Sample records for ptz seizure threshold

  1. The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system.

    PubMed

    Heydari, Azhdar; Davoudi, Shima

    2017-02-01

    Serotonin is a key regulatory neurotransmitter in the CNS which plays an important role in seizure through different receptors, especially the 5HT 1A subtype. The role of sertraline through the 5HT 1A receptor and nitric oxide interaction on the PTZ-induced seizure threshold was investigated in this study. In this study, 70 white male mice were randomly divided into 10 groups including intact control, sham-control and eight experimental groups which received sertraline, 8-OH-DPAT, WAY100635, WAY100635+sertraline, WAY100635+8-OH-DPAT, L-NAME, L-NAME+sertraline and L-NAME+8-OH-DPAT. After 14days of treatment in different groups, the PTZ-induced seizure threshold was assessed and the measurement of nitric oxide metabolites in the brain tissue was done with the Greiss method. The seizure threshold was significantly increased in the sertraline and 8OH-DPAT receiving groups compared to the sham group (P<0.001). In the presence of WAY100635, the effect of both sertraline and 8-OH-DPAT in raising the seizure threshold was more prominent (P<0.001) but on the other hand, in the presence of L-NAME, an increase in the anticonvulsant effect of 8-OH-DPAT was observed, while L-NAME alone had no effect on the seizure threshold (P<0.001). The NO X concentration was significantly decreased in the 8-OH-DPAT_treated group (P<0.01), while the WAY100657 reversed it and the combination of 8-OH-DPAT with L-NAME reduced the NO X levels (P<0.001). These findings support the anticonvulsant effect of SSRIs and selective 5HT 1A receptors, although serotonin receptors other than 5HT 1A subtype may be involved and also it is probable that some anticonvulsant effects of the sertraline and 8-OH-DPAT are through the modulation of nitrergic system. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. Effect of Tadalafil on Seizure Threshold and Activity of Antiepileptic Drugs in Three Acute Seizure Tests in Mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Wyska, Elżbieta; Szafarz, Małgorzata; Doboszewska, Urszula; Wlaź, Piotr

    2018-02-09

    Tadalafil, a selective phosphodiesterase type 5 inhibitor, is a long-acting oral agent for the treatment of erectile dysfunction of multiple etiologies. Although generalized tonic-clonic seizures were reported in a healthy man after taking tadalafil, the influence of tadalafil on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of tadalafil on seizure threshold as well as on the activity of some first- and second-generation antiepileptic drugs in three acute seizure tests in mice. The obtained results showed that tadalafil, at the highest dose tested (20 mg/kg), significantly decreased the threshold for the first myoclonic twitch in the intravenous pentylenetetrazole (i.v. PTZ) seizure test. It did not affect the threshold for generalized clonic seizure and forelimb tonus in the i.v. PTZ, for tonic hindlimb extension in the maximal electroshock seizure threshold test, and for psychomotor seizure in the 6-Hz-induced seizure threshold test. Tadalafil did not alter the anticonvulsant activity of any of the studied antiepileptic drugs in electrically induced seizure tests. Interestingly, tadalafil potentiated the anticonvulsant activity of clonazepam and decreased the anticonvulsant activity of oxcarbazepine in the i.v. PTZ test. These interactions were pharmacodynamic in nature, as tadalafil did not alter clonazepam and oxcarbazepine concentrations both in serum and brain tissue. Furthermore, neither tadalafil alone nor its combinations with the studied antiepileptic drugs produced any significant impairment of motor coordination (assessed in the chimney test), muscular strength (investigated in the grip-strength test), and long-term memory (assessed in the passive avoidance task). In conclusion, tadalafil may increase the risk of myoclonic seizure and decrease the anticonvulsant efficacy of oxcarbazepine. Further studies are warranted to evaluate the safety of tadalafil usage in patients with

  3. Assessment of the Anticonvulsant Potency of Ursolic Acid in Seizure Threshold Tests in Mice.

    PubMed

    Nieoczym, Dorota; Socała, Katarzyna; Wlaź, Piotr

    2018-05-01

    Ursolic acid (UA) is a plant derived compound which is also a component of the standard human diet. It possesses a wide range of pharmacological properties, i.e., antioxidant, anti-inflammatory, antimicrobial and antitumor, which have been used in folk medicine for centuries. Moreover, influence of UA on central nervous system-related processes, i.e., pain, anxiety and depression, was proved in experimental studies. UA also revealed anticonvulsant properties in animal models of epilepsy and seizures. The aim of the present study was to investigate the influence of UA on seizure thresholds in three acute seizure models in mice, i.e., the 6 Hz-induced psychomotor seizure threshold test, the maximal electroshock threshold (MEST) test and the timed intravenous pentylenetetrazole (iv PTZ) infusion test. We also examined its effect on the muscular strength (assessed in the grip strength test) and motor coordination (estimated in the chimney test) in mice. UA at doses of 50 and 100 mg/kg significantly increased the seizure thresholds in the 6 Hz and MEST tests. The studied compound did not influence the seizure thresholds in the iv PTZ test. Moreover, UA did not affect the motor coordination and muscular strength in mice. UA displays only a weak anticonvulsant potential which is dependent on the used seizure model.

  4. Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.

    PubMed

    Jia, Yun-Fang; Li, Ying-Chao; Tang, Yan-Ping; Cao, Jun; Wang, Li-Ping; Yang, Yue-Xiong; Xu, Lin; Mao, Rong-Rong

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is widely distributed in the central nervous system (CNS) including hippocampus, and regulates the balance of excitation and inhibition in CNS, which imply its important role in epilepsy. We used both pharmacological manipulations and transgenic mice to disturb the function of TRPV1 and then studied the effects of these alterations on the susceptibility of pentylenetetrazol (PTZ)-induced seizures. Our results showed that systemic administration of TRPV1 agonist capsaicin (CAP, 40 mg/kg) directly induced tonic-clonic seizures (TCS) without PTZ induction. The severity of seizure was increased in lower doses of CAP groups (5 and 10 mg/kg), although the latency to TCS was delayed. On the other hand, systemic administration of TRPV1 antagonist capsazepine (CPZ, 0.05 and 0.5 mg/kg) and TRPV1 knockout mice exhibited delayed latency to TCS and reduced mortality. Furthermore, hippocampal administration of CPZ (10 and 33 nmol/μL/side) was firstly reported to increase the latency to TCS, decrease the maximal grade of seizure and mortality. It is worth noting that decreased susceptibility of PTZ-induced seizures was observed in hippocampal TRPV1 overexpression mice and hippocampal CAP administration (33 nmol/μL/side), which is opposite from results of systemic agonist CAP. Our findings suggest that the systemic administration of TRPV1 antagonist may be a novel therapeutic target for epilepsy, and alteration of hippocampal TRPV1 function exerts a critical role in seizure susceptibility.

  5. Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.

    PubMed

    Töllner, Kathrin; Twele, Friederike; Löscher, Wolfgang

    2016-04-01

    Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

    PubMed

    Saha, Lekha; Chakrabarti, Amitava; Kumari, Sweta; Bhatia, Alka; Banerjee, Dibyojyoti

    2016-02-01

    Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

  8. Alteration of pentylenetetrazole-induced seizure threshold by chronic administration of ginger (Zingiber officinale) extract in male mice.

    PubMed

    Hosseini, Abdolkarim; Mirazi, Naser

    2015-05-01

    Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 ± 1.91 versus 24.47 ± 1.33 mg/kg, p < 0.001) and significantly prevented generalized clonic (74.64 ± 3.52 versus 47.72 ± 2.31 mg/kg, p < 0.001) and increased the threshold for the forelimb tonic extension (102.6 ± 5.39 versus 71.82 ± 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control group. Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.

  9. A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

    PubMed

    Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

    2005-08-01

    The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

  10. The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs.

    PubMed

    Löscher, Wolfgang; Hoffmann, Katrin; Twele, Friederike; Potschka, Heidrun; Töllner, Kathrin

    2013-11-01

    Recently, the imidazolinone derivative imepitoin has been approved for treatment of canine epilepsy. Imepitoin acts as a low-affinity partial agonist at the benzodiazepine (BZD) site of the GABAA receptor and is the first compound with such mechanism that has been developed as an antiepileptic drug (AED). This mechanism offers several advantages compared to full agonists, including less severe adverse effects and a lack of tolerance and dependence liability, which has been demonstrated in rodents, dogs, and nonhuman primates. In clinical trials in epileptic dogs, imepitoin was shown to be an effective and safe AED. Recently, seizures in dogs have been proposed as a translational platform for human therapeutic trials on new epilepsy treatments. In the present study, we compared the anticonvulsant efficacy of imepitoin, phenobarbital and the high-affinity partial BZD agonist abecarnil in the timed i.v. pentylenetetrazole (PTZ) seizure threshold test in dogs and, for comparison, in mice. Furthermore, adverse effects of treatments were compared in both species. All drugs dose-dependently increased the PTZ threshold in both species, but anticonvulsant efficacy was higher in dogs than mice. At the doses selected for this study, imepitoin was slightly less potent than phenobarbital in increasing seizure threshold, but markedly more tolerable in both species. Effective doses of imepitoin in the PTZ seizure model were in the same range as those suppressing spontaneous recurrent seizures in epileptic dogs. The study demonstrates that low-affinity partial agonists at the benzodiazepine site of the GABAA receptor, such as imepitoin, offer advantages as a new category of AEDs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Effect of harmane on the convulsive threshold in epilepsy models in mice.

    PubMed

    Aricioglu, Feyza; Yillar, Okan; Korcegez, Eylem; Berkman, Kemal

    2003-12-01

    The study investigated the activity of harmane on maximal electroshock seizures (MES) and seizures induced by pentilentetrazole (PTZ) in mice. Initial studies established convulsive current 50 (CC(50)) values or MES and effective dose 50 (ED(50)) for PTZ to produce seizures. Harmane (2.5, 5.0, or 10 mg/kg intraperitoneally) increased the threshold of seizures in MES dose-dependently. The convulsions produced by PTZ were decreased by the low dose of harmane (2.5 mg/kg), but the high dose of harmane (10 mg/kg) resulted in worse grade V convulsions followed by more lethality compared with PTZ alone. Therefore, harmane seems to be protective against grand mal seizures in the MES model but not against a petit mal seizure model (PTZ) in mice.

  12. vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol.

    PubMed

    Schallier, Anneleen; Massie, Ann; Loyens, Ellen; Moechars, Diederik; Drinkenburg, Wilhelmus; Michotte, Yvette; Smolders, Ilse

    2009-01-01

    Glutamate, the most abundant excitatory neurotransmitter in the central nervous system, is well known to be implicated in epileptic seizures. Therefore, impairments in glutamate transport could have an involvement in the mechanism of epileptogenesis. The uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (vGLUTs). There are three known vGLUT isoforms, vGLUT1-3. In this study, we are particularly interested in the vGLUT2 isoform. We investigated the possible role of vGLUT2 in pentylenetetrazol (PTZ)-induced seizure generation. Seizure threshold of PTZ was compared in vGLUT2 heterozygous knock out (HET) and wild type (WT) mice. In comparison with their WT littermates a lower dose of PTZ was needed in the vGLUT2 HET mice until the onset of the first myoclonic jerk. The threshold for PTZ-induced clonic seizure activity was also lower in the vGLUT2 HET mice. These results indicate, for the first time, that vGLUT2 is likely involved in the epileptogenesis of generalized seizures.

  13. Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice.

    PubMed

    Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

    2016-01-01

    Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

  14. Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice

    PubMed Central

    Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

    2016-01-01

    Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more. PMID:28243281

  15. Acute administration of ginger (Zingiber officinale rhizomes) extract on timed intravenous pentylenetetrazol infusion seizure model in mice.

    PubMed

    Hosseini, Abdolkarim; Mirazi, Naser

    2014-03-01

    Zingiber officinale (Zingiberaceae) or ginger, which is used in traditional medicine has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100mg/kg) were administered intraperitonal (i.p.), 2 and 24h before induction of PTZ. Phenobarbital sodium (30mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints (myoclonic, generalized clonus and forelimb tonic extension phase) was recorded. The results showed that the ginger extract has anticonvulsant effects in all the experimental treatment groups of seizure tested as it significantly increased the seizure threshold. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100mg/kg (p<0.001) and significantly prevented generalized clonic (p<0.001) and increased the threshold for the forelimb tonic extension (p<0.01) seizure 2 and 24h before induction of PTZ compared with control group. Based on the results the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory system, antioxidant mechanisms, oxidative stress and calcium channel inhibition. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish).

    PubMed

    Torres-Hernández, Bianca A; Del Valle-Mojica, Lisa M; Ortíz, José G

    2015-07-14

    Anticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs. All drug treatments were administered by immersion in water containing the drug. For assays of anticonvulsant activity, zebrafish were pretreated with: anti-epileptic drugs, valerenic acid, aqueous or ethanolic valerian extracts, or mixtures (phenytoin or clonazepam with valerenic acid or valerian extracts). Seizures were then induced with pentylenetetrazole (PTZ). A behavioral scale was developed for scoring PTZ-induced seizures in adult zebrafish. The seizure latency was evaluated for all pretreatments and control, untreated fish. Valerenic acid and both aqueous and ethanolic extracts of valerian root were also evaluated for their ability to improve survival after pentylenetetrazole-challenge. The assay was validated by comparison with well-studied anticonvulsant drugs (phenytoin, clonazepam, gabapentin and valproate). One-way ANOVA followed by Tukey post-hoc test was performed, using a p < 0.05 level of significance. All treatments were compared with the untreated animals and with the other pretreatments. After exposure to pentylenetetrazole, zebrafish exhibited a series of stereotypical behaviors prior to the appearance of clonic-like movements--convulsions. Both valerenic acid and valerian extracts (aqueous and ethanolic) significantly extended the latency period to the onset of seizure (convulsion) in adult zebrafish. The ethanolic valerian extract was a more potent anticonvulsant than the aqueous extract. Valerenic acid and both valerian extracts interacted synergistically with clonazepam to extended the

  17. Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

    PubMed

    Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

    2014-04-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration.

    PubMed

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.

  19. Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures.

    PubMed

    Kadiyala, Sridhar B; Ferland, Russell J

    2017-03-01

    C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of

  20. Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model

    PubMed Central

    Saha, Lekha; Bhandari, Swati; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

    2014-01-01

    Background and Purpose: Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. Methods: In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. Results: In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. Conclusions: These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy. PMID:25625088

  1. Acute anticonvulsant effects of capric acid in seizure tests in mice.

    PubMed

    Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Żarnowski, Tomasz; Żarnowska, Iwona; Czuczwar, Stanisław J; Gasior, Maciej

    2015-03-03

    Capric acid (CA10) is a 10-carbon medium-chain fatty acid abundant in the medium-chain triglyceride ketogenic diet (MCT KD). The purpose of this study was to characterize acute anticonvulsant effects of CA10 across several seizure tests in mice. Anticonvulsant effects of orally (p.o.) administered CA10 were assessed in the maximal electroshock seizure threshold (MEST), 6-Hz seizure threshold, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests in mice. Acute effects of CA10 on motor coordination were assessed in the grip and chimney tests. Plasma and brain concentrations of CA10 were measured. Co-administration studies with CA10 and another abundant medium-chain fatty acid, caprylic acid (CA8) were performed. CA10 showed significant and dose-dependent anticonvulsant properties by increasing seizure thresholds in the 6-Hz and MEST seizure tests; it was ineffective in the i.v. PTZ seizure test. At higher doses than those effective in the 6-Hz and MEST seizure tests, CA10 impaired motor performance in the grip and chimney tests. An enhanced anticonvulsant response in the 6-Hz seizure test was produced when CA8 and CA10 were co-administered. An acute p.o. administration of CA10 resulted in dose-proportional increases in its plasma and brain concentrations. CA10 exerted acute anticonvulsant effects at doses that produce plasma exposures comparable to those reported in epileptic patients on the MCT KD. An enhanced anticonvulsant effect is observed when CA10 and the other main constituent of the MCT KD, CA8, were co-administered. Thus, acute anticonvulsant properties of CA10 and CA8 may influence the overall clinical efficacy of the MCT KD. Copyright © 2014. Published by Elsevier Inc.

  2. Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection.

    PubMed

    Kola, Phani Kumar; Akula, Annapurna; NissankaraRao, Lakshmi Sudeepthi; Danduga, R Ch Sekhara Reddy

    2017-10-01

    The present study investigated the effects of Naringin on seizure severity, progress of kindling, memory impairment, oxidative stress, neurochemicals, and neural damage in Pentylenetetrazole (PTZ)-induced kindling. Alternate intra-peritoneal injections of PTZ induced kindling at 22 injections of PTZ. In comparison with the PTZ group, pretreatment with Naringin 30 min prior to PTZ administration and on a PTZ-free day was found to lead to a decreased seizure score, a mitigated progress of kindling, decreased transfer latency, and increased total number of arm entries, % alternation behavior in Y maze, and % conditioned avoidance response in a pole climbing apparatus. Biochemical analysis of the frontal and temporal cortexes and the hippocampus of the brain showed that Naringin attenuated the level of lipid peroxidation (MDA) and augmented the reduced glutathione, superoxide dismutase, catalase, and total thiol results in decreased oxidative stress compared with the PTZ group and control group. Investigation of neurochemicals revealed a minute change in gamma amino butyric acid (GABA), glutamate and dopamine, and decreased AChE in the three regions. Increased CA1 neuronal density in the hippocampus and increased cell density in the frontal and temporal regions indicate the potential of naringin to act against PTZ-induced kindling, memory impairment, oxidative stress, neurochemical changes, and histological aberrations. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Overexpressing wild-type γ2 subunits rescued the seizure phenotype in Gabrg2+/Q390X Dravet syndrome mice.

    PubMed

    Huang, Xuan; Zhou, Chengwen; Tian, Mengnan; Kang, Jing-Qiong; Shen, Wangzhen; Verdier, Kelienne; Pimenta, Aurea; MacDonald, Robert L

    2017-08-01

    The mutant γ-aminobutyric acid type A (GABA A ) receptor γ2(Q390X) subunit (Q351X in the mature peptide) has been associated with the epileptic encephalopathy, Dravet syndrome, and the epilepsy syndrome genetic epilepsy with febrile seizures plus (GEFS+). The mutation generates a premature stop codon that results in translation of a stable truncated and misfolded γ2 subunit that accumulates in neurons, forms intracellular aggregates, disrupts incorporation of γ2 subunits into GABA A receptors, and affects trafficking of partnering α and β subunits. Heterozygous Gabrg2 +/Q390X knock-in (KI) mice had reduced cortical inhibition, spike wave discharges on electroencephalography (EEG), a lower seizure threshold to the convulsant drug pentylenetetrazol (PTZ), and spontaneous generalized tonic-clonic seizures. In this proof-of-principal study, we attempted to rescue these deficits in KI mice using a γ2 subunit gene (GABRG2) replacement therapy. We introduced the GABRG2 allele by crossing Gabrg2 +/Q390X KI mice with bacterial artificial chromosome (BAC) transgenic mice overexpressing HA (hemagglutinin)-tagged human γ2 HA subunits, and compared GABA A receptor subunit expression by Western blot and immunohistochemical staining, seizure threshold by monitoring mouse behavior after PTZ-injection, and thalamocortical inhibition and network oscillation by slice recording. Compared to KI mice, adult mice carrying both mutant allele and transgene had increased wild-type γ2 and partnering α1 and β2/3 subunits, increased miniature inhibitory postsynaptic current (mIPSC) amplitudes recorded from layer VI cortical neurons, reduced thalamocortical network oscillations, and higher PTZ seizure threshold. Based on these results we suggest that seizures in a genetic epilepsy syndrome caused by epilepsy mutant γ2(Q390X) subunits with dominant negative effects could be rescued potentially by overexpression of wild-type γ2 subunits. Wiley Periodicals, Inc. © 2017 International

  4. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice.

    PubMed

    Luszczki, Jarogniew J; Zuchora, Marek; Sawicka, Katarzyna M; Kozińska, Justyna; Czuczwar, Stanisław J

    2006-01-01

    This study examines the effect of acute administration of caffeine sodium benzoate (CAF) on the anticonvulsant action of four conventional antiepileptic drugs (AEDs: clonazepam - CZP, ethosuximide - ETS, phenobarbital - PB and valproate - VPA) against pentetrazole (PTZ)-induced clonic seizures in mice. The results indicate that CAF at a dose of 92.4 mg/kg significantly reduced the threshold for PTZ-induced clonic seizures in mice from 69.5 to 51.7 mg/kg (p<0.05), being ineffective at lower doses of 69.3 and 46.2 mg/kg. Moreover, CAF at doses of and 92.4 mg/kg attenuated the protective action of ETS against PTZ-induced seizures, by increasing its median effective dose (ED50) from 127.7 to 182.3 (p<0.05), and 198.3 mg/kg (p<0.01), respectively. In this case, no pharmacokinetic changes in total brain ETS concentrations after systemic ip administration of CAF (at 92.4 mg/kg) were observed, indicating a pharmacodynamic nature of interaction between ETS and CAF in the PTZ-test in mice. In contrast, CAF (at a dose of 92.4 mg/kg reducing the threshold for PTZ-induced seizures) combined with other AEDs (CZP, PB and VPA) did not affect their anticonvulsant action in the PTZ test in mice. Moreover, CAF (92.4 mg/kg) did not alter significantly total brain concentrations of the remaining AEDs (CZP, PB and VPA). The evaluation of potential acute adverse effects produced by AEDs in combination with CAF revealed that neither CAF (up to 92.4 mg/kg) administered alone nor combined with the studied drugs (at doses corresponding to their ED(50) values in the PTZ-test) affected motor performance of animals in the chimney test. In conclusion, the acute exposure to CAF may diminish the antiseizure protection offered by ETS in epileptic patients. Therefore, patients treated with ETS should avoid CAF.

  5. Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

    PubMed

    Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

    2016-03-09

    It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

  6. Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) can be produced in DBA/2J mice, lower seizure threshold and induce abnormal behavior.

    PubMed

    Ganor, Yonatan; Goldberg-Stern, Hadassa; Cohen, Ran; Teichberg, Vivian; Levite, Mia

    2014-04-01

    Anti-GluR3B antibodies (GluR3B Ab's), directed against peptide B/aa372-395 of GluR3 subunit of glutamate/AMPA receptors, are found in ∼35% of epilepsy patients, activate glutamate/AMPA receptors, evoke ion currents, kill neurons and damage the brain. We recently found that GluR3B Ab's also associate with neurological/psychiatric/behavioral abnormalities in epilepsy patients. Here we asked if GluR3B Ab's could be produced in DBA/2J mice, and also modulate seizure threshold and/or cause behavioral/motor impairments in these mice. DBA/2J mice were immunized with the GluR3B peptide in Complete Freund's Adjuvant (CFA), or with controls: ovalbumin (OVA), CFA, or phosphate-buffer saline (PBS). GluR3B Ab's and OVA Ab's were tested. Seizures were induced in all mice by the chemoconvulsant pentylenetetrazole (PTZ) at three time points, each time with less PTZ to avoid non-specific death. Behavior was examined in Open-Field, RotaRod and Grip tests. GluR3B Ab's were produced only in GluR3B-immunized mice, while OVA Ab's were produced only in OVA-immunized mice, showing high Ab's specificity. In GluR3B Ab's negative mice, seizure severity scores and percentages of animals developing generalized seizures declined in response to decreasing PTZ doses. In contrast, both parameters remained unchanged/high in the GluR3B Ab's positive mice, showing that these mice were more susceptible to seizures. The seizure scores associated significantly with the GluR3B Ab's levels. GluR3B Ab's positive mice were also more anxious in Open-Field test, fell faster in RotaRod test, and fell more in Grip test, compared to all the control mice. GluR3B Ab's are produced in DBA/2J mice, facilitate seizures and induce behavioral/motor impairments. This animal model can therefore serve for studying autoimmune epilepsy and abnormal behavior mediated by pathogenic anti-GluR3B Ab's. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

    PubMed

    Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

    2014-01-01

    Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if

  8. Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Kowalczuk-Vasilev, Edyta; Wyska, Elżbieta; Wlaź, Piotr

    2017-07-01

    Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD 50 value of sulforaphane in mice was estimated at 212.67mg/kg, while the TD 50 value - at 191.58mg/kg. In seizure tests, sulforaphane at the highest dose tested (200mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6Hz-induced psychomotor seizure. At doses of 10-200mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150-300mg/kg), hypothermia (at 150-300mg/kg), impairment of motor coordination (at 200-300mg/kg), decrease in skeletal muscle strength (at 250-300mg/kg), and deaths (at 200-300mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200

  9. Acute seizure suppression by transcranial direct current stimulation in rats

    PubMed Central

    Dhamne, Sameer C; Ekstein, Dana; Zhuo, Zhihong; Gersner, Roman; Zurakowski, David; Loddenkemper, Tobias; Pascual-Leone, Alvaro; Jensen, Frances E; Rotenberg, Alexander

    2015-01-01

    Objective Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition. Methods Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS. Results Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition. PMID:26339678

  10. Duration of treatment and activation of α1-containing GABAA receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats

    PubMed Central

    Kovačević, Jovana; Timić, Tamara; Tiruveedhula, Veera V.; Batinić, Bojan; Namjoshi, Ojas A.; Milić, Marija; Joksimović, Srđan; Cook, James M.; Savić, Miroslav M.

