribute to presurgical evaluation of patients with focal epilepsy. Copyright

  18. A probabilistic approach for lateralization of seizure onset zone in drug-resistant epilepsy with bilateral cerebral pathology.

    PubMed

    Arya, Ravindra; Sivaganesan, Siva; Holland, Katherine D; Greiner, Hansel M; Mangano, Francesco T; Horn, Paul S

    2016-07-01

    Lateralization of seizure-onset zone (SOZ) during electroencephalography (EEG) monitoring in people with bilateral potentially epileptogenic lesions is important to facilitate clinical decision making for resective surgery. We develop two Bayesian approaches for estimating the number of consecutive ipsilateral seizures required to lateralize the SOZ to a given lower limit of 95% credible interval (LLI, assuming continuous prior distribution), or to a given posterior probability (assuming mixture of discrete and continuous prior probabilities). With estimation approach, if both the cerebral hemispheres are a priori equi-probable to contain SOZ, then using Jeffrey's prior, a minimum of 9, 18, and 38 consecutive ipsilateral seizures will yield an LLI of 0.81, 0.90, and 0.95 respectively. If one of the hemisphere is a priori more likely to have SOZ, then prior beta distributions with α=3, β=2, and α=4, β=3 will require a minimum of 18 and 24 consecutive ipsilateral seizures to yield an LLI of 0.80. Contrariwise, the testing approach allows approximation of the number of consecutive ipsilateral seizures to lateralize the SOZ depending on an estimate of prior probability of lateralized SOZ, to a desired posterior probability. For a prior probability of 0.5, using uniform prior, mixture model will require 7, 17, and 37 consecutive ipsilateral seizures to lateralize the SOZ with a posterior probability of 0.8, 0.9, and 0.95 respectively. While the reasoning presented here is based on probability theory, it is hoped that it may help clinical decision making and stimulate further validation with actual clinical data. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [Tetraplegia, resuscitation and epileptic seizures after partial colon resection in a 41-year-old woman].

    PubMed

    Wagner, W

    2014-01-01

    A 41-year-old woman, suffering from continuous abdominal pain, only presented a non-specific inflammation of the whole colon and an unclaryfied hyponatriaemia; in spite of the only doubtful explanation by an enormous elongation of the colon, it was partially resected. Thereafter, the patient's decline, hypaesthesia, areflexia and tetraparesis required intensive care. Despite immunoglobulin therapy, assuming a Guillain-Barré syndrome, the patient needed resuscitation, followed by signs of severe hypoxia (high level of neuron-specific enolase, hippocampal lesions). The abdominal pain, hyponatriaemia, persistent tachycardia, sensory deficits, tetraplegia, circulation arrest, later epileptic seizures and unusual urine color were finally explained by an acute intermittent porphyria (AIP). Although the symptoms were classic, the disease was recognized only very late. Indeed, it is so rare that most physicians will never be confronted with an AIP or only once or twice.

  20. A critical role for network structure in seizure onset: a computational modeling approach.

    PubMed

    Petkov, George; Goodfellow, Marc; Richardson, Mark P; Terry, John R

    2014-01-01

    Recent clinical work has implicated network structure as critically important in the initiation of seizures in people with idiopathic generalized epilepsies. In line with this idea, functional networks derived from the electroencephalogram (EEG) at rest have been shown to be significantly different in people with generalized epilepsy compared to controls. In particular, the mean node degree of networks from the epilepsy cohort was found to be statistically significantly higher than those of controls. However, the mechanisms by which these network differences can support recurrent transitions into seizures remain unclear. In this study, we use a computational model of the transition into seizure dynamics to explore the dynamic consequences of these differences in functional networks. We demonstrate that networks with higher mean node degree are more prone to generating seizure dynamics in the model and therefore suggest a mechanism by which increased mean node degree of brain networks can cause heightened ictogenicity.

  1. Clinical and ictal characteristics of infantile seizures: EEG correlation via long-term video EEG monitoring.

    PubMed

    Yu, Hee Joon; Lee, Cha Gon; Nam, Sook Hyun; Lee, Jeehun; Lee, Munhyang

    2013-09-01

    The semiology of infantile seizures often shows different characteristics from that of adults. We performed this study to describe clinical and ictal characteristics of infantile seizures at less than two years of age. A retrospective study was done for infants with epilepsy (ages: 1-24months) who underwent long-term video electroencephalography (EEG) monitoring at Samsung medical center between November 1994 and February 2012. We analyzed the clinical and ictal characteristics of the 56 cases from 51 patients. In 69% of the patients, the seizure onset was before six months of age and the etiology was symptomatic in one third of the patients. Twelve seizure types were identified; spasms (24%), unilateral motor seizures (18%), and generalized tonic seizures (15%) were the three frequent types of seizure. All partial seizures were well correlated with the partial-onset ictal EEG, however 19.4% (7/36) of clinically generalized seizures revealed partial-onset ictal EEG. About one-thirds (4/11) of generalized tonic seizures had its ictal onset on unilateral or bilateral frontal areas and two out of seven generalized myoclonic seizures showed unilateral frontal rhythmic activities. Hypomotor seizures mainly arose from the temporal areas and hypermotor seizures from the frontal regions. Even though most of the seizure semiology of infants is well correlated with ictal EEG, some of the generalized tonic seizures or myoclonic seizures revealed partial-onset ictal EEG suggesting localized epileptic focus. Accurate definition of seizures via video EEG monitoring is necessary for proper management of seizures in infancy, especially in some clinically generalized seizures. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

    PubMed Central

    Zhao, Jianghao; Liu, Tingting; Cai, Yujie; Zhou, Xu; Xing, Huaijie; Wang, Yan; Yin, Mingkang; Zhong, Wangtao; Liu, Zhou; Li, Keshen

    2017-01-01

    Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments. PMID:28242958

  3. Numinous-like auras and spirituality in persons with partial seizures.

    PubMed

    Dolgoff-Kaspar, Rima; Ettinger, Alan B; Golub, Sarit A; Perrine, Kenneth; Harden, Cynthia; Croll, Susan D

    2011-03-01

    This study investigated hyperreligiosity in persons with partial epilepsy by exploring a relationship between aura symptoms and spirituality. It was reasoned that patients with high frequencies of auras that are suggestive of metaphysical phenomena, termed numinous-like auras, would report increased spirituality of an unconventional form, both during their seizures and generally. Numinous-like auras included: dreaminess/feeling of detachment, autoscopy, derealization, depersonalization, time speed alterations, bodily distortions, and pleasure. A high-frequency aura group, low-frequency aura group, and nonseizure reference group were compared on the Expressions of Spirituality-Revised. The High group had significantly greater Experiential/Phenomenological Dimension and Paranormal Beliefs factor scores than the Low group, and significantly greater Experiential/Phenomenological Dimension factor scores than the reference group. There were no differences between the Low group and the reference group. In addition, there were no differences among the three groups on traditional measures of religiosity. The results provide preliminary evidence that epilepsy patients with frequent numinous-like auras have greater ictal and interictal spirituality of an experiential, personalized, and atypical form, which may be distinct from traditional, culturally based religiosity. This form of spirituality may be better described by the term cosmic spirituality than hyperreligiosity. It is speculated that this spirituality is due to an overactivation and subsequent potentiation of the limbic system, with frequent numinous-like auras indicating sufficient activation for this process to occur. It is likely that numinous-like experiences foster cosmic spirituality in a number of circumstances, including seizures, psychosis, near-death experiences, psychedelic drug use, high-elevation exposure, and also normal conditions. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  4. Efficacy and safety of antiepileptic drugs for refractory partial-onset epilepsy: a network meta-analysis.

    PubMed

    Hu, Qingting; Zhang, Fang; Teng, Wenhui; Hao, Fangfang; Zhang, Jing; Yin, Mingxiao; Wang, Naidong

    2017-09-22

    The optimal combination of antiepileptic drugs (AEDs) for the treatment of refractory partial-onset epilepsy is a perpetual point of debate. While several network meta-analyses (NMAs) have been published, conclusions remain controversial, especially since newer AEDs have been introduced. In our review, we included the newer AEDs to evaluate the comparative efficacy and safety of AEDs for the treatment of refractory partial-onset epilepsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (Cochrane Library 2017, Issue 1) from their inception to February 18, 2017. The risk of bias in the included randomized controlled trials (RCTs) was evaluated according to the Cochrane Collaboration's risk of bias tool. An NMA was performed with a Bayesian random-effects model, and we used the surface under the cumulative ranking curve to detect the optimal AEDs. Seventy-six RCTs with 17 AEDs and 20,711 patients were included in the NMAs, which showed that Brivaracetam (BRV), Levetiracetam (LEV), Oxcarbazepine (OXC), Topiramate, Vigabatrin (VGB), and Valproate (VPA) had a greater likelihood of allowing patients to achieve seizure freedom. We also found that LEV was associated with a lower withdrawal rate due to adverse effects than Lacosamide, Eslicarbazepine acetate, OXC, Pregabalin, and Retigabine. LEV, VGB, VPA, and BRV emerged as the agents with the best combination of properties when considering the efficacy and safety outcomes based on the full double-blind treatment period. However, it is critical to perform RCTs and to obtain prospective data from representative cohort studies.

  5. Clinical use of an herbal-derived compound (Huperzine A) to treat putative complex partial seizures in a dog.

    PubMed

    Schneider, Barbara M; Dodman, Nicholas H; Faissler, Dominik; Ogata, Niwako

    2009-08-01

    A Bernese mountain dog was diagnosed with complex partial seizures that were supported by electroencephalographic findings. Clinical signs of the problem included "star gazing," fly snapping, licking, vacuous chewing, and ongoing anxiety. Treatment with Huperzine A, a compound isolated from Chinese club moss with NMDA receptor blocking activity, anticholinesterase activity, and anticonvulsant properties, produced useful suppression of the abnormal behavior for more than months. A relapse occurred when the dog was treated with tramadol for joint pain and the improvement that had been made was not recaptured with Huperzine A. At this stage, phenobarbital therapy was instituted and the dog improved greatly. The role of Huperzine A in controlling seizures is discussed.

  6. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy.

    PubMed

    Leite, J P; Bortolotto, Z A; Cavalheiro, E A

    1990-01-01

    Seizures induced by pilocarpine (PILO) have proven to be a useful procedure for investigating the basic mechanisms essential for generation, spread and motor expression of seizures in rodents. Here we report the long-term effects of PILO in rats. Following PILO (380 mg/kg, IP), 3 distinct phases were observed: 1) an acute period which lasted 1-2 days which corresponds to the pattern of repetitive seizures and status epilepticus; 2) a silent period (4-44 days) characterized by a progressive return to normal EEG and behavior; and 3) a period of recurrent seizures which started 5-45 days after PILO and lasted up to 120 days. These seizures lasted up to 50-60 sec, recurred 2-3 times per week and were more frequent during the light period of the light-dark cycle. These serial events offer a new method to induce spontaneous recurrent seizures in rats.

  7. Catastrophe theory enables moves to be detected towards and away from self-organization: the example of epileptic seizure onset.

    PubMed

    Cerf, Roger

    2006-06-01

    Macroscopic systems with many interacting subunits, when driven far from equilibrium, exhibit self-organization, for example when a pathological rhythm appears suddenly in an epileptic patient. Sudden changes occurring while conditions vary smoothly have, in cases of interest, underlying mathematics that are the subject of Thom's catastrophe theory. The assumption made herein that the system's state variables, akin to order parameters, reduce in practice to only one single real variable, ensures that the system derives from a potential function, and warrants recourse to the catastrophe theory. The order parameter is, furthermore, interpreted as a measure of the electropathophysiological activity in the brain, increasing monotonously with the degree of neuronal synchronism. With two neuronal influences, excitatory and inhibitory, as control parameters, the catastrophe is the archetypal cusp. Implementation of catastrophe theory leads to equations showing that fluctuations in a system's dynamics may be utilised for signalling steps precursory to oncoming catastrophes. Pre-seizure dynamics in epileptic patients exhibit steps towards and away from catastrophe; the steps away are interpreted in terms of homeostatic feedback, consequent on changing patterns of neuronal activity. A number of characteristics of epileptic seizures of differing types merely follow from the geometry of the cusp equilibrium surface. In particular, types of seizures are distinguished by their angle of final approach to onset in parameter space. The measurable parameters by which approach to catastrophe is characterized, may be of use in investigations of the organism's plasticity in epileptic patients, and in tests of therapeutic means for preventing seizures. There is no need to resort to a model, in the usual sense of the word, and therefore no differential equation needs to be set up.

  8. ONSET OF FAST MAGNETIC RECONNECTION IN PARTIALLY IONIZED GASES

    SciTech Connect

    Malyshkin, Leonid M.; Zweibel, Ellen G. E-mail: zweibel@astro.wisc.edu

    2011-10-01

    We consider quasi-stationary two-dimensional magnetic reconnection in a partially ionized incompressible plasma. We find that when the plasma is weakly ionized and the collisions between the ions and the neutral particles are significant, the transition to fast collisionless reconnection due to the Hall effect in the generalized Ohm's law is expected to occur at much lower values of the Lundquist number, as compared to a fully ionized plasma case. We estimate that these conditions for fast reconnection are satisfied in molecular clouds and in protostellar disks.

  9. Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

    PubMed

    Nagy, Szilvia A; Horváth, Réka; Perlaki, Gábor; Orsi, Gergely; Barsi, Péter; John, Flóra; Horváth, Andrea; Kovács, Norbert; Bogner, Péter; Ábrahám, Hajnalka; Bóné, Beáta; Gyimesi, Csilla; Dóczi, Tamás; Janszky, József

    2016-08-01

    In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late

  10. Physics of the Brain: Interaction of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams with the Epilepsy Topion, (the Seizure Onset Area)

    NASA Astrophysics Data System (ADS)

    Stefan, V. Alexander

    A novel method for the possible prevention of epileptic seizures is proposed, based on the multi-ultraviolet-photon beam interaction with the epilepsy topion, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion lead, (within the 10s of milliseconds), to the onset of chaos, (seizure--excessive electrical discharge), and subsequent cascading into adjacent areas. The ultraviolet photons may control the imbalance of sodium and potassium ions and, consequently, may prove to be efficient in the prevention of epileptic seizures. Supported by Nikola Tesla Labs, Stefan University.

  11. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline.

    PubMed

    Hardies, Katia; Cai, Yiying; Jardel, Claude; Jansen, Anna C; Cao, Mian; May, Patrick; Djémié, Tania; Hachon Le Camus, Caroline; Keymolen, Kathelijn; Deconinck, Tine; Bhambhani, Vikas; Long, Catherine; Sajan, Samin A; Helbig, Katherine L; Suls, Arvid; Balling, Rudi; Helbig, Ingo; De Jonghe, Peter; Depienne, Christel; De Camilli, Pietro; Weckhuysen, Sarah

    2016-09-01

    SYNJ1 encodes a polyphosphoinositide phosphatase, synaptojanin 1, which contains two consecutive phosphatase domains and plays a prominent role in synaptic vesicle dynamics. Autosomal recessive inherited variants in SYNJ1 have previously been associated with two different neurological diseases: a recurrent homozygous missense variant (p.Arg258Gln) that abolishes Sac1 phosphatase activity was identified in three independent families with early onset parkinsonism, whereas a homozygous nonsense variant (p.Arg136*) causing a severe decrease of mRNA transcript was found in a single patient with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid substitution (p.Tyr888Cys) was found to impair, but not abolish, the dual phosphatase activity of SYNJ1, whereas three premature stop variants (homozygote p.Trp843* and compound heterozygote p.Gln647Argfs*6/p.Ser1122Thrfs*3) almost completely abolished mRNA transcript production. A genetic follow-up screening in a large cohort of 543 patients with a wide phenotypical range of epilepsies and intellectual disability revealed no additional pathogenic variants, showing that SYNJ1 deficiency is rare and probably linked to a specific phenotype. While variants leading to early onset parkinsonism selectively abolish Sac1 function, our results provide evidence that a critical reduction of the dual phosphatase activity of SYNJ1 underlies a severe disorder with neonatal refractory epilepsy and a neurodegenerative disease course. These findings further expand the clinical spectrum of synaptic dysregulation in patients with severe epilepsy, and emphasize the importance of this biological pathway in seizure pathophysiology.

  12. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis

    PubMed Central

    Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

    2016-01-01

    Background We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. Methods In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. Results We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Conclusions Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype–phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. PMID:26993267

  13. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

    PubMed

    Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

    2016-05-01

    We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype-phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. 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/

  14. Optimized Seizure Detection Algorithm: A Fast Approach for Onset of Epileptic in EEG Signals Using GT Discriminant Analysis and K-NN Classifier

    PubMed Central

    Rezaee, Kh.; Azizi, E.; Haddadnia, J.

    2016-01-01

    Background Epilepsy is a severe disorder of the central nervous system that predisposes the person to recurrent seizures. Fifty million people worldwide suffer from epilepsy; after Alzheimer’s and stroke, it is the third widespread nervous disorder. Objective In this paper, an algorithm to detect the onset of epileptic seizures based on the analysis of brain electrical signals (EEG) has been proposed. 844 hours of EEG were recorded form 23 pediatric patients consecutively with 163 occurrences of seizures. Signals had been collected from Children’s Hospital Boston with a sampling frequency of 256 Hz through 18 channels in order to assess epilepsy surgery. By selecting effective features from seizure and non-seizure signals of each individual and putting them into two categories, the proposed algorithm detects the onset of seizures quickly and with high sensitivity. Method In this algorithm, L-sec epochs of signals are displayed in form of a third-order tensor in spatial, spectral and temporal spaces by applying wavelet transform. Then, after applying general tensor discriminant analysis (GTDA) on tensors and calculating mapping matrix, feature vectors are extracted. GTDA increases the sensitivity of the algorithm by storing data without deleting them. Finally, K-Nearest neighbors (KNN) is used to classify the selected features. Results The results of simulating algorithm on algorithm standard dataset shows that the algorithm is capable of detecting 98 percent of seizures with an average delay of 4.7 seconds and the average error rate detection of three errors in 24 hours. Conclusion Today, the lack of an automated system to detect or predict the seizure onset is strongly felt. PMID:27672628

  15. Seizure Treatment in Transplant Patients

    PubMed Central

    Shepard, Paul W.

    2013-01-01

    Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and

  16. A partial least squares analysis of seizure outcomes following resective surgery for tuberous sclerosis complex in children with intractable epilepsy.

    PubMed

    Ibrahim, George M; Morgan, Benjamin R; Fallah, Aria

    2015-02-01

    Previous studies aimed at identifying predictors of seizure outcomes following resective surgery for tuberous sclerosis complex (TSC) are limited by multicollinearity among predictors, whereby the high degree of correlation between covariates precludes detection of potentially significant findings. Here, we apply a data-driven method, partial least squares (PLS) to model multidimensional variance and study significant patterns in data that are associated with seizure outcomes. Post hoc analysis of 186 children with TSC who underwent resective epilepsy surgery derived from an individual participant data meta-analysis was performed. PLS was used to derive a latent variable (component) that relates clinical covariates with Engel classification. Permutation testing was performed to evaluate the significance of the component, and bootstrapping was used to identify significant contributors to the component. A significant component was identified, which represents the pattern of covariates related to Engel class. The strongest and significant factors contributing to this component were focal ictal electroencephalogram and concordance of electroencephalography (EEG)-magnetic resonance imaging (MRI) abnormality. Interestingly, covariates contributing the least to the seizure-free patient phenotype were continent of treatment and age at the time of surgery. Using a data-driven, multivariate method, PLS, we describe patient phenotypes that are associated with seizure-freedom following resective surgery for TSC.

  17. Standing waves as an explanation for generic stationary correlation patterns in noninvasive EEG of focal onset seizures.

    PubMed

    Müller, Markus Franziskus; Rummel, Christian; Goodfellow, Marc; Schindler, Kaspar

    2014-03-01

    Cerebral electrical activity is highly nonstationary because the brain reacts to ever changing external stimuli and continuously monitors internal control circuits. However, a large amount of energy is spent to maintain remarkably stationary activity patterns and functional inter-relations between different brain regions. Here we examine linear EEG correlations in the peri-ictal transition of focal onset seizures, which are typically understood to be manifestations of dramatically changing inter-relations. Contrary to expectations we find stable correlation patterns with a high similarity across different patients and different frequency bands. This skeleton of spatial correlations may be interpreted as a signature of standing waves of electrical brain activity constituting a dynamical ground state. Such a state could promote the formation of spatiotemporal neuronal assemblies and may be important for the integration of information stemming from different local circuits of the functional brain network.

  18. A 33-year-old patient with human immunodeficiency virus on antiretroviral therapy with efavirenz-induced complex partial seizures: a case report.

    PubMed

    Shehu, Nathan Yakubu; Ojeh, Victor; Osaigbovo, Godwin; Agaba, Patricia; Agbaji, Oche

    2016-04-13

    Efavirenz is a commonly prescribed antiretroviral drug that is largely well tolerated. However, seizure disorder is a rare side effect. Prompt identification and immediate replacement of efavirenz with an alternative drug would effectively stop the seizures. To the best of our knowledge, we present the first reported case in the literature of complex partial seizures arising due to efavirenz. We report a case of a 33-year-old Nigerian man treated with an efavirenz-based antiretroviral regimen for human immunodeficiency virus infection. He presented with seizures soon after commencement of antiretroviral drugs. His magnetic resonance imaging results were unremarkable. His blood levels of sodium, glucose, urea, and creatinine were within normal limits. However, his electroencephalogram showed intermittent bursts of high-voltage sharp waves and spikes bilaterally over frontotemporoparietal regions, a finding consistent with complex partial seizures. His efavirenz plasma level was 209.55 μg/ml. His seizures stopped following a switch to a non-efavirenz-based regimen. This report brings to light the occurrence of complex partial seizures in patients on efavirenz. It also demonstrates the effective resolution of seizures when efavirenz treatment is replaced with a non-efavirenz-based regimen.

  19. Development and pharmacologic characterization of the rat 6 Hz model of partial seizures.

    PubMed

    Metcalf, Cameron S; West, Peter J; Thomson, Kyle E; Edwards, Sharon F; Smith, Misty D; White, H Steve; Wilcox, Karen S

    2017-06-01

    The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis. Numerous prototype ASDs were evaluated in this model using stimulus intensities of 1.5× and 2× the CC97 , which is comparable to the approach used in the mouse 6 Hz seizure model (e.g., 32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine, clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide, tiagabine, topiramate, and sodium valproate. Median effective dose (ED50 ) and median toxic (motor impairment) dose (TD50 ) values were obtained for each compound. Compounds that were effective at the 1.5 × CC97 stimulus intensity at protective index (PI) values >1 included clobazam, ethosuximide, ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that were effective at the 2 × CC97 stimulus intensity at PI values >1 included ezogabine, phenobarbital, and sodium valproate. In a manner similar to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in the differentiation of ASDs, as well as in study design and dose selection for chronic rat models of pharmacoresistant epilepsy. The limited number of established ASDs with demonstrable efficacy at the higher stimulus intensity suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be a useful screening tool for pharmacoresistant seizures. Wiley Periodicals, Inc.

  20. The efficacy of bromides, stiripentol and levetiracetam in two patients with malignant migrating partial seizures in infancy.

    PubMed

    Djuric, Milena; Kravljanac, Ruzica; Kovacevic, Gordana; Martic, Jelena

    2011-03-01

    The syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic problem. In this study, we present two patients who were diagnosed with the disease, based on electroclinical symptoms. The patients were treated with a combination of sodium bromide, stiripentol and levetiracetam. The first patient unequivocally responded, following a course of ineffective conventional drugs, and the second, who was diagnosed and treated immediately, showed a more significant therapeutic response. Antiepileptic drugs, previously reported to be beneficial in case reports, when given concomitantly, may substantially reduce the number and severity of seizures, without influence on psychomotor development. [Published with video sequences].

  1. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.

    PubMed

    Barcia, Giulia; Fleming, Matthew R; Deligniere, Aline; Gazula, Valeswara-Rao; Brown, Maile R; Langouet, Maeva; Chen, Haijun; Kronengold, Jack; Abhyankar, Avinash; Cilio, Roberta; Nitschke, Patrick; Kaminska, Anna; Boddaert, Nathalie; Casanova, Jean-Laurent; Desguerre, Isabelle; Munnich, Arnold; Dulac, Olivier; Kaczmarek, Leonard K; Colleaux, Laurence; Nabbout, Rima

    2012-11-01

    Malignant migrating partial seizures of infancy (MMPSI) is a rare epileptic encephalopathy of infancy that combines pharmacoresistant seizures with developmental delay. We performed exome sequencing in three probands with MMPSI and identified de novo gain-of-function mutations affecting the C-terminal domain of the KCNT1 potassium channel. We sequenced KCNT1 in 9 additional individuals with MMPSI and identified mutations in 4 of them, in total identifying mutations in 6 out of 12 unrelated affected individuals. Functional studies showed that the mutations led to constitutive activation of the channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C. In addition to regulating ion flux, KCNT1 has a non-conducting function, as its C terminus interacts with cytoplasmic proteins involved in developmental signaling pathways. These results provide a focus for future diagnostic approaches and research for this devastating condition.

  2. Ictus expectoratus: a sign of complex partial seizures usually of non-dominant temporal lobe origin.

    PubMed

    Kaplan, P W; Kerr, D A; Olivi, A

    1999-12-01

    Spitting (or expectoration) is rarely seen with seizures. In Western society, spitting is a striking behavioral aberration. A 13-year-old child had intermittent agitated behavior, episodes of rage, spitting and confusion lasting up to 2 minutes. He stood up in church and told the preacher to 'shut up and sit down'. Epilepsy monitoring revealed spitting with polysharp and spike seizures resolved over the right temporal lobe. Magnetic resonance imaging revealed a right temporal lobe ganglioglioma. Spitting seizures resolved after resection. Ictal expectoration is rare. It may occur with epigastric aura, nausea, chewing, swallowing and fumbling. Literature review disclosed 17 cases, 12 of which arose from the non-dominant hemisphere. Most regressed with surgery and anticonvulsants. Copyright 1999 BEA Trading Ltd.