    2014-01-01

    Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of α1-containing GABAA receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24 h after withdrawal from protracted treatment in rats. Withdrawal of 2 mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at α1-containing GABAA receptors, achieved by daily administration of the neutral modulator βCCt (5 mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of βCCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of α1-containing GABAA receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at α1-containing GABAA receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type. PMID:24695241

  11. Reduced susceptibility to induced seizures in the Neuroligin-3(R451C) mouse model of autism.

    PubMed

    Hill-Yardin, Elisa L; Argyropoulos, Andrew; Hosie, Suzanne; Rind, Gil; Anderson, Paul; Hannan, Anthony J; O'Brien, Terence J

    2015-03-04

    Epilepsy is a common comorbidity in patients with autism spectrum disorder (ASD) and several gene mutations are associated with both of these disorders. In order to determine whether a point mutation in the gene for the synaptic protein, Neuroligin-3 (Nlgn3, R451C), identified in patients with ASD alters seizure susceptibility, we administered the proconvulsant pentylenetetrazole (PTZ) to adult male Neuroligin-3(R451C) (NL3(R451C)) and wild type (WT) mice. It has previously been reported that NL3(R451C) mice show altered inhibitory GABAergic activity in brain regions relevant to epilepsy, including the hippocampus and somatosensory cortex. PTZ administration induces absence-seizures at low dose, and generalised convulsive seizures at higher dose. Susceptibility to absence seizures was examined by analysing the frequency and duration of spike-and-wave discharge (SWD) events and accompanying motor seizure activity induced by subcutaneous administration of low dosage (20 or 30mg/kg) PTZ. Susceptibility to generalised convulsive seizures was tested by measuring the response to high dosage (60mg/kg) PTZ using a modified Racine scale. There was no change in the number of SWD events exhibited by NL3(R451C) compared to WT mice following administration of both 20mg/kg PTZ (1.17±0.31 compared to 16.0±11.16 events/30min, NL3(R451C) versus WT, respectively) and 30mg/kg PTZ (7.5±6.54 compared with 27.8±19.9 events/30min, NL3(R451C) versus WT, respectively). NL3(R451C) mice were seizure resistant to generalised convulsive seizures induced by high dose PTZ compared to WT littermates (median latency to first >3s duration clonic seizure; 14.5min versus 7.25min, 95% CI: 1.625-2.375, p=0.0009, NL3(R451C) versus WT, respectively). These results indicate that the R451C mutation in the Nlgn3 gene, associated with ASD in humans, confers resistance to induced seizures, suggesting dysfunction of PTZ-sensitive GABAergic signalling in this mouse model of ASD. Copyright © 2015 Elsevier

  12. Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor.

    PubMed

    Li, Xiaolan; Han, Xinjia; Bao, Junjie; Liu, Yuanyuan; Ye, Aihua; Thakur, Mukesh; Liu, Huishu

    2016-07-01

    A considerable number of studies have demonstrated that nicotine, a α7-nicotinic acetylcholine receptor (α7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14-19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-α, IL-1β, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), and dramatically increased eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α-bungarotoxin, a selective α7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Our findings indicate that the administration of nicotine may attenuate microglial activity and increase eclampsia-like seizure threshold in rat hippocampus through the α7 nicotinic receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission.

    PubMed

    Visweswari, Gopalreddygari; Prasad, Kanchi Siva; Chetan, Pandanaboina Sahitya; Lokanatha, Valluru; Rajendra, Wudayagiri

    2010-03-01

    The study described here was carried out to investigate the anticonvulsant effect of different extracts of Centella asiatica with respect to cholinergic activity on pentylenetetrazol (PTZ)-induced seizures. Rats were randomly divided into eight groups of six rats each: nonepileptic rats treated with saline; PTZ (60 mg/kg, IP)-induced seizure rats treated with saline; PTZ-induced seizure rats pretreated with n-hexane, chloroform, ethyl acetate, n-butanol, and water extracts of C. asiatica; and PTZ-induced seizure rats pretreated with diazepam (2mg/kg body wt). The seized rats pretreated with different extracts were administered a dose of 200mg/kg body wt orally for 1 week before induction of epilepsy. Increased acetylcholine content and decreased acetylcholinesterase activity were recorded in different brain regions during PTZ-induced seizures. Pretreatment with C. asiatica extracts caused recovery of the levels of acetylcholine and acetylcholinesterase. These findings suggest that C. asiatica causes perceptible changes in the cholinergic system as one of the facets of its anticonvulsant activity. (c) 2010 Elsevier Inc. All rights reserved.

  14. Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice.

    PubMed

    Sheikhi, Mehdi; Shirzadian, Armin; Dehdashtian, Amir; Amiri, Shayan; Ostadhadi, Sattar; Ghasemi, Mehdi; Dehpour, Ahmad Reza

    2016-09-01

    Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

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

    Socała, Katarzyna, E-mail: ksocala@op.pl

    Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. Inmore » addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD{sub 50} value of sulforaphane in mice was estimated at 212.67 mg/kg, while the TD{sub 50} value – at 191.58 mg/kg. In seizure tests, sulforaphane at the highest dose tested (200 mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6 Hz-induced psychomotor seizure. At doses of 10–200 mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100 mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300 mg/kg), hypothermia (at 150–300 mg/kg), impairment of motor coordination (at 200–300 mg/kg), decrease in skeletal muscle strength (at 250–300 mg/kg), and deaths (at 200–300 mg/kg). Moreover, blood analysis showed

  16. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

    PubMed

    Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

    2018-03-14

    l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p < 0.0001) and shortened seizure duration ( p = 0.028). In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p < 0.0001) and reduced the activity of catalase enzyme ( p = 0.0006) and increased antioxidant GSH activity ( p < 0.0001). Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p < 0.0001) and β-catenin ( p < 0.0001). Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

  17. Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy.

    PubMed

    Erdogan, Mumin Alper; Yusuf, Dimas; Christy, Joanna; Solmaz, Volkan; Erdogan, Arife; Taskiran, Emin; Erbas, Oytun

    2018-06-07

    Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ). Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.

  18. [(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.

    PubMed

    Bascuñana, Pablo; Javela, Julián; Delgado, Mercedes; Fernández de la Rosa, Rubén; Shiha, Ahmed Anis; García-García, Luis; Pozo, Miguel Ángel

    2016-10-01

    Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

  19. Preventive effect of Coriandrum sativum on neuronal damages in pentylentetrazole-induced seizure in rats

    PubMed Central

    Pourzaki, Mojtaba; Homayoun, Mansour; Sadeghi, Saeed; Seghatoleslam, Masoumeh; Hosseini, Mahmoud; Ebrahimzadeh Bideskan, Alireza

    2017-01-01

    Objective: Coriandrum sativum (C. sativum) as a medicinal plant has been pointed to have analgesic, hypnotic and anti-oxidant effects. In the current study, a possible preventive effect of the hydro-alcoholic extract of the plant on neuronal damages was examined in pentylenetetrazole (PTZ) rat model of seizure. Materials and Methods: Forty male rats were divided into five main groups and treated by (1) saline, (2) PTZ: 100 mg/kg PTZ (i.p) and (3-5) 50, 100 and 200 mg/kg of hydro-alcoholic extract of C. sativum during seven consecutive days before PTZ injection. After electrocorticography (ECoG), the brains were removed to use for histological examination. Results: All doses of the extract reduced duration, frequency and amplitude of the burst discharges while prolonged the latency of the seizure attacks (p<0.05, p<0.01, and p<0.001). Administration of all 3 doses of the extract significantly prevented from production of dark neurons (p<0.01, and p<0.001) and apoptotic cells (p<0.05, p<0.01, and p<0.001) in different areas of the hippocampus compared to PTZ group. Conclusion: The results of this study allow us to conclude that C. sativum, because of its antioxidant properties, prevents from neuronal damages in PTZ rat model of seizure. PMID:28348967

  20. Effects of hydroalcoholic extract of Coriandrum sativum on oxidative damage in pentylenetetrazole-induced seizures in rats

    PubMed Central

    Karami, Reza; Hosseini, Mahmoud; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza; Rakhshandeh, Hassan; Vafaee, Farzaneh; Esmaeilizadeh, Mahdi

    2015-01-01

    Background: An important role for oxidative stress, as a consequence of epileptic seizures, has been suggested. Coriandrum sativum has been shown that have antioxidant effects. Central nervous system depressant effects of C. sativum have also been reported. In this study, the effects of hydroalcoholic extract of aerial parts of the plants on brain tissues oxidative damages following seizures induced by pentylenetetrazole (PTZ) was investigated in rats. Methods: The rats were divided into five groups and treated: (1) Control (saline), (2) PTZ (90 mg/kg, i.p.), (3-5) three doses (100, 500 and 1000 mg/kg of C. sativum extract (CSE) before PTZ. Latencies to the first minimal clonic seizures (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The cortical and hippocampal tissues were then removed for biochemical measurements. Results: The extract significantly increased the MCS and GTCS latencies (P < 0.01, P < 0.001) following PTZ-induced seizures. The malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of the control animals (P < 0.001). Pretreatment with the extract prevented elevation of the MDA levels (P < 0.010–P < 0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in both cortical and hippocampal tissues (P < 0.050). Pre-treatment with the 500 mg/kg of the extract caused a significant prevention of decreased in total thiol concentration in the cortical tissues (P < 0.010). Conclusion: The present study showed that the hydroalcoholic extract of the aerial parts of C. sativum possess significant antioxidant and anticonvulsant activities. PMID:26056549

  1. 2, 5-Disubstituted phthalimides: design, synthesis and anticonvulsant activity in scPTZ and MES models.

    PubMed

    Saadabadi, Atefeh; Kohen, Babak; Irandoust, Maryam; Shafaroudi, Hamed; Mohammadpour, Tara; Rezayat, Mahdi; Davood, Asghar

    2018-05-15

    In this study, fifteenth new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FT-IR, H-NMR, C-NMR and MASS spectroscopy. All the tested compounds were found to be effective in the PTZ model at the dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at the all dose ranges. Compound 3 has illustrated the best efficacy among all compounds and showed more potency than phenytoin in clonic seizure and was potent as phenytoin in tonic seizure. Using a model of the Na channel, these derivatives were docked in the active site. Docking studies displayed that all synthesized compounds have more negative binding energy compare to reference drug and inhibition-constant less than phenytoin that means they can block the receptor more efficiently and usually form hydrophobic interactions or hydrogen binding interaction frequently with the domains I, II, III and rarely with domain IV. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Do preclinical seizure models preselect certain adverse effects of antiepileptic drugs.

    PubMed

    Meldrum, Brian

    2002-06-01

    Classical screening tests (maximal electroshock, MES, and threshold pentylenetetrazol, PTZ) employ non-epileptic rodents and identify antiepileptic drugs (AEDs) with mechanisms of action associated with significant CNS side effects. Thus MES identifies drugs acting on Na+ channels that produce cerebellar toxicity. It may be possible to produce novel AEDs more selectively targeted at voltage-sensitive (VS) ion channels. There is little specific evidence for the likely success of this strategy with subunit selective agents targeted at the different VS Na+ channels. Drugs targeted at specific VS Ca++ channels (T, N, P/Q types) may be useful in generalised seizures. There are many as yet unexplored possibilities relating to K+ channels. GABA related drugs acting on PTZ clonic seizures tend to induce sedation and muscle hypotonia. Studies in mice, particularly with knock-in mutations, but also with subunit selective agents acting via the GABA(A) benzodiazepine site, suggest that it is possible to produce agents which do or do not induce particular side effects (sedative, hypnotic, anxiolytic, muscle relaxant, amnesia, anaesthesia). Whether these findings transfer to man has yet to be established. Acquired epilepsy in rodents (e.g. kindling or spontaneous seizures following chemically- or electrically-induced status epilepticus) or acquired epilepsy in man (following prolonged febrile seizures or traumatic brain injury) is associated with multiple changes in the function and subunit composition of ion channels and receptor molecules. Optimal screening of novel AEDs, both for efficacy and side effects, requires models with receptor and ion channel changes similar to those in the target human syndrome.

  3. Effects of bee products on pentylenetetrazole-induced seizures in the rat.

    PubMed

    Zárraga-Galindo, N; Vergara-Aragón, P; Rosales-Meléndez, S; Ibarra-Guerrero, P; Domínguez-Marrufo, L E; Oviedo-García, R E; Hernández-Ramírez, H; Hernández-Téllez, B; López-Martínez, I E; Sánchez-Cervantes, I; Vázquez-García, M; Santiago, J

    2011-01-01

    Bee products (BP) have been used for centuries as a diet complement with claimed curative properties. The aim of this study was to determine whether oral administration of BP prevented behavioral, histological, and biochemical alterations, caused by pentylenetetrazole (PTZ)-induced kindling in rats. Male Wistar rats were employed to evaluate seizure latency, number and duration, performance in the open field test, histological alterations and mortality following BP administration. Oral administration of BP at two doses, 30 and 60 mg/kg/day, significantly lengthened latency of both clonic and tonic PTZ-induced seizures, decreased the duration and frequency of seizures and reduced mortality. In the Open Field test, BP treated groups showed increases in the number of crossed squares and rearing counts, and on optimal dose, decreases in fecal boli. Histological analysis showed in PTZ (50 and 80 mg/kg) kindling rats, lungs with inflammatory peribronchiolar, and perialveolar infiltrates. In the liver, mild losses of trabeculae, multi-vesiculated hepatocytes (steatosis) and inflammatory infiltrates in hepatic parenchyma were observed. Interestingly, in the heart, fibers were markedly separated. In testis, stratified epithelium of seminal tubules lost its normal structure, tubules had epithelium loss, spermatids were absent, and spermatogonia and Leydig cells diminished. In PTZ kindling rats treated with BP, the lungs had no inflammatory infiltrates, although the heart showed some inflammatory infiltrates. Remaining structures had normal characteristics. These results, suggest that BP can protect rats from effects of PTZ-induced kindling.

  4. Garcinol Upregulates GABAA and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy

    PubMed Central

    Hao, Fang; Jia, Li-Hua; Li, Xiao-Wan; Zhang, Ying-Rui; Liu, Xue-Wu

    2016-01-01

    Background Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy. Recent experimental data have focussed on plant-derived compounds in treatments. Garcinol (camboginol), is a polyisoprenylated benzophenone derived from the fruit of Garcinia indica. We investigated the effects of garcinol in pentylenetetrazole (PTZ)-induced epileptic models. Material/Methods Seizure scores were measured in epilepsy kindled mice. Neuronal degeneration and apoptosis were assessed by Nissl staining, TUNEL assay, and Fluoro-Jade B staining. Immunohistochemistry was performed to evaluate cleaved caspase-3 expressions. Expression of BDNF, TrkB, GABAA, GAD65, Bad, Bcl-2, Bcl-xL, and Bax were determined by western blots. Results Significantly reduced seizure scores and mortality rates were observed with pretreatment with garcinol. Elevated expression of apoptotic proteins and caspase-3 in kindled mice were effectively downregulated by garcinol. Epileptogenic mice presented increased BDNF and TrkB with considerably decreased GABAA and GAD65 expression. Garcinol significantly enhanced GABAA and GAD65 while it suppressed BDNF and TrkB. Garcinol enhanced the performance of mice in Morris water maze tests. Conclusions Garcinol exerts neuroprotective effects via supressing apoptosis and modulating BDNF-TrkB signalling and GAD65/GABAA expressions and also enhanced cognition and memory of the mice. PMID:27855137

  5. Behavioral and genotoxic evaluation of rosmarinic and caffeic acid in acute seizure models induced by pentylenetetrazole and pilocarpine in mice.

    PubMed

    Coelho, Vanessa Rodrigues; Vieira, Caroline Gonçalves; de Souza, Luana Pereira; da Silva, Lucas Lima; Pflüger, Pricila; Regner, Gabriela Gregory; Papke, Débora Kuck Mausolff; Picada, Jaqueline Nascimento; Pereira, Patrícia

    2016-11-01

    The goal of this study was to investigate the effects of rosmarinic acid (RA) and caffeic acid (CA) in the acute pentylenetetrazole (PTZ) and pilocarpine (PIL) seizure models. We also evaluated the effect of RA and CA on the diazepam (DZP)-induced sleeping time test and its possible neuroprotective effect against the genotoxic damage induced by PTZ and PIL. Mice were treated intraperitoneally (i.p.) with saline, RA (2 or 4 mg/kg), or CA (4 or 8 mg/kg) alone or associated to low-dose DZP. After, mice received a single dose of PTZ (88 mg/kg) or PIL (250 mg/kg) and were monitored for the percentage of seizures and the latency to first seizure (LFS) >3 s. Vigabatrin and DZP were used as positive controls. In the DZP-induced sleeping time test, mice were treated with RA and CA and 30 min after receiving DZP (25 mg/kg, i.p.). The alkaline comet assay was performed after acute seizure tests to evaluate the antigenotoxic profiles of RA and CA. The doses of RA and CA tested alone did not reduce the occurrence of seizures induced by PTZ or PIL. The association of 4 mg/kg RA + low-dose DZP was shown to increase LFS in the PTZ model, compared to the group that received only the DZP. In the DZP-induced sleeping time test, the latency to sleep was reduced by 4 mg/kg RA and 8 mg/kg CA. The PTZ-induced genotoxic damage was not prevented by RA or CA, but the PIL-induced genotoxic damage was decreased by pretreatment with 4 mg/kg RA (in cortex) and 4 mg/kg CA (in hippocampus). In conclusion, RA and CA presented neuroprotective effect against PIL-induced genotoxic damage and reduced the latency to DZP-induced sleep. Of the rosmarinic acid, 4 mg/kg enhanced the DZP effect in the increase of latency to clonic PTZ-induced seizures.

  6. The effect of dorsal hippocampal administration of nicotinic and muscarinic cholinergic ligands on pentylenetetrazol-induced generalized seizures in rats.

    PubMed

    Gholami, Morteza; Saboory, Ehsan; Zare, Samad; Roshan-Milani, Shiva; Hajizadeh-Moghaddam, Akbar

    2012-10-01

    In the present study, the effects of intrahippocampal injections of cholinergic ligands on pentylenetetrazol (PTZ)-induced seizures were investigated in rats. The rats were assigned to 1 of the following 9 groups: saline, nicotine (0.5 or 1 μg), atropine (0.25 or 1 μg), oxotremorine-M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). Cholinergic ligands were administered via intrahippocampal infusion 30 min before seizure induction (intraperitoneal injection of 80 mg/kg PTZ). Results show that antagonists caused nonsignificant increases in the latency of tonic-clonic seizures, significant decreases in the duration of tonic-clonic seizures, significant decreases in the latency of death, and increases in mortality rate. Agonists led to increases in the duration of tonic-clonic seizures, decreases in the latency of death, and decreases in mortality rate. These results provide compelling evidence that cholinergic ligands show modulatory effects on a PTZ model of acute seizure in the rat hippocampus. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats.

    PubMed

    Dhir, Ashish; Rogawski, Michael A

    2018-05-01

    Diazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near-steady-state levels, which allowed an assessment of the minimal levels that elevate seizure threshold. The thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein. The pharmacokinetic parameters of diazepam following a single 80-μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters V d , CL, t 1/2α (distribution half-life) and t 1/2β (terminal half-life) for diazepam were, respectively, 608 mL, 22.1 mL/min, 13.7 minutes, and 76.8 minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70 ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations. Diazepam elevates seizure threshold at steady-state plasma concentrations lower than previously recognized. The

  8. Glutamate receptor 1 phosphorylation at Serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability following early life seizures

    PubMed Central

    Rakhade, S.N.; Fitzgerald, E.F.; Klein, P.M.; Zhou, C.; Sun, H; Huganir, R.L.; Jensen, F.E.

    2012-01-01

    Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We previously showed that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of S831 and S845 sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced post-translational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation (GluR1 double phosphomutant (GluR1DPM) mice). Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex following a single episode of pentyleneterazol (PTZ) induced seizures in postnatal day 9 (P9) wild type mouse pups, and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex, and were associated with enhanced seizure susceptibility to later-life kainic acid induced seizures. In contrast, later-life seizure susceptibility following hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for post-translational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue. PMID:23223299

  9. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats

    PubMed Central

    Besio, W.G.; Makeyev, O.; Medvedev, A.; Gale, K.

    2013-01-01

    Purpose To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. Methods The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. Results In the case of the TFS treated group, after TFS, there was a significant (p = 0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p = 0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p= 0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. Conclusions TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced towards the “baseline.” The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. PMID:23290195

  10. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

    PubMed

    Besio, W G; Makeyev, O; Medvedev, A; Gale, K

    2013-07-01

    To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

    PubMed

    Nemes, Ashley D; O'Dwyer, Rebecca; Najm, Imad M; Ying, Zhong; Gonzalez-Martinez, Jorge; Alexopoulos, Andreas V

    2017-10-01

    Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA A ) antagonist used to provoke generalized seizures as a "second hit." LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  12. Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor.

    PubMed

    Amini-Khoei, Hossein; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Haj-Mirzaian, Arvin; Shirzadian, Armin; Hasanvand, Amin; Balali-Dehkordi, Shima; Hassanipoor, Mahsa; Dehpour, Ahmad Reza

    2018-03-20

    Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

  13. Anticonvulsant effects of Senna spectabilis on seizures induced by chemicals and maximal electroshock.

    PubMed

    Nkamguie Nkantchoua, Gisele Claudine; Kameni Njapdounke, Jacqueline Stephanie; Jules Fifen, Jean; Sotoing Taiwe, Germain; Josiane Ojong, Lucie; Kavaye Kandeda, Antoine; Ngo Bum, Elisabeth

    2018-02-15

    Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction on seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-ß-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. It also appears that the oral administration of the decoction of S. spectabilis is more active than the intraperitoneal administration of the ethanolic extract on inhibiting seizures induced by MES and PTZ. Moreover, the plant decoction could interact with GABA A complex receptor probably on the GABA and benzodiazepines sites. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model.

    PubMed

    Dede, Fazilet; Karadenizli, Sabriye; Özsoy, Özgür Doğa; Eraldemir, Fatma Ceyla; Şahin, Deniz; Ateş, Nurbay

    2017-01-01

    It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment. We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA. Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1β, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05). Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1β, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1β, and IL-6 with adenosinergic modulation may decrease seizure severity. © 2017 S. Karger AG, Basel.

  15. Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

    PubMed

    Sanya, E O; Soladoye, A O; Desalu, O O; Kolo, P M; Olatunji, L A; Olarinoye, J K

    2017-03-06

    The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures

  16. Anticonvulsant Effect of Guaifenesin against Pentylenetetrazol-Induced Seizure in Mice.

    PubMed

    Keshavarz, Mojtaba; Showraki, Alireza; Emamghoreishi, Masoumeh

    2013-06-01

    There have been some reports about the possible N-methyl-D-aspartate (NMDA) antagonist activity of Guaifenesin. As drugs with a similar structure to Guaifenesin (i.e. Felbamate) and those with NMDA antagonist activity have been clinically used as anticonvulsants, the aim of this study was to determine whether Guaifenesin has an anticonvulsant effect in an animal model of seizure. Anticonvulsant effect of Guaifenesin was assessed via Pentylenetetrazol (PTZ)-induced convulsion. Male albino mice received Guaifenesin (100, 200, 300, or 400 mg/kg; n=8-10) or 0.25% Tween (vehicle) intraperitoneally 30 minutes before the injection of PTZ (95 mg/kg). Diazepam (3 mg/kg; n=8) was used as a reference drug. The latency time before the onset of myoclonic, clonic, and tonic-clonic convulsions, percentage of animals exhibiting convulsion, and percentage of mortality were recorded. In addition, the effect of Guaifenesin on neuromuscular coordination was assessed using the Rotarod. Guaifenesin at all the studied doses significantly increased the latency to myoclonic and clonic convulsions in a dose-dependent manner. In addition, Guaifenesin at the dose of 300 mg/kg increased the latency to tonic-clonic seizure. The ED50s of Guaifenesin for protection against PTZ-induced clonic and tonic-clonic seizures and death were 744.88 (360-1540), 256 (178-363), and 328 (262-411) mg/kg, respectively. Guaifenesin at all the investigated doses significantly reduced neuromuscular coordination, compared to the vehicle-treated group. These results suggest that Guaifenesin possesses muscle relaxant and anticonvulsant properties and may have a potential clinical use in absence seizure.

  17. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats.

    PubMed

    Anaeigoudari, Akbar; Hosseini, Mahmoud; Karami, Reza; Vafaee, Farzaneh; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza

    2016-01-01

    In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats. The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg). The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p<0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p<0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (p<0.01 - p<0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in the brain tissues (p<0.05). Pretreatment with WF and NBF significantly elevated thiol concentrations in cortical and hippocampal tissues, respectively (p<0.05). The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

  18. Post-traumatic seizure susceptibility is attenuated by hypothermia therapy

    PubMed Central

    Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Sanchez-Molano, Juliana; Kang, Yuan; Alonso, Ofelia F.; Sick, Thomas J.; Dietrich, W. Dalton; Bramlett, Helen M.

    2010-01-01

    Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available anti-epileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and then were maintained at normothermic or moderate hypothermic temperatures for 4 hr. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole (PTZ), a GABAA receptor antagonist. PTZ elicited a significant increase in seizure frequency in TBI normothermic animals as compared to sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss, nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizure. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy. PMID:21044182

  19. Anticonvulsant Effect of Guaifenesin against Pentylenetetrazol-Induced Seizure in Mice

    PubMed Central

    Keshavarz, Mojtaba; Showraki, Alireza; Emamghoreishi, Masoumeh

    2013-01-01

    Background: There have been some reports about the possible N-methyl-D-aspartate (NMDA) antagonist activity of Guaifenesin. As drugs with a similar structure to Guaifenesin (i.e. Felbamate) and those with NMDA antagonist activity have been clinically used as anticonvulsants, the aim of this study was to determine whether Guaifenesin has an anticonvulsant effect in an animal model of seizure. Methods: Anticonvulsant effect of Guaifenesin was assessed via Pentylenetetrazol (PTZ)-induced convulsion. Male albino mice received Guaifenesin (100, 200, 300, or 400 mg/kg; n=8-10) or 0.25% Tween (vehicle) intraperitoneally 30 minutes before the injection of PTZ (95 mg/kg). Diazepam (3 mg/kg; n=8) was used as a reference drug. The latency time before the onset of myoclonic, clonic, and tonic-clonic convulsions, percentage of animals exhibiting convulsion, and percentage of mortality were recorded. In addition, the effect of Guaifenesin on neuromuscular coordination was assessed using the Rotarod. Results: Guaifenesin at all the studied doses significantly increased the latency to myoclonic and clonic convulsions in a dose-dependent manner. In addition, Guaifenesin at the dose of 300 mg/kg increased the latency to tonic-clonic seizure. The ED50s of Guaifenesin for protection against PTZ-induced clonic and tonic-clonic seizures and death were 744.88 (360-1540), 256 (178-363), and 328 (262-411) mg/kg, respectively. Guaifenesin at all the investigated doses significantly reduced neuromuscular coordination, compared to the vehicle-treated group. Conclusion: These results suggest that Guaifenesin possesses muscle relaxant and anticonvulsant properties and may have a potential clinical use in absence seizure. PMID:23825891

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

    PubMed

    Löscher, Wolfgang

    2017-07-01

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

  1. Rapamycin down-regulates KCC2 expression and increases seizure susceptibility to convulsants in immature rats

    PubMed Central

    Huang, Xiaoxing; McMahon, John; Yang, Jun; Shin, Damian; Huang, Yunfei

    2012-01-01

    Summary Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mTOR pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. We found that inhibition of mTOR by rapamycin in immature rats (3 to 4 weeks old) increases the severity of seizures induced by pilocarpine, including lengthening the total seizure duration and reducing the latency to the onset of seizures. Rapamycin also reduces the minimal dose of pentylenetetrazol (PTZ) necessary to induce clonic seizures. However, in mature rats, rapamycin does not significantly change the seizure sensitivity to pilocarpine and PTZ. Likewise, kainate sensitivity was not significantly affected by rapamycin treatment in either mature or immature rats. Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility. PMID:22613737

  2. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

    PubMed Central

    Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

    2010-01-01

    Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

  3. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats

    PubMed Central

    Anaeigoudari, Akbar; Hosseini, Mahmoud; Karami, Reza; Vafaee, Farzaneh; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza

    2016-01-01

    Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats. Materials and Methods: The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg). Results: The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p<0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p<0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (p<0.01 - p<0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in the brain tissues (p<0.05). Pretreatment with WF and NBF significantly elevated thiol concentrations in cortical and hippocampal tissues, respectively (p<0.05). Conclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects. PMID:27222836

  4. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

    PubMed

    Oztas, Berrin; Sahin, Deniz; Kir, Hale; Eraldemir, Fatma Ceyla; Musul, Mert; Kuskay, Sevinç; Ates, Nurbay

    2017-02-01

    The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. Copyright

  5. Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

    PubMed

    Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

    2012-01-01

    As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

  6. Mouse epileptic seizure detection with multiple EEG features and simple thresholding technique

    NASA Astrophysics Data System (ADS)

    Tieng, Quang M.; Anbazhagan, Ashwin; Chen, Min; Reutens, David C.

    2017-12-01

    Objective. Epilepsy is a common neurological disorder characterized by recurrent, unprovoked seizures. The search for new treatments for seizures and epilepsy relies upon studies in animal models of epilepsy. To capture data on seizures, many applications require prolonged electroencephalography (EEG) with recordings that generate voluminous data. The desire for efficient evaluation of these recordings motivates the development of automated seizure detection algorithms. Approach. A new seizure detection method is proposed, based on multiple features and a simple thresholding technique. The features are derived from chaos theory, information theory and the power spectrum of EEG recordings and optimally exploit both linear and nonlinear characteristics of EEG data. Main result. The proposed method was tested with real EEG data from an experimental mouse model of epilepsy and distinguished seizures from other patterns with high sensitivity and specificity. Significance. The proposed approach introduces two new features: negative logarithm of adaptive correlation integral and power spectral coherence ratio. The combination of these new features with two previously described features, entropy and phase coherence, improved seizure detection accuracy significantly. Negative logarithm of adaptive correlation integral can also be used to compute the duration of automatically detected seizures.

  7. Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

    PubMed

    Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

    2017-12-01

    Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

  8. Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

    PubMed

    Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

    2002-12-30

    Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

  9. Novel Visual Sensor Coverage and Deployment in Time Aware PTZ Wireless Visual Sensor Networks.

    PubMed

    Yap, Florence G H; Yen, Hong-Hsu

    2016-12-30

    In this paper, we consider the visual sensor deployment algorithm in Pan-Tilt-Zoom (PTZ) Wireless Visual Sensor Networks (WVSNs). With PTZ capability, a sensor's visual coverage can be extended to reduce the number of visual sensors that need to be deployed. The coverage zone of a visual sensor in PTZ WVSN is composed of two regions, a Direct Coverage Region (DCR) and a PTZ Coverage Region (PTZCR). In the PTZCR, a visual sensor needs a mechanical pan-tilt-zoom operation to cover an object. This mechanical operation can take seconds, so the sensor might not be able to adjust the camera in time to capture the visual data. In this paper, for the first time, we study this PTZ time-aware PTZ WVSN deployment problem. We formulate this PTZ time-aware PTZ WVSN deployment problem as an optimization problem where the objective is to minimize the total visual sensor deployment cost so that each area is either covered in the DCR or in the PTZCR while considering the PTZ time constraint. The proposed Time Aware Coverage Zone (TACZ) model successfully captures the PTZ visual sensor coverage in terms of camera focal range, angle span zone coverage and camera PTZ time. Then a novel heuristic, called Time Aware Deployment with PTZ camera (TADPTZ) algorithm, is proposed to solve the problem. From our computational experiments, we found out that TACZ model outperforms the existing M coverage model under all network scenarios. In addition, as compared to the optimal solutions, the TACZ model is scalable and adaptable to the different PTZ time requirements when deploying large PTZ WVSNs.

  10. Novel Visual Sensor Coverage and Deployment in Time Aware PTZ Wireless Visual Sensor Networks

    PubMed Central

    Yap, Florence G. H.; Yen, Hong-Hsu

    2016-01-01

    In this paper, we consider the visual sensor deployment algorithm in Pan-Tilt-Zoom (PTZ) Wireless Visual Sensor Networks (WVSNs). With PTZ capability, a sensor’s visual coverage can be extended to reduce the number of visual sensors that need to be deployed. The coverage zone of a visual sensor in PTZ WVSN is composed of two regions, a Direct Coverage Region (DCR) and a PTZ Coverage Region (PTZCR). In the PTZCR, a visual sensor needs a mechanical pan-tilt-zoom operation to cover an object. This mechanical operation can take seconds, so the sensor might not be able to adjust the camera in time to capture the visual data. In this paper, for the first time, we study this PTZ time-aware PTZ WVSN deployment problem. We formulate this PTZ time-aware PTZ WVSN deployment problem as an optimization problem where the objective is to minimize the total visual sensor deployment cost so that each area is either covered in the DCR or in the PTZCR while considering the PTZ time constraint. The proposed Time Aware Coverage Zone (TACZ) model successfully captures the PTZ visual sensor coverage in terms of camera focal range, angle span zone coverage and camera PTZ time. Then a novel heuristic, called Time Aware Deployment with PTZ camera (TADPTZ) algorithm, is proposed to solve the problem. From our computational experiments, we found out that TACZ model outperforms the existing M coverage model under all network scenarios. In addition, as compared to the optimal solutions, the TACZ model is scalable and adaptable to the different PTZ time requirements when deploying large PTZ WVSNs. PMID:28042829

  11. Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

    PubMed

    Gersner, R; Ekstein, D; Dhamne, S C; Schachter, S C; Rotenberg, A

    2015-11-01

    Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model

  12. Interaction of prenatal stress and morphine alters prolactin and seizure in rat pups.

    PubMed

    Saboory, Ehsan; Ebrahimi, Loghman; Roshan-Milani, Shiva; Hashemi, Paria

    2015-10-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylenetetrazol (PTZ) induced epileptic behaviors and prolactin blood level (PBL) was investigated in rat offspring. Pregnant Wistar rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, pregnant rats were placed in 25°C water on gestation days 17, 18 and 19 (GD17, GD18 and GD19) for 30 min. In the morphine/saline group, pregnant rats received morphine (10, 12 and 15 mg/kg, IP, on GD17, GD18 and GD19, respectively) or saline (1 ml, IP). In the morphine/saline-stressed group, the rats received morphine or saline and then exposed to stress. On postnatal days 6 and 15 (P6 and P15), blood samples were obtained and PBL was determined. At P15 and P25, the rest of the pups was injected with PTZ to induce seizure. Then, epileptic behaviors of each rat were observed individually. Latency of first convulsion decreased in control-morphine and stressed-saline groups while increased in stressed-morphine rats compared to control-saline group on P15 (P=0.04). Number of tonic-clonic seizures significantly increased in control-morphine and stressed-saline rats compared to control-saline group at P15 (P=0.02). PBL increased in stressed-saline, control-morphine and stress-morphine groups compared to control-saline rats. It can be concluded that prenatal exposure of rats to forced-swim stress and morphine changed their susceptibility to PTZ-induced seizure and PBL during infancy and prepubertal period. Co-administration of morphine attenuated effect of stress on epileptic behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. ACT-Vision: active collaborative tracking for multiple PTZ cameras

    NASA Astrophysics Data System (ADS)

    Broaddus, Christopher; Germano, Thomas; Vandervalk, Nicholas; Divakaran, Ajay; Wu, Shunguang; Sawhney, Harpreet

    2009-04-01

    We describe a novel scalable approach for the management of a large number of Pan-Tilt-Zoom (PTZ) cameras deployed outdoors for persistent tracking of humans and vehicles, without resorting to the large fields of view of associated static cameras. Our system, Active Collaborative Tracking - Vision (ACT-Vision), is essentially a real-time operating system that can control hundreds of PTZ cameras to ensure uninterrupted tracking of target objects while maintaining image quality and coverage of all targets using a minimal number of sensors. The system ensures the visibility of targets between PTZ cameras by using criteria such as distance from sensor and occlusion.

  14. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures.

    PubMed

    Bodda, Chiranjeevi; Tantra, Martesa; Mollajew, Rustam; Arunachalam, Jayamuruga P; Laccone, Franco A; Can, Karolina; Rosenberger, Albert; Mironov, Sergej L; Ehrenreich, Hannelore; Mannan, Ashraf U

    2013-07-01

    An intriguing finding about the gene encoding methyl-CpG binding protein 2 (MeCP2) is that the loss-of-function mutations cause Rett syndrome and duplication (gain-of-function) of MECP2 leads to another neurological disorder termed MECP2 duplication syndrome. To ensure proper neurodevelopment, a precise regulation of MeCP2 expression is critical, and any gain or loss of MeCP2 over a narrow threshold level may lead to postnatal neurological impairment. To evaluate MeCP2 dosage effects, we generated Mecp2(WT_EGFP) transgenic (TG) mouse in which MeCP2 (endogenous plus TG) is mildly overexpressed (approximately 1.5×). The TG MeCP2(WT_EGFP) fusion protein is functionally active, as cross breeding of these mice with Mecp2 knockout mice led to alleviation of major phenotypes in the null mutant mice, including premature lethality. To characterize the Mecp2(WT_EGFP) mouse model, we performed an extensive battery of behavioral tests, which revealed that these mice manifest increased aggressiveness and higher pentylenetetrazole (PTZ)-induced seizure propensity. Evaluation of neuronal parameters revealed a reduction in the number of tertiary branching sites and increased spine density in Mecp2(WT_EGFP) transgenic (TG) neurons. Treatment of TG neurons with epileptogenic compound-PTZ led to a marked increase in amplitude and frequency of calcium spikes. Based on our ex vivo and in vivo data, we conclude that epileptic seizures are manifested as the first symptom when MeCP2 is mildly overexpressed in mice. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Anti-convulsant action and amelioration of oxidative stress by Glycyrrhiza glabra root extract in pentylenetetrazole- induced seizure in albino rats

    PubMed Central

    Chowdhury, Bimalendu; Bhattamisra, Subrat K.; Das, Mangala C.

    2013-01-01

    Objectives: The aim of the present study was to evaluate the anti-convulsant potential of aqueous and ethanol e xtract of Glycyrrhiza glabra (AEGG and EEGG) and its action on markers of oxidant stress in albino rats. Materials and Methods: The aqueous and ethanol extract of Glycyrrhiza glabra was tested at three doses viz. 100, 200, and 400 mg/kg i.p. for its anti-convulsant activity using pentylenetetrazole (PTZ)-induced seizure in rat. The effect of EEGG (400 mg/kg, i.p.) on oxidative stress markers like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) of rat brain tissue homogenate was tested. Results: The onset of seizure was delayed (P < 0.01) by all the three doses of EEGG, but the duration of convulsion was reduced (P < 0.01) only in higher dose level (200 and 400 mg/ kg), whereas AEGG up to 400 mg/kg did not alter any of the parameters significantly. Biochemical analysis of rat brain tissue revealed that MDA was increased (P < 0.01), whereas SOD and CAT were decreased (P < 0.01) in PTZ-induced seizure rat, whereas pre-treatment with EEGG (400 mg/kg) decreased (P < 0.01) the MDA and increased (P < 0.01) both SOD and CAT, indicating attenuation of lipid peroxidation due to increase in antioxidant enzymes. Conclusion: The results demonstrated that EEGG poses anti-convulsant potential and ameliorates ROS induced neuronal damage in PTZ-induced seizure. PMID:23543836

  16. Comparison of the anticonvulsant potency of various diuretic drugs in the maximal electroshock-induced seizure threshold test in mice.

    PubMed

    Załuska, Katarzyna; Kondrat-Wróbel, Maria W; Łuszczki, Jarogniew J

    2018-05-01

    The coexistence of seizures and arterial hypertension requires an adequate and efficacious treatment involving both protection from seizures and reduction of high arterial blood pressure. Accumulating evidence indicates that some diuretic drugs (with a well-established position in the treatment of arterial hypertension) also possess anticonvulsant properties in various experimental models of epilepsy. The aim of this study was to assess the anticonvulsant potency of 6 commonly used diuretic drugs (i.e., amiloride, ethacrynic acid, furosemide, hydrochlorothiazide, indapamide, and spironolactone) in the maximal electroshock-induced seizure threshold (MEST) test in mice. Doses of the studied diuretics and their corresponding threshold increases were linearly related, allowing for the determination of doses which increase the threshold for electroconvulsions in drug-treated animals by 20% (TID20 values) over the threshold in control animals. Amiloride, hydrochlorothiazide and indapamide administered systemically (intraperitoneally - i.p.) increased the threshold for maximal electroconvulsions in mice, and the experimentally-derived TID20 values in the maximal electroshock seizure threshold test were 30.2 mg/kg for amiloride, 68.2 mg/kg for hydrochlorothiazide and 3.9 mg/kg for indapamide. In contrast, ethacrynic acid (up to 100 mg/kg), furosemide (up to 100 mg/kg) and spironolactone (up to 50 mg/kg) administered i.p. had no significant impact on the threshold for electroconvulsions in mice. The studied diuretics can be arranged with respect to their anticonvulsant potency in the MEST test as follows: indapamide > amiloride > hydrochlorothiazide. No anticonvulsant effects were observed for ethacrynic acid, furosemide or spironolactone in the MEST test in mice.

  17. Differential effects of NMDA antagonists microinjections into the nucleus reticularis pontis caudalis on seizures induced by pentylenetetrazol in the rat.

    PubMed

    Manjarrez, J; Alvarado, R; Camacho-Arroyo, I

    2001-07-01

    It has been shown that NMDA antagonists block the tonic but not the clonic component of seizures when they are injected in the oral region of the rat pontine reticular formation (PRF). The participation of the caudal PRF in the effects of NMDA antagonists upon the tonic and the clonic components of generalized seizures induced by pentylenetetrazol (PTZ) is unknown. The aim of the present study was to evaluate the effects of unilateral microinjections of competitive and non-competitive NMDA antagonists, 2-amino-7-phosphonoheptanoic acid (AP-7) and dizocilpine (MK-801), respectively, into the nucleus reticularis pontis caudalis of the rat PRF upon seizures induced by PTZ (70 mg/kg i.p.). MK-801 induced a dose-related decrease both in the incidence of generalized tonic-clonic seizures (GTCS) and in the presence of spikes in the EEG. MK-801 also increased GTCS latency. On the contrary, AP-7 did not have effects on GTCS. Interestingly, it induced ipsilateral circling behavior. These results suggest that in the caudal region of the rat PRF only non-competitive NMDA antagonists should block the generation of tonic and clonic components of generalized seizures.

  18. Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

    PubMed

    Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

    2015-08-06

    JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception.

    PubMed

    de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Falconi-Sobrinho, Luiz Luciano; Biagioni, Audrey Franceschi; Almada, Rafael Carvalho; Dos Anjos-Garcia, Tayllon; Bazaglia-de-Sousa, Guilherme; Khan, Asmat Ullah; Coimbra, Norberto Cysne

    2018-05-12

    Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0 μg/0.2 μL) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0 min) and subsequently at 10-min intervals until 130 min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130 min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. The antiepileptic and neuroprotective effect of the Buxus hyrcana Pojark hydroethanolic extract against the pentylentetrazol induced model of the seizures in the male rats.

    PubMed

    Azizi, Vahid; Allahyari, Farzin; Hosseini, Abdolkarim

    2018-03-06

    The genus Buxus grows up widespread in Europe and Western Asia. It is an important traditional plant that has been used in the treatment of many illnesses. In the present study, the effect of hydroethanolic extract of Buxus hyrcana Pojark (BHP) on the animal model of seizure was studied. In this experimental study, 42 male Wistar rats weighing 220-250 g were randomly selected and were divided into experimental and control groups (six rats per group). The experimental groups were treated by the intraperitoneal (i.p.) single injection of 150, 300, 450, 600 and 750 mg kg -1 of hydroalcoholic extracts of BHP. The control negative group received normal saline (0.9%) and the control positive group received phenobarbital (30 mg kg -1 , i.p.) pre-treatment. Thirty minutes after the treatments, the seizure behaviors were evaluated by the pentylenetetrazole (PTZ) (70 mg kg -1 , i.p.) challenge. In addition, after the experiment, the rats were put to death and their brains were removed for the histological study. The ANOVA demonstrated that compared to the control group, all the BHP doses delayed the initiation and duration of the tonic, colonic and tonic-colonic seizures and significantly reduced the tonic and colonic seizures (p < 0.001). Furthermore, the administration of all five doses of the extract significantly prevented the production of the dark neurons (p < 0.001) in different areas of the hippocampus compared to PTZ group. We can conclude that the BHP extract has beneficial effects for the prevention of the PTZ induced seizure.

  1. Rebound increase in seizure susceptibility but not isolation-induced calls after single administration of clonazepam and Ro 19-8022 in infant rats.

    PubMed

    Mikulecká, A; Mareš, P; Kubová, H

    2011-01-01

    The purpose of our study was to determine whether a single administration of anticonvulsant doses of two ligands of benzodiazepine receptors, clonazepam and Ro 19-8022, leads to development of rebound phenomena in immature 12-day-old rats. Three tests were used: pentylenetetrazole (PTZ)-induced seizures, isolation-induced ultrasonic vocalizations, and motor performance. Susceptibility to the convulsant effects of PTZ decreased 24 hours, but increased 48 hours, after clonazepam administration. Ultrasonic vocalizations were completely suppressed 30 minutes and 3 hours after clonazepam; a moderate inhibitory effect persisted even at 48 hours. Motor abilities were slightly compromised up to 3 hours. Similar effects of Ro 19-8022 on PTZ-induced seizures and ultrasonic vocalizations were observed 24 and 48 hours after administration; motor performance was not affected. Rebound proconvulsant effects followed different time courses after administration of the two benzodiazepine receptor ligands in developing animals. Anxiolytic-like effects of these drugs were still present at the time when animals exhibited rebound proconvulsant effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. 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.

  3. Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus.

    PubMed

    Mirski, Marek A; Ziai, Wendy C; Chiang, Jason; Hinich, Melvin; Sherman, David

    2009-01-01

    Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

  4. 22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.

    PubMed

    Wither, Robert G; Borlot, Felippe; MacDonald, Alex; Butcher, Nancy J; Chow, Eva W C; Bassett, Anne S; Andrade, Danielle M

    2017-06-01

    Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification. Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified. Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  5. Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.

    PubMed

    Shannon, Harlan E; Yang, Lijuan

    2004-01-01

    Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null mutant mice are more susceptible to kainate-induced seizures. In order to better understand the potential role of NPY in epileptogenesis, the present studies investigated the development of amygdala kindling, post-kindling seizure thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in 129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine- and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice either when kindling stimuli were presented once daily for at least 20 days, or, 12 times daily for 2 days. However, during kindling development, the NPY(-/-) mice had higher seizure severity scores and longer afterdischarge durations than the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower afterdischarge thresholds and longer afterdischarge durations than NPY (+/+) mice. Carbamazepine and levetiracetam increased the seizure thresholds of both NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for both kainate- and pilocarpine-induced seizures. The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis. In addition, a lack of NPY does not appear to confer drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in both wild type (WT) and NPY null mutant mice.

  6. Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures

    PubMed Central

    Baxendale, Sarah; Holdsworth, Celia J.; Meza Santoscoy, Paola L.; Harrison, Michael R. M.; Fox, James; Parkin, Caroline A.; Ingham, Philip W.; Cunliffe, Vincent T.

    2012-01-01

    SUMMARY The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities. PMID:22730455

  7. Evaluation of anticonvulsant and nootropic effect of ondansetron in mice.

    PubMed

    Jain, S; Agarwal, N B; Mediratta, P K; Sharma, K K

    2012-09-01

    The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.

  8. Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection.

    PubMed

    Golechha, Mahaveer; Sarangal, Vikas; Bhatia, Jagriti; Chaudhry, Uma; Saluja, Daman; Arya, Dharmveer Singh

    2014-12-01

    Oxidative stress and cognitive impairment are associated with PTZ-induced convulsions. Naringin is a bioflavonoid present in the grapefruit. It is a potent antioxidant, and we evaluated its effect on PTZ-induced convulsions. Rats were pretreated with normal saline, naringin (20, 40, and 80 mg/kg, i.p.), or diazepam (5mg/kg, i.p.) 30 min prior to the administration of PTZ. The administration of PTZ induced myoclonic jerks and generalized tonic-clonic seizures (GTSs). We observed that naringin significantly prolonged the induction of myoclonic jerks dose-dependently. Naringin (80 mg/kg, i.p.) pretreatment protected all rats, and this protective effect was annulled by the GABAA receptor antagonist, flumazenil. In addition, naringin reduced brain MDA and TNF-α levels and conserved GSH. The pretreatment also enhanced the performance of rats in the passive avoidance task. Our observations highlight the antioxidant, antiinflammatory, and anticonvulsant potential of naringin. Also, naringin modulates the GABAA receptor to produce anticonvulsant effects and to ameliorate cognitive impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

    PubMed

    Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline). The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

  10. Novel Vitamin K analogs suppress seizures in zebrafish and mouse models of epilepsy.

    PubMed

    Rahn, J J; Bestman, J E; Josey, B J; Inks, E S; Stackley, K D; Rogers, C E; Chou, C J; Chan, S S L

    2014-02-14

    Epilepsy is a debilitating disease affecting 1-2% of the world's population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit histone deacetylases (HDACs) using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, 2-benzamido-1 4-naphthoquinone (NQN1), significantly decreased swim activity to levels equal to that of valproic acid, 2-n-propylpentanoic acid (VPA). We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogs. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6Hz) and corneal-kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogs for the prevention of seizures and suggest the potential mechanism for this protection may lie in the

  11. DDT exposure of zebrafish embryos enhances seizure susceptibility: relationship to fetal p,p'-DDE burden and domoic acid exposure of California sea lions.

    PubMed

    Tiedeken, Jessica A; Ramsdell, John S

    2009-01-01

    California sea lions have a large body burden of organochlorine pesticides, and over the last decade they have also been subject to domoic acid poisoning. Domoic acid poisoning, previously recognized in adult animals, is now viewed as a major cause of prenatal mortality. The appearance of a chronic juvenile domoic acid disease in the sea lions, characterized by behavioral abnormalities and epilepsy, is consistent with early life poisoning and may be potentiated by organochlorine burden. We investigated the interactive effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility to domoic acid-induced seizures after completion of neurodevelopment. Embryos were exposed (6-30 hr postfertilization) to either o,p'-DDT or p,p'-DDE (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl sulfoxide solution. These larval (7 days postfertilization) fish were then exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic acid; resulting seizure behavior was monitored and analyzed for changes using cameras and behavioral tracking software. Embryonic exposure to DDTs enhanced PTZ seizures and caused distinct and increased seizure behaviors to domoic acid, most notably a type of head-shaking behavior. These studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals at completion of neurodevelopment with greater sensitivity to domoic acid-induced seizures. The body burden levels of p,p'-DDE are close to the range recently found in fetal California sea lions and suggest a potential interactive effect of p,p'-DDE embryonic poisoning and domoic acid toxicity.

  12. The cannabinoid anticonvulsant effect on pentylenetetrazole-induced seizure is potentiated by ultra-low dose naltrexone in mice.

    PubMed

    Bahremand, Arash; Shafaroodi, Hamed; Ghasemi, Mehdi; Nasrabady, Sara Ebrahimi; Gholizadeh, Shervin; Dehpour, Ahmad Reza

    2008-09-01

    Cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to G(i/o) proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. Thus, concerning the seizure modulating properties of both classes of receptors this study investigated whether the ultra-low dose opioid antagonist naltrexone influences cannabinoid anticonvulsant effects. The clonic seizure threshold was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the opioid receptor antagonist naltrexone and a combination of ACEA and naltrexone doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic injection of ultra-low doses of naltrexone (1pg/kg to 1ng/kg, i.p.) significantly potentiated the anticonvulsant effect of ACEA (1mg/kg, i.p.). Moreover, the very low dose of naltrexone (500pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (10 and 100microg/kg). A similar potentiation by naltrexone (500pg/kg) of anticonvulsant effects of non-effective dose of ACEA (1mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data indicate that the interaction between opioid and cannabinoid systems extends to ultra-low dose levels and ultra-low doses of opioid receptor antagonist in conjunction with very low doses of cannabinoids may provide a potent strategy to modulate seizure susceptibility.