  3. Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities.

    PubMed

    Bertoglio, Daniele; Verhaeghe, Jeroen; Santermans, Eva; Amhaoul, Halima; Jonckers, Elisabeth; Wyffels, Leonie; Van Der Linden, Annemie; Hens, Niel; Staelens, Steven; Dedeurwaerdere, Stefanie

    2017-03-01

    Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator protein, a biomarker of inflammation, was imaged by means of positron emission tomography (PET) 2 and 4weeks post-status epilepticus using [(18)F]-PBR111. Translocator protein was highly upregulated 2weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P<0.001), whereas 4weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P<0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of disease (acute, latent - first seizures appearing around 2weeks post-status epilepticus - and chronic phases), for a total of 12weeks, in order to determine SRS frequency for each subject (range 0.00-0.83SRS/day). We found that regional PET uptake at 2 and 4weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (P<0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator protein PET imaging at 2weeks post-status epilepticus, we accurately predicted the frequency of SRS (R=0.92; R(2)=0.86; P<0.0001) at the onset of epilepsy. This study not only demonstrates

  4. Age of onset of mesial temporal lobe epilepsy with hippocampal sclerosis: the effect of apolipoprotein E and febrile seizures.

    PubMed

    Leal, Bárbara; Chaves, João; Carvalho, Cláudia; Bettencourt, Andreia; Freitas, Joel; Lopes, João; Ramalheira, João; Costa, Paulo P; Mendonça, Denisa; Silva, António M; Silva, Berta M

    2017-09-01

    Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most frequent pharmaco-resistant epilepsy. It has been associated with febrile seizures (FS) in childhood. Its aetiology remains unclear but genetic factors are involved. Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE ϵ4 is an isoform of ApoE with altered protein function, previously associated with refractoriness and early onset epilepsy. This study was undertaken to determine if ApoE isoforms are risk factors for MTLE-HS and influence clinical characteristics. A group of 188 MTLE-HS patients (101 F, 87 M, mean age = 44.7 ± 11.6 years, 100 with FS antecedents) was studied and compared with a group of 342 healthy individuals in a case-control genetic association study. Data were analysed with Pearson Chi-squared Test or Student's t test, as appropriated. No differences in ApoE ϵ4 allelic frequencies between MTLE-HS patients and controls or between MTLE-HS subgroups were observed. Nevertheless, ApoE ϵ4 carriers had an earlier MTLE-HS onset (11.0 ± 7.9 years in ApoE ϵ4 carriers vs. 14.4 ± 11.2 years in ApoE ϵ4 non-carriers p < 0.05). Additionally, we observed that MTLE-HS patients with FS antecedents had a statistically significant early disease onset (11.5 ± 8.7 years in FS(+) vs. 16.0 ± 12.1 years in FS(-), p < 0.01). Our data show that ApoE ϵ4 and FS may not participate directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease development in predisposed individuals.

  5. 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.

  6. High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

    PubMed

    Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

    2016-08-01

    Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

  7. Laser-Bioplasma Interaction: The Epilepsy-Topion-Bioplasma, (the Seizure Onset Area) Upon the Action of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams

    NASA Astrophysics Data System (ADS)

    Stefan, V. Alexander

    2016-10-01

    The ultraviolet photons may control the imbalance of sodium and potassium ions in the brain bioplasma and, consequently, may prove to be efficient in the prevention of epileptic seizures. A novel method is based on the multi-ultraviolet-photon beam interaction with the epilepsy-topion-bioplasma, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion-bioplasma lead, (within the 10s of milliseconds), to the onset of chaos, (seizure-excessive electrical discharge), and subsequent cascading into adjacent areas.

  8. Localization value of seizure semiology analyzed by the conditional inference tree method.

    PubMed

    Kim, Dong Wook; Jung, Ki-Young; Chu, Kon; Park, So-Hee; Lee, Seo-Young; Lee, Sang Kun

    2015-09-01

    Although accurate interpretation of seizures is important for the management of patients with epilepsy, studies on the localizing value of seizure semiology and the reliability of the semiology descriptions are scarce. The objective of our study is to investigate the accuracy of video-recorded seizure semiology in the classification and localization of epileptic seizures. We also evaluated the reliability of the semiology descriptions provided by the patients or their caregivers. Video-recorded clinical seizures from 831 consecutive patients (391 females; 31.7 ± 11.6 years) were analyzed retrospectively. Epileptic seizures were classified as generalized and partial seizures, and patients with partial seizures were further divided into five ictal onset areas. In order to analyze the diagnostic value of individual semiologic features for clinical diagnosis, we used the conditional inference tree method. Generalized and partial seizures were differentiated with high accuracy (97.1%), but the accuracy of localization among the five ictal onset areas was relatively low (56.1%), which was largely attributed to the difficulty in the discrimination between mesial and lateral temporal onset seizures. Lateralization of the ictal onset area in partial seizures was possible in 427 (55.1%) patients based on video analysis, nevertheless it was possible in only 158 (20.4%) patients based on historical semiology descriptions. The results of our study suggest that careful observation of seizure semiology may be useful for the differentiation of ictal onset areas. However, the semiologic differentiation between mesial and lateral temporal onset seizures is difficult, and historical semiologic descriptions should be interpreted carefully because of their low reliability. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Ictal tachycardia: its discriminating potential between temporal and extratemporal seizure foci.

    PubMed

    Garcia, M; D'Giano, C; Estellés, S; Leiguarda, R; Rabinowicz, A

    2001-09-01

    A wide variety of CNS lesions have been associated with changes in heart rate (HR). However, in epileptic patients their value to lateralize seizure onset remains controversial. This study aims to assess if HR changes associated with partial onset seizures could be useful in lateralizing seizure onset. We analysed HR changes on 100 seizures from 38 consecutive patients (mean age: 27.5 years) admitted for video-EEG telemetry monitoring. We evaluated the R-R interval 30 seconds before the seizure onset and 10, 20 and 120 seconds after the onset. We assessed whether there was a correlation between HR changes and seizure type, left/right differences and different semiological components for each seizure. We recorded 100 seizures. Three non-lateralized seizures were excluded from the analysis; 63/97 (65%) had left hemisphere onset, mainly from the temporal lobe (57.7%). The mean baseline HR was 77 beats per minute Ictal tachycardia (HR: > or = 107.06 beats per minute) was detected in 32 seizures, with ictal onset from the mesial temporal lobe structures in 23/32; 16/32 occurred during the first 10 seconds and 16/32 during the next 20 seconds from the seizure onset independently of the site of origin. Among the different semiological components for each seizure, only dystonic posturing and automatism correlated with HR increments. We did not find bradycardia in our series. Ictal tachycardia occurs most frequently with seizures arising from the mesial temporal lobe and it may not reliably predict the lateralization of seizure onset.

  10. Community structure analysis of transcriptional networks reveals distinct molecular pathways for early- and late-onset temporal lobe epilepsy with childhood febrile seizures.

    PubMed

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system's constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

  11. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

  12. Novel Loss-of-Function Variants in DIAPH1 Associated With Syndromic Microcephaly, Blindness, and Early Onset Seizures

    PubMed Central

    Al-Maawali, Almundher; Barry, Brenda J.; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A. James; Yang, Edward; Walsh, Christopher A.; Mochida, Ganeshwaran H.; Stoler, Joan M.

    2017-01-01

    Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients’ cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identifieda homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. PMID:26463574

  13. Clinical predictors of seizure recurrence after the first post-ischemic stroke seizure.

    PubMed

    Kim, Hyeon Jin; Park, Kee Duk; Choi, Kyoung-Gyu; Lee, Hyang Woon

    2016-11-05

    The number of patients suffering post-stroke seizure after ischemic stroke (PSSi) is quite considerable, especially because ischemic stroke is more prevalent than hemorrhage in the general population. This study aimed to determine the predicting factors for seizure recurrence in ischemic stroke survivors and develop a clinical scoring system for the prediction of risks for seizure recurrence after the first PSSi. We reviewed 3792 ischemic stroke patients from the Ewha Stroke Registry. A total of 124 (3.3 %) patients who experienced PSSi were recruited (mean follow-up for 44.4 months). Medical records concerning the etiology, functional disability, seizure onset latency from stroke, type of seizure, electroencephalography (EEG), and neuroimaging findings were statistically analyzed to derive a seizure recurrence risk scoring system. Seizures recurred in 35.4 % (17/48) of early PSSi patients (≤1 week since stroke onset) and 48.7 % (37/76) of late PSSi (>1 week) patients. Atrial fibrillation, large sized, and cortical stroke lesion were more common in late onset PSSi compared to those in early onset PSSi (p < 0.05). Seizure recurrence tended to be more prevalent in early PSSi patients with male gender, atrial fibrillation or cortical stroke lesion, severe functional disability, and partial seizures. Seizure recurrence in late PSSi group was more common in patients of young age (≤65 years old), male gender, large lesion size, and partial seizure type. The validity of seizure recurrence risk score in the early PSSi group was better when evaluating based on gender, atrial fibrillation, cortical lesion, functional disability, and partial seizure type, with sensitivity of 70.6 % and specificity of 71.0 %. Our study characterized the high risk group for seizure recurrence in patients with the first PSSi. PSSi patients with high risk score of seizure recurrence had a greater chance of developing epilepsy later. Therefore, they should be considered for

  14. The similarities between the hallucinations associated with the partial epileptic seizures of the occipital lobe and ball lightning observations

    NASA Astrophysics Data System (ADS)

    Cooray, G. K.; Cooray, V.

    2007-12-01

    Ball Lightning was seen and described since antiquity and recorded in many places. Ball lightning is usually observed during thunderstorms but large number of ball lightning observations is also reported during fine weather without any connection to thunderstorms or lightning. However, so far no one has managed to generate them in the laboratory. It is photographed very rarely and in many cases the authenticity of them is questionable. It is possible that many different phenomena are grouped together and categorized simply as ball lightning. Indeed, the visual hallucinations associated with simple partial epileptic seizures, during which the patient remains conscious, may also be categorized by a patient unaware of his or her condition as ball lightning observation. Such visual hallucinations may occur as a result of an epileptic seizure in the occipital, temporo-occipital or temporal lobes of the cerebrum [1,2,3]. In some cases the hallucination is perceived as a coloured ball moving horizontally from the periphery to the centre of the vision. The ball may appear to be rotating or spinning. The colour of the ball can be red, yellow, blue or green. Sometimes, the ball may appear to have a solid structure surrounded by a thin glow or in other cases the ball appears to generate spark like phenomena. When the ball is moving towards the centre of the vision it may increase its intensity and when it reaches the centre it can 'explode' illuminating the whole field of vision. During the hallucinations the vision is obscured only in the area occupied by the apparent object. The hallucinations may last for 5 to 30 seconds and rarely up to a minute. Occipital seizures may spread into other regions of the brain giving auditory, olfactory and sensory sensations. These sensations could be buzzing sounds, the smell of burning rubber, pain with thermal perception especially in the arms and the face, and numbness and tingling sensation. In some cases a person may experience only

  15. Application of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures.

    PubMed

    Feucht, M; Möller, U; Witte, H; Benninger, F; Asenbaum, S; Prayer, D; Friedrich, M H

    1999-03-01

    For many patients who are candidates for epilepsy surgery, non-invasive evaluation fails to provide sufficient information to permit surgical treatment. Since there are also definite risks and considerable costs associated with invasive procedures, new (non-invasive) techniques are required. This study provides empirical evidence that a non-linear approach applied to ictal surface electroencephalograms (EEGs) can help to delineate the area of seizure onset and may prove useful in complementing visual analysis of the EEG. Multichannel EEGs, recorded from eight patients with different drug-resistant localisation-related epilepsies, were analysed using the concept of correlation dimension and two extensions based on the pointwise dimension. The latter also provided results in cases where assessment of the correlation dimension was not feasible. Comparative values between 2 and 6 were accepted as the result of the algorithms, mostly 3-4 for the EEG channels strongly reflecting epileptic activity, and 4-6 for the other signals. The proportion of accepted pointwise values was usually 200-800% for strong epileptic EEG activity compared to the other data. The approach permitted the characterisation of the scalp area reflecting epileptic activity. The results obtained were in perfect concordance with those obtained during pre-surgical work-up and confirmed by the post-operative outcome.

  16. Acute onset of focal seizures, psychiatric features and confusion: a case of autoimmune encephalitis?

    PubMed Central

    Al-Diwani, Adam; Butterworth, Richard J; Nibber, Anjan; Lang, Bethan; Vincent, Angela; Irani, Sarosh R

    2012-01-01

    An elderly woman presented with disorganised thinking, unusual behaviour and clustered episodes of speech arrest accompanied by right-sided face and arm twitching. The following investigations were normal: interictal electroencephalography, brain MRI, cerebrospinal fluid viral PCR and cell count and voltage-gated potassium channel-complex, N-methyl-d-aspartate receptor, gamma-aminobutyric acid (B) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, glycine receptor, glutamic acid decarboxylase and paraneoplastic antibodies. The syndrome showed partial spontaneous resolution but 1 year later, typical postencephalopathic features persisted including disinhibition and alteration of sleep–wake cycle. The most likely clinical diagnosis was autoimmune encephalitis and the broader differential diagnoses are discussed within the article. This case demonstrates the need to be aware of this under-recognised and potentially treatable entity. PMID:23112257

  17. Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl.

    PubMed

    Marashly, Ahmad; Lew, Sean; Koop, Jennifer

    2017-01-01

    Gelastic seizures (GS) are typically associated with hypothalamic hamartomas and present during childhood. However it is now known that GS can be found in focal epilepsies arising from other regions in the brain, including mesial and neocortical frontal, temporal and parietal regions. GS have rarely been described as the presenting manifestation of New Onset Refractory Status Epilepticus (NORSE). In this article we describe a previously healthy 3-year-old who presented with an explosive onset of GS that were refractory to multiple anti-seizure medications. These seizures arose from the right frontal region. An extensive metabolic and immunological evaluation was negative. Her brain magnetic resonance imaging (MRI) was negative, however the Positron Emission Tomography (PET) scan showed a hypermetabolic region in the right frontal inferior gyrus. She underwent a depth electrode evaluation that revealed a widespread irritative zone involving the PET "lesion" as well as mesial and neocortical regions in the right frontal lobe. The seizure onset zone was widespread and non-localizable. However the GS were associated with a clear ictal epileptiform discharge on invasive EEG arising from the depth of the superior frontal gyrus, which was not overlapping with the PET hypermetabolic region. She underwent a right frontal lobectomy sparing the primary motor region in the pre-central gyrus. She has remained seizure free for 15 months since. The pathological analysis showed focal cortical dysplasia type II in the region of the PET scan hypermetabolism. This case expands the clinical spectrum of GS to include cases of NORSE. Additionally the case highlights the role of resective surgery in GS presenting as NORSE and the potentially excellent outcome that can be achieved by early intervention.

  18. Comparison of the health-related quality of life between epileptic patients with partial and generalized seizure

    PubMed Central

    Ashjazadeh, Nahid; Yadollahikhales, Golnaz; Ayoobzadehshirazi, Anaheed; Sadraii, Nazanin; Hadi, Negin

    2014-01-01

    Background: Epilepsy is defined as recurrent unprovoked febrile seizures, which cause disability in patients. This study aims to assess the health-related quality-of-life (QOL) in epileptic patients in Fars Province, southern Iran. Methods:One-hundred epileptic patients, above 18 years, referred to Shiraz University of Medical Sciences affiliated clinics, were included. The QOL of patients with generalized and partial seizure were assessed using the Iranian valid and reliable Sf-36 questionnaire. Patients’ socio-demographic and their disease features were also compared with each other using a questionnaire. Results: In partial epilepsy group (n = 24), the married patients in social functioning (SF) aspect of QOL (64.42 ± 14.29) (P = 0.024), the patients on antiepileptic drugs (AEDs) monotherapy in both physical functioning (PF) (88.75 ± 11.57) (P = 0.030) and SF (75.00 ± 6.68) (P = 0.022) aspects, the employed patients in PF aspect of QOL (P = 0.023) (91.87 ± 8.83) and those with high income in mental health aspect of QOL (P = 0.036 and correlation coefficient = 0.413) got better scores compared with the partial epileptic patients who were single, on polytherapy, unemployed and had low to moderate income. In generalized epilepsy group (n = 76), patients on AEDs monotherapy in PF aspect of QOL (P = 0.025) (78.33 ± 24.36) and employed patients in vitality aspect (P = 0.023) (57.00 ± 28.25) had better scores. Data were analyzed using SPSS for windows. Conclusion: Epilepsy can affect patient’s life in a number of ways such as their lives, marriage, occupation, and education. We can encourage patients to find a partner, continue higher education and try to find a job. PMID:25295153

  19. Impact of perampanel on pharmacokinetics of concomitant antiepileptics in patients with partial‐onset seizures: pooled analysis of clinical trials

    PubMed Central

    Laurenza, Antonio; Ferry, Jim; Hussein, Ziad

    2016-01-01

    Aims To evaluate the impact of perampanel and demographics on clearance of concomitant antiepileptic drugs (AEDs), in patients with refractory partial‐onset seizures. Methods Pooled data from three Phase III clinical studies with adjunctive perampanel were used. Blood samples for evaluation of 11 concomitant AEDs were taken during baseline (before perampanel initiation), and at weeks 10, 14, and 19 during the maintenance phase of perampanel treatment (2–12 mg/day, once daily at bedtime). Models estimating apparent clearance of each concomitant AED were fitted to the data, and the effects of perampanel and demographic variables on clearance were determined. Final models were assessed with goodness of fit plots including population predictions and individual predictions against observations. Results No significant impact of perampanel on clearance was found for clonazepam (n = 81), levetiracetam (n = 330), phenobarbital (n = 54), phenytoin (n = 90), topiramate (n = 226) or zonisamide (n = 93). Statistically significant, but small and not clinically relevant increases in model‐predicted clearance were detected for carbamazepine (+4.3% with 12 mg perampanel; n = 379), clobazam (+3.4% males, +7.7% females, 12 mg; n = 114), lamotrigine (+9.3%, 12 mg; n = 356), and valproic acid (+5.0%, 12 mg; n = 349). Oxcarbazepine clearance was reduced (26%; n = 200), but the clinical relevance is unclear as levels of the active metabolite (the monohydroxy derivative of oxcarbazepine) were not measured. Conclusions Population PK data show that perampanel (2–12 mg/day, once daily at bedtime) has no relevant impact on the clearance of the most commonly used concomitant AEDs. PMID:27038098

  20. Phase-Amplitude Coupling Is Elevated in Deep Sleep and in the Onset Zone of Focal Epileptic Seizures

    PubMed Central

    Amiri, Mina; Frauscher, Birgit; Gotman, Jean

    2016-01-01

    The interactions between different EEG frequency bands have been widely investigated in normal and pathologic brain activity. Phase-amplitude coupling (PAC) is one of the important forms of this interaction where the amplitude of higher frequency oscillations is modulated by the phase of lower frequency activity. Here, we studied the dynamic variations of PAC of high (gamma and ripple) and low (delta, theta, alpha, and beta) frequency bands in patients with focal epilepsy in different sleep stages during the interictal period, in an attempt to see if coupling is different in more or less epileptogenic regions. Sharp activities were excluded to avoid their effect on the PAC. The results revealed that the coupling intensity was generally the highest in stage N3 of sleep and the lowest in rapid eye movement sleep. We also compared the coupling strength in different regions [seizure onset zone (SOZ), exclusively irritative zone, and normal zone]. PAC between high and low frequency rhythms was found to be significantly stronger in the SOZ compared to normal regions. Also, the coupling was generally more elevated in spiking channels outside the SOZ than in normal regions. We also examined how the power in the delta band correlates to the PAC, and found a mild but statistically significant correlation between slower background activity in epileptic channels and the elevated coupling in these channels. The results suggest that an elevated PAC may reflect some fundamental abnormality, even after exclusion of sharp activities and even in the interictal period. PAC may therefore contribute to understanding the underlying dynamics of epileptogenic brain regions. PMID:27536227

  1. Cytochrome c oxidase deficit is associated with the seizure onset zone in young patients with focal cortical dysplasia Type II.

    PubMed

    Miles, Lili; Greiner, Hansel M; Mangano, Francesco T; Horn, Paul S; Leach, James L; Miles, Michael V

    2015-10-01

    It has been postulated that mitochondrial dysfunction may be an important factor in epileptogenesis of intractable epilepsy. The current study tests the hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase dysfunction is associated with the seizure onset zone (SOZ) in patients with focal cortical dysplasia (FCD). Subjects were selected based on: age <19y; epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and sufficient residual cortical tissue to conduct analysis of electron transport chain complex (ETC) activity in SOZ and adjacent cortical regions. In this retrospective study, patients were identified who had sufficient unfixed, frozen brain tissue for biochemical analysis in tissue homogenates. Specimens were subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD Type III or dual pathology. Analysis of ETC activity in resected tissues was conducted independently and without knowledge of the identity, diagnosis, or clinical status of individual subjects. Seventeen patients met the inclusion criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical resections showed decreased CIV activity in the SOZ of the FCDII group (P = 0.003), but no significant CIV difference in adjacent tissues of the FCDI group. Because of the importance of CIV as the terminal and rate-limiting complex in the mitochondrial electron transport chain, these authors conclude that 1) a deficit of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may contribute to the spectrum of FCD neuropathology; and 3) further investigation of CIV in FCD may lead to the discovery of new targets for neuroprotective therapies for patients with intractable epilepsy.

  2. Ictal onset baseline shifts and infraslow activity.

    PubMed

    Rampp, Stefan; Stefan, Hermann

    2012-08-01

    Ictal onset baseline shifts, in surface and intracranial EEG, have been shown to localize focal epilepsies. However, whether direct current EEG amplifiers are required to detect infraslow activity is unresolved. We retrospectively analyzed intracranial EEG data from 24 patients with temporal lobe seizures, who underwent long-term invasive EEG investigation and subsequent surgery. Data were recorded using a DeltaMed/Natus (Paris, France) system with Braintronics Brainbox EEG-1164 (Almere, The Netherlands) with an input filter of 0.1 Hz. Visual comparison of infraslow activity with seizure activity in conventional frequency bands was performed using BESA software (Megis, Gräfeling, Germany). Ictal onset baseline shifts were seen in 52 of 88 partial seizures and in all 11 secondarily generalized tonic-clonic seizures. They preceded ictal activity in conventional frequencies in some cases by several seconds. Topographical distribution was concordant with seizure onsets and distant sites with suspected involvement in seizure generation. It is concluded that ictal onset baseline shifts can be detected by commonly used EEG systems with an input filter of 0.1 Hz and may contribute to identify seizure onset and areas involved in seizure generation.

  3. MELAS with recurrent complex partial seizures, nonconvulsive status epilepticus, psychosis, and behavioral disturbances: case analysis with literature review.

    PubMed

    Kaufman, Kenneth R; Zuber, Nicole; Rueda-Lara, Maria A; Tobia, Anthony

    2010-08-01

    Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is a progressive neurodegenerative disorder associated with polygenetic, maternally inherited, mitochondrial DNA mutations. MELAS has multisystem presentation including neurological, muscular, endocrine, auditory, visual, cardiac, psychiatric, renal, gastrointestinal and dermatological symptoms. Clinical course and prognosis are variable, often leading to cognitive decline, disability, and premature death. Both convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) are reported with MELAS. This report illustrates a case of MELAS with recurrent complex partial seizures, NCSE, confusion, aggressive behaviors, hallucinations, and paranoid delusions. Rapid video/EEG confirmation of diagnosis and aggressive antiepileptic drug intervention are required. Further education of medical professionals regarding this disorder, its appropriate management, and the significance of NCSE is indicated to avoid delay of treatment. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Cardiovascular responses at the onset of exercise with partial neuromuscular blockade in cat and man.

    PubMed Central

    Iwamoto, G A; Mitchell, J H; Mizuno, M; Secher, N H

    1987-01-01

    1. In decerebrated cats the cardiovascular, heart rate and blood pressure responses to static muscle contractions were followed from the onset of stimulation of the cut L7-S1 ventral roots. Heart rate and blood pressure were also followed during maximal voluntary and electrically induced static muscle contractions in man using one leg. In both cat and man contractions were performed under control conditions and tubocurarine-induced neuromuscular blockade. 2. In the cat, heart rate and blood pressure increased 1.7 s after the onset of the contraction. No cardiovascular responses were seen when the muscle contraction was blocked by tubocurarine. 3. In man, both heart rate and blood pressure increased at the onset of voluntary contractions. Partial curarization reduced strength to 39% of control. The heart rate response was unaffected by tubocurarine while the blood pressure response was reduced from 61 to 32 mmHg. 4. Electrical stimulation of the muscles resulted in 75% of voluntary strength in man. The heart rate response was delayed one R-R interval in the electrocardiogram but was as large as during voluntary contractions. During partial curarization the heart rate response was significantly smaller and the blood pressure response was reduced from 11 to 8 mmHg. 5. In conclusion, processes in active muscles elicit an increase in heart rate and blood pressure which depends on the intensity of the muscle contraction developed. However, the immediate cardiovascular responses at the onset of voluntary muscle contractions cannot be accounted for by reflexes generated in the working muscles alone. Images Fig. 2 PMID:3656150

  5. Early Onset of Hypersynchronous Network Activity and Expression of a Marker of Chronic Seizures in the Tg2576 Mouse Model of Alzheimer’s Disease

    PubMed Central

    Bezzina, Charlotte; Verret, Laure; Juan, Cécile; Remaud, Jessica; Halley, Hélène

    2015-01-01

    Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early event in Alzheimer’s disease pathogenesis. Many mouse models of the disease also present neuronal network hypersynchrony, as evidenced by higher susceptibility to pharmacologically-induced seizures, electroencephalographic seizures accompanied by spontaneous interictal spikes and expression of markers of chronic seizures such as neuropeptide Y ectopic expression in mossy fibers. This network hypersynchrony is thought to contribute to memory deficits, but whether it precedes the onset of memory deficits or not in mouse models remains unknown. The earliest memory impairments in the Tg2576 mouse model of Alzheimer’s disease have been observed at 3 months of age. We thus assessed network hypersynchrony in Tg2576 and non-transgenic male mice at 1.5, 3 and 6 months of age. As soon as 1.5 months of age, Tg2576 mice presented higher seizure susceptibility to systemic injection of a GABAA receptor antagonist. They also displayed spontaneous interictal spikes on EEG recordings. Some Tg2576 mice presented hippocampal ectopic expression of neuropeptide Y which incidence seems to increase with age among the Tg2576 population. Our data reveal that network hypersynchrony appears very early in Tg2576 mice, before any demonstrated memory impairments. PMID:25768013

  6. Seizure and Psychosocial Outcomes of Childhood and Juvenile Onset Generalized Epilepsies: Wolf in Sheep's Clothing, or Well-Dressed Wolf?