  13. Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit.

    PubMed

    Cao, W; Shah, H P; Glushakov, A V; Mecca, A P; Shi, P; Sumners, C; Seubert, C N; Martynyuk, A E

    2009-12-01

    Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit. 3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit). Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801. The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.

  14. Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring.

    PubMed

    Hashemi, Paria; Roshan-Milani, Shiva; Saboory, Ehsan; Ebrahimi, Loghman; Soltanineghad, Maryam

    2016-11-01

    Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control-saline (CS), control-alcohol (CA), restraint stress-saline (RS), and restraint stress-alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2 g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas ® tube (twice/day, 1 h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45 mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Proconvulsant Actions of Intrahippocampal Botulinum Neurotoxin B in the Rat

    PubMed Central

    Bröer, Sonja; Zolkowska, Dorota; Gernert, Manuela; Rogawski, Michael A.

    2013-01-01

    Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target SNAP-25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 unit) by convection-enhanced delivery caused a reduction in myoclonic twitch and clonic seizure thresholds in response to intravenous PTZ beginning about 6 days after the infusion. Handling-evoked and spontaneous convulsive seizures were observed in many BoNT/B-treated animals but not in vehicle-treated controls. Spontaneous electrographic seizure discharges were recorded in the dentate gyrus of animals that received local BoNT/B infusion. In addition, there was an increased frequency of interictal epileptiform spikes and sharp waves at the same recording site. BoNT/B treated animals also exhibited tactile hyperresponsivity in comparison with vehicle-treated controls. This is the first demonstration that BoNT/B causes a delayed proconvulsant action when infused into the hippocampus. Local infusion of BoNT/B could be useful as a focal epilepsy model. PMID:23906638

  16. Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro.

    PubMed

    Zhang, Shuqin; Liang, Feng; Wang, Bing; Le, Yuan; Wang, Hua

    2014-03-01

    Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine.

    PubMed

    Payandemehr, Borna; Rahimian, Reza; Bahremand, Arash; Ebrahimi, Ali; Saadat, Seyedehpariya; Moghaddas, Peiman; Fadakar, Kaveh; Derakhshanian, Hoda; Dehpour, Ahmad Reza

    2013-06-13

    The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of l-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, l-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model.

    PubMed

    Dudra-Jastrzebska, Monika; Andres-Mach, Marta M; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanislaw J; Luszczki, Jarogniew J

    2009-11-01

    This study was designed so as to characterize the interactions between levetiracetam (LEV) and the conventional antiepileptic drugs (AEDs) clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice by use of type II isobolographic analysis. Adverse-effect profiles of the drugs in combination were determined and brain AED concentrations were measured. The combinations of VPA and ETS with LEV at the fixed-ratio of 1:2, CZP with LEV (1:20,000), and PB with LEV (1:20) were supra-additive (synergistic) in suppressing seizures. In contrast, VPA and ETS with LEV (1:1, 2:1, and 4:1), CZP with LEV (1:1000, 1:5000, and 1:10,000), and PB with LEV (1:1, 1:5, and 1:10) were additive. No adverse effects were observed. ETS significantly reduced brain LEV concentrations but no other pharmacokinetic changes were observed. The combinations of CZP with LEV (1:20,000); VPA and ETS with LEV (1:2); and PB with LEV (1:20) appear to be favorable combinations exerting supra-additive interactions in suppressing PTZ-induced seizures.

  19. Integration of multispectral face recognition and multi-PTZ camera automated surveillance for security applications

    NASA Astrophysics Data System (ADS)

    Chen, Chung-Hao; Yao, Yi; Chang, Hong; Koschan, Andreas; Abidi, Mongi

    2013-06-01

    Due to increasing security concerns, a complete security system should consist of two major components, a computer-based face-recognition system and a real-time automated video surveillance system. A computerbased face-recognition system can be used in gate access control for identity authentication. In recent studies, multispectral imaging and fusion of multispectral narrow-band images in the visible spectrum have been employed and proven to enhance the recognition performance over conventional broad-band images, especially when the illumination changes. Thus, we present an automated method that specifies the optimal spectral ranges under the given illumination. Experimental results verify the consistent performance of our algorithm via the observation that an identical set of spectral band images is selected under all tested conditions. Our discovery can be practically used for a new customized sensor design associated with given illuminations for an improved face recognition performance over conventional broad-band images. In addition, once a person is authorized to enter a restricted area, we still need to continuously monitor his/her activities for the sake of security. Because pantilt-zoom (PTZ) cameras are capable of covering a panoramic area and maintaining high resolution imagery for real-time behavior understanding, researches in automated surveillance systems with multiple PTZ cameras have become increasingly important. Most existing algorithms require the prior knowledge of intrinsic parameters of the PTZ camera to infer the relative positioning and orientation among multiple PTZ cameras. To overcome this limitation, we propose a novel mapping algorithm that derives the relative positioning and orientation between two PTZ cameras based on a unified polynomial model. This reduces the dependence on the knowledge of intrinsic parameters of PTZ camera and relative positions. Experimental results demonstrate that our proposed algorithm presents substantially

  20. Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit

    PubMed Central

    Cao, W; Shah, HP; Glushakov, AV; Mecca, AP; Shi, P; Sumners, C; Seubert, CN; Martynyuk, AE

    2009-01-01

    Background and purpose: Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit. Experimental approach: 3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit). Key results: Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801. Conclusion and implications: The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders. PMID:20050189

  1. Dcx Re-expression Reduces Subcortical Band Heterotopia and Seizure Threshold in an Animal Model of Neuronal Migration Disorder

    PubMed Central

    Manent, Jean-Bernard; Wang, Yu; Chang, YoonJeung; Paramasivam, Murugan; LoTurco, Joseph J

    2009-01-01

    Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration, and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. PMID:19098909

  2. Calibration of a dual-PTZ camera system for stereo vision

    NASA Astrophysics Data System (ADS)

    Chang, Yau-Zen; Hou, Jung-Fu; Tsao, Yi Hsiang; Lee, Shih-Tseng

    2010-08-01

    In this paper, we propose a calibration process for the intrinsic and extrinsic parameters of dual-PTZ camera systems. The calibration is based on a complete definition of six coordinate systems fixed at the image planes, and the pan and tilt rotation axes of the cameras. Misalignments between estimated and ideal coordinates of image corners are formed into cost values to be solved by the Nelder-Mead simplex optimization method. Experimental results show that the system is able to obtain 3D coordinates of objects with a consistent accuracy of 1 mm when the distance between the dual-PTZ camera set and the objects are from 0.9 to 1.1 meters.

  3. Dynamics of absence seizures

    NASA Astrophysics Data System (ADS)

    Deeba, Farah; Sanz-Leon, Paula; Robinson, Peter

    A neural field model of the corticothalamic system is used to investigate the dynamics of absence seizures in the presence of temporally varying connection strength between the cerebral cortex and thalamus. Variation of connection strength from cortex to thalamus drives the system into seizure once a threshold is passed and a supercritical Hopf bifurcation occurs. The dynamics and spectral characteristics of the resulting seizures are explored as functions of maximum connection strength, time above threshold, and ramp rate. The results enable spectral and temporal characteristics of seizures to be related to underlying physiological variations via nonlinear dynamics and neural field theory. Notably, this analysis adds to neural field modeling of a wide variety of brain activity phenomena and measurements in recent years. Australian Research Council Grants FL1401000225 and CE140100007.

  4. Detection of nonlinear interactions of EEG alpha waves in the brain by a new coherence measure and its application to epilepsy and anti-epileptic drug therapy.

    PubMed

    Sherman, David; Zhang, Ning; Garg, Shikha; Thakor, Nitish V; Mirski, Marek A; White, Mirinda Anderson; Hinich, Melvin J

    2011-04-01

    EEG and field potential rhythms established in the cortex and thalamus may accommodate the propagation of seizures. This article describes the interaction between thalamus and cortex during pentylenetetrazol (PTZ) seizures in rats with and without prior treatment with ethosuximide (ESM), a well-known antiepileptic drug (AED) that raises the threshold for seizures, was given before PTZ. The AED was given before PTZ convulsant administration. We track this thalamo-cortical association with a novel measure we have called the cross-bicoherence gain, or BISCOH. This quantity allows us to measure the spectral coherence in a purely higher order spectralmethodology. BISCOH is able to track the formation of nonlinearities at specific frequencies in the recorded EEG. BISCOH showed a strong increase in low alpha wave harmonic generationat 10 and 12.5 Hz after ESM treatment (p < 0.02 and p < 0.007, respectively). Conventional coherence failed to show distinctive and significant changes in thalamo-cortical coupling after ESM treatment at those frequencies and instead showed changes at 5 Hz. This rise in cortical rhythms is evidence of harmonic generation or new frequency formation in the thalamo-cortical system withAED therapy. BISCOH could become a powerful tool in unraveling changes in coherence due to neuroelectric modulation resulting from drug treatment or electrical stimulation.

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

    PubMed

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

    2011-04-01

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

  6. Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

    PubMed Central

    Sayyah, M.; Khodaparast, A.; Yazdi, A.; Sardari, S.

    2011-01-01

    Background and purpose of the study Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. Methods The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. Results Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. Major conclusion The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent. PMID:22615673

  7. Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

    PubMed

    Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

    2017-05-01

    Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

  8. Effects of cell phone radiation on lipid peroxidation, glutathione and nitric oxide levels in mouse brain during epileptic seizure.

    PubMed

    Esmekaya, Meric Arda; Tuysuz, Mehmet Zahid; Tomruk, Arın; Canseven, Ayse G; Yücel, Engin; Aktuna, Zuhal; Keskil, Semih; Seyhan, Nesrin

    2016-09-01

    The objective of the this study was to evaluate the effects of cellular phone radiation on oxidative stress parameters and oxide levels in mouse brain during pentylenetetrazole (PTZ) induced epileptic seizure. Eight weeks old mice were used in the study. Animals were distributed in the following groups: Group I: Control group treated with PTZ, Group II: 15min cellular phone radiation+PTZ treatment+30min cellular phone radiation, Group III: 30min cellular phone radiation+PTZ treatment+30min cellular phone radiation. The RF radiation was produced by a 900MHz cellular phone. Lipid peroxidation, which is the indicator of oxidative stress was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARS). The glutathione (GSH) levels were determined by the Ellman method. Tissue total nitric oxide (NOx) levels were obtained using the Griess assay. Lipid peroxidation and NOx levels of brain tissue increased significantly in group II and III compared to group I. On the contrary, GSH levels were significantly lower in group II and III than group I. However, no statistically significant alterations in any of the endpoints were noted between group II and Group III. Overall, the experimental findings demonstrated that cellular phone radiation may increase the oxidative damage and NOx level during epileptic activity in mouse brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.

    PubMed

    Świąder, Mariusz J; Paruszewski, Ryszard; Łuszczki, Jarogniew J

    2016-04-01

    The aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e., nicotinic acid benzylamide (Nic-BZA), picolinic acid 2-fluoro-benzylamide (2F-Pic-BZA), picolinic acid benzylamide (Pic-BZA), (RS)-methyl-alanine-benzylamide (Me-Ala-BZA), isonicotinic acid benzylamide (Iso-Nic-BZA), and (R)-N-methyl-proline-benzylamide (Me-Pro-BZA)] in the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions (seizure activity) were produced in mice by means of a current (sine-wave, 50Hz, 500V, strength from 4 to 18mA, ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA administered systemically (ip) in a dose-dependent manner increase the threshold for maximal electroconvulsions in mice. Linear regression analysis of Nic-BZA, 2F-Pic-BZA, Pic-BZA, MeAla-BZA, IsoNic-BZA, and Me-Pro-BZA doses and their corresponding threshold increases allowed determining threshold increasing doses by 20% (TID20 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 values in the MEST test for Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA were 7.45mg/kg, 7.72mg/kg, 8.74mg/kg, 15.11mg/kg, 21.95mg/kg and 28.06mg/kg, respectively. The studied benzylamide derivatives can be arranged with respect to their anticonvulsant potency in the MEST test as follows: Nic-BZA>2F-Pic-BZA>Pic-BZA>Me-Ala-BZA>Iso-Nic-BZA>Me-Pro-BZA. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Transcranial focal stimulation via concentric ring electrodes reduced power of pentylenetetrazole-induced seizure activity in rat electroencephalogram.

    PubMed

    Makeyev, Oleksandr; Liu, Xiang; Koka, Kanthaiah; Kay, Steven M; Besio, Walter G

    2011-01-01

    As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. In this study we applied noninvasive transcranial focal stimulation (TFS) via concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ) to assess the effect of TFS on the electrographic activity. Grand average power spectral densities were calculated to compare different stages of seizure development. They showed a significant difference between the TFS treated group and the control group. In case of the TFS treated group, after TFS, the power spectral density was reduced further towards a pre-seizure "baseline" than it was for the control group. The difference is the most drastic in delta, theta and alpha frequency bands. Application of general likelihood ratio test showed that TFS significantly (p<0.001) reduced the power of electrographic seizure activity in the TFS treated group compared to controls in more than 86% of the cases. These results suggest that TFS may have an anticonvulsant effect.

  11. Phenomenal enhancement of optical nonlinearity in PTZ-I based ZnS/ZnSe nanocomposites

    NASA Astrophysics Data System (ADS)

    Divyasree, M. C.; Shiju, E.; Vijisha, M. V.; Ramesan, M. T.; Chandrasekharan, K.

    2018-05-01

    The enhanced nonlinear optical properties of phenothiazine-iodine (PTZ-I) charge transfer complex (CTC) on composite formation with ZnS/ZnSe nanostructures are reported. The interaction between the components was confirmed by the FTIR spectra. Structural and morphological changes on nanocomposite formation were analyzed by scanning electron microscopy and X-ray diffraction spectra. The absorption and emission features of both the nanocomposites and their constituent components were studied. Nonlinear optical properties of all the samples in nanosecond regime were investigated by the Z-scan technique using Nd: YAG laser with 532 nm wavelength and 7 ns pulse width. The optical nonlinearity of PTZ-I CTC was found to be improved considerably on composite formation and the new systems can be proposed as excellent candidates for photonic devices. Enhanced optical nonlinearity of the composites could be attributed to charge/energy transfer mechanism between PTZ-I CTC and the nanostructures.

  12. Controlled-release oxycodone-induced seizures.

    PubMed

    Klein, Moti; Rudich, Zvia; Gurevich, Boris; Lifshitz, Matityahu; Brill, Silviu; Lottan, Michael; Weksler, Natan

    2005-11-01

    The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

  13. Effect of the Leaf Essential Oil from Cinnamosma madagascariensis Danguy on Pentylenetetrazol-induced Seizure in Rats.

    PubMed

    Rakotosaona, Rianasoambolanoro; Randrianarivo, Emmanuel; Rasoanaivo, Philippe; Nicoletti, Marcello; Benelli, Giovanni; Maggi, Filippo

    2017-10-01

    In the Malagasy traditional practices, the smoke from burning leaves of Cinnamosma madagascariensis Danguy is inhaled to treat brain disorders such as dementia, epilepsy, and headache. In the present work, we have evaluated the in vivo anticonvulsant effects of the essential oil from leaves of C. madagascariensis (CMEO). CMEO was isolated by steam distillation. The anticonvulsant activity of CMEO (0.4 and 0.8 ml/kg bw) administered subcutaneously was evaluated on pentylenetetrazol (PTZ)-induced seizures in Wistar rats; diazepam was used as positive control. Linalool, limonene, and myrcene were the major CMEO constituents. At the dose of 0.8 ml/kg, CMEO completely arrested the PTZ-induced convulsions with moderate sedative effects. The traditional anticonvulsant use of C. madagascariensis was confirmed allowing us to candidate molecules from CMEO as potential drugs to treat convulsions associated with strong agitation. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  14. Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster.

    PubMed

    Soares, Deividi C S; Portela, José L R; Roos, Daniel H; Rodrigues, Nathane R; Gomes, Karen K; Macedo, Giulianna E; Posser, Thais; Franco, Jeferson L; Hassan, Waseem; Puntel, Robson L

    2018-05-01

    PTZ is a convulsive agent that acts via selective blockage of GABA A receptor channels, whereas 4-AP leads to a convulsive episode via blockage of K + channels. However, the mechanism(s) by which pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) cause toxicity to Drosophila melanogaster needs to be properly explored, once it will help in establishing an alternative model for development of proper therapeutic strategies and also to counteract the changes associated with exposure to both epileptic drugs. For the purpose, we investigated the effects of exposure (48 h) to PTZ (60 mM) and/or 4-AP (20 mM) on survival, locomotor performance, and biochemical markers in the body and/or head of flies. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open field test as compared to non-treated flies. 4-AP also caused a significant increase in the reactive species (RS) and protein carbonyl (PC) content in the body and head. Also a significant increase in catalase and acetylcholinesterase (AChE) activities was observed in the body. In the same vein, PTZ exposure resulted in a significant increase in RS, thiobarbituric acid reactive substances (TBARS), PC content, and catalase activity in the body. PTZ exposure also caused a significant increase in AChE activity both in body and head. It is important to note that PTZ-treated flies also down-regulated the NRF 2 expression. Moreover, both 4AP- and PTZ-fed flies presented a significant decrease in MTT reduction, down-regulation, and inhibition of SOD in body. However, SOD was significantly more active in the head of both 4-AP and PTZ-treated flies. Our findings provide evidence regarding the toxicological potential of both PTZ and/or 4-AP to flies. This model will help in decoding the underlying toxicological mechanisms of the stated drugs. It will also help to properly investigate the therapeutic strategies and to counteract the drastic changes associated with both epileptogenic drugs.

  15. Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

    PubMed

    Rathor, Naveen; Arora, Tarun; Manocha, Sachin; Patil, Amol N; Mediratta, Pramod K; Sharma, Krishna K

    2014-03-01

    The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity. © 2013 Royal Pharmaceutical Society.

  16. Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice.

    PubMed

    Faghihi, Nastaran; Mohammadi, Mohammad Taghi

    2017-06-01

    Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

  17. Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

    PubMed

    Gupta, N; Bhargava, V K; Pandhi, P

    2000-05-01

    The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

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

    PubMed

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

    2018-05-01

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

  19. The effect of various opiate receptor agonists on the seizure threshold in the rat. Is dynorphin an endogenous anticonvulsant?

    PubMed

    Przewłocka, B; Stala, L; Lasoń, W; Przewłocki, R

    1983-01-01

    The effects of various opiate receptor agonists on the seizure threshold after an intravenous infusion of pentylenetetrazol were investigated in rats. The mu- and epsilon-receptor agonists, morphine (20-40 micrograms) and beta-endorphin (5-10 micrograms) show proconvulsant properties towards clonic and tonic seizures. The delta-receptor agonist (D-Ala2,D-Leu5-enkephalin, DADL 5-40 micrograms) and alpha-neoendorphin (20-40 micrograms) show pro- and anticonvulsant properties towards clonic and tonic seizures, respectively. Anticonvulsant properties of DADL are possibly due to its action on the spinal cord, since after the intrathecal injection this effect is still observed. Similarities between DADL and alpha-neoendorphin suggest that they may act through the same receptor. The kappa-receptor agonist dynorphin A (5-20 micrograms) and its degradation-resistant analogue D-Arg-dynorphin1-13 (10 micrograms) show significant anticonvulsant properties. Our present results suggest that the kappa-receptor agonist dynorphin may act physiologically as an endogenous anticonvulsant, in contrast to other opioid peptides.

  20. Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats

    PubMed Central

    Carter, Angela N.; Born, Heather A.; Levine, Amber T.; Dao, An T.; Zhao, Amanda J.; Lee, Wai L.

    2017-01-01

    Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology. PMID:28612047

  1. 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.

  2. Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats.

    PubMed

    A, Mahmoudi; M B, Shojaeifard; S, Nematollahii; S M J, Mortazavi; A R, Mehdizadeh

    2018-06-01

    Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi "off"), sham 2 (distilled water + Wi-Fi "off"), sham 3 (distilled water + Wi-Fi "on"), and intervention group 2 (PTZ + Wi-Fi "on"). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and " time to show convulsion with score 6 " were not statistically significant (P>0.05). Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy.

  3. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    PubMed

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  4. Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model

    PubMed Central

    Choo, Brandon Kar Meng; Kundap, Uday P.; Kumari, Yatinesh; Hue, Seow-Mun; Othman, Iekhsan; Shaikh, Mohd Farooq

    2018-01-01

    Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish. PMID:29527169

  5. Threshold to N-methyl-D-aspartate-induced seizures in mice undergoing chronic nutritional magnesium deprivation is lowered in a way partly responsive to acute magnesium and antioxidant administrations.

    PubMed

    Maurois, Pierre; Pages, Nicole; Bac, Pierre; German-Fattal, Michèle; Agnani, Geneviève; Delplanque, Bernadette; Durlach, Jean; Poupaert, Jacques; Vamecq, Joseph

    2009-02-01

    Magnesium deficiency may be induced by a diet impoverished in magnesium. This nutritional deficit promotes chronic inflammatory and oxidative stresses, hyperexcitability and, in mice, susceptibility to audiogenic seizures. Potentiation by low-magnesium concentrations of the opening of N-methyl-D-aspartate (NMDA) receptor/calcium channel in in vitro and ex vivo studies, and responsiveness to magnesium of in vivo brain injury states are now well established. By contrast, little or no specific attention has been, however, paid to the in vivo NMDA receptor function/excitability in magnesium deficiency. The present work reports for the first time that, in mice undergoing chronic nutritional deprivation in magnesium (35 v. 930 parts per million for 27 d in OF1 mice), NMDA-induced seizure threshold is significantly decreased (38 % of normal values). The attenuation in the drop of NMDA seizure threshold (percentage of reversal) was 58 and 20 % upon acute intraperitoneal administrations of magnesium chloride hexahydrate (28 mg magnesium/kg) and the antioxidant ebselen (20 mg/kg), respectively. In nutritionally magnesium-deprived animals, audiogenic seizures are completely prevented by these compound doses. Taken as a whole, our data emphasise that chronic magnesium deprivation in mice is a nutritional in vivo model for a lowered NMDA receptor activation threshold. This nutritional model responds remarkably to acute magnesium supply and moderately to acute antioxidant administration.

  6. Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures

    PubMed Central

    Kaminski, Rafal M.; Shippenberg, Toni S.; Witkin, Jeffrey M.; Rocha, Beatriz A.

    2005-01-01

    Norepinephrine (NE) has been reported to modulate neuronal excitability and act as endogenous anticonvulsant. In the present study we used NE transporter knock-out mice (NET-KO), which are characterized by high levels of extracellular NE, to investigate the role of endogenous NE in seizure susceptibility. Seizure thresholds for cocaine (i.p.), pentylenetetrazol (i.v.) and kainic acid (i.v.) were compared in NET-KO, heterozygous (NET-HT) and wild type (NET-WT) female mice. The dose-response curve for cocaine-induced convulsions was significantly shifted to the right in NET-KO mice, indicating higher seizure thresholds. The threshold doses of pentylenetetrazol that induced clonic and tonic seizures were also significantly higher in NET-KO when compared to NET-WT mice. Similarly, NET-KO mice displayed higher resistance to convulsions engendered by kainic acid. For all drugs tested, the response of NET-HT mice was always intermediate. These data provide further support for a role of endogenous NE in the control of seizure susceptibility. PMID:15911120

  7. Anticonvulsant activity of DNS II fraction in the acute seizure models.

    PubMed

    Raza, Muhammad Liaquat; Zeeshan, Mohammad; Ahmad, Manzoor; Shaheen, Farzana; Simjee, Shabana U

    2010-04-21

    Delphinium nordhagenii belongs to family Ranunculaceae, it is widely found in tropical areas of Pakistan. Other species of Delphinium are reported as anticonvulsant and are traditionally used in the treatment of epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii was subjected to bioassay-guided fractionation and the most active fraction, i.e. DNS II acetone was chosen for further testing in the acute seizure models of epilepsy to study the antiepileptic potential in male mice. Different doses (60, 65 and 70mg/kg, i.p.) of DNS II acetone fraction of Delphinium nordhagenii was administered 30min prior the chemoconvulsant's injection in the male mice. Convulsive doses of chemoconvulsants (pentylenetetrazole 90mg/kg, s.c. and picrotoxin 3.15mg/kg, s.c.) were used. The mice were observed 45-90min for the presence of seizures. Moreover, four different doses of DNS II (60, 65, 70 and 100mg/kg, i.p.) were tested in the MES test. The DNS II acetone fraction of Delphinium nordhagenii has exhibited the anticonvulsant actions by preventing the seizures against PTZ- and picrotoxin-induced seizure as well as 100% seizure protection in MES test. The results are comparable with standard AEDs (diazepam 7.5mg/kg, i.p. and phenytoin 20mg/kg, i.p.). These findings suggest that the Delphinium nordhagenii possesses the anticonvulsant activity. Further analysis is needed to confirm the structure and target the extended activity profile. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.

    PubMed

    Albertson, T E; Walby, W F

    1988-01-01

    The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and supranthreshold (400 microA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.

  9. [The ability of NMDA glutamate receptor blockers to prevent a pentylenetetrazole kindling in mice and morphological changes in the hippocampus].

    PubMed

    Vasil'ev, D S; Tumanova, N L; Lavrent'eva, V V; Starshinova, L A; Zhabko, E P; Lukomskaia, N Ia; Zhuravin, I A; Magazanik, L G

    2013-09-01

    We investigated in mice the relationship between convulsions and morphological changes of hippocampal neurons that arise in the development of pentylentetrazol (PTZ)-induced kindling. The kindling was caused by of 35 mg/kg PTZ i.p. 3 times a week for a month. By the end of this period, 70% of the mice responded to the injections of PTZ with pronounced clonic or tonic-clonic seizures. The hippocampal slices (layer stratum pyramidale, CA1, Nissl's stain) obtained from mice exhibiting seizures revealed a large number of modified cells (24.7 +/- 2.1%). These hyperchromic neurons have been characterized by a decrease of the size cell body, there was a loss of turgor, the body cells shrink, and dendritic spines curl. Part of the cells took the shape of elongated neck. Such modified the dark type of neurons contained only 2.3 +/- 2.3% in the hippocampus of intact mice, and 30% of the mice resistant to the convulsive action ofPTZ during the period of observation. The expression of protein NeuN (Fox3) in hippocamal neuron including the hyperchromic once suggests that neurons on the whole did not die and were relatively viable. Preventive administration of NMDA receptor blockers (0.5 mg/kg, memantine 0.1 mg/kg or IEM-1958 1 mg/kg, s.c.) 30 minutes prior to PTZ reduced the proportion of mice which exhibited PTZ kindling from 70% to 40%. The modified neurons were observed in which the PTZ kindling due to the blocker presence did not develop, i.e., the same as in intact mice. Contrary, 24.0 +/- 5.6% of hyperchromic neurons were found in the hippocampal slices from mice manifested seizures, despite the co-administration of NMDA blockers. The data obtained indicate that modified neurons are the result of seizures suffered by the animals in the course of PTZ kindling, and that the blockade of NMDA glutamate receptors can suppress manifestations of seizures and the accompanying morphological changes of hippocampal neurons.

  10. Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.

    PubMed

    Emoto, Miho C; Yamato, Mayumi; Sato-Akaba, Hideo; Yamada, Ken-ichi; Fujii, Hirotada G

    2015-11-03

    Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Epileptogenic effects of G protein-coupled estrogen receptor 1 in the rat pentylenetetrazole kindling model of epilepsy.

    PubMed

    Kurt, Akif Hakan; Bosnak, Mehmet; Inan, Salim Yalcın; Celik, Ahmet; Uremis, Muhammed Mehdi

    2016-02-01

    G protein-coupled estrogen receptor 1 (GPER-1) has been demonstrated in several parts of the brain and may play an important role in estrogen downstream signaling pathway. However, the effects of this receptor on epileptic seizure are not clearly known. Therefore, the effects of GPER-1 agonist, G-1, GPER-1 antagonist, G-15 and the main estrogenic hormone, 17β-estradiol were investigated on seizures and brain tissue oxidative damages induced by pentylenetetrazole (PTZ) in rats. In this study, 30 adult male Wistar albino rats were used. Due to intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35mg/kg) which was repeated 12 times every 48h, chemical kindling occurred and kindling seizure was recorded for 30min. The rats were injected with 17β-estradiol (5μg/kg, ip) or G-1 (5μg/kg, ip), G-15 (5μg/kg, ip), Saline, Ethanol and Dimethyl sulfoxide (DMSO) 30min before each dose of PTZ. Observed seizures were classified between the phase 0-5. Thirty minutes later when the last 12. PTZ administration, all rats were sacrificed and the brain cortex, hippocampus sections were removed and the tissue superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) levels on these tissues were studied. GPER1 agonist, G-1 and estrogenic hormone, 17β-estradiol significantly increased the development of PTZ kindling the seizures. However, GPER1 antagonist, G-15 did not change the development of PTZ kindling the seizures. In the cortex and hippocampus homogenates, the NO levels after G-1 administration had significantly increased (p<0.05) compared to the PTZ groups but SOD activities and MDA levels demonstrated no difference between the groups. This is the first study that explores that GPER-1 receptors have epileptogenic effect on PTZ-induced kindling rat. GPER1 may mediate the epileptogenic effect of estrogens by changing the oxidative or anti-oxidative parameters in the brain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences

  12. Localizing seizure-onset zones in presurgical evaluation of drug-resistant epilepsy by electroencephalography/fMRI: effectiveness of alternative thresholding strategies.

    PubMed

    Hauf, M; Jann, K; Schindler, K; Scheidegger, O; Meyer, K; Rummel, C; Mariani, L; Koenig, T; Wiest, R

    2012-10-01

    Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy. Sixteen patients with focal epilepsy were examined by using simultaneous 92-channel EEG and BOLD fMRI. The temporal fluctuation of epileptiform signals on the EEG was extracted by independent component analysis to predict the hemodynamic responses to the IEDs. We applied 3 different threshold criteria to detect hemodynamic responses within the SOZ: 1) PA, 2) a fixed threshold at P < .05 corrected for multiple comparison (FWE), and 3) FAV (4000 ± 200 activated voxels within the brain). PA identified the SOZ in 9 of 16 patients; FWE resulted in concordant BOLD signal correlates in 11 of 16, and FAV in 13 of 16 patients. Hemodynamic responses were detected within the resected areas in 5 (PA), 6 (FWE), and 8 (FAV) of 10 patients who remained seizure-free after surgery. EEG/fMRI is a noninvasive tool for the presurgical work-up of patients with epilepsy, which can be performed during seizure-free periods and is complementary to the ictal electroclinical assessment. Our findings suggest that the effectiveness of EEG/fMRI in delineating the SOZ may be further improved by the additional use of alternative analysis strategies such as FAV.

  13. Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction.

    PubMed

    Spellman, Timothy; Peterchev, Angel V; Lisanby, Sarah H

    2009-07-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These

  14. Pregabalin monotherapy in patients with partial-onset seizures

    PubMed Central

    Kwan, Patrick; Fakhoury, Toufic; Pitman, Verne; DuBrava, Sarah; Knapp, Lloyd; Yurkewicz, Lorraine

    2014-01-01

    Objective: To assess pregabalin monotherapy for partial-onset seizures using a historical-controlled conversion-to-monotherapy design. Methods: Adults with inadequately controlled partial-onset seizures while receiving 1 or 2 antiepileptic drugs during an 8-week prospective baseline were randomized to double-blind monotherapy with pregabalin 600 or 150 mg/d (4:1) for 20 weeks (8-week conversion and 12-week monotherapy period). The primary endpoint was the seizure-related exit rate for pregabalin 600 mg/d, based on discontinuations due to predefined criteria. Efficacy was declared if the upper limit of the 95% confidence interval for the exit rate was below a historical-control threshold of 74%, with stepwise evaluation using a threshold of 68%. Results: The trial was stopped early for positive efficacy after an interim analysis in 125 patients. The full study population included 161 patients, with 148 evaluable for efficacy. The mean time since epilepsy diagnosis was 14 years. Overall, 54.3% (600 mg/d) and 46.9% (150 mg/d) of patients completed 20 weeks of double-blind treatment. Seizure-related exit rate in the 600 mg/d group (27.5%; 95% confidence interval, 17.8%–37.2%) was significantly below the 74% and 68% thresholds (p < 0.001 for both). Eight patients on 600 mg/d and 2 on 150 mg/d were seizure-free throughout pregabalin monotherapy. Pregabalin's overall safety profile was consistent with prior trials. Conclusions: Pregabalin monotherapy was safe and efficacious for patients with inadequately controlled partial-onset seizures. Classification of evidence: This study provides Class III evidence that patients with inadequately controlled partial-onset seizures switched to pregabalin monotherapy have fewer seizure-related exit events compared with historical controls switched to pseudo-placebo monotherapy. PMID:24415567

  15. An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold

    PubMed Central

    Chiavegato, Angela; Zonta, Micaela; Cammarota, Mario; Brondi, Marco; Vetri, Francesco; Uva, Laura; Pozzan, Tullio; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

    2010-01-01

    Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures. PMID:20405049

  16. Focal Electrically Administered Seizure Therapy (FEAST): A novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction

    PubMed Central

    Spellman, Timothy; Peterchev, Angel V.; Lisanby, Sarah H.

    2009-01-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified via scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings

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

    PubMed Central

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

    2016-01-01

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

  18. Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.

    PubMed

    Simão, Fabrício; Habekost Oliveira, Victória; Lahorgue Nunes, Magda

    2016-10-01

    Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. © 2016 Wiley Periodicals, Inc.

  19. Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

    PubMed

    Mathieson, Sean R; Livingstone, Vicki; Low, Evonne; Pressler, Ronit; Rennie, Janet M; Boylan, Geraldine B

    2016-10-01

    Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Post-phenobarbital seizures showed significantly lower amplitude (p<0.001) and involved fewer EEG channels at the peak of seizure (p<0.05). No other features or SDA detection rates showed a statistical difference. These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

    PubMed

    Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

    2015-08-01

    Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

  1. Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats

    PubMed Central

    A., Mahmoudi; M.B., Shojaeifard; S., Nematollahii; S.M.J., Mortazavi; A.R., Mehdizadeh

    2018-01-01

    Background: Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. Materials and Methods: 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi “off”), sham 2 (distilled water + Wi-Fi “off”), sham 3 (distilled water + Wi-Fi “on”), and intervention group 2 (PTZ + Wi-Fi “on”). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Results: Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and “ time to show convulsion with score 6 ” were not statistically significant (P>0.05). Conclusion: Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy. PMID:29951445

  2. [The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose].

    PubMed

    Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

    The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Publicado por Elsevier Editora Ltda.

  3. The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose.

    PubMed

    Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

    The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Published by Elsevier Editora Ltda.

  4. Seizure Suppression by High Temperature via cAMP Modulation in Drosophila.

    PubMed

    Saras, Arunesh; Tanouye, Mark A

    2016-10-13

    Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (para bss1 , eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration. Copyright © 2016 Saras and Tanouye.

  5. Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

    PubMed

    Rahmati, Batool; Khalili, Mohsen; Roghani, Mehrdad; Ahghari, Parisa

    2013-06-21

    Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Evaluation of possible antioxidant and anticonvulsant effects of the ethyl acetate fraction from Platonia insignis Mart. (Bacuri) on epilepsy models.

    PubMed

    Júnior, Joaquim Soares da Costa; de Almeida, Antonia Amanda C; Tomé, Adriana da Rocha; Citó, Antonia Maria das Graças Lopes; Saffi, Jenifer; de Freitas, Rivelilson Mendes

    2011-12-01

    The aim of present study was to examine the effects of the ethyl acetate fraction (EAF) from Platonia insignis on lipid peroxidation level, nitrite formation, and superoxide dismutase and catalase activities in rat striatum prior to pilocarpine-induced seizures as well as to explore its anticonvulsant activity in adult rats prior to pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures. Wistar rats were treated with vehicle, atropine (25mg/kg), EAF (0.1, 1, and 10mg/kg), pilocarpine (400mg/kg, P400 group), PTZ (60 mg/kg, PTZ group), PIC (8 mg/kg, PIC group), atropine+P400, EAF+P400, EAF+PTZ, or EAF+PIC. Significant decreases in number of crossings and rearings were observed in the P400 group. The EAF 10+P400 group also had significant increases in these parameters. In addition, in rats treated with P400, there were significant increases in lipid peroxidation and nitrite levels; however, there were no alterations in SOD and catalase activities. In the EAF 10+P400 group, lipid peroxidation and nitrite levels significantly decreased and SOD and catalase activities significantly increased after pilocarpine-induced seizures. Additionally, effects of the EAF were evaluated in PTZ and PIC models. EAF did not increase the latency to development of convulsions induced with PTZ and PIC at the doses tested. Our findings strongly support the hypothesis that EAF does not have anticonvulsant activity in the different models of epilepsy studied. Our results indicate that in the in vivo model of pilocarpine-induced seizures, EAF has antioxidant activity, but not anticonvulsant properties at the doses tested. Copyright © 2011. Published by Elsevier Inc.

  7. Anticonvulsant Effect of the Aqueous Extract and Essential Oil of Carum Carvi L. Seeds in a Pentylenetetrazol Model of Seizure in Mice

    PubMed Central

    Showraki, Alireza; Emamghoreishi, Masoumeh; Oftadegan, Somayeh

    2016-01-01

    Background: Carum carvi L. (caraway), known as black zeera in Iran, has been indicated for the treatment of epilepsy in Iranian folk medicine. This study evaluated whether the aqueous extract and essential oil of caraway seeds have anticonvulsant effects in mice. Methods: The anticonvulsant effects of the aqueous extract (200, 400, 800, 1600, and 3200 mg/kg, i.p.) and essential oil (25, 50, 100, 200, and 400 mg/kg, i.p.) of caraway were assessed using pentylenetetrazol (PTZ; 95 mg/kg i.p.) induced convulsions. Diazepam (3 mg/kg) was used as positive control. The latency time before the onset of myoclonic, clonic, and tonic convulsions and the percentage of mortality were recorded. In addition, the effect of caraway on neuromuscular coordination was evaluated using the rotarod performance test. Results: The extract and essential oil dose-dependently increased the latency time to the onset of myoclonic (ED50, 1257 and 62.2 mg/kg, respectively) and clonic (ED50, 929 and 42.3 mg/kg, respectively) seizures. The extract and essential oil of caraway prevented the animals from tonic seizure with ED50s of 2142.4 and 97.6 mg/kg, respectively. The extract and essential oil of caraway protected 28.6 and 71.4% of the animals from PTZ-induced death, respectively, and had no significant effect on neuromuscular coordination. Conclusion: This study showed that the aqueous extract and essential oil of caraway had anticonvulsant properties. However, the essential oil was more potent and effective than was the aqueous extract as an anticonvulsant. Additionally, the anticonvulsant effect of caraway was not due to a muscle relaxant activity. These findings support the acclaimed antiepileptic effect of caraway in folk medicine and propose its potential use in petit mal seizure in humans. PMID:27217604

  8. Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

    PubMed Central

    Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

    2015-01-01

    Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

  9. How do you approach seizures in the high altitude traveler?

    PubMed

    Maa, Edward H

    2011-01-01

    Counseling patients who suffer first-time or break- through seizures can be difficult, particularly when controllable external factors may be contributing to the lowering of their seizure threshold. High altitude as a potential trigger for seizures is a common question in our epilepsy clinics in Colorado, and this article reviews the existing anecdotal literature, presents our local experience with high altitude seizures (HAS), offers possible mechanisms to explain how high altitude may trigger seizures, and suggests an initial work-up and prophylactic strategies for future high altitude exposures.

  10. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

    PubMed

    Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

    2014-05-01

    Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Collaborative real-time scheduling of multiple PTZ cameras for multiple object tracking in video surveillance

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Che; Huang, Chung-Lin

    2013-03-01

    This paper proposes a multi-PTZ-camera control mechanism to acquire close-up imagery of human objects in a surveillance system. The control algorithm is based on the output of multi-camera, multi-target tracking. Three main concerns of the algorithm are (1) the imagery of human object's face for biometric purposes, (2) the optimal video quality of the human objects, and (3) minimum hand-off time. Here, we define an objective function based on the expected capture conditions such as the camera-subject distance, pan tile angles of capture, face visibility and others. Such objective function serves to effectively balance the number of captures per subject and quality of captures. In the experiments, we demonstrate the performance of the system which operates in real-time under real world conditions on three PTZ cameras.

  12. Predictors of Seizure Threshold in Right Unilateral Ultrabrief Electroconvulsive Therapy: Role of Concomitant Medications and Anaesthesia Used.

    PubMed

    Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Smith, Deidre; Loo, Colleen K

    2015-01-01

    An individualized approach to maximize electroconvulsive therapy (ECT) efficacy and minimize cognitive side effects is to treat patients relative to their seizure threshold (ST). However, although Right Unilateral-Ultrabrief (0.3 ms) (RUL-UB) ECT is increasingly used in clinical settings as an effective form of ECT with minimal cognitive effects, there is sparse data regarding predictors of ST. To analyze the relationship between ST and clinical and demographic factors in a sample of patients treated with RUL-UB ECT. Clinical, demographic and ECT data from 179 patients in ECT research studies were examined. Seizure threshold was titrated at the first ECT session. ECT was performed with a Thymatron(®) or Mecta(®) device, with thiopentone (2.5-5 mg/kg) or propofol (1-2 mg/kg) anaesthesia. Medications taken at the time of ST titration were documented. The association between ST and candidate predictor variables was examined with regression analysis. Multiple regression analyses showed that 34% of the variance in ST (P < 0.001) could be predicted. Older age (R(2) = 0.194, P < 0.001), propofol (vs thiopentone) (R(2) = 0.029, P ≤ 0.01) and higher anaesthetic dose (mg in propofol equivalents) (R(2) = 0.029, P < 0.05) were found to be predictors of higher initial ST. Treatment with lithium (R(2) = 0.043, P < 0.01) and study site (R(2) = 0.019, P < 0.05) significantly predicted lower initial ST. Empirical titration is recommended for accurate determination of ST in patients receiving RUL-UB ECT. Novel findings of this study are that propofol anaesthesia resulted in higher ST than thiopentone and concomitant treatment with lithium treatment lowered ST. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Seizure Termination by Acidosis Depends on ASIC1a

    PubMed Central

    Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

    2008-01-01

    SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

  14. Seizure disorders in 43 cattle.

    PubMed

    D'Angelo, A; Bellino, C; Bertone, I; Cagnotti, G; Iulini, B; Miniscalco, B; Casalone, C; Gianella, P; Cagnasso, A

    2015-01-01

    Large animals have a relatively high seizure threshold, and in most cases seizures are acquired. No published case series have described this syndrome in cattle. To describe clinical findings and outcomes in cattle referred to the Veterinary Teaching Hospital of the University of Turin (Italy) because of seizures. Client-owned cattle with documented evidence of seizures. Medical records of cattle with episodes of seizures reported between January 2002 and February 2014 were reviewed. Evidence of seizures was identified based on the evaluation of seizure episodes by the referring veterinarian or 1 of the authors. Animals were recruited if physical and neurologic examinations were performed and if diagnostic laboratory test results were available. Forty-three of 49 cases fulfilled the inclusion criteria. The mean age was 8 months. Thirty-one animals were male and 12 were female. Piedmontese breed accounted for 39/43 (91%) animals. Seizures were etiologically classified as reactive in 30 patients (70%) and secondary or structural in 13 (30%). Thirty-six animals survived, 2 died naturally, and 5 were euthanized for reasons of animal welfare. The definitive cause of reactive seizures was diagnosed as hypomagnesemia (n = 2), hypocalcemia (n = 12), and hypomagnesemia-hypocalcemia (n = 16). The cause of structural seizures was diagnosed as cerebrocortical necrosis (n = 8), inflammatory diseases (n = 4), and lead (Pb) intoxication (n = 1). The study results indicate that seizures largely are reported in beef cattle and that the cause can be identified and successfully treated in most cases. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. TRPV1 deletion exacerbates hyperthermic seizures in an age-dependent manner in mice.

    PubMed

    Barrett, Karlene T; Wilson, Richard J A; Scantlebury, Morris H

    2016-12-01

    Febrile seizures (FS) are the most common seizure disorder to affect children. Although there is mounting evidence to support that FS occur when children have fever-induced hyperventilation leading to respiratory alkalosis, the underlying mechanisms of hyperthermia-induced hyperventilation and links to FS remain poorly understood. As transient receptor potential vanilloid-1 (TRPV1) receptors are heat-sensitive, play an important role in adult thermoregulation and modulate respiratory chemoreceptors, we hypothesize that TRPV1 activation is important for hyperthermia-induced hyperventilation leading to respiratory alkalosis and decreased FS thresholds, and consequently, TRPV1 KO mice will be relatively protected from hyperthermic seizures. To test our hypothesis we subjected postnatal (P) day 8-20 TRPV1 KO and C57BL/6 control mice to heated dry air. Seizure threshold temperature, latency and the rate of rise of body temperature during hyperthermia were assessed. At ages where differences in seizure thresholds were identified, head-out plethysmography was used to assess breathing and the rate of expired CO 2 in response to hyperthermia, to determine if the changes in seizure thresholds were related to respiratory alkalosis. Paradoxically, we observed a pro-convulsant effect of TRPV1 deletion (∼4min decrease in seizure latency), and increased ventilation in response to hyperthermia in TRPV1 KO compared to control mice at P20. This pro-convulsant effect of TRPV1 absence was not associated with an increased rate of expired CO 2 , however, these mice had a more rapid rise in body temperature following exposure to hyperthermia than controls, and the expected linear relationship between body weight and seizure latency was absent. Based on these findings, we conclude that deletion of the TRPV1 receptor prevents reduction in hyperthermic seizure susceptibility in older mouse pups, via a mechanism that is independent of hyperthermia-induced respiratory alkalosis, but

  16. Antiepileptic and antipsychotic activities of standardized Śilājatu (Shilajit) in experimental animals

    PubMed Central

    Durg, Sharanbasappa; Veerapur, Veeresh P.; Thippeswamy, B. S.; Ahamed, Syed Mansoor

    2015-01-01

    Background: Śilājatu (Shilajit; SJ) is claimed in traditional Indian medical practice to be useful in the treatment of nervous disorders, epilepsy and as antistress. Aim: To investigate whether SJ possesses antiepileptic and antipsychotic activities in rodents. Materials and Methods: Isonicotinyl hydrazine (INH), pentylenetetrazole (PTZ), apomorphine, phenytoin, diazepam, haloperidol and other chemicals of analytical grade were procured from standard companies. The antiepileptic activity of SJ was assessed using maximal electro shock (MES)-induced seizures in rats, INH and PTZ-induced seizures in mice. The antipsychotic effect of SJ was evaluated using apomorphine-induced climbing and stereotyped behaviours respectively, in mice and rats. Settings and Designs: SJ (25 and 50 mg/kg, p.o.) was given orally once daily for 15 days in all the rodent models. On the test day, SJ was administered 1 h prior to electric shock or chemical inducers (INH/PTZ/apomorphine) in experimental animals; the animals were then observed for different phases of seizures and psychotic behaviours. In addition, gamma-aminobutyric acid (GABA) content in the brain of rats and mice was estimated in seizure models. Statistical Analysis: The data were expressed as mean ± standard error of mean. Statistical comparisons were performed by one-way ANOVA followed by Tukey's post-test using Graph Pad Prism version 5.0, USA. A P < 0.05 was considered significant. Results and Conclusions: SJ pretreatment significantly inhibited the seizures induced by MES, INH and PTZ in a dose dependent manner. Further, SJ augmented brain GABA levels to normal, decreased by INH and PTZ in mice brain. SJ pretreatment also significantly inhibited the climbing and stereotyped behaviours induced by apomorphine. The present data seems to confirm the antiepileptic activity of SJ which may be because of enhancing the GABAergic system. The antipsychotic activity observed may be due to anti-dopaminergic and/or GABA

  17. Antiepileptic and antipsychotic activities of standardized Śilājatu (Shilajit) in experimental animals.

    PubMed

    Durg, Sharanbasappa; Veerapur, Veeresh P; Thippeswamy, B S; Ahamed, Syed Mansoor

    2015-01-01

    Śilājatu (Shilajit; SJ) is claimed in traditional Indian medical practice to be useful in the treatment of nervous disorders, epilepsy and as antistress. To investigate whether SJ possesses antiepileptic and antipsychotic activities in rodents. Isonicotinyl hydrazine (INH), pentylenetetrazole (PTZ), apomorphine, phenytoin, diazepam, haloperidol and other chemicals of analytical grade were procured from standard companies. The antiepileptic activity of SJ was assessed using maximal electro shock (MES)-induced seizures in rats, INH and PTZ-induced seizures in mice. The antipsychotic effect of SJ was evaluated using apomorphine-induced climbing and stereotyped behaviours respectively, in mice and rats. SJ (25 and 50 mg/kg, p.o.) was given orally once daily for 15 days in all the rodent models. On the test day, SJ was administered 1 h prior to electric shock or chemical inducers (INH/PTZ/apomorphine) in experimental animals; the animals were then observed for different phases of seizures and psychotic behaviours. In addition, gamma-aminobutyric acid (GABA) content in the brain of rats and mice was estimated in seizure models. The data were expressed as mean ± standard error of mean. Statistical comparisons were performed by one-way ANOVA followed by Tukey's post-test using Graph Pad Prism version 5.0, USA. A P < 0.05 was considered significant. SJ pretreatment significantly inhibited the seizures induced by MES, INH and PTZ in a dose dependent manner. Further, SJ augmented brain GABA levels to normal, decreased by INH and PTZ in mice brain. SJ pretreatment also significantly inhibited the climbing and stereotyped behaviours induced by apomorphine. The present data seems to confirm the antiepileptic activity of SJ which may be because of enhancing the GABAergic system. The antipsychotic activity observed may be due to anti-dopaminergic and/or GABA-mimetic actions.

  18. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

    PubMed

    Rusan, Zeid M; Kingsford, Olivia A; Tanouye, Mark A

    2014-01-01

    Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  19. Limbic system seizures and aggressive behavior (superkindling effects).

    PubMed

    Andy, O J; Velamati, S

    1978-01-01

    This study was done to further analyze the neural mechanisms underlying aggressive behavior associated with psychomotor or temporal lobe seizures. The studies revealed that superkindling the aggressive system by sequential stimulations at seizure-inducing thresholds, of two or more sites in the limbic, hypothalamic, and basal ganglia structures facilitated the production of aggressive seizures. Aggressive behavior in the freely moving cat was evaluated in relation to the occurrence of hissing and growling during stimulation, after-discharge and postictal period. The behavior was correlated with the frequency of the elicited seizures and the seizure durations. Aggression did develop as a component behavioral manifestation of the limbic (psychomotor) seizure. Development of aggressive seizures was facilitated by "priming" the aggressive system. Optimum levels of aggressive behavior occurred with seizures of medium duration. Catecholamine blockers tended to attentuate the occurrence of aggression, whereas the agonist tended to facilitate it. Once the aggressive system was rendered hyperexcitable, exteroceptive stimuli also evoked aggressive attack behavior. It was concluded that repeatedly recurring limbic system seizures through superkindling mechanisms can eventually render the limbic-basal ganglia-preoptico-hypothalamic aggressive system hyper-responsive to both recurring seizures and to exteroceptive stimuli with resulting aggressive behavior with or without an accompanying seizure.