    PubMed

    Nickels, Katherine

    2015-01-01

    Studies of generalized electroclinical syndromes can provide guidance regarding long-term seizure, cognitive, and psychosocial outcomes. Childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and idiopathic generalized epilepsy with generalized tonic-clonic seizures alone are electroclinical syndromes typically associated with normal intellect and good response to antiseizure medications. However, studies have demonstrated significantly poorer psychosocial outcomes than expected for these syndromes, regardless of seizure control. Potential causes for this include underlying abnormalities in social skills, social stigma, and underlying abnormalities in brain development and maturation.

  7. The influence of manganese supplementation on seizure onset and severity, and brain monoamines in the genetically epilepsy prone rat.

    PubMed

    Critchfield, J W; Carl, G F; Keen, C L

    1993-01-01

    Human and experimental animal studies suggest a relationship between low Mn status and seizures. The genetically epilepsy prone rat (GEPR), which has low tissue Mn levels, was studied in the context of Mn supplementation. Manganese was provided at 45 micrograms/g diet (control) or 1000 micrograms/g diet (supplemented) to dams during pregnancy and lactation, then to the offspring after weaning. Offspring were tested for seizure susceptibility as young adults; tissue trace elements, brain monoamines and brain glutamine synthetase activity were measured as endpoint biochemical indices. Supplementation, although developmentally encompassing and highly effective in elevating tissue Mn levels, had no effect on seizure latency or severity. Similarly, brain monoamine concentrations and glutamine synthetase activities were resistant to Mn supplementation. Notably, the GEPR was confirmed to have low whole brain glutamine synthetase activity. These findings suggest that seizure activity in the GEPR does not stem from an increased nutritional/metabolic need for Mn.

  8. Coexistence of early onset sarcoidosis and partial interferon-γ receptor 1 deficiency.

    PubMed

    Çakan, Mustafa; Keskindemirci, Gonca; Aydoğmuş, Çiğdem; Akı, Hilal; Hatipoğlu, Nevin; Kıyak, Aysel; Aydoğan, Gönül; Aktay-Ayaz, Nuray

    2016-01-01

    Pediatric sarcoidosis comprises a spectrum of childhood granulomatous inflammatory conditions. Pathological hallmark of the disease is granuloma formation that is seen in the affected tissues and almost any organ or system can be involved. There are two forms of pediatric sarcoidosis. One is seen in older children and the clinical picture is very similar to that of adult sarcoidosis and the other one is seen in early childhood. Sarcoidosis in early childhood can be divided as Blau syndrome (familial form) and early onset sarcoidosis (sporadic form). In both of the diseases there is a defect in the NOD2/CARD15 gene. The typical triad of early onset sarcoidosis is polyarthritis, dermatitis and uveitis. Interferon-γ receptor 1 deficiency is caused by defects in the IFNγR1 gene and non-tuberculosis mycobacterial pathogens are the leading causes of infections that start in early childhood. Herein we report a patient who presented with the symptoms of early onset sarcoidosis and also had partial interferon-γ receptor 1 deficiency that presented with BCG-osis. In addition to anti-mycobacterial treatment, methotrexate and prednisolone were used in therapy.

  9. Efficacy of lacosamide by focal seizure subtype.

    PubMed

    Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko

    2014-10-01

    The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment.

  10. Parvalbumin disappears from GABAergic CA1 neurons of the gerbil hippocampus with seizure onset while its presence persists in the perforant path.

    PubMed

    Scotti, A L; Kalt, G; Bollag, O; Nitsch, C

    1997-06-20

    Mongolian gerbils are epilepsy prone animals, a trait observable at the behavioural level during the 2nd month of life. As a unique species difference, gerbils express the calcium-binding protein parvalbumin (PV) in the perforant path from the entorhinal cortex to the hippocampus. In this study, we determined the time of appearance of PV in the layer II neurons of the entorhinal cortex and the perforant path terminals in gerbils between post-natal days 30 and 50. Signs of low grade seizures were observed in few animals from P40 onward. PV stain in the entorhinal cortex and perforant path terminals was already detectable at P30, well before the onset of behavioural seizures and did not change with age. It is suggested that the presence of PV in this pathway may be related to the generation early in life of an epileptogenic focus in the limbic forebrain. Altered inhibitory hippocampal circuits have also been suggested as a cause of seizures in the gerbil. Therefore, we quantitated hippocampal GABA-immunoreactive neurons and the PV-immunoreactive subpopulation. A group of gerbils with a high density of stained pyramidal interneurons in CA1 and one lacking PV-stained perikarya could be distinguished at P40 and P50. The density of GABA-immunoreactive nerve cells however, remained the same in both groups and through the ages studied. Thus, perikaryal PV is lost from intact GABAergic nerve cells at the same time as behavioural seizures are observed. The loss of PV from GABAergic neurons may affect their functional properties and be instrumental for the maintainance of behavioural seizures.

  11. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

    PubMed

    Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

    2017-04-01

    The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  12. Reliability of seizure semiology in patients with 2 seizure foci.

    PubMed

    Rathke, Kevin M; Schäuble, Barbara; Fessler, A James; So, Elson L

    2011-06-01

    To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient. Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs). Epilepsy monitoring unit of referral comprehensive epilepsy program. Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years. The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread. Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test). Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

  13. The association between Chiari-like malformation, ventriculomegaly and seizures in cavalier King Charles spaniels.

    PubMed

    Driver, C J; Chandler, K; Walmsley, G; Shihab, N; Volk, H A

    2013-02-01

    Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P=0.10 and 0.71, respectively). Seizures were classified as having partial onset in 61% of individuals in the study population (95% CI 42.41-76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported.

  14. Vitamin B(6) treatment of intractable seizures.

    PubMed

    Ohtahara, Shunsuke; Yamatogi, Yasuko; Ohtsuka, Yoko

    2011-10-01

    Vitamin B(6) (VB(6))-related seizures include clinical seizures associated with VB(6) deficiency and dependency. Both types of seizures are suppressed by VB(6). We proposed VB(6)-responsive seizures as the third category of VB(6)-related seizures in 1977. Vitamin B(6)-responsive seizures decrease or disappear in response to high-dose oral VB(6). Seizure onset in most of our cases occurred within the first year of life, although this varied between 3 months and 5 years. Etiologically, such cases were not only idiopathic or cryptogenic, but also symptomatic and associated with organic brain lesions. The tryptophan load test was usually negative. Vitamin VB(6)-responsive seizures or epilepsy were usually West syndrome (WS), however may also include Lennox-Gastaut syndrome, grand mal or partial motor seizures. High-dose VB(6) treatment administered to 216 consecutive WS cases had an overall response rate of 13.9%, being high not only in cryptogenic cases (32%), but also in symptomatic WS (11.5%) associated with identifiable brain pathologies. Notably, responsive patients had excellent long-term seizure and mental outcomes without the need for conventional antiepileptic medication. A gradual increase in clinical response to VB(6) was noted with increasing the VB(6) dose from 30 to 50-100mg/day, and a dramatic increase in clinical response with high-dose VB(6) (100-400mg). Little clinical response was noted with administration of low dose VB(6) (10-30 mg/day). Thus, high-dose oral VB(6) treatment is recommended in all WS patients at time of initial treatment for a minimum of 10 days, considering the safety and rapid onset of efficacy, usually within 1 week, of this treatment. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: a phase 1, randomized controlled study.

    PubMed

    Mann, Donald; Liu, Jing; Chew, Marci L; Bockbrader, Howard; Alvey, Christine W; Zegarac, Elizabeth; Pellock, John; Pitman, Verne W

    2014-12-01

    To evaluate the safety, tolerability, and pharmacokinetics (PK) of pregabalin as adjunctive therapy in children with refractory partial seizures. This was a phase 1, randomized, placebo-controlled, parallel-group, escalating-dose, multiple-dose study comprising a 7-day, double-blind treatment period and a single-blind, single dose of pregabalin administered to all children on day 8. Children in four age cohorts (1-23 months, 2-6, 7-11, and 12-16 years) received one of four doses of pregabalin (2.5, 5, 10, or 15 mg/kg/day) or placebo. Safety and tolerability were assessed throughout the study. Steady-state and single-dose PK parameters on day 8 were analyzed using standard noncompartmental procedures. Sixty-five children received at least one dose of treatment. Four pregabalin-treated children discontinued treatment, three of whom received 15 mg/kg/day. Two children experienced serious adverse events, one of whom received pregabalin 15 mg/kg/day. During double-blind treatment, the most common adverse events reported in the pregabalin-treated population were somnolence (27.1%) and dizziness (12.5%). Steady-state pregabalin peak and total exposure in each age cohort appeared to increase linearly with dose. Apparent oral clearance (CL/F) was directly related to creatinine clearance, consistent with adults. CL/F normalized for body weight was 43% higher in patients weighing <30 kg. Steady-state and single-dose PK were consistent. Pregabalin at doses up to 10 mg/kg/day in children aged 1 month to 16 years, and at doses up to 15 mg/kg/day in those aged <6 years, demonstrated acceptable safety and tolerability. For children weighing <30 kg, a dose increase of 40% (mg/kg dosing) is required to achieve comparable exposure with adults or children weighing ≥30 kg. These data will inform dose selection in phase 3 trials of the efficacy and safety of adjunctive pregabalin in children with refractory partial seizures. Wiley Periodicals, Inc. © 2014 International League Against

  16. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology.

    PubMed

    Fisher, Robert S; Cross, J Helen; French, Jacqueline A; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Zuberi, Sameer M

    2017-04-01

    The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  17. Peri-ictal yawning lateralizes the seizure onset zone to the nondominant hemisphere in patients with temporal lobe epilepsy.

    PubMed

    Kuba, Robert; Musilová, Klára; Brázdil, Milan; Rektor, Ivan

    2010-11-01

    The main aim of this retrospective study was to investigate the incidence and lateralizing value of peri-ictal yawning in patients with temporal lobe epilepsy (TLE) who underwent successful surgery for epilepsy (Engel class I outcome at the 2-year follow-up visit). We reviewed a total of 97 patients (59 men and 38 women). Fifty-three patients had TLE arising from the nondominant temporal lobe, and 44 had TLE arising from the dominant temporal lobe. In total, we reviewed 380 seizures. Of those, 202 seizures arose from the nondominant temporal lobe and 178 from the dominant one. Peri-ictal yawning was observed in 4 of 97 patients (4.1%) and in 7 of 380 seizures (1.8%), in the postictal period in all cases. Peri-ictal yawning occurred only in patients with right-sided, nondominant TLE. It may have a lateralizing value.

  18. Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

    PubMed

    Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

    2017-07-27

    Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

  19. Febrile seizures.

    PubMed

    Mewasingh, Leena D

    2010-11-24

    Simple febrile seizures are generalised in onset, last <15 minutes, and do not occur more than once in 24 hours. Complex febrile seizures are longer lasting, have focal symptoms, and can recur within 24 hours. This review only deals with simple febrile seizures. About 2% to 5% of children in the USA and Western Europe, and 6% to 9% of infants and children in Japan will have experienced at least one febrile seizure by the age of 5 years. Simple febrile seizures may slightly increase the risk of developing epilepsy, but have no known adverse effects on behaviour, scholastic performance, or neurocognition. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments given during episodes of fever in children with one or more previous simple febrile seizures? What are the effects of long-term (daily, for >1 month) anticonvulsant treatment in children with a history of simple febrile seizures? What are the effects of treatments on reducing the risk of subsequent epilepsy in children with a history of simple febrile seizures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants (intermittent or continuous) and antipyretic treatments (physical antipyretic measures, paracetamol, ibuprofen).

  20. Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

    PubMed

    Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

    2015-03-01

    Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Prevalence and risk factors of seizure clusters in adult patients with epilepsy.

    PubMed

    Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Wong, Rebecca A; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil

    2017-07-01

    In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also

  2. Neuronal heterotopia with capillary penetration of neurons and cortical dysplasia in a patient with complex partial seizures. Case report.

    PubMed

    Jay, V; Becker, L E; Otsubo, H; Hwang, P; Hoffman, H J; Armstrong, D C

    1993-04-01

    Unusual pathological findings were encountered in a temporal lobectomy specimen from a 9-year-old boy with intractable complex partial seizures. Magnetic resonance imaging revealed an enlarged left temporal lobe, with diffuse high signal intensity over the cortex and poor gray-white differentiation on T2-weighted imaging; single-photon emission computerized tomography showed decreased blood flow. Active epileptiform discharges were identified in the left temporal lobe with focal slow waves and generalized epileptiform paroxysms. Pathologically, the cortex revealed changes of focal cortical dysplasia with extensive disorganization of neuronal morphology, layering, and orientation as well as focal polymicrogyria. The cortical-white matter junction was indistinct with extensive neuronal heterotopias in the white matter. Large pale balloon cells akin to those seen in tuberous sclerosis were found scattered within the cortex and white matter. The most striking finding was that of a heterotopic nodule in the white matter, which revealed abnormal neurons with penetration of cell bodies by capillaries. Ultrastructurally, there were no degenerative changes in these neurons, and this unusual phenomenon is attributed to a developmental disturbance affecting neuronal, glial, and vascular elements.

  3. Single Nucleotide Variations in CLCN6 Identified in Patients with Benign Partial Epilepsies in Infancy and/or Febrile Seizures

    PubMed Central

    Yamamoto, Toshiyuki; Shimojima, Keiko; Sangu, Noriko; Komoike, Yuta; Ishii, Atsushi; Abe, Shinpei; Yamashita, Shintaro; Imai, Katsumi; Kubota, Tetsuo; Fukasawa, Tatsuya; Okanishi, Tohru; Enoki, Hideo; Tanabe, Takuya; Saito, Akira; Furukawa, Toru; Shimizu, Toshiaki; Milligan, Carol J.; Petrou, Steven; Heron, Sarah E.; Dibbens, Leanne M.; Hirose, Shinichi; Okumura, Akihisa

    2015-01-01

    Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI. We identified a non-synonymous single nucleotide variation (SNV) in the voltage-sensitive chloride channel 6 gene (CLCN6). A cohort study of 48 BPEI patients without PRRT2 mutations revealed a different CLCN6 SNV in a patient, his sibling and his father who had a history of febrile seizures (FS) but not BPEI. Another study of 48 patients with FS identified an additional SNV in CLCN6. Chloride channels (CLCs) are involved in a multitude of physiologic processes and some members of the CLC family have been linked to inherited diseases. However, a phenotypic correlation has not been confirmed for CLCN6. Although we could not detect significant biological effects linked to the identified CLCN6 SNVs, further studies should investigate potential CLCN6 variants that may underlie the genetic susceptibility to convulsive disorders. PMID:25794116

  4. NONCONVULSIVE SEIZURES AFTER SUBARACHNOID HEMORRHAGE: MULTIMODAL DETECTION AND OUTCOMES

    PubMed Central

    Claassen, Jan; Perotte, Adler; Albers, David; Kleinberg, Samantha; Schmidt, J. Michael; Tu, Bin; Badjatia, Neeraj; Lantigua, Hector; Hirsch, Lawrence J.; Mayer, Stephan A.; Connolly, E. Sander; Hripcsak, George

    2013-01-01

    Objective Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood. Methods We analyzed intracortical EEG and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury. Results Intracortical seizures were seen in 38% of patients and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (P=0.001), blood pressure (P<0.001), and respiratory rate (P<0.001). There were trends for rising cerebral perfusion pressure (P=0.03) and intracranial pressure (P =0.06) seen after seizure onset. Intracortical seizure associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (P=0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs. 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively). Interpretation We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in regional cerebral blood flow. These real-world physiologic observations may permit more successful translation of laboratory research to the bedside. PMID:23813945

  5. Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes.

    PubMed

    Claassen, Jan; Perotte, Adler; Albers, David; Kleinberg, Samantha; Schmidt, J Michael; Tu, Bin; Badjatia, Neeraj; Lantigua, Hector; Hirsch, Lawrence J; Mayer, Stephan A; Connolly, E Sander; Hripcsak, George

    2013-07-01

    Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood. We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury. Intracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p = 0.001), blood pressure (p < 0.001), and respiratory rate (p < 0.001). There were trends for rising cerebral perfusion pressure (p = 0.03) and intracranial pressure (p = 0.06) seen after seizure onset. Intracortical seizure-associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p = 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively). We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside. © 2013 American Neurological Association.

  6. A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures.

    PubMed

    Elger, Christian E; Stefan, Hermann; Mann, Allison; Narurkar, Milind; Sun, Yijun; Perdomo, Carlos

    2010-02-01

    To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs). A 24-week multicenter Phase II clinical study was conducted (n=647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase. The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase - the primary efficacy outcome measure - was statistically significant in favor of rufinamide (estimated slope=-0.049, P=0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a >or=50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P=0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were observed. These results suggest that in the dose range of 400-1600mg/day, add-on rufinamide therapy may benefit patients with inadequately controlled partial seizures and is generally well tolerated. These data also suggest that higher doses may confer additional efficacy without adversely affecting safety and tolerability.

  7. Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

    PubMed

    Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

    2015-11-23

    Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

  8. Epileptic Seizures From Abnormal Networks: Why Some Seizures Defy Predictability

    PubMed Central

    Azhar, Feraz; Kudela, Pawel; Bergey, Gregory K.; Franaszczuk, Piotr J.

    2011-01-01

    Summary Seizure prediction has proven to be difficult in clinically realistic environments. Is it possible that fluctuations in cortical firing could influence the onset of seizures in an ictal zone? To test this, we have now used neural network simulations in a computational model of cortex having a total of 65,536 neurons with intercellular wiring patterned after histological data. A spatially distributed Poisson driven background input representing the activity of neighboring cortex affected 1% of the neurons. Gamma distributions were fit to the interbursting phase intervals, a non-parametric test for randomness was applied, and a dynamical systems analysis was performed to search for period-1 orbits in the intervals. The non-parametric analysis suggests that intervals are being drawn at random from their underlying joint distribution and the dynamical systems analysis is consistent with a nondeterministic dynamical interpretation of the generation of bursting phases. These results imply that in a region of cortex with abnormal connectivity analogous to a seizure focus, it is possible to initiate seizure activity with fluctuations of input from the surrounding cortical regions. These findings suggest one possibility for ictal generation from abnormal focal epileptic networks. This mechanism additionally could help explain the difficulty in predicting partial seizures in some patients. PMID:22169211

  9. Epileptic seizures from abnormal networks: why some seizures defy predictability.

    PubMed

    Anderson, William S; Azhar, Feraz; Kudela, Pawel; Bergey, Gregory K; Franaszczuk, Piotr J

    2012-05-01

    Seizure prediction has proven to be difficult in clinically realistic environments. Is it possible that fluctuations in cortical firing could influence the onset of seizures in an ictal zone? To test this, we have now used neural network simulations in a computational model of cortex having a total of 65,536 neurons with intercellular wiring patterned after histological data. A spatially distributed Poisson driven background input representing the activity of neighboring cortex affected 1% of the neurons. Gamma distributions were fit to the interbursting phase intervals, a non-parametric test for randomness was applied, and a dynamical systems analysis was performed to search for period-1 orbits in the intervals. The non-parametric analysis suggests that intervals are being drawn at random from their underlying joint distribution and the dynamical systems analysis is consistent with a nondeterministic dynamical interpretation of the generation of bursting phases. These results imply that in a region of cortex with abnormal connectivity analogous to a seizure focus, it is possible to initiate seizure activity with fluctuations of input from the surrounding cortical regions. These findings suggest one possibility for ictal generation from abnormal focal epileptic networks. This mechanism additionally could help explain the difficulty in predicting partial seizures in some patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Mean daily plasma concentrations of beta-endorphin, leu-enkephalin, ACTH, cortisol, and DHEAS in epileptic patients with complex partial seizures evolving to generalized tonic-clonic seizures.

    PubMed

    Marek, Bogdan; Kajdaniuk, Dariusz; Kos-Kudła, Beata; Kapustecki, Janusz; Swietochowska, Elzbieta; Ostrowska, Zofia; Siemińska, Lucyna; Nowak, Mariusz; Głogowska-Szelag, Joanna; Borgiel-Marek, Halina; Ciesielska-Kopacz, Nelly; Foltyn, Wanda; Pierzchała, Krystyna; Krysiak, Robert; Bienek, Radosław

    2010-01-01

    A multitude of mechanisms have been implicated in the pathophysiology of epilepsy. To assess mean daily plasma concentrations of ACTH, cortisol, DHEAS, leu-enkephalin, and beta-endorphin in epileptic patients with complex partial seizures evolving to tonic-clonic in relation to frequency of seizure occurrence (groups with seizure occurrences - several per week and several per year) and duration of the disease (groups less than and more than 10 years). We decided to analyse mean daily values of beta-endorphin and leu-enkephalin because of significant differences in concentrations of these substances in blood during the day. The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test. Mean daily concentrations of ACTH and cortisol in the blood of the patients with epilepsy were higher in comparison with those of the healthy volunteers, independently of the frequency of seizures and duration of the disease. Mean daily concentrations of beta-endorphin in the blood of the patients with epilepsy were higher in the groups of patients with more severe clinical course of disease (with more frequently occurring epilepsy seizures and longer duration of the disease) in comparison with healthy subjects. Mean daily concentrations of leu-enkephalin in the blood of the patients with epilepsy were higher in the group of patients with short duration of the disease in comparison with the group with long duration of the disease. 1. Pituitary-adrenal axis hyperactivity is observed in patients with clinically active epilepsy, independently of the frequency of seizures and duration of the disease. 2. Changes in endogenous opioid system activity are related to the clinical activity of epilepsy - beta-endorphin concentrations

  11. Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures.

    PubMed

    Sandyk, R

    1992-01-01

    The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Therapeutic Hypothermia for Refractory Status Epilepticus in a Child with Malignant Migrating Partial Seizures of Infancy and SCN1A Mutation: A Case Report

    PubMed Central

    Shein, Steven L.; Reynolds, Thomas Q.; Gedela, Satyanarayana; Kochanek, Patrick M.

    2012-01-01

    Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children. PMID:23667778

  13. Prevention of epileptic seizures by taurine.

    PubMed

    El Idrissi, Abdeslem; Messing, Jeffrey; Scalia, Jason; Trenkner, Ekkhart

    2003-01-01

    Parenteral injection of kainic acid (KA), a glutamate receptor agonist, causes severe and stereotyped behavioral convulsions in mice and is used as a rodent model for human temporal lobe epilepsy. The goal of this study is to examine the potential anti-convulsive effects of the neuro-active amino acid taurine, in the mouse model of KA-induced limbic seizures. We found that taurine (43 mg/Kg, s.c.) had a significant antiepileptic effect when injected 10 min prior to KA. Acute injection of taurine increased the onset latency and reduced the occurrence of tonic seizures. Taurine also reduced the duration of tonic-clonic convulsions and mortality rate following KA-induced seizures. Furthermore, taurine significantly reduced neuronal cell death in the CA3 region of the hippocampus, the most susceptible region to KA in the limbic system. On the other hand, supplementation of taurine in drinking water (0.05%) for 4 continuous weeks failed to decrease the number or latency of partial or tonic-clonic seizures. To the contrary, we found that taurine-fed mice showed increased susceptibility to KA-induced seizures, as demonstrated by a decreased latency for clonic seizures, an increased incidence and duration of tonic-clonic seizures, increased neuronal death in the CA3 region of the hippocampus and a higher post-seizure mortality of the animals. We suggest that the reduced susceptibility to KA-induced seizures in taurine-injected mice is due to an increase in GABA receptor function in the brain which increases the inhibitory drive within the limbic system. This is supported by our in vitro data obtained in primary neuronal cultures showing that taurine acts as a low affinity agonist for GABA(A) receptors, protects neurons against kainate excitotoxic insults and modulates calcium homeostasis. Therefore, taurine is potentially capable of treating seizure-associated brain damage.