  20. Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice.

    PubMed

    Agarwal, Nidhi Bharal; Agarwal, Nitin Kumar; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

    2011-04-01

    Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Determination of feature generation methods for PTZ camera object tracking

    NASA Astrophysics Data System (ADS)

    Doyle, Daniel D.; Black, Jonathan T.

    2012-06-01

    Object detection and tracking using computer vision (CV) techniques have been widely applied to sensor fusion applications. Many papers continue to be written that speed up performance and increase learning of artificially intelligent systems through improved algorithms, workload distribution, and information fusion. Military application of real-time tracking systems is becoming more and more complex with an ever increasing need of fusion and CV techniques to actively track and control dynamic systems. Examples include the use of metrology systems for tracking and measuring micro air vehicles (MAVs) and autonomous navigation systems for controlling MAVs. This paper seeks to contribute to the determination of select tracking algorithms that best track a moving object using a pan/tilt/zoom (PTZ) camera applicable to both of the examples presented. The select feature generation algorithms compared in this paper are the trained Scale-Invariant Feature Transform (SIFT) and Speeded Up Robust Features (SURF), the Mixture of Gaussians (MoG) background subtraction method, the Lucas- Kanade optical flow method (2000) and the Farneback optical flow method (2003). The matching algorithm used in this paper for the trained feature generation algorithms is the Fast Library for Approximate Nearest Neighbors (FLANN). The BSD licensed OpenCV library is used extensively to demonstrate the viability of each algorithm and its performance. Initial testing is performed on a sequence of images using a stationary camera. Further testing is performed on a sequence of images such that the PTZ camera is moving in order to capture the moving object. Comparisons are made based upon accuracy, speed and memory.

  2. Automated video-based detection of nocturnal convulsive seizures in a residential care setting.

    PubMed

    Geertsema, Evelien E; Thijs, Roland D; Gutter, Therese; Vledder, Ben; Arends, Johan B; Leijten, Frans S; Visser, Gerhard H; Kalitzin, Stiliyan N

    2018-06-01

    People with epilepsy need assistance and are at risk of sudden death when having convulsive seizures (CS). Automated real-time seizure detection systems can help alert caregivers, but wearable sensors are not always tolerated. We determined algorithm settings and investigated detection performance of a video algorithm to detect CS in a residential care setting. The algorithm calculates power in the 2-6 Hz range relative to 0.5-12.5 Hz range in group velocity signals derived from video-sequence optical flow. A detection threshold was found using a training set consisting of video-electroencephalogaphy (EEG) recordings of 72 CS. A test set consisting of 24 full nights of 12 new subjects in residential care and additional recordings of 50 CS selected randomly was used to estimate performance. All data were analyzed retrospectively. The start and end of CS (generalized clonic and tonic-clonic seizures) and other seizures considered desirable to detect (long generalized tonic, hyperkinetic, and other major seizures) were annotated. The detection threshold was set to the value that obtained 97% sensitivity in the training set. Sensitivity, latency, and false detection rate (FDR) per night were calculated in the test set. A seizure was detected when the algorithm output exceeded the threshold continuously for 2 seconds. With the detection threshold determined in the training set, all CS were detected in the test set (100% sensitivity). Latency was ≤10 seconds in 78% of detections. Three/five hyperkinetic and 6/9 other major seizures were detected. Median FDR was 0.78 per night and no false detections occurred in 9/24 nights. Our algorithm could improve safety unobtrusively by automated real-time detection of CS in video registrations, with an acceptable latency and FDR. The algorithm can also detect some other motor seizures requiring assistance. © 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

  3. Synthesis and biological evaluation of novel 2,3-disubstituted benzofuran analogues of GABA as neurotropic agents.

    PubMed

    Coaviche-Yoval, Arturo; Luna, Hector; Tovar-Miranda, Ricardo; Soriano-Ursua, Marvin Antonio; Trujillo-Ferrara, Jose G

    2018-05-23

    Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries. To evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. The ligands with the best physicochemical attributes were docked on two GABA receptors (the alpha-1 subunit of GABAA-R and GBR1 subunit of GABAB-R). Selected benzofuran derivatives were synthesized by a multistep procedure and characterized. To examine the neurotropic effects, mice were pretreated with different concentrations of the compounds prior to PTZ- or 4-AP-induced seizures. We assessed acute toxicity, motor behavior, and the effects on seizures. The tested ligands that complied with Lipinski's rule of five were tested in silico with GABAA-R (ΔG = -5.51 to -5.84 kcal/mol) at the allosteric site for benzodiazepines. They bound to a similar cluster of residues as the reference compound (gaboxadol, ΔG = -5.51 kcal/mol). Synthesis was achieved with good overall yields (42-9.7%). Two compounds were selected for biological tests (BZF-7 and rac-BZF-10) on a mouse model of seizures, induced by pentylenetetrazol (PTZ) or 4-aminopyridine (4-AP). PTZ-induced seizures are associated with GABA receptors, and those 4-AP-induced with the blockage of the delayed rectifier-type potassium channel, which promotes the release of the NMDA-sensitive glutamatergic ionotropic receptor and other neurotransmitters. The biological assays demonstrated that BZF-7 and rac-BZF-10 do not protect against seizures. Indeed, BZF-7 increased the number of PTZ-induced seizures and decreased latency time. The 4-AP model apparently showed a potentiation of seizure effects after administration of the BZF-analogues, evidenced by the incidence and severity of the seizures and reduced latency time. The results suggest that the test

  4. Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality

    PubMed Central

    Buchanan, Gordon F; Murray, Nicholas M; Hajek, Michael A; Richerson, George B

    2014-01-01

    Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Defects in central control of breathing are important contributors to the pathophysiology of SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined the effect of 5-HT neurone elimination or 5-HT reduction on seizure risk and seizure-induced mortality. Adult Lmx1bf/f/p mice, which lack >99% of 5-HT neurones in the CNS, and littermate controls (Lmx1bf/f) were subjected to acute seizure induction by maximal electroshock (MES) or pilocarpine, variably including electroencephalography, electrocardiography, plethysmography, mechanical ventilation or pharmacological therapy. Lmx1bf/f/p mice had a lower seizure threshold and increased seizure-induced mortality. Breathing ceased during most seizures without recovery, whereas cardiac activity persisted for up to 9 min before terminal arrest. The mortality rate of mice of both genotypes was reduced by mechanical ventilation during the seizure or 5-HT2A receptor agonist pretreatment. The selective serotonin reuptake inhibitor citalopram reduced mortality of Lmx1bf/f but not of Lmx1bf/f/p mice. In C57BL/6N mice, reduction of 5-HT synthesis with para-chlorophenylalanine increased MES-induced seizure severity but not mortality. We conclude that 5-HT neurones raise seizure threshold and decrease seizure-related mortality. Death ensued from respiratory failure, followed by terminal asystole. Given that SUDEP often occurs in association with generalised seizures, some mechanisms causing death in our model might be shared with those leading to SUDEP. This model may help determine the relationship between seizures, 5-HT system dysfunction, breathing and death, which may lead to novel ways to prevent SUDEP. PMID:25107926

  5. Is the first seizure epilepsy--and when?

    PubMed

    Lawn, Nicholas; Chan, Josephine; Lee, Judy; Dunne, John

    2015-09-01

    Epilepsy has recently been redefined to include a single unprovoked seizure if the probability of recurrence is ≥60% over the following 10 years. This definition is based on the estimated risk of a third seizure after two unprovoked seizures, using the lower-limit 95% confidence interval (CI) at 4 years, and does not account for the initially high recurrence rate after first-ever seizure that rapidly falls with increasing duration of seizure freedom. We analyzed long-term outcomes after the first-ever seizure, and the influence of duration of seizure freedom on the likelihood of seizure recurrence, and their relevance to the new definition of epilepsy. Prospective analysis of 798 adults with a first-ever unprovoked seizure seen at a hospital-based first seizure clinic between 2000 and 2011. The likelihood of seizure recurrence was analyzed according to the duration of seizure freedom, etiology, electroencephalography (EEG), and neuroimaging findings. The likelihood of seizure recurrence at 10 years was ≥60% in patients with epileptiform abnormalities on EEG or neuroimaging abnormalities, therefore, meeting the new definition of epilepsy. However, the risk of recurrence was highly time dependent; after a brief period (≤12 weeks) of seizure freedom, no patient group continued to fulfill the new definition of epilepsy. Of 407 patients who had a second seizure, the likelihood of a third seizure at 4 years was 68% (95% CI 63-73%) and at 10 years was 85% (95% CI 79-91%). The duration of seizure freedom following first-ever seizure substantially influences the risk of recurrence, with none of our patients fulfilling the new definition of epilepsy after a short period of seizure freedom. When a threshold was applied based on the 10-year risk of a third seizure from our data, no first-seizure patient group ever had epilepsy. These data may be utilized in a definition of epilepsy after a first-ever seizure. Wiley Periodicals, Inc. © 2015 International League Against

  6. The anticonvulsant action of AHR-11748 on kindled amygdaloid seizures in rats.

    PubMed

    Albertson, T E; Walby, W F

    1987-03-01

    The anticonvulsant effectiveness of AHR-11748 (3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) was evaluated in the kindled amygdaloid seizure model in rats. Doses of AHR-11748 that did not cause prestimulation toxicity significantly attenuated elicited afterdischarge durations and the severity of the accompanying behavioral convulsive response in previously kindled rats. AHR-11748 (25-100 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and suprathreshold (400 microA) paradigms. AHR-11748 (50-100.mg/kg) reduced suprathreshold elicited after discharges and seizure severity. Utilizing a suprathreshold kindling paradigm, the maximum anticonvulsant effectiveness for the 100 mg/kg i.p. dose of AHR-11748 was seen at 180 min. AHR-11748 significantly elevated seizure thresholds only at the 100 mg/kg dose. AHR-11748 (25-100 mg/kg) significantly reduced the severity of threshold elicited seizures. When AHR-11748 (50 and 100 mg/kg i.p.) was administered daily during kindling acquisition, the number of daily trials necessary to complete kindling significantly increased. A reduction in both the duration and the severity of the responses induced by the daily stimulations during the acquisition period was seen with AHR-11748 treatment. This study has demonstrated that AHR-11748 significantly modifies both the acquisition of kindling and the fully kindled amygdaloid seizures at doses that do not cause behavioral toxicity.

  7. Intraoperative Seizures: Anesthetic and Antiepileptic Drugs.

    PubMed

    Uribe, Alberto; Zuleta-Alarcon, Alix; Kassem, Mahmoud; Sandhu, Gurneet S; Bergese, Sergio D

    2017-01-01

    Epilepsy is a common condition with up to 1% prevalence in the general population. In the perioperative course of neurologic surgery patients, the use of prophylactic and therapeutic antiepileptic drugs is a common practice. Nonetheless, there is limited evidence supporting the use of prophylactic antiepileptics to prevent perioperative seizures and there are no guidelines for which anesthetic technique is preferred. To discuss the seizurogenic potential of anesthetic drugs and to discuss intraoperative seizures in neurosurgical patients. We performed a search of the literature available in PubMed and Ovid MEDLINE. We also included articles identified in the review of the references of these articles. The incidence of seizures is heterogenic among neurosurgical patients. Seizure prophylaxis is widely administered despite limited available evidence of its effectiveness. In epileptic patients, the recommendation is to continue antiepileptic drugs in the perioperative setting. In these patients, anesthesiologists may also limit the use of medications that alter the seizure threshold and avoid medications that pose significant pharmacological interaction with antiepileptic drugs. In conclusion, a knowledgeable multidisciplinary perioperative team is essential to avoid, identify and treat intraoperative seizures competently. In patients with a history of epilepsy it is recommended to continue antiepileptic therapy. Therefore, clinical judgment should guide the decision of administering seizure prophylaxis in neurosurgery patients according to an individual assessment of potential risk for seizures. Furthermore, there is a need for randomized controlled trials that support new protocols and/or guidelines for anesthetic and perioperative regimens to prevent and treat intraoperative seizures. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures.

    PubMed

    Rakhade, Sanjay N; Fitzgerald, Erin F; Klein, Peter M; Zhou, Chengwen; Sun, Hongyu; Huganir, Richard L; Hunganir, Richard L; Jensen, Frances E

    2012-12-05

    Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We showed previously that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) and Serine 845 (S845) sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced posttranslational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild-type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation [GluR1 double-phosphomutant (GluR1 DPM) mice]. Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex after a single episode of pentyleneterazol-induced seizures in postnatal day 7 (P7) wild-type mouse pups and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild-type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex and were associated with enhanced seizure susceptibility to later-life kainic-acid-induced seizures. In contrast, later-life seizure susceptibility after hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for posttranslational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue.

  9. Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

    PubMed

    de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Franceschi; Falconi-Sobrinho, Luiz Luciano; Dos Anjos-Garcia, Tayllon; Coimbra, Norberto Cysne

    2016-10-01

    Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    PubMed

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Pregestational stress attenuated fertility rate in dams and increased seizure susceptibility in offspring.

    PubMed

    Mahmoodkhani, Maryam; Saboory, Ehsan; Roshan-Milani, Shiva; Azizi, Negar; Karimipour, Mojtaba; Rasmi, Yosef; Gholinejad, Zafar

    2018-02-01

    Many studies have found that stress during pregnancy is linked to an increased incidence of epileptic behaviors and reproductive disorders. However, few works have investigated the effect of pregestational stress on seizure susceptibility in the offspring. We investigated the effect of pregestational stress on epileptic behaviors in the offspring as well as fertility rate in dams. The male and female rats were randomly divided into four groups to form a combination of control and stressed groups for each sex. The rats were subjected to predatory stress (exposed to a cat) twice per day for 50 (male) and 15 (female) consecutive days. At the end of the stress procedure, the rats were coupled as follows: both male and female control (M C -F C ), male stressed/female control (M S -F C ), male control/female stressed (M C -F S ), and both male and female stressed (M S -F S ). Then, the puppies born from these groups were counted and evaluated for pentylentetrazole (PTZ)-induced seizure. There was no significant difference between the male and female pups in each identical group in terms of litter size and epileptic behaviors, except duration of tail rigidity and duration of immobility. The total score of seizure increased in all the stressed groups, but more severely in the M S -F S group. However, the onset of the first epileptic behavior and tonic-clonic seizure significantly decreased in the stressed groups. Moreover, fertility rate significantly decreased in the stressed groups compared with the control group, but there was no significant difference in terms of litter size between the groups. These data revealed the impact of pregestational stress during spermatogenesis and oogenesis on fertility rate in dams and epileptic behaviors in the offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Seizure burden is independently associated with short term outcome in critically ill children

    PubMed Central

    Payne, Eric T.; Zhao, Xiu Yan; Frndova, Helena; McBain, Kristin; Sharma, Rohit; Hutchison, James S.

    2014-01-01

    Seizures are common among critically ill children, but their relationship to outcome remains unclear. We sought to quantify the relationship between electrographic seizure burden and short-term neurological outcome, while controlling for diagnosis and illness severity. Furthermore, we sought to determine whether there is a seizure burden threshold above which there is an increased probability of neurological decline. We prospectively evaluated all infants and children admitted to our paediatric and cardiac intensive care units who underwent clinically ordered continuous video-electroencephalography monitoring over a 3-year period. Seizure burden was quantified by calculating the maximum percentage of any hour that was occupied by electrographic seizures. Outcome measures included neurological decline, defined as a worsening Paediatric Cerebral Performance Category score between hospital admission and discharge, and in-hospital mortality. Two hundred and fifty-nine subjects were evaluated (51% male) with a median age of 2.2 years (interquartile range: 0.3 days–9.7 years). The median duration of continuous video-electroencephalography monitoring was 37 h (interquartile range: 21–56 h). Seizures occurred in 93 subjects (36%, 95% confidence interval = 30–42%), with 23 (9%, 95% confidence interval = 5–12%) experiencing status epilepticus. Neurological decline was observed in 174 subjects (67%), who had a mean maximum seizure burden of 15.7% per hour, compared to 1.8% per hour for those without neurological decline (P < 0.0001). Above a maximum seizure burden threshold of 20% per hour (12 min), both the probability and magnitude of neurological decline rose sharply (P < 0.0001) across all diagnostic categories. On multivariable analysis adjusting for diagnosis and illness severity, the odds of neurological decline increased by 1.13 (95% confidence interval = 1.05–1.21, P = 0.0016) for every 1% increase in maximum hourly seizure burden. Seizure burden was not

  13. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

    PubMed Central

    Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

    2006-01-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

  14. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

    PubMed

    Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

    2006-07-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

  15. Rapid focal cooling attenuates cortical seizures in a primate epilepsy model.

    PubMed

    Ren, Guoping; Yan, Jiaqing; Tao, Guoxian; Gan, Yunmeng; Li, Donghong; Yan, Xi; Fu, Yongjuan; Wang, Leiming; Wang, Weimin; Zhang, Zhiming; Yue, Feng; Yang, Xiaofeng

    2017-09-01

    Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys. The rapid focal cooling was implemented by using a thermoelectric (Peltier) device. As a result, the average durations of seizures and interictal intervals before cooling were 94.3±4.0s and 62.3±6.9s, respectively. When the cortex was cooled to 20°C or 18°C, there was no effect on seizure duration (109.4±30.0s, 91.3±19.3s) or interictal duration (99.4±26.8s, 83.2±11.5s, P>0.05). But when the cortex was cooled to 16°C, the seizure duration was reduced to 54.1±4.9s and the interictal duration was extended to 175.0±16.7s (P<0.05). Electroencephalogram spectral analysis showed that the power of delta, alpha, beta, gamma and ripples bands in seizures were significantly reduced at 20°C and 18°C. At 16°C, the power of theta band in seizures was also significantly reduced along with the other bands. Our data reveal that the temperature threshold in rapid focal cooling required to significantly shorten neocortical seizures in nonhuman primates is 16°C, and inhibition of electroencephalogram broadband spectrum power, especially power of theta band, may be the underlying mechanism to control seizures. Copyright © 2017. Published by Elsevier Inc.

  16. Short-term fasting, seizure control and brain amino acid metabolism.

    PubMed

    Yudkoff, Marc; Daikhin, Yevgeny; Nissim, Ilana; Horyn, Oksana; Luhovyy, Bogdan; Lazarow, Adam; Nissim, Itzhak

    2006-01-01

    The ketogenic diet is an effective treatment for seizures, but the mechanism of action is unknown. It is uncertain whether the anti-epileptic effect presupposes ketosis, or whether the restriction of calories and/or carbohydrate might be sufficient. We found that a relatively brief (24 h) period of low glucose and low calorie intake significantly attenuated the severity of seizures in young Sprague-Dawley rats (50-70 gms) in whom convulsions were induced by administration of pentylenetetrazole (PTZ). The blood glucose concentration was lower in animals that received less dietary glucose, but the brain glucose level did not differ from control blood [3-OH-butyrate] tended to be higher in blood, but not in brain, of animals on a low-glucose intake. The concentration in brain of glutamine increased and that of alanine declined significantly with low-glucose intake. The blood alanine level fell more than that of brain alanine, resulting in a marked increase ( approximately 50%) in the brain:blood ratio for alanine. In contrast, the brain:blood ratio for leucine declined by about 35% in the low-glucose group. When animals received [1-(13)C]glucose, a metabolic precursor of alanine, the appearance of (13)C in alanine and glutamine increased significantly relative to control. The brain:blood ratio for [(13)C]alanine exceeded 1, indicating that the alanine must have been formed in brain and not transported from blood. The elevated brain(alanine):blood(alanine) could mean that a component of the anti-epileptic effect of low carbohydrate intake is release of alanine from brain-to-blood, in the process abetting the disposal of glutamate, excess levels of which in the synaptic cleft would contribute to the development of seizures.

  17. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.

    PubMed

    Rodriguez-Alvarez, Natalia; Jimenez-Mateos, Eva M; Dunleavy, Mark; Waddington, John L; Boylan, Geraldine B; Henshall, David C

    2015-11-01

    Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    PubMed

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.

    PubMed

    Albertson, T E; Walby, W F

    1987-01-01

    The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied. No modification in the rate of kindling or the expression of the elicited seizures was noted during the acquisition phase. Further studies with additional fully amygdaloid kindled rats failed to show significant modification of suprathreshold or threshold elicited seizures after single 30-60 mg/kg i.p. doses of GM1 ganglioside. Despite previous studies which have shown antibodies to GM1 ganglioside to be convulsive, no anticonvulsant activity was demonstrated in this study with exogenous GM1 ganglioside using a battery of kindled-amygdaloid seizure tests in the rat.

  20. 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

  1. 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

  2. Comparative studies on the effects of clinically used anticonvulsants on the oxidative stress biomarkers in pentylenetetrazole-induced kindling model of epileptogenesis in mice.

    PubMed

    Mazhar, Faizan; Malhi, Saima M; Simjee, Shabana U

    2017-01-01

    Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice. Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase. Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (p<0.001), nitric oxide synthase activity (p<0.05), peroxide levels (p<0.05), and malondialdehyde (p<0.05). Levetiracetam and felbamate significantly decreased lipid and protein peroxidation whereas topiramate was found to reduce lipid peroxidation only. An AED that produces anticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity.

  3. Dynamic, cell type-specific roles for GABAergic interneurons in a mouse model of optogenetically inducible seizures

    PubMed Central

    Khoshkhoo, Sattar; Vogt, Daniel; Sohal, Vikaas S.

    2016-01-01

    SUMMARY GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later. Optogenetically inhibiting VIP interneurons consistently increased seizure threshold and reduced seizure duration. Inhibiting PV+ and SOM+ interneurons had mixed effects on seizure initiation, but consistently reduced seizure duration. Thus, while their roles may evolve during seizures, PV+ and SOM+ interneurons ultimately help maintain ongoing seizures. These results show how an optogenetically-induced seizure model can be leveraged to pinpoint a new target for seizure control: VIP interneurons. PMID:28041880

  4. Validation of an automated seizure detection algorithm for term neonates

    PubMed Central

    Mathieson, Sean R.; Stevenson, Nathan J.; Low, Evonne; Marnane, William P.; Rennie, Janet M.; Temko, Andrey; Lightbody, Gordon; Boylan, Geraldine B.

    2016-01-01

    Objective The objective of this study was to validate the performance of a seizure detection algorithm (SDA) developed by our group, on previously unseen, prolonged, unedited EEG recordings from 70 babies from 2 centres. Methods EEGs of 70 babies (35 seizure, 35 non-seizure) were annotated for seizures by experts as the gold standard. The SDA was tested on the EEGs at a range of sensitivity settings. Annotations from the expert and SDA were compared using event and epoch based metrics. The effect of seizure duration on SDA performance was also analysed. Results Between sensitivity settings of 0.5 and 0.3, the algorithm achieved seizure detection rates of 52.6–75.0%, with false detection (FD) rates of 0.04–0.36 FD/h for event based analysis, which was deemed to be acceptable in a clinical environment. Time based comparison of expert and SDA annotations using Cohen’s Kappa Index revealed a best performing SDA threshold of 0.4 (Kappa 0.630). The SDA showed improved detection performance with longer seizures. Conclusion The SDA achieved promising performance and warrants further testing in a live clinical evaluation. Significance The SDA has the potential to improve seizure detection and provide a robust tool for comparing treatment regimens. PMID:26055336

  5. Seizures in an Alzheimer's disease patient as a complication of colonoscopy premedication with meperidine.

    PubMed

    Nagler, Jerry; Hammarth, Patricia M; Poppers, David M

    2008-01-01

    We describe the first reported case of generalized tonic-clonic seizures induced by meperidine premedication for a colonoscopy procedure in a 63-year-old woman with Alzheimer's disease. The active metabolite of meperidine, normeperidine, is postulated to be the precipitating cause of the seizures, although a cholinesterase inhibitor and an N-methyl-D: -aspartate receptor antagonist, both routinely used for treatment of Alzheimer's disease, may have contributed by reducing the seizure threshold. The neuronal changes which occur in Alzheimer's disease can themselves also predispose to seizures. We recommend avoidance of meperidine for all flexible endoscopic procedures on patients with Alzheimer's disease and in any patient with a condition that predisposes to seizures, and suggest the use of alternative opioids.

  6. Down-regulation of Homer1b/c protects against chemically induced seizures through inhibition of mTOR signaling.

    PubMed

    Cao, Lei; Tian, Ye; Jiang, Yi; Zhang, Ge-Juan; Lei, Hui; Di, Zheng-Li

    2015-01-01

    Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. Reducing Homer1b/c expression has been shown in previous studies to be protective against excitotoxic insults, implicating Homer1b/c in the physiological regulation of aberrant neuronal excitability. To test the efficacy of a Homer1b/c reducing therapy for disorders with a detrimental hyperexcitability profile in mice, we used small interfere RNA (siRNA) to decrease endogenous Homer1b/c expression in mouse hippocampus. The baseline motor and cognitive behavior was measured by sensorimotor tests, Morris water maze and elevated plus maze tasks. The anti-epileptic effects of Homer1b/c knockdown were determined in two chemically induced seizure models induced by Picrotoxin (PTX) or pentylenetetrazole (PTZ) administration. The results of sensorimotor tests, Morris water maze and elevated plus maze tasks showed that Homer1b/c reduction had no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced Homerb/c protein had less severe seizures than control mice. Total Homer1b/c protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of Homer1b/c. In addition, the phosphorylation of mammalian target of rapamycin (mTOR) and its target protein S6 was significantly inhibited in Homer1b/c down-regulated mice. Homer1b/c knockdown-induced inhibition of mTOR pathway was partially ablated by the metabotropic glutamate receptor 5 (mGluR5) agonist CHPG. Our results demonstrate that endogenous Homer1b/c is integral for regulating neuronal hyperexcitability in adult animals and suggest that reduction of Homer1b/c could protect against chemically induced seizures through inhibition mTOR pathway. © 2015 S. Karger AG, Basel.