  14. Influence analysis for high-dimensional time series with an application to epileptic seizure onset zone detection

    PubMed Central

    Flamm, Christoph; Graef, Andreas; Pirker, Susanne; Baumgartner, Christoph; Deistler, Manfred

    2013-01-01

    Granger causality is a useful concept for studying causal relations in networks. However, numerical problems occur when applying the corresponding methodology to high-dimensional time series showing co-movement, e.g. EEG recordings or economic data. In order to deal with these shortcomings, we propose a novel method for the causal analysis of such multivariate time series based on Granger causality and factor models. We present the theoretical background, successfully assess our methodology with the help of simulated data and show a potential application in EEG analysis of epileptic seizures. PMID:23354014

  15. Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life

    PubMed Central

    Thevenon, Julien; Milh, Mathieu; Feillet, François; St-Onge, Judith; Duffourd, Yannis; Jugé, Clara; Roubertie, Agathe; Héron, Delphine; Mignot, Cyril; Raffo, Emmanuel; Isidor, Bertrand; Wahlen, Sandra; Sanlaville, Damien; Villeneuve, Nathalie; Darmency-Stamboul, Véronique; Toutain, Annick; Lefebvre, Mathilde; Chouchane, Mondher; Huet, Frédéric; Lafon, Arnaud; de Saint Martin, Anne; Lesca, Gaetan; El Chehadeh, Salima; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; Odent, Sylvie; Villard, Laurent; Philippe, Christophe; Faivre, Laurence; Rivière, Jean-Baptiste

    2014-01-01

    Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy. PMID:24995870

  16. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life.

    PubMed

    Thevenon, Julien; Milh, Mathieu; Feillet, François; St-Onge, Judith; Duffourd, Yannis; Jugé, Clara; Roubertie, Agathe; Héron, Delphine; Mignot, Cyril; Raffo, Emmanuel; Isidor, Bertrand; Wahlen, Sandra; Sanlaville, Damien; Villeneuve, Nathalie; Darmency-Stamboul, Véronique; Toutain, Annick; Lefebvre, Mathilde; Chouchane, Mondher; Huet, Frédéric; Lafon, Arnaud; de Saint Martin, Anne; Lesca, Gaetan; El Chehadeh, Salima; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; Odent, Sylvie; Villard, Laurent; Philippe, Christophe; Faivre, Laurence; Rivière, Jean-Baptiste

    2014-07-03

    Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy.

  17. Intrinsic ictal dynamics at the seizure focus: effects of secondary generalization revealed by complexity measures.

    PubMed

    Jouny, Christophe C; Adamolekun, Bola; Franaszczuk, Piotr J; Bergey, Gregory K

    2007-02-01

    Partial seizures (PSs) may be self-limited regional events or propagate further and secondarily generalize. The mechanisms and dynamics of secondarily generalized tonic-clonic seizures (GTCSs) are not well understood. Methods with which to assess the dynamic of those events are also limited. Seizures were analyzed from patients with intractable partial seizures undergoing monitoring with intracranial electrodes. Inclusion in this study required patients to have at least one PS and one GTCS. From >120 patients, seven patients fulfilled these criteria, three with mesial temporal (MTLE) onset seizures and four with neocortical lesional (NCLE) onset seizures. In total, 50 seizures were analyzed by using the matching pursuit (MP) method and the Gabor atom density (GAD), a measure of signal complexity derived from the MP method. The GAD complexity pattern at the seizure focus for the initial ictal period is remarkably consistent in a given patient, regardless of whether secondary generalization occurs. Secondary generalization produces greater modification of seizure activity at the focus in patients with NCLE than in patients with MTLE. In seizures from four patients with NCLE, secondary generalization resulted in an average increase of 115% in complexity at the focus compared to PSs. GAD shows that seizure dynamics of PSs are often very stereotyped from seizure to seizure in a given patient, particularly during early ictal evolution. Secondary generalization is more likely to produce changes in the duration and dynamics at the seizure focus in NCLE patients compared with MTLE patients. These observations suggest distinct mechanisms (e.g., feedback) that are operational during secondary generalization.

  18. Influence on ictal seizure semiology of rapid withdrawal of carbamazepine and valproate in monotherapy.

    PubMed

    Zhou, Dong; Wang, Ying; Hopp, Peter; Kerling, Frank; Kirchner, Annette; Pauli, Elisabeth; Stefan, Hermann

    2002-04-01

    To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation. Therapeutic intensive seizure analysis (TISA) with video-EEG monitoring was used in 33 patients with pharmacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded. A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED-free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED-free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases. Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure-onset characteristics, which speaks in favor of its use in presurgical evaluation.

  19. Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

    PubMed Central

    Sunkaraneni, Soujanya; Passarell, Julie A; Ludwig, Elizabeth A; Fiedler-Kelly, Jill; Pitner, Janet K; Grinnell, Todd A; Blum, David

    2017-01-01

    Purpose Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. Conclusion This model-based assessment supports conversion to ESL 800 mg QD monotherapy

  20. Absence of Liver Toxicity in Perampanel-Treated Subjects: Pooled results from partial seizure phase III perampanel clinical studies.

    PubMed

    Laurenza, Antonio; Yang, Haichen; Williams, Betsy; Zhou, Sharon; Ferry, Jim

    2015-07-01

    The liver plays a major role in the metabolism and elimination of many antiepileptic drugs (AEDs), including perampanel. Some of the metabolites identified for perampanel are likely formed via reactive intermediates, which have the potential to covalently bind to protein and cause idiosyncratic toxicities, including hepatotoxicity. The approved AED perampanel is a selective, noncompetitive AMPA receptor antagonist. The safety and tolerability of perampanel have been well documented in 3 double-blind, randomized, placebo-controlled, phase III studies. Here we report the effects of perampanel on liver function in patients from the phase III studies to assess the potential for liver toxicity. Following 6-week baseline, patients (≥12 years old) with drug-resistant partial seizures were randomized to once-daily double-blind treatment (6-week titration, 13-week maintenance) with 2, 4, 8, or 12mg perampanel (n=1038) or with placebo (n=442). Clinical laboratory tests for hepatobiliary laboratory parameters were evaluated at baseline and at end of treatment. These included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and total bilirubin. Treatment-emergent markedly abnormal values (an increase in NCI-CTC grade relative to baseline and a grade ≥2) and treatment-emergent adverse events (TEAEs) related to hepatobiliary parameters were also recorded. Mean hepatobiliary values were within normal ranges at baseline and end of treatment for all perampanel groups and placebo. Mean changes from baseline to end of treatment were small. The incidence of markedly abnormal results was very low for perampanel and placebo. TEAEs related to hepatobiliary parameters occurred in 0.4% of perampanel patients and 0% of placebo patients. Hepatobiliary disorders included cholelithiasis (n=3 in perampanel) and abnormal hepatic function (n=1 in perampanel). None of the events were serious or led to perampanel discontinuation. No

  1. Adjunctive pregabalin vs gabapentin for focal seizures

    PubMed Central

    Glue, Paul; Friedman, Daniel; Almas, Mary; Yardi, Nandan; Knapp, Lloyd; Pitman, Verne; Posner, Holly B.

    2016-01-01

    Objective: To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin. Methods: The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase. Results: A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was −58.65 and −47.7 (SD 48.3) for pregabalin and −57.43 and −45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval −6.0 to 7.0). Safety profiles were comparable and consistent with prior trials. Conclusions: The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials. ClinicalTrials.gov identifier: NCT00537940. Classification of evidence: This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations. PMID:27521437

  2. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    ERIC Educational Resources Information Center

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  3. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    ERIC Educational Resources Information Center

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  4. Absence seizure

    MedlinePlus

    Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  5. Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2.

    PubMed

    Guerrini, R; Bonanni, P; Patrignani, A; Brown, P; Parmeggiani, L; Grosse, P; Brovedani, P; Moro, F; Aridon, P; Carrozzo, R; Casari, G

    2001-12-01

    We describe a pedigree in which eight individuals presented with a non-progressive disorder with onset between the ages of 12 and 50 years. It was characterized by predominantly distal, semi-continuous rhythmic myoclonus (all patients), generalized tonic-clonic seizures (all patients) and complex partial seizures (three patients). Most individuals had rarely suffered seizures and had a normal cognitive level, but three individuals with intractable seizures had mild mental retardation. The pattern of inheritance was autosomal dominant with high penetrance. We defined this disorder as autosomal dominant cortical myoclonus and epilepsy (ADCME). All patients had frontotemporal as well as generalized interictal EEG abnormalities. A neurophysiological study of the myoclonus suggested a cortical origin. Back-averaging of the data generated a series of waves with a frequency that mirrored the frequency of EMG bursts. Frequency analysis identified significant peaks with coherence between EMG and EEG, which were recorded over the contralateral rolandic area in five patients. The frequency of coherence was 8-25 Hz and phase spectra confirmed that EEG activity preceded EMG activity by 8-15 ms. In two individuals there was also significant coherence between the ipsilateral EEG and EMG, consistent with the transcallosal spread of myoclonic activity. The C-reflex at rest was enhanced and somatosensory and visual evoked potentials were of high amplitude. The resting motor threshold intensity to transcranial magnetic stimulation was significantly reduced (38%; SD +/- 7; P = 0.01) and the post-motor evoked potential silent period (101 ms; SEM +/- 10) was significantly shortened compared with the controls (137 ms; SEM +/- 18). These clinical and neuro- physiological characteristics suggest diffuse cortical hyperexcitability and high propensity for intra-hemispheric and inter-hemispheric cortical spread, as well as rhythmic myoclonic activity. Genome-wide linkage analysis identified a

  6. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy. PMID:21081551

  7. Seizure susceptibility due to antihistamines in febrile seizures.

    PubMed

    Takano, Tomoyuki; Sakaue, Yuko; Sokoda, Tatsuyuki; Sawai, Chihiro; Akabori, Shie; Maruo, Yoshihiro; Taga, Takashi; Ohno, Masaki; Takeuchi, Yoshihiro

    2010-04-01

    The aim of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The study population comprised 14 patients with simple febrile seizures and 35 patients with complex febrile seizures. Detailed clinical manifestations were compared between patients with and without administration of antihistamine. The time from fever detection to the seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than that in nonantihistamine group. Interleukin-1beta is thought to be associated with causing febrile seizures via its dual role as a pyrogen and convulsant substance. Moreover, interleukin-1beta may activate the turnover of hypothalamic neural histamine. These considerations, along with the present results, suggest that the depletion of hypothalamic neuronal histamine induced by antihistamines may increase neuronal excitability, thereby increasing seizure susceptibility in patients with febrile seizures. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Treatment of malignant migrating partial epilepsy of infancy with rufinamide: report of five cases.

    PubMed

    Vendrame, Martina; Poduri, Annapurna; Loddenkemper, Tobias; Kluger, Gerhard; Coppola, Giangennaro; Kothare, Sanjeev V

    2011-03-01

    The syndrome of malignant migrating partial seizures of infancy (MMPEI) is characterized by early onset of multiple seizures types, highly pharmaco-resistant seizures, and overall poor prognosis. In this study, we investigated retrospectively the efficacy of rufinamide (RUF) in five infants with MMPEI, by examining seizure type and frequency, EEG features and antiepileptic drug use. The data demonstrate that two of the five patients showed good efficacy and tolerability for RUF with a > 50% reduction in seizure frequency. The use of RUF for the treatment of MMPEI may therefore provide some hope for such infants and should be further validated. [Published with video sequences].

  9. Specific and nonspecific multiple unit activities during the onset of pentylenetetrazol seizures. II. Acute lesions interrupting nonspecific system connections.

    PubMed

    Velasco, F; Velasco, M; Maldonado, H; Estrada-Villanueva, F

    1976-12-01

    Nonspecific cortical, thalamic, mesencephalic, and pontine multiple unit activities (MUA) and changes in EEG and MUS of the sciatic nerve after threshold pentylenetetrazol activation were studied in three groups of animals in which neuronal connections were interrupted at three different levels of the central nervous system: spinal, mesencephalic, and prethalamic. Maximal increments of nonspecific MUA and maximal increments and maximal decrements of sciatic MUA after pentylenetetrazol from each group of lesioned animals were statistically compared with tose observed in intact animals. 1. Pentylenetetrazol threshold for producing cortical tonic-clonic EEG discharges was increased in animals with nesencephaic and prethalamic lesions but was not modified in animals with spinal transection. 2. Cortical MUA maximal increment was significantly decreased in mesencephalic and prethalamic lesioned animals, whereas thalamic MUA maximal increment was significantly decreased in mesencephalic and significantly increased in prethalamic lesioned animals. Pontine MUA maximal increment was significantly increased in spinal, mesencephalic, and prethalamic lesioned animals, and mesencephalic M-A maximal increment was not significantly modified in either prethalamic lesioned or in spinal transected animals. 3. Sciatic MUA maximal increment and maximal decrement were significatly decreased in spinal transected animals, whereas only maximal increment was significantly decreased in mesencephalic and only maximal decrement was significantly decreased in prethalamic lesioned animals. These results based on lesion experiments permit us to infer than under normal cinditions the development of generalized seizures induced by threshold pentylenetetrazol injection is highly dependent upon the neuronal interactions between nonspecific structures at different levels of the central nervous system. The possible nature of these neuronal interactions in the intact animals is discussed.

  10. Improving Early Seizure Detection

    PubMed Central

    Jouny, Christophe C.; Franaszczuk, Piotr J.; Bergey, Gregory K.

    2011-01-01

    Over the last decade, the search for a method able to reliably predict seizures hours in advance has been largely replaced by a more realistic goal of very early detection of seizure onset which would allow therapeutic or warning devices to be triggered prior to the onset of disabling clinical symptoms. We explore in this article the steps along the pathway from data acquisition to closed loop applications that can and should be considered to design the most efficient early seizure detection. Microelectrodes, high-frequency oscillations, high sampling rate, high-density arrays, and modern analysis techniques are all elements of the recording and detection process that in combination with modeling studies can provide new insights into the dynamics of seizure onsets. Each of these step needs to be considered if one wants to implement improved detection devices that will favorably impact the quality of life of patients. PMID:22078518

  11. Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis).

    PubMed

    Casciato, S; Di Bonaventura, C; Lapenta, L; Fattouch, J; Ferrazzano, G; Fanella, M; Di Fabio, F; Pasquini, M; Amendolea, M A; Manfredi, M; Prencipe, M; Giallonardo, A T

    2011-12-01

    Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a rare condition whose pathogenesis is unknown, though autoimmune-mediated mechanisms are thought to be involved. The prevalent neurological manifestations of this disorder are epileptic seizures and psychocognitive disorders associated with EEG alterations. High anti-thyroid antibody titers (particularly in cerebrospinal fluid) and the effectiveness of steroid therapy are usually considered to be crucial elements in the diagnostic process. We describe a 19-year-old female patient who had been referred to the psychiatric unit because of behavioral disorders characterized predominantly by delirium with sexual content. She developed recurrent focal seizures characterized by atypical ictal semiology (repetitive forceful yawning) and a rare EEG pattern (recurrent seizures arising from the left temporal region without evident "encephalopathic" activity). The presence of anti-thyroperoxidase antibodies in her cerebrospinal fluid and a good response to steroids confirmed the diagnosis of HE. The atypical presentation in the case we describe appears to widen the electroclinical spectrum of HE and highlights its importance for differential diagnosis purposes in the neuropsychiatric setting. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide.

    PubMed

    Villanueva, Vicente; López, Francisco Javier; Serratosa, José María; González-Giraldez, Beatriz; Campos, Dulce; Molins, Albert; Rodriguez Uranga, Juan; Mauri, José Angel; Salas-Puig, Javier; Toledo, Manuel; Sánchez-Alvarez, Juan Carlos; Moreno, Antonio; Serrano-Castro, Pedro J; Saiz-Diaz, Rosa Ana; González de la Aleja, Jesús; de la Peña, Pilar; Asensio, Montserrat

    2013-11-01

    Lacosamide is approved as adjunctive therapy for focal epilepsies. The number of antiepileptic drugs (AEDs) tried is associated with prognosis. This multicenter, retrospective, observational study (LACO-EXP) in Spain in 500 adult patients with focal epilepsies examined the efficacy and tolerability of add-on lacosamide. Factors associated with better efficacy/tolerability were analyzed. After 12months, the responder rate (≥50% reduction in seizure frequency) was 57.1%, and the seizure-free rate was 14.9%. Efficacy was better when lacosamide was the first or second add-on AED, although there was a small chance to be seizure-free even for patients who had received ≤10 prior AEDs. The mechanism of action of concomitant AEDs is important in all the stages, but differences are smaller in the early stages. Lacosamide was generally well tolerated. A slower dosage-titration schedule was associated with a lower adverse event rate. Further investigation of the timing of initiation of lacosamide add-on therapy and ideal combinations of AEDs is required.

  13. Febrile seizures

    PubMed Central

    2014-01-01

    Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination. PMID:25324864

  14. Game-related seizures presenting with two types of clinical features.

    PubMed

    Chuang, Yao-Chung; Chang, Wen-Neng; Lin, Tsu-Kung; Lu, Cheng-Hsien; Chen, Shang-Der; Huang, Chi-Ren

    2006-03-01

    We evaluated 22 patients with epileptic seizures in which the seizures were triggered by various games or game-related materials. Based on whether spontaneous seizure coexisted or not, these 22 patients were divided into two groups. Ten patients who experienced seizures exclusively while playing or watching specific games were referred to as Group I, while 12 patients that had both game-induced and spontaneous seizures were classified as Group II. The patients in Group I had a middle-age onset (39.1 years) with a male predominance (90%). The electroencephalogram (EEG) or brain magnetic resonance imaging revealed non-specific abnormalities in 60%, and the partial onset seizure was recognized in 30% of patients. Antiepileptic drugs had uncertain benefits in this group. In Group II, patients had a male predominance (67%), with onset during adolescence (16.3 years). Most of them had generalized tonic-clonic seizures, myoclonic seizures, and absences, and 42% showed epileptiform discharge on EEG. These 12 patients were categorized into idiopathic generalized epilepsies. Although photosensitivity was an important factor, higher mental activity seemed to be significant precipitants of seizures in Group II. Antiepileptic drugs were necessary and valproic acid alone or combined with clonazepam was effective in this group. The results showed that game-related seizures are not a unique and homogeneous syndrome and may consist of different mechanisms. Teenage onset, coexistent spontaneous seizure, and associated idiopathic generalized epilepsies were crucial factors in the determination of antiepileptic drug therapy. Moreover, avoiding the related games altogether may be a more productive preventive measure.

  15. Distinct EEG seizure patterns reflect different seizure generation mechanisms

    PubMed Central

    Salami, Pariya; Lévesque, Maxime; Gotman, Jean

    2015-01-01

    Low-voltage fast (LVF)- and hypersynchronous (HYP)-seizure onset patterns can be recognized in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80–200 Hz) and fast ripples (250–500 Hz) have been linked to each pattern, with ripples predominating during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the contribution of neural networks with distinct transmitter signaling characteristics. Here, we tested this hypothesis by analyzing the seizure activity induced with the K+ channel blocker 4-aminopyridine (4AP, 4–5 mg/kg ip), which enhances both glutamatergic and GABAergic transmission, or the GABAA receptor antagonist picrotoxin (3–5 mg/kg ip); rats were implanted with electrodes in the hippocampus, the entorhinal cortex, and the subiculum. We found that LVF onset occurred in 82% of 4AP-induced seizures whereas seizures after picrotoxin were always HYP. In addition, high-frequency oscillation analysis revealed that 4AP-induced LVF seizures were associated with higher ripple rates compared with fast ripples (P < 0.05), whereas picrotoxin-induced seizures contained higher rates of fast ripples compared with ripples (P < 0.05). These results support the hypothesis that two distinct patterns of seizure onset result from different pathophysiological mechanisms. PMID:25652916

  16. Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

    PubMed

    Jobst, Barbara C; Kapur, Ritu; Barkley, Gregory L; Bazil, Carl W; Berg, Michel J; Bergey, Gregory K; Boggs, Jane G; Cash, Sydney S; Cole, Andrew J; Duchowny, Michael S; Duckrow, Robert B; Edwards, Jonathan C; Eisenschenk, Stephan; Fessler, A James; Fountain, Nathan B; Geller, Eric B; Goldman, Alica M; Goodman, Robert R; Gross, Robert E; Gwinn, Ryder P; Heck, Christianne; Herekar, Aamr A; Hirsch, Lawrence J; King-Stephens, David; Labar, Douglas R; Marsh, W R; Meador, Kimford J; Miller, Ian; Mizrahi, Eli M; Murro, Anthony M; Nair, Dileep R; Noe, Katherine H; Olejniczak, Piotr W; Park, Yong D; Rutecki, Paul; Salanova, Vicenta; Sheth, Raj D; Skidmore, Christopher; Smith, Michael C; Spencer, David C; Srinivasan, Shraddha; Tatum, William; Van Ness, Paul; Vossler, David G; Wharen, Robert E; Worrell, Gregory A; Yoshor, Daniel; Zimmerman, Richard S; Skarpaas, Tara L; Morrell, Martha J

    2017-06-01

    Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable

  17. Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy.

    PubMed

    Doucet, Gaëlle E; Sharan, Ashwini; Pustina, Dorian; Skidmore, Christopher; Sperling, Michael R; Tracy, Joseph I

    2015-01-01

    Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.

  18. A review of sleepwalking (somnambulism): the enigma of neurophysiology and polysomnography with differential diagnosis of complex partial seizures.

    PubMed

    Hughes, John R

    2007-12-01

    The goal of this report is to review all aspects of sleepwalking (SW), also known as somnambulism. Various factors seem to initiate SW, especially drugs, stress, and sleep deprivation. As an etiology, heredity is important, but other conditions include thyrotoxicosis, stress, and herpes simplex encephalitis. Psychological characteristics of sleepwalkers often include aggression, anxiety, panic disorder, and hysteria. Polysomnographic characteristics emphasize abnormal deep sleep associated with arousal and slow wave sleep fragmentation. In the differential diagnosis, the EEG is important to properly identify a seizure disorder, rather than SW. Associated disorders are Tourette's syndrome, sleep-disordered breathing, and migraine. Various kinds of treatment are discussed, as are legal considerations, especially murder during sleepwalking.

  19. Pregabalin add-on treatment in patients with partial seizures: a novel evaluation of flexible-dose and fixed-dose treatment in a double-blind, placebo-controlled study.

    PubMed

    Elger, Christian E; Brodie, Martin J; Anhut, Henning; Lee, Caroline M; Barrett, Jeannette A

    2005-12-01

    To evaluate pregabalin as add-on therapy for patients with partial seizures administered as fixed dose or as flexible dose adjusted to optimal seizure reduction and tolerability. Patients receiving antiepileptic drugs (98.8% between 1 and 3 AEDs; 1.2% on more than 3 AEDs) and experiencing > or =4 partial seizures during the 6-week baseline period and no 4-week seizure-free interval were randomized (1:2:2) to placebo (n = 73), pregabalin fixed dose (600 mg/day BID; n = 137), or pregabalin flexible dose (n = 131; 150 and 300 mg/day for 2 weeks each; 450 and 600 mg/day for 4 weeks each, BID) for 12 weeks. Dosage could be adjusted based on tolerability and maintained when a 4-week seizure-free period was achieved. Primary efficacy parameter was reduction in seizure frequency from baseline. Both pregabalin regimens significantly reduced seizure frequency compared with placebo, by 35.4%, for flexible dose (p = 0.0091) and 49.3% for fixed dose (p = 0.0001) versus 10.6% for placebo, and the fixed-dose group was superior to the flexible-dose group (p = 0.0337). Most adverse events were mild or moderate. Discontinuation rates due to adverse events were 6.8% (placebo), 12.2% (pregabalin flexible dose), and 32.8% (pregabalin fixed dose). Patients receiving pregabalin fixed dose discontinued due to adverse event earlier than other groups. Pregabalin administered twice daily, either as fixed (600 mg/day), or as flexible (150-600 mg/day) dose, was highly effective and generally well-tolerated as add-on therapy for partial seizures with or without secondary generalization. Lower incidence of adverse events and discontinuations were achieved in patients receiving pregabalin when dosing was individualized to optimize efficacy and tolerability.

  20. Absence Seizure (Petit Mal Seizure)

    MedlinePlus

    ... Staff Absence seizures involve brief, sudden lapses of consciousness. They're more common in children than adults. ... have seizures, the brain's usual electrical activity is altered. During an absence seizure, these electrical signals repeat ...

  1. Lack of effect of perampanel on QT interval duration: Results from a thorough QT analysis and pooled partial seizure Phase III clinical trials.

    PubMed

    Yang, Haichen; Laurenza, Antonio; Williams, Betsy; Patten, Anna; Hussein, Ziad; Ferry, Jim

    2015-08-01

    Perampanel is a selective, noncompetitive AMPA receptor antagonist approved as adjunctive treatment for partial seizures. To assess potential for delayed cardiac repolarization, a Phase I thorough QT study was performed, supplemented by plasma concentration-QT data modeled from 3 pooled Phase III studies. The Phase I thorough QT study (double-blind, combined fixed-sequence, parallel-group) quantified the effect of perampanel (6 mg once daily for 7 days, followed by dose escalation to a single 8-mg dose, a single 10-mg dose, then 12 mg once daily for 7 days), moxifloxacin positive control (single 400-mg dose on Day 16), and placebo on QT interval duration in healthy subjects (N = 261). Electrocardiograms were recorded at baseline, Day 7 (post 6 mg dose), and Day 16 (post 12 mg dose). Statistical comparisons were between the highest approved perampanel dose (12 mg) versus placebo, a "mid-therapeutic" dose (6 mg) versus placebo, and moxifloxacin versus placebo. Acknowledging that the Phase I thorough QT study could not incorporate a true "supratherapeutic" dose due to length of titration and tolerability concerns in healthy subjects, Phase III studies of perampanel included expanded electrocardiogram safety evaluations specifically intended to support concentration-QT response modeling. The lack of effect of perampanel on the QT interval is shown from pooled analysis of 3 double-blind, placebo-controlled, 19-week, Phase III studies with perampanel doses ≤ 12 mg (N = 1038, total perampanel; and N=442, placebo) in patients with partial seizures. QT measures were corrected for heart rate using Fridericia's (QTcF; the primary endpoint) and Bazett's (QTcB) formulas. In the Phase I thorough QT study, the positive control moxifloxacin caused peak time-matched, baseline-adjusted, placebo-corrected (ΔΔ) QTcF of 12.15 ms at 4h postdose, confirming a drug effect on QTc interval and study assessment sensitivity. Mean baseline-adjusted (Δ) QTcF versus nominal time curves were

  2. Localization of pediatric seizure semiology.

    PubMed

    Vendrame, Martina; Zarowski, Marcin; Alexopoulos, Andreas V; Wyllie, Elaine; Kothare, Sanjeev V; Loddenkemper, Tobias

    2011-10-01

    The aim of this study was to evaluate the relationship between semiology of seizures in children and adolescents to the corresponding EEG localization. Charts of 225 consecutive pediatric epilepsy patients undergoing Video-EEG monitoring (VEM) over 2 years were reviewed. Seizure semiology recorded during VEM was classified according to ILAE seizure semiology terminology and EEG localization, and analyzed based on onset as defined by the EEG data (generalized, frontal, temporal, parietal, occipital or multilobar). A total of 1008 seizures were analyzed in 225 children (mean age 8.5 years, range 0-20), with 50% boys. Auras and seizures with automatisms arose predominantly from the temporal lobes (p<0.001). Tonic, clonic and tonic-clonic seizures had most commonly generalized onset (p<0.001). Hypomotor seizures were most frequently seen from the frontal lobes (p<0.001). Hypermotor seizures had most commonly temporal lobe or multiple lobe onset (p<0.001 and p<0.05 respectively). Atonic, myoclonic seizures and epileptic spasms had almost exclusively a generalized onset (p<0.001). Different seizure semiologies relate to specific brain regions, with overlap between focal and generalized semiological seizure types, as identified electrographically. Semiology of seizures can provide important information for epilepsy localization, and should not be overlooked, especially in patients undergoing pre-surgical evaluation. Separation of clinical seizure description and EEG findings may be useful, in particular when only incomplete information is available. i.e. during the first office visit. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. 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.