  7. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.

    PubMed

    Hassanzadeh, Parichehr; Arbabi, Elham; Atyabi, Fatemeh; Dinarvand, Rassoul

    2017-06-15

    Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Evaluation of pro-convulsant risk in the rat: spontaneous and provoked convulsions.

    PubMed

    Esneault, Elise; Peyon, Guillaume; Froger-Colléaux, Christelle; Castagné, Vincent

    2015-01-01

    The aim of the present study was to evaluate the utility of different tests performed in the absence or presence of factors promoting seizures in order to evaluate the pro-convulsant effects of drugs. We studied the effects of theophylline in the rat since this is a well-known pro-convulsant substance in humans. The occurrence of spontaneous convulsions following administration of theophylline was evaluated by observation in the Irwin Test and by measuring brain activity using video-EEG recording in conscious telemetered animals. Theophylline was also tested in the electroconvulsive shock (ECS) threshold and pentylenetetrazole (PTZ)-induced convulsions tests, two commonly used models of provoked convulsions. In the Irwin test, theophylline induced convulsions in 1 out of 6 rats at 128 mg/kg. Paroxysmal/seizure activity was also observed by video-EEG recording in 4 out of the 12 animals tested at 128 mg/kg, in presence of clonic convulsions in 3 out of the 4 rats. Paroxysmal activity was observed in two rats in the absence of clear behavioral symptoms, indicating that some precursor signs can be detected using video-EEG. Clear pro-convulsant activity was shown over the dose-range 32-128 mg/kg in the ECS threshold and PTZ-induced convulsions tests. Evaluation of spontaneous convulsions provides information on the therapeutic window of a drug and the translational value of the approach is increased by the use of video-EEG. Tests based on provoked convulsions further complement the evaluation since they try to mimic high risk situations. Measurement of both spontaneous and provoked convulsions improves the evaluation of the pro-convulsant risk of novel pharmacological substances. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Postoperative seizure outcome-guided machine learning for interictal electrocorticography in neocortical epilepsy.

    PubMed

    Park, Seong-Cheol; Chung, Chun Kee

    2018-06-01

    The objective of this study was to introduce a new machine learning guided by outcome of resective epilepsy surgery defined as the presence/absence of seizures to improve data mining for interictal pathological activities in neocortical epilepsy. Electrocorticographies for 39 patients with medically intractable neocortical epilepsy were analyzed. We separately analyzed 38 frequencies from 0.9 to 800 Hz including both high-frequency activities and low-frequency activities to select bands related to seizure outcome. An automatic detector using amplitude-duration-number thresholds was used. Interictal electrocorticography data sets of 8 min for each patient were selected. In the first training data set of 20 patients, the automatic detector was optimized to best differentiate the seizure-free group from not-seizure-free-group based on ranks of resection percentages of activities detected using a genetic algorithm. The optimization was validated in a different data set of 19 patients. There were 16 (41%) seizure-free patients. The mean follow-up duration was 21 ± 11 mo (range, 13-44 mo). After validation, frequencies significantly related to seizure outcome were 5.8, 8.4-25, 30, 36, 52, and 75 among low-frequency activities and 108 and 800 Hz among high-frequency activities. Resection for 5.8, 8.4-25, 108, and 800 Hz activities consistently improved seizure outcome. Resection effects of 17-36, 52, and 75 Hz activities on seizure outcome were variable according to thresholds. We developed and validated an automated detector for monitoring interictal pathological and inhibitory/physiological activities in neocortical epilepsy using a data-driven approach through outcome-guided machine learning. NEW & NOTEWORTHY Outcome-guided machine learning based on seizure outcome was used to improve detections for interictal electrocorticographic low- and high-frequency activities. This method resulted in better separation of seizure outcome groups than others reported in the

  10. Design and Synthesis of Novel Phenylpiperazine Derivatives as Potential Anticonvulsant Agents.

    PubMed

    Habib, Monica M W; Abdelfattah, Mohamed A O; Abadi, Ashraf H

    2015-12-01

    Eighteen new 5-benzylidene-3-(4-arylpiperazin-1-ylmethyl)-2-thioxo-imidazolidin-4-ones were designed as hybrid structures from previously reported anticonvulsant compounds, synthesized and tested for anticonvulsant activity. Initial anticonvulsant screening was performed using the strychnine (2 mg/kg IP) potent generalized-induced seizure and pentylenetetrazole (PTZ) (60 mg/kg IP) acute clonic-induced convulsion screens in mice. All the molecules were found to be effective in at least one seizure model, compounds 10, 13, 15, 17, and 18 were active against both types of seizures induced. Compound 13 turned out to be the most active candidate within the strychnine model, having an average survival time of 6 min close to that of the positive control phenytoin, while compound 8 showed 100% protection from the induced PTZ seizures, resembling the protection of the positive control phenobarbital. Initial SAR studies for anticonvulsant activity are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A low computation cost method for seizure prediction.

    PubMed

    Zhang, Yanli; Zhou, Weidong; Yuan, Qi; Wu, Qi

    2014-10-01

    The dynamic changes of electroencephalograph (EEG) signals in the period prior to epileptic seizures play a major role in the seizure prediction. This paper proposes a low computation seizure prediction algorithm that combines a fractal dimension with a machine learning algorithm. The presented seizure prediction algorithm extracts the Higuchi fractal dimension (HFD) of EEG signals as features to classify the patient's preictal or interictal state with Bayesian linear discriminant analysis (BLDA) as a classifier. The outputs of BLDA are smoothed by a Kalman filter for reducing possible sporadic and isolated false alarms and then the final prediction results are produced using a thresholding procedure. The algorithm was evaluated on the intracranial EEG recordings of 21 patients in the Freiburg EEG database. For seizure occurrence period of 30 min and 50 min, our algorithm obtained an average sensitivity of 86.95% and 89.33%, an average false prediction rate of 0.20/h, and an average prediction time of 24.47 min and 39.39 min, respectively. The results confirm that the changes of HFD can serve as a precursor of ictal activities and be used for distinguishing between interictal and preictal epochs. Both HFD and BLDA classifier have a low computational complexity. All of these make the proposed algorithm suitable for real-time seizure prediction. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Opiate-induced seizures: a study of mu and delta specific mechanisms.

    PubMed

    Snead, O C

    1986-08-01

    Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.

  13. Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

    PubMed Central

    Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

    2018-01-01

    Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

  14. Different ketogenesis strategies lead to disparate seizure outcomes.

    PubMed

    Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

    2018-07-01

    Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

  15. Enhanced susceptibility to stress and seizures in GAD65 deficient mice

    PubMed Central

    Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D

    2018-01-01

    Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation. PMID:29377906

  16. Enhanced susceptibility to stress and seizures in GAD65 deficient mice.

    PubMed

    Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D; Koh, Sookyong

    2018-01-01

    Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.

  17. Influence of picolinic acid on seizure susceptibility in mice.

    PubMed

    Cioczek-Czuczwar, Anna; Czuczwar, Piotr; Turski, Waldemar Andrzej; Parada-Turska, Jolanta

    2017-02-01

    The mechanism of drug resistance in epilepsy remains unknown. Picolinic acid (PIC) is an endogenous metabolite of the kynurenine pathway and a chelating agent added to dietary supplements. Both inhibitory and excitatory properties of PIC were reported. The aim of this study was to determine the influence of exogenously applied PIC upon the electroconvulsive threshold and the activity of chemical convulsants in eight models of epilepsy in mice. All experiments were performed on adult male Swiss albino mice. Electroconvulsions were induced through ear clip electrodes. The electroconvulsive threshold (current strength necessary to induce tonic seizures in 50% of the tested group - CS 50 ) was estimated for control animals and animals pretreated with PIC. To determine the possible convulsant activity of PIC, it was administered subcutaneously or intracerebroventricularly in increasing doses to calculate the CD 50 values (doses of convulsants necessary to produce seizures in 50% of the animals). Chemical convulsions were induced by challenging the animals with increasing doses of convulsant to calculate the CD 50 values. The following convulsants were used: 4-aminopyridine, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, bicuculline, N-methyl-d-aspartate, nicotine, pentylenetrazole, pilocarpine hydrochloride and strychnine nitrate. PIC significantly decreased the electroconvulsive threshold and, after intracerebroventricular injection, but not subcutaneous, produced convulsions. Of the studied convulsants, only the activity of pilocarpine hydrochloride was significantly enhanced by PIC. PIC enhances seizure activity and potentially may play a role in the pathogenesis of drug resistant epilepsy. Future studies should focus on the interactions between PIC and antiepileptic drugs. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  18. Seizure clustering.

    PubMed

    Haut, Sheryl R

    2006-02-01

    Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

  19. OmniBird: a miniature PTZ NIR sensor system for UCAV day/night autonomous operations

    NASA Astrophysics Data System (ADS)

    Yi, Steven; Li, Hui

    2007-04-01

    Through a SBIR funding from NAVAIR, we have successfully developed an innovative, miniaturized, and lightweight PTZ UCAV imager called OmniBird for UCAV taxiing. The proposed OmniBird will be able to fit in a small space. The designed zoom capability allows it to acquire focused images for targets ranging from 10 to 250 feet. The innovative panning mechanism also allows the system to have a field of view of +/- 100 degrees within the provided limited spacing (6 cubic inches). The integrated optics, camera sensor, and mechanics solution will allow the OmniBird to stay optically aligned and shock-proof under harsh environments.

  20. Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

    PubMed

    Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

    2015-05-15

    The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

  1. Seizures

    MedlinePlus

    ... Your Child Has a Seizure Print en español Crisis convulsivas (convulsiones) Seizures are caused by a sudden surge of electrical activity in the brain. A seizure usually affects how a person looks or acts for a ...

  2. Design and synthesis of some new 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-ureas as potent anticonvulsant and antidepressant agents.

    PubMed

    Mishra, Chandra Bhushan; Kumari, Shikha; Tiwari, Manisha

    2016-05-01

    A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29-42) were designed, synthesized and evaluated for their anticonvulsant activity by using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurotoxicity was checked by rotarod assay. Most of the test compounds were found effective in both seizure tests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl-urea) exhibited marked anticonvulsant activity in MES as well as scPTZ tests. The phase II anticonvulsant quantification study of compound 30 indicates the ED50 value of 28.5 mg/kg against MES induced seizures. In addition, this compound also showed considerable protection against pilocarpine induced status epilepticus in rats. Seizures induced by 3-mercaptopropionic acid model and thiosemicarbazide were significantly attenuated by compound 30, which suggested its broad spectrum of anticonvulsant activity. Interestingly, compound 30 displayed better antidepressant activity than standard drug fluoxetine. Moreover, compound 30 appeared as a non-toxic chemical entity in sub-acute toxicity studies.

  3. Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

    PubMed Central

    Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-01-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  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. Design, synthesis, and anticonvulsant activity of new hybrid compounds derived from 2-(2,5-dioxopyrrolidin-1-yl)propanamides and 2-(2,5-dioxopyrrolidin-1-yl)butanamides.

    PubMed

    Kamiński, Krzysztof; Zagaja, Mirosław; Łuszczki, Jarogniew J; Rapacz, Anna; Andres-Mach, Marta; Latacz, Gniewomir; Kieć-Kononowicz, Katarzyna

    2015-07-09

    The library of 27 new 1-(4-phenylpiperazin-1-yl)- or 1-(morpholin-4-yl)-(2,5-dioxopyrrolidin-1-yl)propanamides and (2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents was synthesized. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5, 10, 11, and 24 displayed the broad spectra of activity across the preclinical seizure models, namely, the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-hertz (6 Hz) model of pharmacoresistant limbic seizures. The highest protection was demonstrated by 11 (ED50 MES = 88.4 mg/kg, ED50 scPTZ = 59.9 mg/kg, ED50 6 Hz = 21.0 mg/kg). This molecule did not impair the motor coordination of animals in the chimney test even at high doses (TD50 > 1500 mg/kg), yielding superb protective indexes (PI MES > 16.97, PI PTZ > 25.04, PI 6 Hz > 71.43). As a result, 11 displayed distinctly better safety profile than clinically relevant AEDs ethosuximide, lacosamide, or valproic acid.

  6. 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].

  7. Automatic seizure detection in SEEG using high frequency activities in wavelet domain.

    PubMed

    Ayoubian, L; Lacoma, H; Gotman, J

    2013-03-01

    Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80-500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  8. Automatic seizure detection in SEEG using high frequency activities in wavelet domain

    PubMed Central

    Ayoubian, L.; Lacoma, H.; Gotman, J.

    2015-01-01

    Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80–500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. PMID:22647836

  9. 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…

  10. A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

    PubMed Central

    Westmark, Cara Jean

    2014-01-01

    Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer’s disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold. PMID:25232349

  11. Termination of seizure clusters is related to the duration of focal seizures.

    PubMed

    Ferastraoaru, Victor; Schulze-Bonhage, Andreas; Lipton, Richard B; Dümpelmann, Matthias; Legatt, Alan D; Blumberg, Julie; Haut, Sheryl R

    2016-06-01

    Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal

  12. An epileptic seizures detection algorithm based on the empirical mode decomposition of EEG.

    PubMed

    Orosco, Lorena; Laciar, Eric; Correa, Agustina Garces; Torres, Abel; Graffigna, Juan P

    2009-01-01

    Epilepsy is a neurological disorder that affects around 50 million people worldwide. The seizure detection is an important component in the diagnosis of epilepsy. In this study, the Empirical Mode Decomposition (EMD) method was proposed on the development of an automatic epileptic seizure detection algorithm. The algorithm first computes the Intrinsic Mode Functions (IMFs) of EEG records, then calculates the energy of each IMF and performs the detection based on an energy threshold and a minimum duration decision. The algorithm was tested in 9 invasive EEG records provided and validated by the Epilepsy Center of the University Hospital of Freiburg. In 90 segments analyzed (39 with epileptic seizures) the sensitivity and specificity obtained with the method were of 56.41% and 75.86% respectively. It could be concluded that EMD is a promissory method for epileptic seizure detection in EEG records.

  13. Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice.

    PubMed

    Rashid, Davood; Panda, B P; Vohora, Divya

    2015-11-01

    Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Identifying seizure clusters in patients with psychogenic nonepileptic seizures.

    PubMed

    Baird, Grayson L; Harlow, Lisa L; Machan, Jason T; Thomas, Dave; LaFrance, W C

    2017-08-01

    The present study explored how seizure clusters may be defined for those with psychogenic nonepileptic seizures (PNES), a topic for which there is a paucity of literature. The sample was drawn from a multisite randomized clinical trial for PNES; seizure data are from participants' seizure diaries. Three possible cluster definitions were examined: 1) common clinical definition, where ≥3 seizures in a day is considered a cluster, along with two novel statistical definitions, where ≥3 seizures in a day are considered a cluster if the observed number of seizures statistically exceeds what would be expected relative to a patient's: 1) average seizure rate prior to the trial, 2) observed seizure rate for the previous seven days. Prevalence of clusters was 62-68% depending on cluster definition used, and occurrence rate of clusters was 6-19% depending on cluster definition. Based on these data, clusters seem to be common in patients with PNES, and more research is needed to identify if clusters are related to triggers and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

    PubMed

    Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

    2017-08-01

    Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

  16. Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy.

    PubMed

    Witkin, J M; Smith, J L; Ping, X; Gleason, S D; Poe, M M; Li, G; Jin, X; Hobbs, J; Schkeryantz, J M; McDermott, J S; Alatorre, A I; Siemian, J N; Cramer, J W; Airey, D C; Methuku, K R; Tiruveedhula, V V N P B; Jones, T M; Crawford, J; Krambis, M J; Fisher, J L; Cook, J M; Cerne, R

    2018-05-03

    HZ-166 has previously been characterized as an α2,3-selective GABA A receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity. KRM-II-81 was active against electroshock-induced convulsions in mice, pentylenetetrazole (PTZ)-induced convulsions in rats, elevations in PTZ-seizure thresholds, and amygdala-kindled seizures in rats with efficacies greater than that of diazepam. KRM-II-81 was also active in the 6 Hz seizure model in mice. Structural analogs of KRM-II-81 but not the ester, HZ-166, were active in all models in which they were evaluated. We further evaluated KRM-II-81 in human cortical epileptic tissue where it was found to significantly-attenuate picrotoxin- and AP-4-induced increases in firing rate across an electrode array. These molecules generally had a wider margin of separation in potencies to produce anticonvulsant effects vs. motor impairment on an inverted screen test than did diazepam. Ester bioisosters of HZ-166 are thus presented as novel agents for the potential treatment of epilepsy acting via selective positive allosteric amplification of GABA A signaling through α2/α3-containing GABA receptors. The in vivo data from the present study can serve as a guide to dosing parameters that predict engagement of central GABA A receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Absence Seizure (Petit Mal Seizure)

    MedlinePlus

    ... people have many episodes daily, which interfere with school or daily activities. A child may have absence seizures for some time before an adult notices the seizures, because they're so brief. A decline in a child's learning ability may be the first sign of this ...

  18. Effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazol-induced epileptic behaviors in infant and prepubertal rats.

    PubMed

    Ebrahimi, Loghman; Saboory, Ehsan; Roshan-Milani, Shiva; Hashemi, Paria

    2014-09-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. Many reports have shown an interaction between morphine- and stress-induced behavioral changes in adult rats. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazole (PTZ)-induced epileptic behaviors was investigated in rat offspring to address effect of the interaction between morphine and stress. Pregnant rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, the rats were placed in 25 °C water on 17-19 days of pregnancy. In the morphine/saline group, the rats received morphine/saline on the same days. In the morphine/saline-stressed group, they were exposed to stress and received morphine/saline simultaneously. On postnatal day 15 (P15), blood samples were collected to determine corticosterone (COS) level. On P15 and P25, PTZ was injected to the rest of pups to induce seizure. Then, epileptic behaviors of each rat were individually observed. Latency of tonic-colonic seizures decreased in control-morphine and stressed-saline groups while increasing in stressed-morphine rats compared to control-saline group on P15. Duration of tonic-colonic seizures significantly increased in control-morphine and stressed-saline rats compared to stressed-morphine and control-saline rats on P15, but not P25. COS levels increased in stressed-saline group but decreased in control-morphine group compared to control-saline rats. Body weight was significantly higher in morphine groups than saline treated rats. Prenatal exposure to forced-swim stress potentiated PTZ-induced seizure in the offspring rats. Co-administration of morphine attenuated effect of stress on body weight, COS levels, and epileptic behaviors. © 2014 Wiley Periodicals, Inc.

  19. Prolonged Febrile Seizures in the Immature Rat Model Enhance Hippocampal Excitability Long Term

    PubMed Central

    Dube, Celine; Chen, Kang; Eghbal-Ahmadi, Mariam; Brunson, Kristen; Soltesz, Ivan; Baram, Tallie Z.

    2011-01-01

    Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. PMID:10716253

  20. The effect of propofol-remifentanil anesthesia on selected seizure quality indices in electroconvulsive therapy.

    PubMed

    Dinwiddie, Stephen H; Glick, David B; Goldman, Morris B

    2012-07-01

    Use of a short-acting opiate to potentiate anesthetic induction agents has been shown to increase seizure duration in electroconvulsive therapy (ECT), but little is known of the effect of this combination on indices of seizure quality. To determine whether anesthetic modality affects commonly provided indices of seizure quality. Twenty-five subjects were given propofol 2 mg/kg body weight for their first ECT session, at which time seizure threshold was titrated. Subjects thereafter alternated between that anesthetic regimen or propofol 0.5 mg/kg plus remifentanil 1 mcg/kg. Linear mixed models with random subject effect, adjusting for electrode placement, electrical charge, and number of treatments, were fit to estimate effect of anesthesia on seizure duration and several standard seizure quality indices (average seizure energy, time to peak electroencephalography (EEG) power, maximum sustained power, interhemispheric coherence, early and midictal EEG amplitude, and maximum sustained interhemispheric EEG coherence). Propofol-remifentanil anesthesia significantly lengthened seizure duration and was associated with longer time to reach maximal EEG power and coherence as well as maximal degree of interhemispheric EEG coherence. No effect was seen on early ictal amplitude or average seizure energy index. Propofol-remifentanil anesthesia prolongs seizure duration and has a significant effect on some, but not all, measures of seizure quality. This effect may be of some benefit in cases where adequate seizures are otherwise difficult to elicit. Varying anesthetic technique may allow more precise investigation of the relationships between and relative impacts of commonly used seizure quality indices on clinical outcomes and ECT-related cognitive side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Predicting seizure by modeling synaptic plasticity based on EEG signals - a case study of inherited epilepsy

    NASA Astrophysics Data System (ADS)

    Zhang, Honghui; Su, Jianzhong; Wang, Qingyun; Liu, Yueming; Good, Levi; Pascual, Juan M.

    2018-03-01

    This paper explores the internal dynamical mechanisms of epileptic seizures through quantitative modeling based on full brain electroencephalogram (EEG) signals. Our goal is to provide seizure prediction and facilitate treatment for epileptic patients. Motivated by an earlier mathematical model with incorporated synaptic plasticity, we studied the nonlinear dynamics of inherited seizures through a differential equation model. First, driven by a set of clinical inherited electroencephalogram data recorded from a patient with diagnosed Glucose Transporter Deficiency, we developed a dynamic seizure model on a system of ordinary differential equations. The model was reduced in complexity after considering and removing redundancy of each EEG channel. Then we verified that the proposed model produces qualitatively relevant behavior which matches the basic experimental observations of inherited seizure, including synchronization index and frequency. Meanwhile, the rationality of the connectivity structure hypothesis in the modeling process was verified. Further, through varying the threshold condition and excitation strength of synaptic plasticity, we elucidated the effect of synaptic plasticity to our seizure model. Results suggest that synaptic plasticity has great effect on the duration of seizure activities, which support the plausibility of therapeutic interventions for seizure control.

  2. The effects of inferior olive lesion on strychnine seizure

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

    Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

    1990-10-01

    Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable ({sup 3}H)AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding in cerebella from inferior olive-lesioned rats was observed, but no difference in ({sup 3}H)AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10 imine) were tested asmore » anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the ({sup 3}H)AMPA binding data.« less

  3. 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. ...

  4. Febrile seizures

    MedlinePlus

    ... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

  5. Seizures and Teens: Sorting Out Seizures--Part Two

    ERIC Educational Resources Information Center

    Devinsky, Orrin

    2006-01-01

    In adolescents, diagnosing seizures can be challenging and can lead to many pitfalls. Because seizures are episodic and unpredictable events, they usually do not occur in the doctor's office. Thus, a diagnosis of epilepsy is usually based on information presented by the person with seizures and their family. Together with results of diagnostic…

  6. Etiology of a genetically complex seizure disorder in Celf4 mutant mice

    PubMed Central

    Wagnon, Jacy L.; Mahaffey, Connie L.; Sun, Wenzhi; Yang, Yan; Chao, Hsiao-Tuan; Frankel, Wayne N.

    2011-01-01

    Mice deficient for the gene encoding the RNA-binding protein CELF4 (CUGBP, ELAV-like family member 4) have a complex seizure phenotype that includes both convulsive and non-convulsive seizures, depending upon gene dosage and strain background, modeling genetically complex epilepsy. Invertebrate CELF is associated with translational control in fruit fly ovary epithelium and with neurogenesis and neuronal function in the nematode. Mammalian CELF4 is expressed widely during early development, but is restricted to the central nervous system in adult. To better understand the etiology of the seizure disorder of Celf4 deficient mice, we studied seizure incidence with spatial and temporal conditional knockout Celf4 alleles. For convulsive seizure phenotypes, it is sufficient to delete Celf4 in adulthood at seven weeks of age. This timing is in contrast to absence-like non-convulsive seizures, which require deletion before the end of the first postnatal week. Interestingly, selective deletion of Celf4 from cerebral cortex and hippocampus excitatory neurons, but not from inhibitory neurons, is sufficient to lower seizure threshold and to promote spontaneous convulsions. Correspondingly, Celf4 deficient mice have altered excitatory, but not inhibitory, neurotransmission as measured by patch-clamp recordings of cortical layer V pyramidal neurons. Finally, immunostaining in conjunction with an inhibitory neuron-specific reporter shows that CELF4 is expressed predominantly in excitatory neurons. Our results suggest that CELF4 plays a specific role in regulating excitatory neurotransmission. We posit that altered excitatory neurotransmission resulting from Celf4 deficiency underlies the complex seizure disorder in Celf4 mutant mice. PMID:21745337

  7. Curcumin inhibits amygdaloid kindled seizures in rats.

    PubMed

    DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

    2009-06-20

    Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

  8. 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.

  9. In Vitro Antimicrobial Activity of Razupenem (SMP-601, PTZ601) against Anaerobic Bacteria▿

    PubMed Central

    Tran, Chau Minh; Tanaka, Kaori; Yamagishi, Yuka; Goto, Takatsugu; Mikamo, Hiroshige; Watanabe, Kunitomo

    2011-01-01

    We evaluated the in vitro antianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroides spp. (MIC90s of 2 μg/ml), with MIC90 values of 0.06, 0.03, and 0.5 μg/ml against Prevotella spp., Porphyromonas spp., and Fusobacterium spp., respectively. Clinical isolates of anaerobic Gram-positive cocci, Eggerthella spp., and Clostridium spp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml). PMID:21343447

  10. Automated seizure detection systems and their effectiveness for each type of seizure.

    PubMed

    Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

    2016-08-01

    Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. Copyright © 2016. Published by Elsevier Ltd.

  11. Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis.