  4. Classification of clinical semiology in epileptic seizures in neonates.

    PubMed

    Nagarajan, Lakshmi; Palumbo, Linda; Ghosh, Soumya

    2012-03-01

    The clinical semiology of 61 neonatal seizures with EEG correlates, in 24 babies was analysed. Most seizures (89%) had multiple features during the EEG discharge. The seizures were classified using the prominent clinical feature at onset, and all features seen during the seizure, using an extended classification scheme. Orolingual features occurred most frequently at onset (30%), whereas ocular phenomena occurred most often during the seizure (70%). Orolingual, ocular and autonomic features were seen at onset in 55% of the seizures. Seizure onsets with clonic, tonic and hypomotor features were seen in 20%, 8% and 18% respectively. Clinico-electrical correlations were as follows. The EEG discharge involved both hemispheres in 54% of all seizures, in clonic seizures this was 93%. Focal clonic seizures were associated with EEG seizure onset from the contralateral hemisphere. Majority of the clonic and hypomotor seizures had a left hemisphere ictal EEG onset. Orolingual seizures frequently started from the right hemisphere, whereas ocular and autonomic seizures arose from either hemisphere. There was no significant difference in mortality, morbidity, abnormal neuroimaging and EEG background abnormalities in babies with or without clonic seizures. This study provides insights into neuronal networks that underpin electroclinical seizures, by analysing and classifying the obvious initial clinical features and those during the seizure. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  5. Evidence for the perirhinal cortex as a requisite component in the seizure network following seizure repetition in an inherited form of generalized clonic seizures.

    PubMed

    Raisinghani, Manish; Faingold, Carl L

    2005-06-28

    Perirhinal cortex (PRh) is strongly implicated in neuronal networks subserving forebrain-driven partial onset seizures, but whether PRh plays a role in generalized onset seizures is unclear. The moderate seizure severity substrain of genetically epilepsy-prone rats (GEPR-3s) exhibits generalized onset clonic audiogenic seizures (AGS), but following repetitive AGS (AGS kindling), an additional behavior, facial and forelimb (F&F) clonus emerges immediately following generalized clonus. F&F clonus is thought to be driven from forebrain structures. The present in vivo study used PRh focal blockade or extracellular PRh neuronal recording with simultaneous behavioral observations to examine the role played by PRh in AGS neuronal networks before and after AGS kindling in GEPR-3s. Bilateral microinjection of an NMDA receptor antagonist [2-amino-7-phosphonoheptanoic acid, AP7 (0.2-7.5 nmol/side)] into PRh did not affect generalized clonus before or after AGS kindling. However, complete and reversible blockade of only the F&F clonic seizure behavior was induced by AP7 (1 and 7.5 nmol) in AGS-kindled GEPR-3s. Significant increases in PRh neuronal responses to acoustic stimuli occurred after AGS kindling. Tonic PRh neuronal firing patterns appeared during generalized clonus before and after AGS kindling. During F&F clonus, burst firing, an indicator of increased excitability, appeared in PRh neurons. These neurophysiological and microinjection findings support a critical role of PRh in generation of this AGS kindling-induced convulsive behavior. These data are the first indication that PRh participates importantly in the neuronal network for AGS as a result of AGS kindling and demonstrate a previously unknown involvement of PRh in generalized onset seizures.

  6. Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

    PubMed Central

    2010-01-01

    Background and aims There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones. Methods 3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I). Results The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters. Conclusions Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to

  7. GABAergic networks jump-start focal seizures

    PubMed Central

    de Curtis, Marco; Avoli, Massimo

    2016-01-01

    Summary Abnormally enhanced glutamatergic excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by firm evidence, and it will be challenged here. A general reduction of unit firing has been indeed observed in association with low-voltage fast activity at the onset of seizures recorded during presurgical intracranial monitoring in patients with focal, drug-resistant epilepsies. Moreover, focal seizures in animal models start with increased γ-aminobutyric acid (GABA)ergic interneuronal activity that silences principal cells. In vitro studies have shown that synchronous activation of GABAA receptors occurs at seizure onset and causes sizeable elevations in extracellular potassium, thus facilitating neuronal recruitment and seizure progression. A paradoxical involvement of GABAergic networks is required for the initiation of focal seizures characterized by low-voltage fast activity, which represents the most common seizure-onset pattern in focal epilepsies. PMID:27061793

  8. Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas.

    PubMed

    Chapman, Kevin E; Kim, Do-Young; Rho, Jong M; Ng, Yu-Tze; Kerrigan, John F

    2011-05-01

    Seizures associated with hypothalamic hamartoma (HH) are notoriously intractable to medical therapy, and while surgical resection affords most affected patients with complete or near seizure-freedom, there remains a need to identify alternative treatments. In this retrospective study, we identified six patients from a large cohort of 220 patients with HH who were treated with the ketogenic diet (KD). Four patients had a 50-90% reduction in multiple seizure types (including gelastic, partial-onset and atonic seizures), and two individuals failed to respond. In order to study possible mechanisms, we then performed microelectrode recordings of small neurons in surgically resected HH tissue slices. Exposure to ketone bodies decreased spontaneous firing in 5 of 7 small HH neurons. These preliminary results suggest that seizures associated with HH may respond favorably to the KD, and that ketone bodies might directly modulate the intrinsic epileptogenicity of HH tissue.

  9. The effect of recurrent seizures on cognitive, behavioral, and quality-of-life outcomes after 12 months of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy.

    PubMed

    Lee, Sang-Ahm; Kim, Min Ju; Lee, Hyang-Woon; Heo, Kyoung; Shin, Dong-Jin; Song, Hong-Ki; Kim, Ok-Joon; Kim, Seon-Ok; Lee, Byung-In

    2015-12-01

    The purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy. Seizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist-90 (SCL-90), and the Quality of Life in Epilepsy-31 (QOLIE-31) were administered at baseline and after 48 weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model. A group-by-time interaction was identified for the total QOLIE-31 score (p<0.05) and score on two QOLIE-31 subscales (social function: p<0.001 and seizure worry: p<0.001), with a significant improvement over time only present in the SF group (all p<0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p<0.01) and number of recognition hits on the California Verbal Learning Test (p<0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48 weeks (p<0.01). There was no significant group-by-time interaction for any dimension of the SCL-90. Recurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Improving early seizure detection.

    PubMed

    Jouny, Christophe C; Franaszczuk, Piotr J; Bergey, Gregory K

    2011-12-01

    Over the last decade, the search for a method able to reliably predict seizures hours in advance has been largely replaced by the more realistic goal of very early detection of seizure onset, which would allow therapeutic or warning devices to be triggered prior to the onset of disabling clinical symptoms. We explore in this article the steps along the pathway from data acquisition to closed-loop applications that can and should be considered to design the most efficient early seizure detection. Microelectrodes, high-frequency oscillations, high sampling rate, high-density arrays, and modern analysis techniques are all elements of the recording and detection process that in combination with modeling studies can provide new insights into the dynamics of seizure onsets. Each of these steps needs to be considered if detection devices that will favorably impact the quality of life of patients are to be implemented. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. [Ecstatic seizures].

    PubMed

    Likhachev, S A; Astapenko, A V; Osos, E L; Zmachynskaya, O L; Gvishch, T G

    2015-01-01

    Ecstatic seizures is a rare manifestation of epilepsy. They were described for the first time by F.M. Dostoevsky. Currently, the description of ecstatic seizures is possible to find in the scientific literature. The description of the own observation of a patient with emotional-affective seizures is presented. A role of the anterior insular cortex in the ecstatic seizures origin is discussed. The similarities between the feelings reported during ecstatic seizures and the feelings experienced under the effect of stimulant addictive drugs are described. The possible reasons of the low frequency of emotional-affective seizures are considered.

  12. Seizure semiology identifies patients with bilateral temporal lobe epilepsy.

    PubMed

    Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

    2015-01-01

    Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Seizure ending signs in patients with dyscognitive focal seizures.

    PubMed

    Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

    2015-09-01

    Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

  14. [Epileptic seizures in childhood: from seizure type to diagnosis].

    PubMed

    Milh, M; Ticus, I; Villeneuve, N; Hugonencq, C; Mancini, J; Chabrol, B

    2008-02-01

    Epileptic seizures can be difficult to recognize in infancy and childhood because the semeiology can be misleading. Already, in the acute phase, precise assessment of the seizure is required, with active questioning about circumstances of occurrence, clinical manifestations and postictal symptoms. Laboratory tests and toxicologic screening should only be performed according to the circumstances and clinical examination in order to distinguish between symptomatic seizure and epilepsy at the beginning. Epilepsy consists in repetition of several unprovoked epileptic seizure. Assessment of the age of onset, type of seizures, interictal EEG and the neuropsychological profile are instrumental for both the diagnosis of epileptic syndrome and the choice of the right treatment. Epileptic seizures cause distress to parents and the fear they experience of death must always be taken into account.

  15. Febrile and other occasional seizures.

    PubMed

    Bast, T; Carmant, L

    2013-01-01

    Seizures with fever that result from encephalitis or meningitis usually occur late in the course of febrile illness, and are focal and prolonged. Febrile seizures are by far the most common affecting 5% of the population, followed by posttraumatic seizures and those observed in the setting of a toxic, infectious, or metabolic encephalopathy. This chapter reviews the clinical presentation of the three most common forms, due to fever, trauma, and intoxication. Febrile seizures carry no cognitive or mortality risk. Recurrence risk is increased by young age, namely before 1 year of age. Febrile seizures that persist after the age of 6 years are usually part of the syndrome of Generalized epilepsy febrile seizures plus. These febrile seizures have a strong link with epilepsy since non-febrile seizures may occur later in the same patient and in other members of the same family with an autosomal dominant transmission. Complex febrile seizures, i.e., with focal or prolonged manifestations or followed by focal defect, are related to later mesial temporal epilepsy with hippocampal sclerosis; risk factors are seizure duration and brain malformation. Prophylactic treatment is usually not required in febrile seizures. Early onset of complex seizures is the main indication for AED prophylaxis. Early posttraumatic seizures, i.e., within the first week, are often focal and indicate brain trauma: contusion, hematoma, 24 hours amnesia, and depressed skull fracture are major factors of posttraumatic epilepsy. Prophylaxis with antiepileptic drugs is not effective. Various psychotropic drugs, including antiepileptics, may cause seizures. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Using Lorenz plot and Cardiac Sympathetic Index of heart rate variability for detecting seizures for patients with epilepsy.

    PubMed

    Jeppesen, Jesper; Beniczky, Sandor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

    2014-01-01

    Tachycardia is often seen during epileptic seizures, but it also occurs during physical exercise. In order to assess whether focal epileptic seizures can be detected by short term moving window Heart Rate Variability (HRV) analysis, we modified the geometric HRV method, Lorenz plot, to consist of only 30, 50 or 100 R-R intervals per analyzed window. From each window we calculated the longitudinal (L) and transverse (T) variability of Lorenz plot to retrieve the Cardiac Sympathetic Index (CSI) as (L/T) and "Modified CSI" (described in methods), and compared the maximum during the patient's epileptic seizures with that during the patient's own exercise and non-seizure sessions as control. All five analyzed patients had complex partial seizures (CPS) originating in the temporal lobe (11 seizures) during their 1-5 days long term video-EEG monitoring. All CPS with electroencephalographic correlation were selected for the HRV analysis. The CSI and Modified CSI were correspondently calculated after each heart beat depicting the prior 30, 50 and 100 R-R intervals at the time. CSI (30, 50 and 100) and Modified CSI (100) showed a higher maximum peak during seizures than exercise/non-seizure (121-296%) for 4 of the 5 patients within 4 seconds before till 60 seconds after seizure onset time even though exercise maximum HR exceeded that of the seizures. The results indicate a detectable, sudden and inordinate shift towards sympathetic overdrive in the sympathovagal balance of the autonomic nervous system just around seizure-onset for certain patients. This new modified moving window Lorenz plot method seems promising way of constructing a portable ECG-based epilepsy alarm for certain patients with epilepsy who needs aid during seizure.

  17. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

    PubMed

    Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

    2014-04-01

    Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  18. Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling.

    PubMed

    Cooray, Gerald K; Sengupta, Biswa; Douglas, Pamela; Englund, Marita; Wickstrom, Ronny; Friston, Karl

    2015-09-01

    We characterised the pathophysiology of seizure onset in terms of slow fluctuations in synaptic efficacy using EEG in patients with anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis. EEG recordings were obtained from two female patients with anti-NMDA-R encephalitis with recurrent partial seizures (ages 19 and 31). Focal electrographic seizure activity was localised using an empirical Bayes beamformer. The spectral density of reconstructed source activity was then characterised with dynamic causal modelling (DCM). Eight models were compared for each patient, to evaluate the relative contribution of changes in intrinsic (excitatory and inhibitory) connectivity and endogenous afferent input. Bayesian model comparison established a role for changes in both excitatory and inhibitory connectivity during seizure activity (in addition to changes in the exogenous input). Seizures in both patients were associated with a sequence of changes in inhibitory and excitatory connectivity; a transient increase in inhibitory connectivity followed by a transient increase in excitatory connectivity and a final peak of excitatory-inhibitory balance at seizure offset. These systematic fluctuations in excitatory and inhibitory gain may be characteristic of (anti NMDA-R encephalitis) seizures. We present these results as a case study and replication to motivate analyses of larger patient cohorts, to see whether our findings generalise and further characterise the mechanisms of seizure activity in anti-NMDA-R encephalitis.

  19. Febrile seizures.

    PubMed

    Patterson, Janet L; Carapetian, Stephanie A; Hageman, Joseph R; Kelley, Kent R

    2013-12-01

    Febrile seizures are the most common form of childhood seizures, affecting 2% to 5% of children. They are considered benign and self-limiting; however, a febrile seizure is a terrifying event for most parents, and is one of the most common causes of trips to the emergency room. A febrile seizure is "an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever but without evidence of intracranial infection or defined cause." This definition excludes seizures with fever in children who have had a prior afebrile seizure. In 2011, The American Academy of Pediatrics (AAP) published a clinical practice guideline defining a febrile seizure as "a seizure accompanied by fever (temperature ≥ 100.4°F or 38°C by any method), without central nervous system infection, that occurs in infants and children 6 through 60 months of age." Febrile seizures are further classified as simple or complex. This article reviews the evaluation, management, and prognosis of simple and complex seizures, including febrile status epilepticus. Copyright 2013, SLACK Incorporated.

  20. Ictal scalp EEG recording during sleep and wakefulness: diagnostic implications for seizure localization and lateralization.

    PubMed

    Buechler, Robbie D; Rodriguez, Alcibiades J; Lahr, Brian D; So, Elson L

    2008-02-01

    To determine the localizing value of electroencephalography (EEG) for seizures during sleep versus seizures during wakefulness, we compared scalp EEG for 58 seizures that occurred during sleep with 76 seizures during wake in 28 consecutive patients with temporal lobe epilepsy. Regression analysis showed that seizures during sleep are 2.5 times more likely to have focal EEG onset (p = 0.01) and 4 times more likely to correctly localize seizure onset (p = 0.04) than seizures during wake. EEG seizure onset preceded clinical onset by a longer duration in sleep seizures (mean, 4.69 s) than in wake seizures (mean, 1.23 s; p < 0.01). Sleep seizures showed fewer artifacts, but the difference was not significant (p = 0.07). For temporal lobectomy candidates undergoing video-EEG monitoring, the recording of seizures during sleep may be favored.

  1. Predicting Epileptic Seizures in Advance

    PubMed Central

    Moghim, Negin; Corne, David W.

    2014-01-01

    Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance. PMID:24911316

  2. Remote effects of focal hippocampal seizures on the rat neocortex.

    PubMed

    Englot, Dario J; Mishra, Asht M; Mansuripur, Peter K; Herman, Peter; Hyder, Fahmeed; Blumenfeld, Hal

    2008-09-03

    Seizures have both local and remote effects on nervous system function. Whereas propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation; however, we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multimodal studies of partial and secondarily generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast polyspike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging weighted for blood oxygenation and blood volume, demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures, and increases in all of these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness.

  3. Myocardial infarction following convulsive and nonconvulsive seizures.

    PubMed

    Montepietra, Sara; Cattaneo, Luigi; Granella, Franco; Maurizio, Annarita; Sasso, Enrico; Pavesi, Giovanni; Bortone, Ermelinda

    2009-06-01

    Myocardial infarction (MI) has been rarely reported in association with seizures, and only of convulsive type. We describe a series of five patients observed over a 4-year period, who presented MI immediately following seizures, either convulsive or nonconvulsive. Patient 1 had pre-existent coronary disease (CD) and presented multiple focal nonconvulsive seizures. Patient 2 had no CD, normal coronary angiography and presented secondary generalized convulsive seizures. Patient 3 had no history of CD, normal angiography and had a first single convulsive seizure. Patient 4 had severe CD and suffered from a single convulsive event. Patient 5 had a partial and a generalized seizure and had no known CD. MI following seizures is not an exceptional event and can occur in a spectrum of conditions including single or repeated, convulsive or nonconvulsive seizures, in patients with or without pre-existing coronary disease. We suggest that the occurrence of MI should be considered in epileptic patients during and shortly after seizures.

  4. The clinical and neurobehavioral course of Down syndrome and dementia with or without new-onset epilepsy.

    PubMed

    Gholipour, Taha; Mitchell, Sara; Sarkis, Rani A; Chemali, Zeina

    2017-03-01

    Adult patients with Down syndrome (DS) are at higher risk of developing Alzheimer-type dementia and epilepsy. The relationship between developing dementia and the risk of developing seizures in DS is poorly characterized to date. In addition, treatment response and medication tolerability have not been rigorously studied. We identified 220 patients with a diagnosis of DS and dementia. Those without a history of developing seizures (DD) were compared to patients with new-onset seizures (DD+S) after the age of 35. Electronic records were reviewed for demographics, seizure characteristics, cognitive status, and psychiatric comorbidities. Of the patients included for analysis, twenty-six out of 60 patients had new-onset seizures or developed seizures during the follow-up period (the DD+S group) with a median onset of 2.0years after the dementia diagnosis. Generalized tonic-clonic seizures were the most common seizure type (61.5% of DD+S). Sixteen (61.5%) patients were reported to have myoclonus. Levetiracetam was the most commonly used initial medication, with the majority (73%) of patients treated achieving partial or complete seizure control. The DD+S patients tended to have a similar burden of new-onset neuropsychiatric symptoms compared to the DD group. New-onset epilepsy seems to occur early in the course of dementia in DS patients. Patients generally respond to treatment. A great burden of neuropsychiatric symptoms is seen. Future studies need to explore the relationship between β-amyloid accumulation and epileptiform activity and attend to the care and needs of DS patients with dementia and seizures. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Febrile Seizures

    MedlinePlus

    ... to pinpoint factors that can help predict which children are likely to have reoccurring or prolonged febrile seizures. Investigators continue to monitor the long-term impact that febrile seizures might have on intelligence, behavior, school achievement, and the development of epilepsy. ...

  6. Seizures in Alzheimer's disease.

    PubMed

    Born, H A

    2015-02-12

    Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Seizure response dogs: evaluation of a formal training program.

    PubMed

    Kirton, A; Winter, A; Wirrell, E; Snead, O C

    2008-10-01

    Evidence supporting seizure-related behaviors in dogs is emerging. The methods of seizure response dog (SRD) training programs are unstudied. A standardized survey was retrospectively applied to graduates of a large SRD program. Subjective changes in quality of life (QOL) parameters were explored. Data were captured on animal characteristics, training methods, response and alerting behaviors, effects on seizure frequency, and accuracy of epilepsy diagnosis. Twenty-two patients (88%) participated (median age=34, range=12-66, 73% female). Most had childhood-onset epilepsy (87%) that was refractory with averages of 36 seizures/month and 4.8 medications failed. All had neurologist-confirmed epilepsy, most being symptomatic partial (64%). SRD behaviors were reliable, including emergency response system activation in 27%. All reported SRD-related QOL improvements (major 82%, moderate 18%) across multiple parameters. Spontaneous alerting behavior developed in 59%. That SRD programs may select genuine epilepsy patients, instill valuable assistance skills, and generate meaningful QOL improvements supports further seizure dog research.

  8. Audiogenic reflex seizures in cats

    PubMed Central

    Lowrie, Mark; Bessant, Claire; Harvey, Robert J; Sparkes, Andrew; Garosi, Laurent

    2015-01-01

    Objectives This study aimed to characterise feline audiogenic reflex seizures (FARS). Methods An online questionnaire was developed to capture information from owners with cats suffering from FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Results Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalised tonic–clonic seizures (GTCSs) in this population. Other features include a late onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high-frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One-third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96), with an improvement over time in some (23/96). Only 33/96 and 11/90 owners, respectively, felt the GTCSs and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health, becoming less responsive (43/50), not jumping (41/50), becoming uncoordinated or weak in the pelvic limbs (24/50) and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years, with 42/50 owners stating these signs affected their cat’s QoL. Conclusions and relevance In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric onset. Further studies are warranted to investigate potential genetic predispositions to this condition. PMID:25916687

  9. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  10. [Partial visual seizures induced by non-ketosic hyperglycemia: magnetic resonance imaging and visual evoked potential descriptions. A study of two cases reports with radiologic and electrophysiologic abnormalities].

    PubMed

    Donat, A; Guilloton, L; Bonnet, C; Depreux, G; Lamboley, J-L; Drouet, A

    2013-02-01

    Non-ketosic hyperglycemia (NKH) may increase the likelihood of focal epileptic seizures, including commonly motor expression; rarely, they can have a visual expression. The authors describe the observation of two men, who were hospitalized for visual manifestations; with episodes of homonymous hemianopia and hallucinations, revealing occipital seizure, secondary to NKH. Clinical data and characteristics of the investigations, including radiological imaging (MRI) and electrophysiological results of visual evoked potentials (VEP) are specified. MRI showed transitory low signal on T2 and FLAIR in occipital areas. Spectro-MR identified a moderate diminution of the NAA and lipids spikes, compatible with laminar necrosis. VEP revealed a transient decrease of the P100 amplitude. These two observations underline the existence of acute symptomatic seizures with a visual starting point which is often indicative of diabetes. Through these observations with a review of 28 patients from the literature, MR imaging characteristics and possible anomalies collected on VEP are discussed. Such seizures are resistant to anticonvulsant treatment and respond best to insulin and rehydration. The visual manifestations indicative of seizures with an occipital starting point in the context of NKH are possible enabling rapid initiation of effective symptomatic treatment with insulin. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Early Seizure Detection Using Neuronal Potential Similarity: A Generalized Low-Complexity and Robust Measure.

    PubMed

    Bandarabadi, Mojtaba; Rasekhi, Jalil; Teixeira, Cesar A; Netoff, Theoden I; Parhi, Keshab K; Dourado, Antonio

    2015-08-01

    A novel approach using neuronal potential similarity (NPS) of two intracranial electroencephalogram (iEEG) electrodes placed over the foci is proposed for automated early seizure detection in patients with refractory partial epilepsy. The NPS measure is obtained from the spectral analysis of space-differential iEEG signals. Ratio between the NPS values obtained from two specific frequency bands is then investigated as a robust generalized measure, and reveals invaluable information about seizure initiation trends. A threshold-based classifier is subsequently applied on the proposed measure to generate alarms. The performance of the method was evaluated using cross-validation on a large clinical dataset, involving 183 seizure onsets in 1785 h of long-term continuous iEEG recordings of 11 patients. On average, the results show a high sensitivity of 86.9% (159 out of 183), a very low false detection rate of 1.4 per day, and a mean detection latency of 13.1 s from electrographic seizure onsets, while in average preceding clinical onsets by 6.3 s. These high performance results, specifically the short detection latency, coupled with the very low computational cost of the proposed method make it adequate for using in implantable closed-loop seizure suppression systems.

  12. Gelastic seizures and low-grade hypothalamic astrocytoma: a case report.

    PubMed

    Coppola, Giangennaro; Spagnoli, Diego; Sciscio, Nicola; Russo, Francesco; Villani, Roberto Matteo

    2002-04-01

    The typical, well recognized childhood epilepsy syndrome caused by hypothalamic hamartoma is characterized by early-onset, stereotyped attacks of uncontrollable laughter, frequent refractory seizures with progressive cognitive deterioration and severe behavioral problems. Here, we report a 17-year-old patient with gelastic phenomenon started in the neonatal period, later on associated with drug resistant polymorphic seizures, intellectual deficit and behavioral disorders, who improved by partial resection of an expected hypothalamic hamartoma that, in turn, resulted to be a hypothalamic low-grade astrocytoma.

  13. [Seizures revealing phosphocalcic metabolism abnormalities].

    PubMed

    Hmami, F; Chaouki, S; Benmiloud, S; Souilmi, F Z; Abourazzak, S; Idrissi, M; Atmani, S; Bouharrou, A; Hida, M

    2014-01-01

    Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical manifestations, but overt symptoms may be sparse. One unusual presentation is onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism. This situation can lead to delayed diagnosis, with inefficacity of the antiepileptic drugs. We report five cases of adolescence-onset epilepsy with unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical examination revealed signs of hypocalcemia, confirmed biologically. Full testing disclosed the origin of the seizures: hypoparathyroidism in three patients and pseudohypoparathyroidism in the other two. In four of five patients, computed tomography showed calcification of the basal ganglia, defining Fahr's syndrome. The patients were treated with oral calcium and active vitamin D (1-alphahydroxy vitamin D3). Seizure frequency progressively decreased and serum calcium levels returned to normal. These cases illustrate the importance of the physical examination and of routine serum calcium assay in patients with new-onset epileptic seizures in order to detect hypocalcemia secondary to hypoparathyroidism.

  14. Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine.

    PubMed

    Vossler, D G; Lee, J K; Ko, T S

    1999-05-01

    Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.

  15. Safe Treatment of Seizures in the Setting of HIV/AIDS

    PubMed Central

    Birbeck, Gretchen L.

    2013-01-01

    OPINION STATEMENT HIV+ patients are at increased risk for developing seizures due to the vulnerability of the central nervous system to HIV-associated diseases, immune dysfunction and metabolic disturbances. In patients with acute seizures, standard protocols still apply with urgent seizure cessation being the priority. Management of the person with established epilepsy who contracts HIV is challenging, but the decision to initiate chronic antiepileptic drug (AED) therapy in an HIV+ patient is also difficult. Chronic treatment guidelines emphasize the interactions between AEDs and antiretroviral (ARV) medications, but provide no explicit advice regarding when to initiate an AED, what medication to select, and/or the duration of treatment. Epidemiologic data regarding seizure recurrence risk in HIV+ individuals is not available. The risk of further seizures likely depends upon the underlying etiology for the seizure(s) and patients’ immune status and may be increased by the use of efavirenz (an ARV). The issues for consideration include AED-ARV interactions, organ dysfunction, seizure type, and drug side effects which may worsen or be confused with symptoms of HIV and/or epilepsy. Co-administration of enzyme inducing (EI)-AEDs and ARVs can result in virological failure, breakthrough seizure activity, AED toxicity and/or ARV toxicity. Where available, the AED of choice in HIV+ patients is levetiracetam due to its broad spectrum activity, ease of use, minimal drug interactions, and favorable side effect profile. Lacosamide, gabapentin, and pregabalin are also favored choices in patients with partial onset seizures and/or those failing levetiracetam. Where newer AEDs are not available, valproic acid may be the treatment of choice in terms of an AED which will not cause enzyme induction-associated ARV failure, but its side effect profile causes other obvious problems. In resource-limited settings (RLS) where only EI-AEDs are available, there are no good treatment

  16. Pretreatment seizure semiology in childhood absence epilepsy.

    PubMed

    Kessler, Sudha Kilaru; Shinnar, Shlomo; Cnaan, Avital; Dlugos, Dennis; Conry, Joan; Hirtz, Deborah G; Hu, Fengming; Liu, Chunyan; Mizrahi, Eli M; Moshé, Solomon L; Clark, Peggy; Glauser, Tracy A

    2017-07-19

    To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome. © 2017 American Academy of Neurology.

  17. Prediction of seizure control in non-ketotic hyperglycemic induced seizures

    PubMed Central

    2009-01-01

    Background To study the factors predictive for seizure control in non-ketotic hyperglycemic induced seizures (NKHS). Methods We studied 21 patients who were clinically diagnosed as NKHS at Khon Kaen University hospital, Thailand. Multiple linear regression analysis was used to identify the factors predictive for seizure control. Results Most patients had no previous history of diabetes and presented with repetitive partial seizures. The mean number of seizure attacks was 45 times prior to admission. The average duration to terminate seizure was 36 hours and significantly predicted by frequency of seizures (estimate 0.9, p value 0.013). Conclusion Frequency of seizures is the only predictive factor for the success of seizure control in NKHS. PMID:20003412

  18. Development of later life spontaneous seizures in a rodent model of hypoxia induced neonatal seizures

    PubMed Central

    Rakhade, Sanjay N; Klein, Peter; Huynh, Thanthao; Hilario-Gomez, Cristina; Kosaras, Bela; Rotenberg, Alexander; Jensen, Frances E.

    2011-01-01

    Summary Purpose To study the development of epilepsy following hypoxia-induced neonatal seizures in Long Evans rats and to establish the presence of spontaneous seizures in this model of early life seizures. Methods Long-Evans rat pups were subjected to hypoxia-induced neonatal seizures at postnatal day 10 (P10). Epidural cortical electroencephalography (EEG) and hippocampal depth electrodes were used to detect the presence of seizures in later adulthood (>P60). In addition, subdermal wire electrode recordings were used to monitor age at onset and progression of seizures in the juvenile period, at intervals between P10–P60. Timm staining was performed to evaluate mossy fiber sprouting in the hippocampi of P100 adult rats that had experienced neonatal seizures. Key Findings In recordings made from adult rats (P60–P180), the prevalence of epilepsy in cortical and hippocampal EEG recordings was 94.4% following early life hypoxic seizures. These spontaneous seizures were identified by characteristic spike and wave activity on EEG accompanied by behavioral arrest and facial automatisms (electroclinical seizures). Phenobarbital injection transiently abolished spontaneous seizures. EEG in the juvenile period (P10–60) showed that spontaneous seizures first occurred approximately 2 weeks after the initial episode of hypoxic seizures. Following this period, spontaneous seizure frequency and duration progressively increased with time. Furthermore, significantly increased sprouting of mossy fibers was observed in the CA3 pyramidal cell layer of the hippocampus in adult animals following hypoxia-induced neonatal seizures. Notably, Fluoro-Jade B staining confirmed that hypoxic seizures at P10 did not induce acute neuronal death. Significance The rodent model of hypoxia-induced neonatal seizures leads to the development of epilepsy in later life, accompanied by increased mossy fiber sprouting. In addition, this model appears to exhibit a seizure-free latent period

  19. Dopey's seizure.

    PubMed

    Dan, B; Christiaens, F

    1999-06-01

    Angelman syndrome is a neurogenetic condition namely characterized by developmental delay, virtual absence of expressive verbal language, peculiar organization of movement, seizures and happy demeanor. This syndrome has been recognized since 1965, but it seems that Walt Disney presented an original depiction of it in his first full-length animated film, including myoclonic jerks and an apparently generalized tonic-clonic seizure. Copyright 1999 BEA Trading Ltd.

  20. Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation.

    PubMed

    Sherer, David M; Dalloul, Mudar; Stimphil, Raphael; Hellmann, Mira; Khoury-Collado, Fady; Osho, Joseph; Fomitcheva, Larissa; Brennan, Kelly J; Abulafia, Ovadia

    2006-04-01

    Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with partial and complete hydatidiform moles. We present an unusual case in which a patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound findings were consistent with a partial hydatidiform mole. Within 24 hours of the onset of symptoms, the patient developed severe hemolysis, elevated liver enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9) cells/L. Termination of pregnancy was performed with rapid resolution of signs, symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at karyotype analysis. This case demonstrates the acuteness in which life-threatening maternal conditions can arise with this uncommon complication of pregnancy, and the importance of correct identification of the characteristic ultrasonographic findings associated with a partial hydatidiform mole.

  1. Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures.

    PubMed

    García-Morales, Irene; Delgado, Rafael Toledano; Falip, Mercé; Campos, Dulce; García, María Eugenia; Gil-Nagel, Antonio

    2011-12-01

    This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures. 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. Semiology of hypermotor (hyperkinetic) seizures.

    PubMed

    Alqadi, Khalid; Sankaraneni, Ram; Thome, Ursula; Kotagal, Prakash

    2016-01-01

    Hypermotor seizures (HMSs) consist of complex movements involving proximal segments of the limbs and trunk that appear violent and inappropriate for the situation. We analyzed hypermotor seizure videos in seizure-free patients (Engel class I) following resective epilepsy surgery. After completion of video analysis, we reviewed EEG and neuroimaging data. Search of our epilepsy surgery database yielded 116 patients classified as having hypermotor seizures between 1996 and 2013. From this subset, 17/31 (55%) patients had been seizure-free for >6months (mean follow-up: 3.3years). Mean seizure duration was 35s (range: 6-91s), of which the HM phase lasted a mean of 22s (range: 3-53s). In 16 patients (95%), hypermotor activity was seen at or within 10s of clinical seizure onset. Type I semiology occurred in 6 patients, type II semiology in 10 patients, and 1 patient exhibited features of both. Type I and type II semiologies were noted in patients who had frontal lobe as well as extrafrontal resections. Nonversive head and body turning occurred in 10 patients (ranging from 90° to 270°) which was ipsilateral to the side of resection in all patients and seen both in frontal and extrafrontal resections. Six out of eleven patients with abnormal MRI and 4/6 patients with nonlesional MRI underwent invasive EEG evaluation. Eight patients (47%) had frontal lobe resection, 4/17 (23%) patients had temporal lobe resection, and one patient each had parietal lobe, insular, temporoparietooccipital, or motor sparing resection; 1 patient had functional hemispherectomy. Hypermotor semiology typically occurs at or within 10s after seizure onset. Ipsilateral head/body turning appears to be of lateralizing value whereas asymmetry of limb movement was not lateralizing. Hypermotor semiology is most often seen in frontal lobe epilepsy but may occur in seizures arising from other locations. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Generalized tonic-clonic seizure

    MedlinePlus

    ... Seizure - grand mal; Grand mal seizure; Seizure - generalized; Epilepsy - generalized seizure ... occur as part of a repeated, chronic illness (epilepsy). Some seizures are due to psychological problems (psychogenic).

  4. Association between hypocapnia and febrile seizures.

    PubMed

    Kilicaslan, Buket; Erol, Ilknur; Ozkale, Yasemin; Saygi, Semra; Sariturk, Cagla

    2014-05-01

    The purpose of this study is to determine whether hyperthermia-induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. This is only the second study to measure pCO2 and pH values in children with febrile seizures. This prospective case-control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures. Venous blood gas analyses were measured both from the febrile seizure and control group. There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of febrile seizures.

  5. Electroencephalography after a single unprovoked seizure.

    PubMed

    Debicki, Derek B

    2017-07-01

    Electroencephalography (EEG) is an essential diagnostic tool in the evaluation of seizure disorders. In particular, EEG is used as an additional investigation for a single unprovoked seizure. Epileptiform abnormalities are related to seizure disorders and have been shown to predict recurrent unprovoked seizures (i.e., a clinical definition of epilepsy). Thus, the identification of epileptiform abnormalities after a single unprovoked seizure can inform treatment options. The current review addresses the relationship between EEG abnormalities and seizure recurrence. This review also addresses factors that are found to improve the yield of recording epileptiform abnormalities including timing of EEG relative to the new-onset seizure, use of repeat studies, use of sleep deprivation and prolonged recordings. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Seizure Prediction: Methods

    PubMed Central

    Carney, Paul R.; Myers, Stephen; Geyer, James D.

    2011-01-01

    Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. PMID:22078526

  7. Epilepsy in children with a history of febrile seizures.

    PubMed

    Lee, Sang Hyun; Byeon, Jung Hye; Kim, Gun Ha; Eun, Baik-Lin; Eun, So-Hee

    2016-02-01

    Febrile seizure, the most common type of pediatric convulsive disorder, is a benign seizure syndrome distinct from epilepsy. However, as epilepsy is also common during childhood, we aimed to identify the prognostic factors that can predict epilepsy in children with febrile seizures. The study comprised 249 children at the Korea University Ansan Hospital who presented with febrile seizures. The relationship between the subsequent occurrence of epilepsy and clinical factors including seizure and fever-related variables were analyzed by multivariate analysis. Twenty-five patients (10.0%) had additional afebrile seizures later and were diagnosed with epilepsy. The subsequent occurrence of epilepsy in patients with a history of febrile seizures was associated with a seizure frequency of more than 10 times during the first 2 years after seizure onset (P<0.001). Factors that were associated with subsequent occurrence of epilepsy were developmental delay (P<0.001), preterm birth (P=0.001), multiple seizures during a febrile seizure attack (P=0.005), and epileptiform discharges on electroencephalography (EEG) (P=0.008). Other factors such as the age at onset of first seizure, seizure duration, and family history of epilepsy were not associated with subsequent occurrence of epilepsy in this study. Febrile seizures are common and mostly benign. However, careful observation is needed, particularly for prediction of subsequent epileptic episodes in patients with frequent febrile seizures with known risk factors, such as developmental delay, history of preterm birth, several attacks during a febrile episode, and epileptiform discharges on EEG.

  8. 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.

  9. Genetic effects on sleep/wake variation of seizures

    PubMed Central

    Winawer, Melodie R.; Shih, Jerry; Beck, Erin S.; Hunter, Jessica E.; Epstein, Michael P.

    2016-01-01

    Summary Objective There is a complex bidirectional relationship between sleep and epilepsy. Sleep/wake timing of seizures has been investigated for several individual seizure types and syndromes, but few large-scale studies of the timing of seizures exist in people with varied epilepsy types. In addition, the genetic contributions to seizure timing have not been well studied. Methods Sleep/wake timing of seizures was determined for 1,395 subjects in 546 families enrolled in the Epilepsy Phenome/Genome Project (EPGP). We examined seizure timing among subjects with different epilepsy types, seizure types, epilepsy syndromes, and localization. We also examined the familial aggregation of sleep/wake occurrence of seizures. Results Seizures in nonacquired focal epilepsy (NAFE) were more likely to occur during sleep than seizures in generalized epilepsy (GE), for both convulsive (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.59–7.52) and nonconvulsive seizures (OR 4.2, 95% CI 2.48–7.21). Seizures occurring within 1 h of awakening were more likely to occur in patients with GE than with NAFE for both convulsive (OR 2.3, 95% CI 1.54– 3.39) and nonconvulsive (OR 1.7, 95% CI 1.04–2.66) seizures. Frontal onset seizures were more likely than temporal onset seizures to occur during sleep. Sleep/wake timing of seizures in first-degree relatives predicted timing of seizures in the proband. Significance We found that sleep/wake timing of seizures is associated with both epilepsy syndrome and seizure type. In addition, we provide the first evidence for a genetic contribution to sleep/wake timing of seizures in a large group of individuals with common epilepsy syndromes. PMID:26948972

  10. Genetic effects on sleep/wake variation of seizures.

    PubMed

    Winawer, Melodie R; Shih, Jerry; Beck, Erin S; Hunter, Jessica E; Epstein, Michael P

    2016-04-01

    There is a complex bidirectional relationship between sleep and epilepsy. Sleep/wake timing of seizures has been investigated for several individual seizure types and syndromes, but few large-scale studies of the timing of seizures exist in people with varied epilepsy types. In addition, the genetic contributions to seizure timing have not been well studied. Sleep/wake timing of seizures was determined for 1,395 subjects in 546 families enrolled in the Epilepsy Phenome/Genome Project (EPGP). We examined seizure timing among subjects with different epilepsy types, seizure types, epilepsy syndromes, and localization. We also examined the familial aggregation of sleep/wake occurrence of seizures. Seizures in nonacquired focal epilepsy (NAFE) were more likely to occur during sleep than seizures in generalized epilepsy (GE), for both convulsive (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.59-7.52) and nonconvulsive seizures (OR 4.2, 95% CI 2.48-7.21). Seizures occurring within 1 h of awakening were more likely to occur in patients with GE than with NAFE for both convulsive (OR 2.3, 95% CI 1.54-3.39) and nonconvulsive (OR 1.7, 95% CI 1.04-2.66) seizures. Frontal onset seizures were more likely than temporal onset seizures to occur during sleep. Sleep/wake timing of seizures in first-degree relatives predicted timing of seizures in the proband. We found that sleep/wake timing of seizures is associated with both epilepsy syndrome and seizure type. In addition, we provide the first evidence for a genetic contribution to sleep/wake timing of seizures in a large group of individuals with common epilepsy syndromes. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  11. Seizure characteristics in Pallister-Killian syndrome.

    PubMed

    Candee, Meghan S; Carey, John C; Krantz, Ian D; Filloux, Francis M

    2012-12-01

    Pallister-Killian syndrome (PKS) is a congenital disorder attributed to supernumerary isochromosome 12p mosaicism. Craniofacial dysmorphism, learning impairment and seizures are considered cardinal features. However, little is known regarding the seizure and epilepsy patterns in PKS. To better define the prevalence and spectrum of seizures in PKS, we studied 51 patients (39 male, 12 female; median age 4 years and 9 months; age range 7 months to 31 years) with confirmed 12p tetrasomy. Using a parent-based structured questionnaire, we collected data regarding seizure onset, frequency, timing, semiology, and medication therapy. Patients were recruited through our practice, at PKS Kids family events, and via the PKS Kids website. Epilepsy occurred in 27 (53%) with 23 (85%) of those with seizures having seizure onset prior to 3.5 years of age. Mean age at seizure onset was 2 years and 4 months. The most common seizure types were myoclonic (15/27, 56%), generalized convulsions (13/27, 48%), and clustered tonic spasms (similar to infantile spasms; 8/27, 30%). Thirteen of 27 patients with seizures (48%) had more than one seizure type with 26 out of 27 (96%) ever having taken antiepileptic medications. Nineteen of 27 (70%) continued to have seizures and 17/27 (63%) remained on antiepileptic medication. The most commonly used medications were: levetiracetam (10/27, 37%), valproic acid (10/27, 37%), and topiramate (9/27, 33%) with levetiracetam felt to be "most helpful" by parents (6/27, 22%). Further exploration of seizure timing, in-depth analysis of EEG recordings, and collection of MRI data to rule out confounding factors is warranted.

  12. Frontal Lobe Seizures

    MedlinePlus

    Frontal lobe seizures Overview By Mayo Clinic Staff Frontal lobe seizures are a common form of epilepsy, a ... seizures originate in the front of the brain. Frontal lobe seizures may also be caused by abnormal brain ...

  13. Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

    PubMed

    Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

    2016-02-01

    This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Lipopolysaccharide potentiates hyperthermia-induced seizures

    PubMed Central

    Eun, Baik-Lin; Abraham, Jayne; Mlsna, Lauren; Kim, Min Jung; Koh, Sookyong

    2015-01-01

    Background Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. Methods The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2–2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1GFP/+ mice. Results Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. Conclusions Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS. PMID:26357586

  15. Lipopolysaccharide potentiates hyperthermia-induced seizures.

    PubMed

    Eun, Baik-Lin; Abraham, Jayne; Mlsna, Lauren; Kim, Min Jung; Koh, Sookyong

    2015-08-01

    Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2-2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice. Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS.

  16. Electrographic seizures in pediatric ICU patients

    PubMed Central

    Arndt, Daniel H.; Carpenter, Jessica L.; Chapman, Kevin E.; Cornett, Karen M.; Gallentine, William B.; Giza, Christopher C.; Goldstein, Joshua L.; Hahn, Cecil D.; Lerner, Jason T.; Loddenkemper, Tobias; Matsumoto, Joyce H.; McBain, Kristin; Nash, Kendall B.; Payne, Eric; Sánchez, Sarah M.; Fernández, Iván Sánchez; Shults, Justine; Williams, Korwyn; Yang, Amy; Dlugos, Dennis J.

    2013-01-01

    Objectives: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. Methods: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. Results: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. Conclusions: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality. PMID:23794680

  17. Selective frontal, parietal, and temporal networks in generalized seizures.

    PubMed

    Blumenfeld, Hal; Westerveld, Michael; Ostroff, Robert B; Vanderhill, Susan D; Freeman, Jason; Necochea, Alexandro; Uranga, Paula; Tanhehco, Tasha; Smith, Arien; Seibyl, John P; Stokking, Rik; Studholme, Colin; Spencer, Susan S; Zubal, I George

    2003-08-01

    Are "generalized" seizures truly generalized? Generalized tonic-clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic-clonic seizures. Study of human tonic-clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic-clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. (99m)Tc-hexamethylpropylene amine oxime injections during seizures provide a "snapshot" of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic-clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

  18. Complex Partial Epilepsy Associated with Temporal Lobe Developmental Venous Anomaly.

    PubMed

    Sohail, Amna; Xiong, Zhengming; Qureshi, Mushtaq H; Qureshi, Adnan I

    2015-05-01

    Developmental venous anomalies (DVA) are found incidentally but sometimes patients with these anomalies present with varying degrees of neurologic manifestations. We report a patient with early onset complex partial epilepsy and associated DVA and discuss the natural history, neuroimaging and clinical characteristics, and management. A 21-year-old man presented with a history of complex partial epilepsy with secondary generalization which started at the age of 4 years. An electroencephalogram (EEG) was performed which demonstrated spike and wave discharges predominantly in the left frontotemporal region. A magnetic resonance imaging (MRI) was performed which demonstrated a linear flow void suggestive of a DVA. The angiogram demonstrated DVA that connected with the left transverse venous sinus and an anastomotic vein between the straight sinus and the transverse venous sinus traversing the brain parenchyma. He was started on carbamezipine for the treatment of complex partial seizures. Temporal lobe DVA may be associated with complex partial seizures and can be diagnosed by MRI and angiographic findings.

  19. Febrile seizures

    MedlinePlus

    ... workup, which includes an EEG , head CT , and lumbar puncture (spinal tap) . Further testing may be needed if the child: Is younger than 9 months or older than 5 years Has a brain, nerve, or developmental disorder Had the seizure in only ...

  20. Seizure prognosis of patients with low-grade tumors.

    PubMed

    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  1. Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage.

    PubMed

    Lin, Chih-Lung; Dumont, Aaron S; Lieu, Ann-Shung; Yen, Chen-Po; Hwang, Shith-Lin; Kwan, Aij-Lie; Kassell, Neal F; Howng, Shen-Long

    2003-12-01

    The reported incidence, timing, and predictive factors of perioperative seizures and epilepsy after subarachnoid hemorrhage (SAH) have differed considerably because of a lack of uniform definitions and variable follow-up periods. In this study the authors evaluate the incidence, temporal course, and predictive factors of perioperative seizures and epilepsy during long-term follow up of patients with SAH who underwent surgical treatment. Two hundred seventeen patients who survived more than 2 years after surgery for ruptured intracranial aneurysms were enrolled and retrospectively studied. Episodes were categorized into onset seizures (< or = 12 hours of initial hemorrhage), preoperative seizures, postoperative seizures, and late epilepsy, according to their timing. The mean follow-up time was 78.7 months (range 24-157 months). Forty-six patients (21.2%) had at least one seizure post-SAH. Seventeen patients (7.8%) had onset seizures, five (2.3%) had preoperative seizures, four (1.8%) had postoperative seizures, 21 (9.7%) had at least one seizure episode after the 1st week postoperatively, and late epilepsy developed in 15 (6.9%). One (3.8%) of 26 patients with perioperative seizures (onset, preoperative, or postoperative seizure) had late epilepsy at follow up. The mean latency between the operation and the onset of late epilepsy was 8.3 months (range 0.3-19 months). Younger age (< 40 years old), loss of consciousness of more than 1 hour at ictus, and Fisher Grade 3 or greater on computerized tomography scans proved to be significantly related to onset seizures. Onset seizure was also a significant predictor of persistent neurological deficits (Glasgow Outcome Scale Scores 2-4) at follow up. Factors associated with the development of late epilepsy were loss of consciousness of more than 1 hour at ictus and persistent postoperative neurological deficit. Although up to one fifth of patients experienced seizure(s) after SAH, more than half had seizure(s) during the

  2. [Psychogenic non epileptic seizures: a review].

    PubMed

    Auxéméry, Y; Hubsch, C; Fidelle, G

    2011-04-01

    a physical brain disorder playing a role in their development: head injury may contribute to the pathogenesis of PNES. New-onset psychogenic seizures after resective epilepsy surgery or other intracranial neurosurgery have been described. Recent studies found psychogenic seizure disorders associated with brain pathology in the right hemisphere, non specific interictal electroencephalography abnormalities, magnetic resonance imaging changes and neuropsychological deficits. However, complex partial seizures of frontal origin might present similar characteristics with PNES and could be confused with the latter. There is actually no clear agreement as the best treatment plan for PNES patients. The PNES diagnosis has to be clearly communicated to the patient. Nevertheless, even after a correct diagnosis is made a high proportion of PNES patients continue to have seizures, serious disability and bad self-reported quality of life. Furthermore, seizure remission cannot be considered a comprehensive measure of medical or psychosocial outcome. Nearly half of the patients who become seizure free remain unproductive and many of these patients continue to have symptoms of psychopathology including other somatoform, depressive, and anxiety disorders. Even if psychiatric comorbidities have to be treated by a psychiatrist? who could also suggest a psychotherapy, in all cases the importance of a neurologist continuing to follow post-diagnosis PNES patients is essential. PNES is a diagnostic and therapeutic challenge that is costly to patients and to society at large. Further studies are needed to understand this dissociative psychiatric disorder and to propose therapeutic guidelines. Copyright © 2010. Published by Elsevier Masson SAS.

  3. The relationship between childhood conduct disorder and adult antisocial behavior is partially mediated by early-onset alcohol abuse.

    PubMed

    Khalifa, Najat; Duggan, Conor; Howard, Rick; Lumsden, John

    2012-10-01

    Early-onset alcohol abuse (EOAA) was previously found to both mediate and moderate the effect of childhood conduct disorder (CD) on adult antisocial behavior (ASB) in an American community sample of young adults (Howard, R., Finn, P. R., Gallagher, J., & Jose, P. (2011). Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behavior. Journal of Forensic Psychiatry and Psychology. Advance online publication. doi:10.1080/14789949.2011.641996). This study tested whether this result would generalize to a British forensic sample comprising 100 male forensic patients with confirmed personality disorder. Results confirmed that those in whom EOAA co-occurred with CD showed the highest level of personality pathology, particularly Cluster B traits and antisocial/borderline comorbidity. Those with co-occurring CD with EOAA, compared with those showing only CD, showed more violence in their criminal history and greater recreational drug use. Regression analysis showed that both EOAA and CD predicted adult ASB when covariates were controlled. Further analysis showed that EOAA significantly mediated but did not moderate the effect of CD on ASB. The failure to demonstrate an exacerbating effect of EOAA on the relationship between CD and ASB likely reflects the high prevalence of CD in this forensic sample. Some implications of these findings are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  4. Patient-Specific Early Seizure Detection from Scalp EEG

    PubMed Central

    Minasyan, Georgiy R.; Chatten, John B.; Chatten, Martha Jane; Harner, Richard N.

    2010-01-01

    Objective Develop a method for automatic detection of seizures prior to or immediately after clinical onset using features derived from scalp EEG. Methods This detection method is patient-specific. It uses recurrent neural networks and a variety of input features. For each patient we trained and optimized the detection algorithm for two cases: 1) during the period immediately preceding seizure onset, and 2) during the period immediately following seizure onset. Continuous scalp EEG recordings (duration 15 – 62 h, median 25 h) from 25 patients, including a total of 86 seizures, were used in this study. Results Pre-onset detection was successful in 14 of the 25 patients. For these 14 patients, all of the testing seizures were detected prior to seizure onset with a median pre-onset time of 51 sec and false positive rate was 0.06/h. Post-onset detection had 100% sensitivity, 0.023/hr false positive rate and median delay of 4 sec after onset. Conclusions The unique results of this study relate to pre-onset detection. Significance Our results suggest that reliable pre-onset seizure detection may be achievable for a significant subset of epilepsy patients without use of invasive electrodes. PMID:20461014

  5. In silico validation and structure activity relationship study of a series of pyridine-3-carbohydrazide derivatives as potential anticonvulsants in generalized and partial seizures.

    PubMed

    Sinha, Reema; Sara, Udai Vir Singh; Khosa, Ratan Lal; Stables, James; Jain, Jainendra

    2013-06-01

    A series of twelve compounds (Compounds RNH1-RNH12) of acid hydrazones of pyridine-3-carbohydrazide or nicotinic acid hydrazide was synthesized and evaluated for anticonvulsant activity by MES, scPTZ, minimal clonic seizure and corneal kindling seizure test. Neurotoxicity was also determined for these compounds by rotarod test. Results showed that halogen substitution at meta and para position of phenyl ring exhibited better protection than ortho substitution. Compounds RNH4 and RNH12, were found to be the active analogs displaying 6Hz ED50 of 75.4 and 14.77 mg/kg while the corresponding MES ED50 values were 113.4 and 29.3 mg/kg respectively. In addition, compound RNH12 also showed scPTZ ED50 of 54.2 mg/kg. In the series, compound RNH12 with trifluoromethoxy substituted phenyl ring was the most potent analog exhibiting protection in all four animal models of epilepsy. Molecular docking study has also shown significant binding interactions of these two compounds with 1OHV, 2A1H and 1PBQ receptors. Thus, N-[(meta or para halogen substituted) benzylidene] pyridine-3-carbohydrazides could be used as lead compounds in anticonvulsant drug design and discovery.

  6. The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive parkinsonism with generalized seizures

    PubMed Central

    Krebs, Catharine E.; Karkheiran, Siamak; Powell, James C.; Cao, Mian; Makarov, Vladimir; Darvish, Hossein; Di Paolo, Gilbert; Walker, Ruth H.; Shahidi, Gholam Ali; Buxbaum, Joseph D.; De Camilli, Pietro; Yue, Zhenyu; Paisán-Ruiz, Coro

    2013-01-01

    This study aimed to elucidate the genetic causes underlying early-onset parkinsonism (EOP) in a consanguineous Iranian family. To attain this, homozygosity mapping and whole-exome sequencing were performed. As a result, a homozygous mutation (c.773G>A; p.Arg258Gln) lying within the NH2-terminal Sac1-like inositol phosphatase domain of polyphosphoinositide phosphatase synaptojanin 1 (SYNJ1), which has been implicated in the regulation of endocytic traffic at synapses, was identified as the disease-segregating mutation. This mutation impaired the phosphatase activity SYNJ1 against its Sac1 domain substrates in vitro. We concluded that the SYNJ1 mutation identified here is responsible for the EOP phenotype seen in our patients probably due to deficiencies in its phosphatase activity and consequent impairment of its synaptic functions. Our finding not only opens new avenues of investigation in the synaptic dysfunction mechanisms associated with parkinsonism, but also suggests phosphoinositide metabolism as a novel therapeutic target for parkinsonism. PMID:23804563

  7. Imaging DC MEG Fields Associated with Epileptic Onset

    NASA Astrophysics Data System (ADS)

    Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

    2004-10-01

    Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

  8. Soy infant formula and seizures in children with autism: a retrospective study.

    PubMed

    Westmark, Cara J

    2014-01-01

    Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR = 2.6, 95% CI = 1.3-5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR = 2.2, 95% CI = 1.1-4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR = 4.8, 95% CI = 1.0-23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm

  9. Remote effects of focal hippocampal seizures on the rat neocortex

    PubMed Central

    Englot, Dario J.; Mishra, Asht M.; Mansuripur, Peter K.; Herman, Peter; Hyder, Fahmeed; Blumenfeld, Hal

    2008-01-01

    Seizures have both local and remote effects on nervous system function. While propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation, however we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multi-modal studies of partial and secondarily-generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast poly-spike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging (fMRI) weighted for blood oxygenation (BOLD) and blood volume (CBV), demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures; and increases in all these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness. PMID:18768701

  10. Seizure Control of Current Shunt on Rats with Temporal Lobe Epilepsy and Neocortical Epilepsy

    PubMed Central

    Zhang, Limin; Liang, Shuli; Zhang, Guojun; Liu, Zhizhong; Lv, Hong; Fang, Fang; Wang, Yajie; Zhang, Shaohui; Kang, Xixiong

    2014-01-01

    Purpose To examine the effects of current shunt on rats with temporal lobe epilepsy and neocortex epilepsy. Experimental Design A kainic acid (KA)-induced model of temporal lobe seizure and a penicillin-induced model of neocortical partial seizure were used in this study. Rats of each model were randomly allocated into two groups: control and model groups. The model group was further divided into the KA or penicillin group, sham conduction group and conduction group. The current shunt was realized through the implantation of a customized conduction electrode. After surgery, electroencephalogram (EEG) was recorded for two hours for each rat under anesthesia. Subsequently, the rats were video monitored for 72 h to detect the occurrence of behavioral seizures upon awakening. The average number and duration of seizures on EEG and the number of behavioral seizures were measured. Results In KA model, the number of total EEG seizures in conduction group (9.57±2.46) was significantly less than that in sham conduction group (15.13±3.45) (p<0.01). The duration of EEG seizures in conduction group (26.13±7.81 s) was significantly shorter than that in sham conduction group (34.17±7.25 s) (p = 0.001). A significant reduction of behavioral seizures was observed in the conduction group compared with KA (p = 0.000) and sham conduction groups (p = 0.000). In penicillin model, there was a 61% reduction in total EEG seizures in conduction group compared with sham conduction group (p<0.01), and the duration of EEG seizures in conduction group (6.29±2.64 s) was significantly shorter than that in the sham conduction group (12.07±3.81 s) (p = 0.002). A significant reduction of behavioral seizures was observed in conduction group compared with penicillin (p<0.01) and sham conduction groups (p<0.01). Conclusion Current shunt effectively reduces the onset and severity of seizures. Current shunt therapy could be an effective alternative minimally invasive approach for

  11. Nonlesional central lobule seizures: use of awake cortical mapping and subdural grid monitoring for resection of seizure focus.

    PubMed

    Cohen-Gadol, Aaron A; Britton, Jeffrey W; Collignon, Frederic P; Bates, Lisa M; Cascino, Gregory D; Meyer, Fredric B

    2003-06-01

    Surgical treatment options for intractable seizures caused by a nonlesional epileptogenic focus located in the central sulcus region are limited. The authors describe an alternative surgical approach for treating medically refractory nonlesional perirolandic epilepsy. Five consecutive patients who were treated between 1996 and 2000 for nonlesional partial epilepsy that had originated in the central lobule were studied. The patients' ages ranged from 16 to 56 years (mean 28.6 years; there were four men and one woman). The duration of their epilepsy ranged from 8 to 39 years (mean 20.2 years), with a mean seizure frequency of 19 partial seizures per week. Preoperative assessment included video electroencephalography (EEG) and subtracted ictal-interictal single-photon emission computerized tomography coregistered with magnetic resonance imaging (SISCOM). Patients underwent an awake craniotomy stereotactically guided by the ictal EEG and SISCOM studies. Cortical stimulation was used to identify the sensorimotor cortex and to reproduce the patient's aura. A subdural grid was then implanted based on these results. Subsequent postoperative ictal electrocorticographic recordings and cortical stimulation further delineated the site of seizure onset and functional anatomy. During a second awake craniotomy, a limited resection of the epileptogenic central lobule region was performed while function was continuously monitored intraoperatively. One resection was limited to the precentral gyrus, two to the postcentral gyrus, and in two the excisions involved regions of both the pre- and postcentral gyri. In three patients a hemiparesis occurred postsurgery but later resolved. In the four patients whose resection involved the postcentral gyms, transient cortical sensory loss and apraxia occurred, which completely resolved in three. Two patients are completely seizure free, two have experienced occasional nondisabling seizures, and one patient has benefited from a more than 75

  12. Acute provoked reflex seizures induced by thinking.

    PubMed

    Nevler, Naomi; Gandelman-Marton, Revital

    2012-11-01

    Thinking epilepsy is a rare form of reflex epilepsy that can be induced by specific cognitive tasks, and occurs mainly in idiopathic generalized epilepsies. We report a case of complex partial seizures triggered by thinking in a young man with acute bacterial meningitis and a remote head injury. This case illustrates that thinking-induced reflex seizures can be partial and can be provoked by an acute brain insult.

  13. The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy.

    PubMed

    Schmeiser, B; Zentner, J; Steinhoff, B J; Brandt, A; Schulze-Bonhage, A; Kogias, E; Hammen, T

    2017-10-01

    After surgery for intractable mesiotemporal lobe epilepsy (mTLE) seizures recur in 30-40%. One predictor for seizure recurrence is the distribution of seizure onset and interictal epileptiform discharges (IED). Our study focused on lateralization and extent of epileptiform activity regarding postoperative seizure persistence and the effect of reoperation. This study comprises 426 consecutive patients operated for intractable mTLE. Impact of preoperative seizure onset and IED on the persistence of seizures and results of reoperation were analyzed. One year after surgery, 27% of patients with mTLE experienced persistent seizures (Engel II-IV). Preoperative bilateral seizure onset in EEG was predictive for postoperative seizure recurrence (Engel II-IV: 64%). Seizure foci and IED exceeding the temporal lobe in the ipsilateral hemisphere were not found to be associated with worse seizure outcome (Engel I: 72% and 75%) compared to patients with seizure foci confined to the ipsilateral temporal lobe (Engel I: 75% and 76%). Moreover, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED did not negatively affect seizure freedom if seizure onset was strictly limited to the affected temporal lobe (Engel I: 85% and 65%, respectively). 60% of patients reoperated in the ipsilateral temporal lobe for persistent seizures became seizure free. Preoperative bilateral ictal foci are a negative predictor for seizure outcome. Contrarily, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED had favorable seizure outcome if seizure onset is strictly limited to the affected temporal lobe. Reoperation for seizure persistence constitutes a promising therapeutic option. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Oral baclofen in cerebral palsy: possible seizure potentiation?

    PubMed

    Hansel, Donna E; Hansel, Christian R W; Shindle, Michael K; Reinhardt, Elsie M; Madden, LaVerne; Levey, Eric B; Johnston, Michael V; Hoon, Alexander H

    2003-09-01

    Baclofen, a gamma-aminobutyric acid agonist, is widely used to treat spasticity of cerebral and spinal origin. Patients with both acute baclofen overdose and withdrawal have developed seizures. After several reports of new-onset seizures in children treated with oral baclofen at our institution, we reviewed our experience regarding possible effects of baclofen on seizure induction in a childhood movement disorders program over a 2-year period. Of 54 children (ages 1-10) treated with oral baclofen, 19 (35%) had a prior history of seizures. Five children (14%) developed new-onset seizures after starting baclofen. Although epilepsy is very common in children with cerebral palsy, these findings raise the possibility that baclofen may potentiate seizures in certain young children with cerebral palsy. Further study of the effects of baclofen on seizures is warranted.

  15. Seizures and Epilepsy in Alzheimer’s Disease

    PubMed Central

    Friedman, Daniel; Honig, Lawrence S.; Scarmeas, Nikolaos

    2013-01-01

    Introduction Many studies have shown that patients with Alzheimer’s disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome and progression vary widely between studies. Methods Literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG)studies, and treatment responses. Finally, we consider limitations and methodological issues. Results There is considerable variability in the reported prevalence and incidence of seizures in patients with AD - with reported lifetime prevalence rates of 1.5 - 64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. Conclusions The literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. PMID:22070283

  16. Febrile seizures: risks, evaluation, and prognosis.

    PubMed

    Graves, Reese C; Oehler, Karen; Tingle, Leslie E

    2012-01-15

    Febrile seizures are common in the first five years of life, and many factors that increase seizure risk have been identified. Initial evaluation should determine whether features of a complex seizure are present and identify the source of fever. Routine blood tests, neuroimaging, and electroencephalography are not recommended, and lumbar puncture is no longer recommended in patients with uncomplicated febrile seizures. In the unusual case of febrile status epilepticus, intravenous lorazepam and buccal midazolam are first-line agents. After an initial febrile seizure, physicians should reassure parents about the low risk of long-term effects, including neurologic sequelae, epilepsy, and death. However, there is a 15 to 70 percent risk of recurrence in the first two years after an initial febrile seizure. This risk is increased in patients younger than 18 months and those with a lower fever, short duration of fever before seizure onset, or a family history of febrile seizures. Continuous or intermittent antiepileptic or antipyretic medication is not recommended for the prevention of recurrent febrile seizures.

  17. A network analysis of the dynamics of seizure.

    PubMed

    Burns, Samuel P; Sritharan, Duluxan; Jouny, Christophe; Bergey, Gregory; Crone, Nathan; Anderson, William S; Sarma, Sridevi V

    2012-01-01

    Seizures are events that spread through the brain's network of connections and create pathological activity. To understand what is occurring in the brain during seizure we investigated the time progression of the brain's state from seizure onset to seizure suppression. Knowledge of a seizure's dynamics and the associated spatial structure is important for localizing the seizure foci and determining the optimal location and timing of electrical stimulation to mitigate seizure development. In this study, we analyzed intracranial EEG data recorded in 2 human patients with drug-resistant epilepsy prior to undergoing resection surgery using network analyses. Specifically, we computed a time sequence of connectivity matrices from iEEG (intracranial electroencephalography) recordings that represent network structure over time. For each patient, connectivity between electrodes was measured using the coherence in the band of frequencies with the strongest modulation during seizure. The connectivity matrices' structure was analyzed using an eigen-decomposition. The leading eigenvector was used to estimate each electrode's time dependent centrality (importance to the network's connectivity). The electrode centralities were clustered over the course of each seizure and the cluster centroids were compared across seizures. We found, for each patient, there was a consistent set of centroids that occurred during each seizure. Further, the brain reliably evolved through the same progression of states across multiple seizures including characteristic onset and suppression states.

  18. Seizure Disorders in Pregnancy

    MedlinePlus

    ... Seizures that cause a loss of consciousness and violent, jerking movements, called grand mal seizures , are especially ... of seizure that causes loss of consciousness and violent, jerking movements. Intrauterine Device: A small device that ...

  19. Epilepsy or seizures - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000128.htm Epilepsy or seizures - discharge To use the sharing features on this page, please enable JavaScript. You have epilepsy . People with epilepsy have seizures. A seizure is ...

  20. Pre-seizure state identified by diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei

    2014-01-01

    In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a ``pre-seizure'' state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

  1. 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.

  2. Recurrent prolonged fugue states as the sole manifestation of epileptic seizures.

    PubMed

    Khwaja, Geeta A; Duggal, Ashish; Kulkarni, Amit; Chaudhry, Neera; Gupta, Meena; Chowdhury, Debashish; Bohra, Vikram

    2013-10-01

    A fugue state is defined as an altered state of consciousness with varying degrees of motor activity and amnesia for the event. It may last for hours to days and may be psychogenic or organic in nature. Epileptic fugue states can be encountered in patients with absence or complex partial nonconvulsive status epilepticus or may occur as a postictal phenomenon in patients with generalized seizures. "absence status epilepticus" (AS) is rare and seen in only 2.6% of the cases with "childhood absence epilepsy" (CAE). The diagnosis of AS can be elusive, but sudden onset and termination of the fugue state, classical electroencephalogram (EEG) features, and response to a therapeutic trial of benzodiazepines helps in confirming the diagnosis and differentiating it from nonepileptic fugue states. We report a childhood onset case, with a 10 years history of recurrent episodes of prolonged fugue state lasting for up to 24 h, as the sole manifestation of epileptic seizures. The EEG features were suggestive of an AS, but there was no history of typical absences, myoclonus, or generalized tonic clonic seizures. This unusual and rare case cannot be categorized into one of the defined epilepsy syndromes like CAE but belongs to a recently identified syndrome of idiopathic generalized epilepsy known as "Absence status epilepsy" in which AS is the sole or the predominant seizure type.

  3. Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

    PubMed

    Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

    2017-08-01

    Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Reflex Seizures Triggered by Diaper Change in Dravet Syndrome.

    PubMed

    Subki, Ahmed H; Alasmari, Aishah S; Jan, Fadi M; Moria, Feras A; Jan, Mohammed M

    2016-07-01

    Dravet syndrome (DS) is a severe epilepsy syndrome characterized by early onset of multiple types of seizures. We report the first case of reflex seizures triggered by diaper change in a girl at 9 months old and 2 years old with a mutation in the SCN1A gene causing DS. Reflex seizures have been reported in patients with DS provoked by increased body temperature or visual stimulation. The case we report widens the spectrum of triggers causing reflex seizures in children with DS. Cortical hyperexcitability resulting from the genetic defect explains the tendency to experience such reflex seizures.

  5. Nerve agent-induced seizures and their pharmacological modulation

    SciTech Connect

    McDonough, J.H.; Shih, T.M.; Adams, N.L.; Koviak, T.A.; Cook, L.A.

    1993-05-13

    Intoxication with nerve agents produces prolonged central nervous system seizures (status epilepticus) that can produce irreversible brain pathology (15). This report summarizes our recent findings regarding the neurotransmitter changes that occur in discrete brain regions as a function of seizure duration and the differential effectiveness of anticholinergic, benzodiazepine and excitatory amino acid (EAA) antagonist drugs in terminating soman-induced seizures when given at different times after seizure onset. These results are discussed in relation to a model we have proposed to explain the sequence of electrophysiological, biochemical and neurochemical events and mechanisms controlling nerve agent-induced seizures.

  6. Seizures and Teens: Stress, Sleep, & Seizures

    ERIC Educational Resources Information Center

    Shafer, Patricia Osborne

    2007-01-01

    Most parents are used to erratic sleep patterns and mood swings in their teenagers. When these occur in an adolescent with seizures, however, the parent may wonder if sleep and mood problems are related to seizures. Sorting out the cause and effects of sleep in an adolescent with seizures can be confusing. Since stress can be a contributor to both…

  7. Seizures and Teens: Stress, Sleep, & Seizures

    ERIC Educational Resources Information Center

    Shafer, Patricia Osborne

    2007-01-01

    Most parents are used to erratic sleep patterns and mood swings in their teenagers. When these occur in an adolescent with seizures, however, the parent may wonder if sleep and mood problems are related to seizures. Sorting out the cause and effects of sleep in an adolescent with seizures can be confusing. Since stress can be a contributor to both…

  8. Hallervorden-Spatz Syndrome with Seizures.

    PubMed

    Gothwal, Sunil; Nayan, Swati

    2016-04-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene.

  9. Hallervorden–Spatz Syndrome with Seizures

    PubMed Central

    Gothwal, Sunil; Nayan, Swati

    2016-01-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene. PMID:27303611

  10. On the nature of seizure dynamics

    PubMed Central

    Stacey, William C.; Quilichini, Pascale P.; Ivanov, Anton I.

    2014-01-01

    Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical

  11. Increased number of febrile seizures in children born very preterm: relation of neonatal, febrile and epileptic seizures and neurological dysfunction to seizure outcome at 16 years of age.

    PubMed

    Herrgård, Eila A; Karvonen, Marjo; Luoma, Laila; Saavalainen, Pia; Määttä, Sara; Laukkanen, Eila; Partanen, Juhani

    2006-12-01

    In prematurely born population, a cascade of events from initial injury in the developing brain to morbidity may be followed. The aim of our study was to assess seizures in prematurely born children from birth up to 16 years and to evaluate the contribution of different seizures, and of neurological dysfunction to the seizure outcome. Pre- and neonatal data and data from neurodevelopmental examination at 5 years of 60 prospectively followed children born at or before 32 weeks of gestation, and of 60 matched term controls from the 2 year birth cohort were available from earlier phases of the study. Later seizure data were obtained from questionnaires at 5, 9, and 16 years, and from hospital records and parent interviews. In the preterm group, 16 children (27%) exhibited neonatal seizures, 10 children (17%) had seizures during febrile illness and 5 children had epilepsy. Eight children had only febrile seizures, and 3 of these had both multiple simple and complex febrile seizures and neurodevelopmental dysfunction. None of the 8 children had experienced neonatal seizures, 6 had a positive family history of seizures, but none developed epilepsy. The children with epilepsy had CP and neurocognitive problems, and all but one had experienced neonatal seizures; two of them had also had fever-induced epileptic seizures. In controls 3 children (5%) had simple febrile seizures. Children born very preterm have increased rate of febrile seizures compared to the controls. However, no cascade from initial injury via febrile seizures to epilepsy could be shown during the follow-up of 16 years. Symptomatic epilepsy in prematurely born children is characterised by neonatal seizures, major neurological disabilities and early onset of epilepsy.

  12. Absence seizures effects on reading revealed by video-electroencephalography.

    PubMed

    Poblano, A; Ibarra, J; Muñiz, A; Garza, S

    2001-01-01

    The effects of absence seizures on reading have not been studied. The purpose of this paper is to show some alterations in reading during absence seizures in patients with video-electroencephalographic recordings. Patients were selected if absences seizures were the only type of seizures. They were studied at rest with eyes closed and while reading aloud a text by simultaneous bipolar electroencephalographic and video recordings. Eight patients were studied with 34 events. Absences ranged from 1-12 events in twenty-five minutes recording, seizures duration ranged from 1.5-16 seconds. Brief seizures results on non-stop reading, but reading arrest with latency of 1-3 seconds after seizure onset were present in the longer events. Post-absence amnesia ranged from 1-4.5 seconds. Re-start reading occurs mainly in other reading place in the text, but two patients in one event re-started reading in the right place. Classic symptoms during absence were present and reading alterations found were: reading arrest, lost of reading point, bradylexia, dysprosodic reading, grapheme substitution, reading loudness reduction, repeating of phrases. Events occurred without patient seizure awareness, except in one patient by means of the time lost between onset to the end of the event. This study showed that acute reading alterations during absence seizures are frequent in longer seizures, producing many neuropsychological symptoms that alter reading without seizure awareness.

  13. Can Seizure-Alert Dogs predict seizures?

    PubMed

    Brown, Stephen W; Goldstein, Laura H

    2011-12-01

    An index observation where a dog was trained to alert to, as well as respond to, human tonic-clonic seizures led to further research and refinement of training techniques. This was followed by anecdotal reports of pet dogs spontaneously anticipating human epileptic seizures. An industry has since developed training Seizure-Alert Dogs (SADs) to give humans warnings of their seizures. In some cases this has been accompanied by a reduction in seizure frequency. SADs may be trained along with the person with epilepsy, responding specifically to that person's seizures, or may be trained separately. Recent sceptical reports of non-epileptic seizures in some people with SADs have cast doubt on dogs' ability to anticipate true epileptic seizures. This may reflect selection criteria for training programmes as well as training methods used, but does not necessarily indicate that SADs might not be able to predict epileptic seizures. Whether the seizures are epileptic or non-epileptic, it is speculated that SADs probably alert to subtle pre-ictal human behaviour changes, but may also be sensitive to heart rate or olfactory cues. As yet, however, no rigorous data exist as to whether seizure prediction by SADS is better than chance, and what false positive and negative prediction rates might be.

  14. Intracerebral temperature alterations associated with focal seizures.

    PubMed

    Yang, Xiao-Feng; Chang, Jong Hee; Rothman, Steven M

    2002-12-01

    Because focal seizures produce an increase in local cerebral metabolism and blood flow, we wanted to determine whether they might lead to changes in brain temperature. We induced focal neocortical seizures by microinjection of 4-aminopyridine (4-AP) into the rat motor cortex. The temperature on the dura immediately over the injection site, or 8 mm away, was measured with a thermocouple and in some experiments relative blood flow was monitored with a laser Doppler probe. In animals that did not receive 4-AP, brain and rectal temperature remained fairly constant at 33.5 and 37.2 degrees C, respectively, over a 2 h monitoring period. In animals treated with 4-AP, brain temperature over the seizure focus rose an average of 0.3 degrees C, within a few seconds of seizure onset, while rectal temperature remained constant. The seizure-induced temperature rise was preceded by an increase in cortical blood flow. The temperature, but not blood flow, was also elevated 8 mm away from the seizure focus. When blood flow was increased independently of neuronal activity, by elevating pCO(2), brain temperature also rose by about 0.3 degrees C. Focal seizures in anesthetized rats produce a small, but statistically significant increase in local brain temperature, as a result of increased blood flow that brings brain temperature closer to body temperature. In humans, seizures could actually cause a reduction in brain temperature, because brain temperature is normally higher than body temperature.

  15. Clinical characteristics of seizures associated with viral gastroenteritis in children.

    PubMed

    Ueda, Hitoshi; Tajiri, Hitoshi; Kimura, Sadami; Etani, Yuri; Hosoi, Gaku; Maruyama, Tomoko; Noma, Haruyoshi; Kusumoto, Yoshio; Takano, Tomoko; Baba, Yoshiko; Nagai, Toshizaburo

    2015-01-01

    We analyzed the clinical features of seizures during gastroenteritis in children by comparing the norovirus and rotavirus pathogen, and the impact of fever, if present, during the seizure episodes. Retrospective analysis was performed on 293 consecutive pediatric patients admitted with viral gastroenteritis to Osaka General Hospital between November 2007 and May 2009. Eighteen patients developed seizures, 12 of whom were positive for norovirus and six for rotavirus, as revealed by antigen detection. Of these 18 seizure patients, eight presented without fever (the aFS group) and 10 presented with febrile episodes (FS group). Seizure patients in the rotavirus group (83%) were more likely to be febrile than those in the norovirus group (58%). Compared with the aFS group, 90% of patients in the FS group presented seizures at an early stage of gastroenteritis. The frequency of clustered seizures in the FS group was considerably higher than that of febrile seizures in general and was also as high as that of "convulsions with mild gastroenteritis (CwG)". All seizure patients, whether febrile or afebrile, presented with generalized tonic clonic seizures (GTCS), complex partial seizures (CPS), or both. Diazepam (DZP) was less effective and carbamazepine (CBZ) was completely effective for the cessation of seizures in the FS group, similar to the drug response observed in CwG. The causative pathogen (norovirus or rotavirus) affected the frequency of febrile episodes during gastroenteritis, but fever had little effect on the clinical features of seizures. However, seizures occurred earlier during gastroenteritis in the FS group. On the whole, the clinical features of febrile seizures during viral gastroenteritis may closely resemble those of "convulsions with mild gastroenteritis" (CwG) than those of febrile seizures in general with respect to the frequency of clustered seizures and the antiepileptic drug responses and may have a pathogenic mechanism distinct from those of

  16. Epilepsy in children with a history of febrile seizures

    PubMed Central

    Lee, Sang Hyun; Byeon, Jung Hye; Kim, Gun Ha; Eun, Baik-Lin

    2016-01-01

    Purpose Febrile seizure, the most common type of pediatric convulsive disorder, is a benign seizure syndrome distinct from epilepsy. However, as epilepsy is also common during childhood, we aimed to identify the prognostic factors that can predict epilepsy in children with febrile seizures Methods The study comprised 249 children at the Korea University Ansan Hospital who presented with febrile seizures. The relationship between the subsequent occurrence of epilepsy and clinical factors including seizure and fever-related variables were analyzed by multivariate analysis. Results Twenty-five patients (10.0%) had additional afebrile seizures later and were diagnosed with epilepsy. The subsequent occurrence of epilepsy in patients with a history of febrile seizures was associated with a seizure frequency of more than 10 times during the first 2 years after seizure onset (P<0.001). Factors that were associated with subsequent occurrence of epilepsy were developmental delay (P<0.001), preterm birth (P=0.001), multiple seizures during a febrile seizure attack (P=0.005), and epileptiform discharges on electroencephalography (EEG) (P=0.008). Other factors such as the age at onset of first seizure, seizure duration, and family history of epilepsy were not associated with subsequent occurrence of epilepsy in this study. Conclusion Febrile seizures are common and mostly benign. However, careful observation is needed, particularly for prediction of subsequent epileptic episodes in patients with frequent febrile seizures with known risk factors, such as developmental delay, history of preterm birth, several attacks during a febrile episode, and epileptiform discharges on EEG. PMID:26958066

  17. Seizure precipitants in a community-based epilepsy cohort.

    PubMed

    Wassenaar, Merel; Kasteleijn-Nolst Trenité, Dorothée G A; de Haan, Gerrit-Jan; Carpay, Johannes A; Leijten, Frans S S

    2014-04-01

    Epileptic seizures can be provoked by several factors. Better understanding of these factors may improve a patient's sense of control and could reduce seizures. In daily practice, the recognition of seizure precipitants relies heavily on clinical or video-EEG evidence, which can be difficult to obtain. Studies of seizure provocation are largely based on selected hospital-based patient populations, which may lead to biased occurrence estimates. Self-reported seizure precipitants are rarely studied, yet are necessary to understand the experiences of patients and improve epilepsy management. We performed a cross-sectional community-based study of 248 epilepsy patients, selected by pharmacy records of anti-epileptic drug use. Self-reported seizure precipitants and potential associated characteristics were assessed using questionnaires. Almost half of all patients (47 %) reported one or more seizure precipitants, of which stress, sleep deprivation, and flickering lights were the most common. In this community-based setting, light-provoked seizures were especially frequent compared to the literature. Idiopathic generalized epilepsy (IGE), a lower age at seizure onset, and having auras or prodromes were found to be important independent prognostic factors associated with provoked seizures. IGE and a younger age at seizure onset have been linked to provoked seizures in earlier reports. The finding of auras or prodromes as a prognostic factor was unexpected, though case reports have described provoked seizures in patients having auras. Assessment of these factors may facilitate the early recognition of seizure precipitants in daily clinical practice. This is important for the optimization of epilepsy management for a large group of patients, as provoked seizures are expected to occur frequently.

  18. Seizure types and frequency in patients who "fail" temporal lobectomy for intractable epilepsy.

    PubMed

    Englot, Dario J; Lee, Anthony T; Tsai, Catherine; Halabi, Cathra; Barbaro, Nicholas M; Auguste, Kurtis I; Garcia, Paul A; Chang, Edward F

    2013-11-01

    Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who "fail" surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency? To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures. We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010. Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5). Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.

  19. Comparison of Motor Activity and Sleep in Patients with Complex Partial Seizures on Levetiracetam Treatment and a Group of Healthy Subjects

    PubMed Central

    Yilmaz, Hikmet

    2007-01-01

    Purpose: Levetiracetam-treated patients commonly report daytime drowsiness, fatique, asthenia and decreasing of motor activity. However the origin of these reported side effects are still debated, we aimed to clarify effect of levetiracetam on sleep. Therefore this prospective study was conducted to evaluate the effects of levetiracetam on motor activity, amount and continuity of sleep and napping. Methods: Various tests were performed on twenty two patients treated with levetiracetam (10 monotherapy, 12 add-on therapy) at least three days before the initiation of treatment, and consecutively for five to eight days at the third week of treatment. These tests included sleep logs, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Modified Maintenance of Wakefulness Test and actimetric measurements. In order to evaluate the sleep behavior of these patients the following sleep parameters were estimated: bedtime, wake-up time, sleep-onset time, sleep-offset time, sleep latency, total sleep time, wake time after sleep onset, fragmentation index, total activity score, nap episodes, total nap duration and sleep efficiency. Twenty members of staff from our hospital (Doctor, nurse, secretary, civil servant etc.) were evaluated as control subjects in the study. Results: After three-week treatment with levetiracetam (in particular with add-on therapy), Epworth Sleepiness Scale scores, napping episodes and total nap durations increased and sleep latencies decreased. While durations of Modified Maintenance of Wakefulness Test and total activity scores decreased. However the total sleep time and the sleep efficiency did not show any difference from the pre-treatment values. Conclusions: Our results suggest that levetiracetam leads to drowsiness by decreasing the daily motor activity and increasing the naps; however this agent does not have any major effects on total sleep time and sleep efficiency during night. Actimetric analyses give information about continuity of

  20. Partial tandem duplication of mtDNA-tRNA(Phe) impairs mtDNA translation in late-onset mitochondrial myopathy.

    PubMed

    Arzuffi, Paola; Lamperti, Costanza; Fernandez-Vizarra, Erika; Tonin, Paola; Morandi, Lucia; Zeviani, Massimo

    2012-01-01

    An 80-year-old woman (PI) has been suffering of late onset progressive weakness and wasting of lower-limb muscles, accompanied by high creatine kinase levels in blood. A muscle biopsy, performed at 63 years, showed myopathic features with partial deficiency of cytochrome c oxidase. A second biopsy taken 7 years later confirmed the presence of a mitochondrial myopathy but also of vacuolar degeneration and other morphological features resembling inclusion body myopathy. Her 46-year-old daughter (PII) and 50-year-old son (PIII) are clinically normal, but the creatine kinase levels were moderately elevated and the EMG was consistently myopathic in both. Analysis of mitochondrial DNA sequence revealed in all three patients a novel, homoplasmic 15 bp tandem duplication adjacent to the 5' end of mitochondrial tRNA(Phe) gene, encompassing the first 11 nucleotides of this gene and the four terminal nucleotides of the adjacent D-loop region. Both mutant fibroblasts and cybrids showed low oxygen consumption rate, reduced mitochondrial protein synthesis, and decreased mitochondrial tRNA(Phe) amount. These findings are consistent with an unconventional pathogenic mechanism causing the tandem duplication to interfere with the maturation of the mitochondrial tRNA(Phe) transcript.

  1. Seizure Anticipation Techniques: State of the Art and Future Requirements

    DTIC Science & Technology

    2001-10-25

    pattern recognition tech- niques such as recurrent neuronal networks [23], cellular neu- ronal networks [24], or fuzzy clustering [25]. Usually these...open and reprogrammable analysis systems based on e.g. field programmable generic arrays (FPGA) or cellular neuronal networks (CNN, [24,29]) appear to be...occurrence of seizures. 110100100010000100000 electrical seizure onset duration of pre-seizure state [s] FFT AR/ARMA wavelet decomposition + neuronal

  2. Instruction manual for the ILAE 2017 operational classification of seizure types.

    PubMed

    Fisher, Robert S; Cross, J Helen; D'Souza, Carol; French, Jacqueline A; Haut, Sheryl R; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Schulze-Bonhage, Andreas; Somerville, Ernest; Sperling, Michael; Yacubian, Elza Márcia; Zuberi, Sameer M

    2017-04-01

    This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system.

  3. Out-of-body experiences associated with seizures

    PubMed Central

    Greyson, Bruce; Fountain, Nathan B.; Derr, Lori L.; Broshek, Donna K.

    2014-01-01

    Alterations of consciousness are critical factors in the diagnosis of epileptic seizures. With these alterations in consciousness, some persons report sensations of separating from the physical body, experiences that may in rare cases resemble spontaneous out-of-body experiences. This study was designed to identify and characterize these out-of-body-like subjective experiences associated with seizure activity. Fifty-five percent of the patients in this study recalled some subjective experience in association with their seizures. Among our sample of 100 patients, 7 reported out-of-body experiences associated with their seizures. We found no differentiating traits that were associated with patients' reports of out-of-body experiences, in terms of either demographics; medical history, including age of onset and duration of seizure disorder, and seizure frequency; seizure characteristics, including localization, lateralization, etiology, and type of seizure, and epilepsy syndrome; or ability to recall any subjective experiences associated with their seizures. Reporting out-of-body experiences in association with seizures did not affect epilepsy-related quality of life. It should be noted that even in those patients who report out-of-body experiences, such sensations are extremely rare events that do not occur routinely with their seizures. Most patients who reported out-of-body experiences described one or two experiences that occurred an indeterminate number of years ago, which precludes the possibility of associating the experience with the particular characteristics of that one seizure or with medications taken or other conditions at the time. PMID:24592228

  4. Pilocarpine-induced seizures in rodents--17 years on.

    PubMed

    Turski, W A

    2000-01-01

    In 1983, we reported that intracerebral or systemic administration of cholinergic agents produced seizures and seizure-related brain damage in rodents. During the following 17 years, seizures induced by cholinomimetic drugs became a popular model of epilepsy. Seizures can by produced by cholinergic agonists acting directly at muscarinic receptors or by drugs enhancing cholinergic transmission due to the inhibition of acetylcholinesterase activity. Status epilepticus evoked by pilocarpine in rodents triggers long-lasting changes which can be described as: (I) acute-onset seizures lasting for several hours, (II) a silent period characterized by normalization of electroencephalographic patterns lasting for days, and (III) spontaneous recurrent seizures lasting for life. Therefore, seizures induced by cholinomimetics in rodents are of value for studies of basic mechanisms of epileptogenesis and action of antiepileptic drugs.

  5. Tiagabine in clinical practice: effects on seizure control and behavior.

    PubMed

    Vossler, David G; Morris, George L; Harden, Cynthia L; Montouris, Georgia; Faught, Edward; Kanner, Andres M; Fix, Aaron; French, Jacqueline A

    2013-08-01

    Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Levetiracetam monotherapy for late poststroke seizures in the elderly.

    PubMed

    Kutlu, Gulnihal; Gomceli, Yasemin B; Unal, Yasemin; Inan, Levent E

    2008-10-01

    Stroke is the most common cause of seizures in the elderly. Antiepileptic drugs are used to treat most patients with late poststroke seizures. The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) in patients aged 60 or older with late-onset poststroke seizures. This prospective study evaluated patients 60 years of age or older, who had at least two late-onset poststroke seizures and were given LEV monotherapy. Demographic data and seizure and stroke characteristics were recorded. Outpatient visits were made after 2, 4, 6, 9, and 12 months and every 3 months thereafter, and the effectiveness and tolerability of LEV were investigated. Thirty-four patients with a mean age of 69.76+/-6.41 were included in this study. Average seizure frequency before treatment was 3.61+/-3.02/month. Mean follow-up time was 17.68+/-3.24 months. At daily doses of 1000-2000 mg, 82.4% of the patients were seizure free, and 7 patients (20.6%) had side effects. LEV was discontinued in one patient because of severe somnolence. Two patients were switched to another antiepileptic drug because of uncontrolled seizures despite an increase in dose up to 3000 mg/day. LEV monotherapy can be effective and well tolerated in elderly patients with late-onset poststroke seizures.

  7. Sheehan's syndrome presenting as postpartum seizures.

    PubMed

    Jain, G; Singh, D; Kumar, S

    2010-05-01

    We report a case where a patient presented with generalised tonic-clonic seizures secondary to nausea, vomiting and dehydration. She had suffered a postpartum haemorrhage six months previously. On laboratory assessment hyponatraemia and low hormone concentrations suggested pituitary failure. The diagnosis was confirmed by magnetic resonance imaging of the head, which showed a partially empty sella turcica. Given the severity of the morbidity in this case we emphasise that Sheehan's syndrome should be suspected in women presenting with postpartum seizures.

  8. Detection of early seizures by diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Hajihashemi, M. Reza; Zhou, Junli; Carney, Paul R.; Jiang, Huabei

    2015-03-01

    In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

  9. Ketogenic diet therapy is effective in encephalitis with refractory seizures.

    PubMed

    Matsuzono, Kosuke; Kurata, Tomoko; Deguchi, Shoko; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2014-10-01

    Although ketogenic diet therapy is effective in refractory seizures in childhood, its effect on adult encephalitis with similar refractory seizures and prolonged encephalopathy has not been well reported. We report here a case of a 22-year-old man with acute encephalitis with refractory repetitive partial seizures (AERRPS). Partial seizures of the face developed to repeated generalized convulsions, which were refractory against anti-epileptic drugs and a high dose of propofol. After struggling for 9 months, he dramatically recovered after ketogenic diet therapy. Ketogenic diet therapy may be an important tool to help cure AERRPS.

  10. Methylxanthines, seizures, and excitotoxicity.

    PubMed

    Boison, Detlev

    2011-01-01

    Clinical evidence, in particular the wide use of theophylline as a bronchodilator, suggests that methylxanthines can cause seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by their antagonizing the brain's own anticonvulsant adenosine. Recent evidence suggests that adenosine dysfunction is a pathological hallmark of epilepsy contributing to seizure generation and seizure spread. Conversely, adenosine augmentation therapies are effective in seizure suppression and prevention, whereas adenosine receptor antagonists such as methylxanthines generally exacerbate seizures. The impact of the methylxanthines caffeine and theophylline on seizures and excitotoxicity depends on timing, dose, and acute versus chronic use. New findings suggest a role of free radicals in theophylline-induced seizures, and adenosine-independent mechanisms for seizure generation have been proposed.

  11. Pre-seizure state identified by diffuse optical tomography

    PubMed Central

    Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei

    2014-01-01

    In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. PMID:24445927

  12. Hyperkinetic motor seizures: a common semiology generated by two different cortical seizure origins.

    PubMed

    Vaugier, Lisa; McGonigal, Aileen; Lagarde, Stanislas; Trébuchon, Agnes; Szurhaj, William; Derambure, Philippe; Bartolomei, Fabrice

    2017-08-22

    We report a 37-year-old, right-handed patient with drug-resistant focal epilepsy whose seizures were characterized by explosive hyperkinetic behaviour. Video-SEEG revealed bifocal organization of epilepsy with two distinct cortical origins of seizures: the right temporal pole and left temporal lateral and perisylvian cortex. Irrespective of the cortical pattern of seizure onset, the hyperkinetic semiology was extremely similar. This supports a major role for "final common pathway" subcortical circuits in the genesis of the hyperkinetic semiology in this patient.

  13. Canine and feline epileptic seizures and the lunar cycle: 2,507 seizures (2000-2008).

    PubMed

    Browand-Stainback, Laura; Levesque, Donald; McBee, Matthew

    2011-01-01

    Epileptic seizures in 211 canine and feline patients diagnosed with idiopathic epilepsy were evaluated for temporal significance in relation to the lunar cycle. Seizure counts were compared among each of the eight individual lunar phases, among each of eight exact lunar phase dates, and by percent of lunar illumination using generalized estimating equations. No statistical significance was found in any of these comparisons excluding a relationship between the onset of epileptic seizures and the phases of the moon. Alteration in anticonvulsant treatment or monitoring of canine and feline patients with idiopathic epilepsy at large was not warranted based on the lunar cycle.

  14. Vagus nerve stimulation: a novel approach for prevention and control of refractory seizures.

    PubMed

    Bhattacharya, S K; Das, B P; Rauniar, G P; Sangraula, H

    2007-01-01

    In order to understand the brain function and to treat various neuropsychiatric illnesses including epilepsy, continued search and discovery of newer antiepileptic drugs has failed to revolutionize the approach in the management of this complex disorder. Moreover, in close to 30% of epilepsy patients, the seizure control is either not satisfactory or it is intractable to pharmacotherapy. Amongst the non-pharmacological treatment options for refractory epilepsy, vagus nerve stimulation occupies a unique position as an adjunctive treatment in prevention and control of partial-onset seizures in adults and adolescents older than 12 years. Though the precise mode of action of VNS is still debatable an honest attempt has been mode here to review all possible literatures available on VNS to establish its role in the management of this complex disorder.

  15. [Lamotrigine add-on therapy for childhood-onset refractory epilepsy: comparison of the efficacy between 3 months and 6 months after initiation].

    PubMed

    Watanabe, Kiyoko; Kobayashi, Katsuhiro; Endoh, Fumika; Yoshinaga, Harumi; Ohtsuka, Yoko

    2011-11-01

    We investigated the effect of lamotrigine (LTG) add-on therapy in 50 patients with childhood-onset refractory epilepsy (25 males and 25 females): 15 with localization-related epilepsy, 33 with generalized epilepsy, and 2 with undetermined epilepsy. Twenty-four patients had experienced a period of West syndrome during their clinical course. Age at the start of LTG therapy ranged from 2 years 6 months to 41 years 2 months: <16 years in 43 and > or = 16 years in 7. Seizure frequency was > or = 1 per day in 36 patients (72%) and > or = 1 per week in 14 (28%). We increased the LTG dosage every two weeks in accordance with usage recommendations. We evaluated efficacy at two points: 3 and 6 months after the start of LTG. At the 6-month point, seizure freedom was achieved in 2 patients (4%), > or = 50% seizure reduction in 14 (28%), 25 to 50% seizure reduction in 20 (40%), no effect in 6 (12%), and aggravation in 4 (8%). Only 4 patients (8%) stopped LTG therapy within 6 months due to LTG-related mild skin rash in 2 and suspicion of seizure aggravation in the other 2. In terms of seizure types, seizure freedom or > or = 50% seizure reduction was achieved in 29% for epileptic spasms, 32% for tonic seizures, and 29% for partial seizures. A comparison between the 3- and 6-month points revealed that the efficacy level was increased or maintained in 77% of the patients and decreased in 23%. In most cases, the highest level of efficacy appeared within 3 months with doses that were smaller than maintenance doses. Observed CNS-related adverse effects included somnolence in 16 patients, irritability in 14, and sleep disturbance in 11. Positive psychotropic effects in daily activities were seen in 28 patients (56%). These effects appeared regardless of the change in seizure frequency with doses that were smaller than maintenance doses.

  16. Probability of detection of clinical seizures using heart rate changes.

    PubMed

    Osorio, Ivan; Manly, B F J

    2015-08-01

    Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. Ketogenic diet: Predictors of seizure control.

    PubMed

    Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

    2017-01-01

    The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings.

  19. Ketogenic diet: Predictors of seizure control

    PubMed Central

    Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

    2017-01-01

    Background: The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. Methods: A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Results: Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Conclusion: Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings. PMID:28620490

  20. Ictal electroencephalograms in neonatal seizures: characteristics and associations.

    PubMed

    Nagarajan, Lakshmi; Ghosh, Soumya; Palumbo, Linda

    2011-07-01

    The characteristics of ictal electroencephalograms in 160 neonatal seizures of 43 babies were correlated with mortality and neurodevelopmental outcomes. Neonatal seizures are focal at onset, most frequently temporal, and often occur during sleep. Twenty-one percent of babies with seizures died, and 76% of survivors manifested neurodevelopmental impairment during 2-6-year follow-up. A low-amplitude ictal electroencephalogram discharge was associated with increased mortality, and a frequency of <2 Hz with increased morbidity. Status epilepticus, ictal fractions, multiple foci, and bihemispheric involvement did not influence outcomes. Of 160 seizures, 99 exhibited no associated clinical features (electrographic seizures). Neonatal seizures with clinical correlates (electroclinical seizures) exhibited a higher amplitude and frequency of ictal electroencephalogram discharge than electrographic seizures. During electroclinical seizures, the ictal electroencephalogram was more likely to involve larger areas of the brain and to cross the midline. Mortality and morbidity were similar in babies with electroclinical and electrographic seizures, emphasizing the need to diagnose and treat both types. Ictal electroencephalogram topography has implications for electrode application during limited-channel, amplitude-integrated electroencephalograms. We recommend temporal and paracentral electrodes. Video electroencephalograms are important in diagnosing neonatal seizures and providing useful information regarding ictal electroencephalogram characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom.

    PubMed

    Meguins, Lucas Crociati; Adry, Rodrigo Antônio Rocha da Cruz; Silva Júnior, Sebastião Carlos da; Pereira, Carlos Umberto; Oliveira, Jean Gonçalves de; Morais, Dionei Freitas de; Araújo Filho, Gerardo Maria de; Marques, Lúcia Helena Neves

    2015-11-01

    To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome. A retrospective study was conducted with patients with temporal low-grade gliomas (LGG). Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 ± 8.4 (9-68 years). The mean age at seizure onset was 25.7 ± 9.2 (11-66 years). Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6%) were Engel I; seventeen (26.2%) Engel II; four (6.2%) Engel III and two (3.1%) Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6%) with total resection and in only 3 (33.3%) patients with partial resection. Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom.

  2. Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA.

    PubMed

    Traul, David E; Traul, Christine S; Matsumoto, Julie; Goodkin, Howard P

    2008-09-01

    We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity.

  3. Evolving functional network properties and synchronizability during human epileptic seizures

    NASA Astrophysics Data System (ADS)

    Schindler, Kaspar A.; Bialonski, Stephan; Horstmann, Marie-Therese; Elger, Christian E.; Lehnertz, Klaus

    2008-09-01

    We assess electrical brain dynamics before, during, and after 100 human epileptic seizures with different anatomical onset locations by statistical and spectral properties of functionally defined networks. We observe a concave-like temporal evolution of characteristic path length and cluster coefficient indicative of a movement from a more random toward a more regular and then back toward a more random functional topology. Surprisingly, synchronizability was significantly decreased during the seizure state but increased already prior to seizure end. Our findings underline the high relevance of studying complex systems from the viewpoint of complex networks, which may help to gain deeper insights into the complicated dynamics underlying epileptic seizures.

  4. Transition to seizure: from "macro"- to "micro"-mysteries.

    PubMed

    Zhang, Z J; Valiante, T A; Carlen, P L

    2011-12-01

    One of the most terrifying aspects of epilepsy is the sudden and apparently unpredictable transition of the brain into the pathological state of an epileptic seizure. The pathophysiology of the transition to seizure still remains mysterious. Herein we review some of the key concepts and relevant literatures dealing with this enigmatic transitioning of brain states. At the "MACRO" level, electroencephalographic (EEG) recordings at ti