    PubMed

    Luszczki, Jarogniew J; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanislaw J

    2006-11-01

    Isobolographic analysis was used to characterize the interactions between stiripentol (STP) and clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice. The anticonvulsant and acute adverse (neurotoxic) effects of STP in combination with the various conventional antiepileptic drugs (AEDs), at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the PTZ and chimney tests in mice using the isobolographic analysis. Additionally, protective indices (PI) and benefit indices (BI) were calculated to identify their pharmacological profiles so that a ranking in relation to advantageous combination could be established. Moreover, adverse-effect paradigms were determined by use of the step-through passive avoidance task (long-term memory), threshold for the first pain reaction, grip-strength test (neuromuscular tone), and the hot plate test (acute thermal pain). Brain AED concentrations were also measured so as to ascertain any pharmacokinetic contribution to the pharmacodynamic interactions. All AED combinations comprising of STP and CZP, ETS, PB, and VPA (at the fixed ratios of 1:3, 1:1 and 3:1) were additive in terms of clonic seizure suppression in the PTZ test. However, these interactions were complicated by changes in brain AED concentrations consequent to pharmacokinetic interactions. Thus STP significantly increased total brain ETS and PB concentrations, and decreased VPA concentrations, but was without effect on CZP concentrations. In contrast, PB significantly decreased and VPA increased total brain STP concentrations while CZP and ETS were without effect. Furthermore, while isobolographic analysis revealed that STP and CZP in combination, at the fixed ratios of 1:1 and 3:1, were supraadditive (synergistic; p < 0.05), the combinations of STP with CZP (1:3), ETS, PB, or VPA (at all fixed ratios of 1:3, 1:1, and 3:1) were barely additivity in terms of acute neurotoxic adverse

  12. 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.

  13. Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission.

    PubMed

    Kadiyala, Sridhar B; Yannix, Joshua Q; Nalwalk, Julia W; Papandrea, Dominick; Beyer, Barbara S; Herron, Bruce J; Ferland, Russell J

    2016-07-13

    The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7-12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure-ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication

  14. Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma.

    PubMed

    Kast, R E; Lefranc, F; Karpel-Massler, G; Halatsch, M-E

    2012-12-01

    Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question "Why should a sulfone antibiotic reduce seizures?". We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.

  15. Automated tracking of a figure skater by using PTZ cameras

    NASA Astrophysics Data System (ADS)

    Haraguchi, Tomohiko; Taki, Tsuyoshi; Hasegawa, Junichi

    2009-08-01

    In this paper, a system for automated real-time tracking of a figure skater moving on an ice rink by using PTZ cameras is presented. This system is intended for support in training of skating, for example, as a tool for recording and evaluation of his/her motion performances. In the processing procedure of the system, an ice rink region is extracted first from a video image by region growing method, then one of hole components in the obtained rink region is extracted as a skater region. If there exists no hole component, a skater region is estimated from horizontal and vertical intensity projections of the rink region. Each camera is automatically panned and/or tilted so as to keep the skater region on almost the center of the image, and also zoomed so as to keep the height of the skater region within an appropriate range. In the experiments using 5 practical video images of skating, it was shown that the extraction rate of the skater region was almost 90%, and tracking with camera control was successfully done for almost all of the cases used here.

  16. Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

    PubMed Central

    Kadiyala, Sridhar B.; Yannix, Joshua Q.; Nalwalk, Julia W.; Papandrea, Dominick; Beyer, Barbara S.; Herron, Bruce J.

    2016-01-01

    The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with

  17. Seizures

    MedlinePlus

    ... wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. NIH: National Institute of Neurological Disorders and Stroke

  18. 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

  19. Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

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

    Talathi, S. S.

    Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizuremore » detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.« less

  20. Temporal epilepsy seizures monitoring and prediction using cross-correlation and chaos theory.

    PubMed

    Haddad, Tahar; Ben-Hamida, Naim; Talbi, Larbi; Lakhssassi, Ahmed; Aouini, Sadok

    2014-01-01

    Temporal seizures due to hippocampal origins are very common among epileptic patients. Presented is a novel seizure prediction approach employing correlation and chaos theories. The early identification of seizure signature allows for various preventive measures to be undertaken. Electro-encephalography signals are spectrally broken down into the following sub-bands: delta; theta; alpha; beta; and gamma. The proposed approach consists of observing a high correlation level between any pair of electrodes for the lower frequencies and a decrease in the Lyapunov index (chaos or entropy) for the higher frequencies. Power spectral density and statistical analysis tools were used to determine threshold levels for the lower frequencies. After studying all five sub-bands, the analysis has revealed that the seizure signature can be extracted from the delta band and the high frequencies. High frequencies are defined as both the gamma band and the ripples occurring within the 60-120 Hz sub-band. To validate the proposed approach, six patients from both sexes and various age groups with temporal epilepsies originating from the hippocampal area were studied using the Freiburg database. An average seizure prediction of 30 min, an anticipation accuracy of 72%, and a false-positive rate of 0% were accomplished throughout 200 h of recording time.

  1. Early Detection of Human Focal Seizures Based on Cortical Multiunit Activity

    PubMed Central

    Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

    2014-01-01

    Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz – 6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

  2. Treating acute seizures with benzodiazepines: does seizure duration matter?

    PubMed

    Naylor, David E

    2014-10-01

    Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self-sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA-A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re-arrangements of receptor subunits that all contribute to long-term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first-line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long-term harm.

  3. Automated detection of videotaped neonatal seizures based on motion segmentation methods.

    PubMed

    Karayiannis, Nicolaos B; Tao, Guozhi; Frost, James D; Wise, Merrill S; Hrachovy, Richard A; Mizrahi, Eli M

    2006-07-01

    This study was aimed at the development of a seizure detection system by training neural networks using quantitative motion information extracted by motion segmentation methods from short video recordings of infants monitored for seizures. The motion of the infants' body parts was quantified by temporal motion strength signals extracted from video recordings by motion segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by direct thresholding, by clustering of the pixel velocities, and by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The computational tools and procedures developed for automated seizure detection were tested and evaluated on 240 short video segments selected and labeled by physicians from a set of video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). The experimental study described in this paper provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. Depending on the decision scheme used for interpreting the responses of the trained neural networks, the best neural networks exhibited sensitivity above 90% or specificity above 90%. The best among the motion segmentation methods developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of this phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion trajectory signals produced by motion tracking methods. A video system based upon automated analysis potentially offers a number of advantages. Infants who are at risk for

  4. In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures.

    PubMed

    Gharibi Loron, Ali; Sardari, Soroush; Narenjkar, Jamshid; Sayyah, Mohammad

    2017-01-01

    Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA) make it as a good candidate for designing and development of the new anticonvulsant medications. Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection of the screened compounds to mice. Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED50 values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED50 values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA.

  5. In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures

    PubMed Central

    Loron, Ali Gharibi; Sardari, Soroush; Narenjkar, Jamshid; Sayyah, Mohammad

    2017-01-01

    Background: Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA) make it as a good candidate for designing and development of the new anticonvulsant medications. Methods: Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection of the screened compounds to mice. Results: Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED50 values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED50 values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. Conclusion: Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA. PMID:27592363

  6. Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke.

    PubMed

    Fox, Christine K; Glass, Hannah C; Sidney, Stephen; Smith, Sabrina E; Fullerton, Heather J

    2016-06-07

    To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke. We retrospectively identified a population-based cohort of children with perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy (≥1 remote seizure and maintenance anticonvulsant treatment) at last follow-up. Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period. During a median follow-up of 7.1 years (interquartile range 3.2-10.5), 37 children had ≥1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval [CI] 13%-30%) cumulative incidence by 1 year of age, 46% (CI 35%-58%) by 5 years, and 54% (CI 41%-67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3-5.8). Children with neonatal seizures had a 69% (CI 48%-87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant. Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk. © 2016 American Academy of Neurology.

  7. Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

    PubMed

    Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

    2016-11-25

    Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

  8. Anticonvulsant effect of Persea americana Mill (Lauraceae) (Avocado) leaf aqueous extract in mice.

    PubMed

    Ojewole, John A O; Amabeoku, George J

    2006-08-01

    Various morphological parts of Persea americana Mill (Lauraceae) (avocado) are widely used in African traditional medicines for the treatment, management and/or control of a variety of human ailments, including childhood convulsions and epilepsy. This study examined the anticonvulsant effect of the plant's leaf aqueous extract (PAE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Like the reference anticonvulsant agents used, Persea americana leaf aqueous extract (PAE, 100-800 mg/kg i.p.) significantly (p < 0.05-0.001) delayed the onset of, and antagonized, pentylenetetrazole (PTZ)-induced seizures. The plant's leaf extract (PAE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but only weakly antagonized bicuculline (BCL)-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that 'avocado' leaf aqueous extract (PAE) produces its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain. The findings of this study indicate that Persea americana leaf aqueous extract possesses an anticonvulsant property, and thus lends pharmacological credence to the suggested ethnomedical uses of the plant in the management of childhood convulsions and epilepsy.

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

    PubMed

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

    2018-04-19

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

  10. Differences in Seizure Expression Between Magnetic Seizure Therapy and Electroconvulsive Shock.

    PubMed

    Cycowicz, Yael M; Rowny, Stefan B; Luber, Bruce; Lisanby, Sarah H

    2018-06-01

    Evidence suggests that magnetic seizure therapy (MST) results in fewer side effects than electroconvulsive treatment, both in humans treated with electroconvulsive therapy (ECT) as well as in the animal preclinical model that uses electroconvulsive shock (ECS). Evidence suggests that MST results in fewer cognitive side effects than ECT. Although MST offers enhanced control over seizure induction and spread, little is known about how MST and ECT seizures differ. Seizure characteristics are associated with treatment effect. This study presents quantitative analyses of electroencephalogram (EEG) power after electrical and magnetic seizure induction and anesthesia-alone sham in an animal model. The aim was to test whether differential neurophysiological characteristics of the seizures could be identified that support earlier observations that the powers of theta, alpha, and beta but not delta frequency bands were lower after MST when compared with those after ECS. In a randomized, sham-controlled trial, 24 macaca mulatte received 6 weeks of daily sessions while scalp EEG was recorded. Electroencephalogram power was quantified within delta, theta, alpha, and beta frequency bands. Magnetic seizure therapy induced lower ictal expression in the theta, alpha and beta frequencies than ECS, but MST and ECS were indistinguishable in the delta band. Magnetic seizure therapy showed less postictal suppression than ECS. Increasing electrical dosage increased ictal power, whereas increasing MST dosage had no effect on EEG expression. Magnetic seizure therapy seizures have less robust electrophysiological expression than ECS, and these differences are largest in the alpha and beta bands. The relevance of these differences in higher frequency bands to clinical outcomes deserves further exploration. Contrasting EEG in ECS and MST may lead to insights on the physiological underpinnings of seizure-induced amnesia and to finding ways to reduce cognitive side effects.

  11. Seizure development after stroke.

    PubMed

    Misirli, H; Ozge, A; Somay, G; Erdoğan, N; Erkal, H; Erenoğlu, N Y

    2006-12-01

    Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

  12. Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs.

    PubMed Central

    Dolin, S. J.; Patch, T. L.; Rabbani, M.; Siarey, R. J.; Bowhay, A. R.; Little, H. J.

    1990-01-01

    1. The effects of the calcium channel blocking agent, nitrendipine, were studied on seizures in mice produced during withdrawal from chronic benzodiazepine treatment and on the development of tolerance to benzodiazepines. 2. Nitrendipine produced a dose-dependent decrease in seizure incidence, when seizures were produced by the partial inverse agonist FG7142 during withdrawal from seven days treatment with flurazepam. 3. Nitrendipine did not raise the seizure thresholds in naïve mice to the full inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), or to the gamma-aminobutyric acid (GABA) antagonist, bicuculline. 4. When given concurrently with flurazepam for seven days, nitrendipine did not affect the incidence of seizures during flurazepam withdrawal. 5. When given concurrently with the benzodiazepines, nitrendipine did not prevent the development of tolerance to midazolam general anaesthesia or tolerance to the ataxic actions of flurazepam or midazolam. 6. Chronic treatment with flurazepam for seven days did not affect the Kd or Bmax of [3H]-nimodipine binding in mouse whole brain or cerebral cortex. 7. These results with benzodiazepines are partially in contrast with those for ethanol, where nitrendipine not only decreased ethanol withdrawal seizures when given acutely, but also prevented the development of tolerance and withdrawal signs when given concurrently with ethanol. However, they do confirm the selectivity of nitrendipine for withdrawal-induced seizures. PMID:1963805

  13. Athletes with seizure disorders.

    PubMed

    Knowles, Byron Don; Pleacher, Michael D

    2012-01-01

    Individuals with seizure disorders have long been restricted from participation in certain sporting activities. Those with seizure disorders are more likely than their peers to have a sedentary lifestyle and to develop obesity. Regular participation in physical activity can improve both physical and psychosocial outcomes for persons with seizure disorders. Seizure activity often is reduced among those patients who regularly engage in aerobic activity. Recent literature indicates that the diagnosis of seizure disorders remains highly stigmatizing in the adolescent population. Persons with seizure disorders may be more accepted by peer groups if they are allowed to participate in sports and recreational activities. Persons with seizure disorders are encouraged to participate in regular aerobic activities. They may participate in team sports and contact or collision activities provided that they utilize appropriate protective equipment. There seems to be no increased risk of injury or increasing seizure activity as the result of such participation. Persons with seizure disorders still are discouraged from participating in scuba diving and skydiving. The benefits of participation in regular sporting activity far outweigh any risk to the athlete with a seizure disorder who chooses to participate in sports.

  14. Functional neurotoxicity evaluation of noribogaine using video-EEG in cynomolgus monkeys.

    PubMed

    Authier, Simon; Accardi, Michael V; Paquette, Dominique; Pouliot, Mylène; Arezzo, Joseph; Stubbs, R John; Gerson, Ronald J; Friedhoff, Lawrence T; Weis, Holger

    2016-01-01

    Continuous video-electroencephalographic (EEG) monitoring remains the gold standard for seizure liability assessments in preclinical drug safety assessments. EEG monitored by telemetry was used to assess the behavioral and EEG effects of noribogaine hydrochloride (noribogaine) in cynomolgus monkeys. Noribogaine is an iboga alkaloid being studied for the treatment of opioid dependence. Six cynomolgus monkeys (3 per gender) were instrumented with EEG telemetry transmitters. Noribogaine was administered to each monkey at both doses (i.e., 160 and 320mg/kg, PO) with an interval between dosing of at least 6days, and the resulting behavioral and EEG effects were evaluated. IV pentylenetetrazol (PTZ), served as a positive control for induced seizures. The administration of noribogaine at either of the doses evaluated was not associated with EEG evidence of seizure or with EEG signals known to be premonitory signs of increased seizure risk (e.g., sharp waves, unusual synchrony, shifts to high-frequency patterns). Noribogaine was associated with a mild reduction in activity levels, increased scratching, licking and chewing, and some degree of poor coordination and related clinical signs. A single monkey exhibited brief myoclonic movements that increased in frequency at the high dose, but which did not appear to generalize, cluster or to be linked with EEG abnormalities. Noribogaine was also associated with emesis and partial anorexia. In contrast, PTZ was associated with substantial pre-ictal EEG patterns including large amplitude, repetitive sharp waves leading to generalized seizures and to typical post-ictal EEG frequency attenuation. EEG patterns were within normal limits following administration of noribogaine at doses up to 320mg/kg with concurrent clinical signs that correlated with plasma exposures and resolved by the end of the monitoring period. PTZ was invariably associated with EEG paroxysmal activity leading to ictal EEG. In the current study, a noribogaine

  15. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.

    PubMed

    Marques, Thiago Henrique Costa; Marques, Maria Leonildes Boavista Gomes Castelo Branco; Medeiros, Jand-Venes Rolim; Lima, Tamires Cardoso; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2014-09-01

    Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (p<0.05) in PILO, PTZ and PTX groups when compared with vehicle. However, these effects were not reversed by flumazenil, benzodiazepine (BZD) antagonist used to investigate the CC action mechanism. Our results suggest that acute treatment with CC at the doses tested can exert anticonvulsant effects in PILO, PTZ and PTX epilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant

  16. Seizure Disorders in Pregnancy

    MedlinePlus

    ... If I have a seizure disorder, can it cause problems during pregnancy? • What risks are associated with having a seizure ... If I have a seizure disorder, can it cause problems during pregnancy? Seizure disorders can affect pregnancy in several ways: • ...

  17. Efficacy of the ketogenic diet in the 6-Hz seizure test

    PubMed Central

    Hartman, Adam L.; Lyle, Megan; Rogawski, Michael A.; Gasior, Maciej

    2008-01-01

    SUMMARY Purpose Since the ketogenic diet is effective in drug-resistant epilepsies, we sought to determine whether it is active in the 6-Hz seizure test, which identifies agents with a broader spectrum of activity than conventional antiepileptic screening tests. Methods Male (3–4 week old) NIH Swiss mice were fed a normal or ketogenic diet ad libitum for 2–21 days. The intensity of the corneal stimulation current required to elicit seizures in the 6-Hz test was measured. Blood glucose and β-hydroxybutyrate were measured on the day of seizure testing. Results CC50 (current intensity producing seizures in 50% of mice tested) was 50.6 mA and 15 mA in mice fed for 12 days with a ketogenic or normal diet, respectively (p < 0.001). CC50 was elevated in separate experiments after 16, but not 2, 5, and 21 days of ketogenic diet exposure. CC50 values of growing mice fed the normal diet does not differ, indicating CC50 does not vary with mouse weight during a rapid growth phase. β-Hydroxybutyrate was significantly higher, and glucose was significantly lower in mice fed the ketogenic diet than those fed the normal diet. Blood glucose and β-hydroxybutyrate levels did not correlate with CC50. Discussion The ketogenic diet significantly elevates the seizure threshold in the 6-Hz test in a time-specific manner. Protection from seizures in this model was not related to level of ketosis. CC50 was insensitive to body weight in mice fed the normal diet, demonstrating that the 6-Hz model can assess anticonvulsant regimens where weight is a confounding factor. PMID:18070095

  18. Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

    PubMed

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

    2016-11-01

    This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

    PubMed

    Jason, Eva Åndell; Tomson, Torbjörn; Carlsson, Sofia; Tedroff, Kristina; Åmark, Per

    2018-07-01

    To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year exhibited the highest prevalence of comorbidities as well as OR for repeated seizures. A combination of young age and comorbidity was associated with an OR for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without comorbidities 76% were seizure free 13-24 months after the index seizure or after initiation of AED treatment compared to 53% of children with comorbidities. This study indicates that neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without

  20. Synthesis, and anticonvulsant activity of new amides derived from 3-methyl- or 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetic acids.

    PubMed

    Obniska, Jolanta; Rapacz, Anna; Rybka, Sabina; Góra, Małgorzata; Kamiński, Krzysztof; Sałat, Kinga; Żmudzki, Paweł

    2016-04-15

    This paper describes the synthesis of the library of 22 new 3-methyl- and 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetamides as potential anticonvulsant agents. The maximal electroshock (MES) and the subcutaneous pentylenetetrazole (scPTZ) seizure models were used for screening all the compounds. The 6 Hz model of pharmacoresistant limbic seizures was applied for studying selected derivatives. Six amides were chosen for pharmacological characterization of their antinociceptive activity in the formalin model of tonic pain as well as local anesthetic activity was assessed in mice. The pharmacological data indicate on the broad spectra of activity across the preclinical seizure models. Compounds 10 (ED50=32.08 mg/kg, MES test) and 9 (ED50=40.34 mg/kg, scPTZ test) demonstrated the highest potency. These compounds displayed considerably better safety profiles than clinically relevant antiepileptic drugs phenytoin, ethosuximide, or valproic acid. Several molecules showed antinociceptive and local anesthetic properties. The in vitro radioligand binding studies demonstrated that the influence on the sodium and calcium channels may be one of the essential mechanisms of action. Copyright © 2016. Published by Elsevier Ltd.

  1. Febrile Seizures

    MedlinePlus

    ... seizures in infants and children, doctors sometimes perform tests to be sure that the seizures are not caused by an underlying or more serious health condition. For example, meningitis, an infection of the membranes surrounding the ...

  2. EEG analysis of seizure patterns using visibility graphs for detection of generalized seizures.

    PubMed

    Wang, Lei; Long, Xi; Arends, Johan B A M; Aarts, Ronald M

    2017-10-01

    The traditional EEG features in the time and frequency domain show limited seizure detection performance in the epileptic population with intellectual disability (ID). In addition, the influence of EEG seizure patterns on detection performance was less studied. A single-channel EEG signal can be mapped into visibility graphs (VGS), including basic visibility graph (VG), horizontal VG (HVG), and difference VG (DVG). These graphs were used to characterize different EEG seizure patterns. To demonstrate its effectiveness in identifying EEG seizure patterns and detecting generalized seizures, EEG recordings of 615h on one EEG channel from 29 epileptic patients with ID were analyzed. A novel feature set with discriminative power for seizure detection was obtained by using the VGS method. The degree distributions (DDs) of DVG can clearly distinguish EEG of each seizure pattern. The degree entropy and power-law degree power in DVG were proposed here for the first time, and they show significant difference between seizure and non-seizure EEG. The connecting structure measured by HVG can better distinguish seizure EEG from background than those by VG and DVG. A traditional EEG feature set based on frequency analysis was used here as a benchmark feature set. With a support vector machine (SVM) classifier, the seizure detection performance of the benchmark feature set (sensitivity of 24%, FD t /h of 1.8s) can be improved by combining our proposed VGS features extracted from one EEG channel (sensitivity of 38%, FD t /h of 1.4s). The proposed VGS-based features can help improve seizure detection for ID patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Leaving tissue associated with infrequent intracranial EEG seizure onsets is compatible with post-operative seizure freedom

    PubMed Central

    Huang, Cyrus; Marsh, Eric D.; Ziskind, Daniela M.; Celix, Juanita M.; Peltzer, Bradley; Brown, Merritt W.; Storm, Phillip B.; Litt, Brian; Porter, Brenda E.

    2013-01-01

    Identify seizure onset electrodes that need to be resected for seizure freedom in children undergoing intracranial electroencephalography recording for treatment of medically refractory epilepsy. All children undergoing intracranial electroencephalography subdural grid electrode placement at the Children’s Hospital of Philadelphia from 2002-2008 were asked to enroll. We utilized intraoperative pictures to determine the location of the electrodes and define the resection cavity. A total of 15 patients had surgical fields that allowed for complete identification of the electrodes over the area of resection. Eight of 15 patients were seizure free after a follow up of 1.7 to 8 yr. Only one seizure-free patient had complete resection of all seizure onset associated tissue. Seizure free patients had resection of 64.1% of the seizure onset electrode associated tissue, compared to 35.2% in the not seizure free patients (p=0.05). Resection of tissue associated with infrequent seizure onsets did not appear to be important for seizure freedom. Resecting ≥ 90% of the electrodes from the predominant seizure contacts predicted post-operative seizure freedom (p=0.007). The best predictor of seizure freedom was resecting ≥ 90% of tissue involved in majority of a patient’s seizures. Resection of tissue under infrequent seizure onset electrodes was not necessary for seizure freedom. PMID:24563805

  4. Anticonvulsant Effects of the Hydroalcoholic Extract of Alpinia officinarum Rhizomesin Mice: Involvement of Benzodiazepine and Opioid Receptors

    PubMed Central

    Nejad, Shaghayegh Rezvani; Motevalian, Manijeh; Fatemi, Iman; Shojaii, Asie

    2017-01-01

    Background and Purpose Epilepsy is one of the most common serious neurological conditions. The current therapeutic treatment of epilepsy with modern antiepileptic drugs is associated with side effects, dose-related and chronic toxicity, and teratogenic effects and in approximately 30% of the patients is ineffective. Alpinia officinarum is used in Iranian traditional medicine for treatment of different diseases like back pain and seizure. Methods In this study, anticonvulsant effects of hydroalcoholic extract of Alpinia officinarum rhizomes were examined by using pentylentetrazole (PTZ) model in mice. Alpinia officinarum rhizomes extract (200, 400 and 600 mg/kg), diazepam (1 mg/kg) and normal saline (10 mL/kg) were injected (ip) 30 minutes before PTZ (90 mg/kg, ip). The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For further clarification of the mechanism of action for Alpinia officinarum, flumazenil (2 mg/kg, ip) and naloxone (5 mg/kg, ip) were also injected 5 minutes before Alpinia officinarum extract. Results Alpinia officinarum extract at the doses of 200 and 400 mg/kg prolonged the time of onset of seizure and decreased the duration of seizures compared to control (saline) group (p < 0.05). At the dose of 600 mg/kg, percentage of seizure protection was 16.66%. Naloxone and flumazenil could suppress anticonvulsant effects of Alpinia officinarum. Conclusions It seems that Alpinia officinarum could be a good candidate and be useful for seizure control and treatment, and in these effects, opioid and benzodiazepine receptors might probably be involved. PMID:28775953

  5. Anticonvulsant Effects of the Hydroalcoholic Extract of Alpinia officinarum Rhizomesin Mice: Involvement of Benzodiazepine and Opioid Receptors.

    PubMed

    Nejad, Shaghayegh Rezvani; Motevalian, Manijeh; Fatemi, Iman; Shojaii, Asie

    2017-06-01

    Epilepsy is one of the most common serious neurological conditions. The current therapeutic treatment of epilepsy with modern antiepileptic drugs is associated with side effects, dose-related and chronic toxicity, and teratogenic effects and in approximately 30% of the patients is ineffective. Alpinia officinarum is used in Iranian traditional medicine for treatment of different diseases like back pain and seizure. In this study, anticonvulsant effects of hydroalcoholic extract of Alpinia officinarum rhizomes were examined by using pentylentetrazole (PTZ) model in mice. Alpinia officinarum rhizomes extract (200, 400 and 600 mg/kg), diazepam (1 mg/kg) and normal saline (10 mL/kg) were injected (ip) 30 minutes before PTZ (90 mg/kg, ip). The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For further clarification of the mechanism of action for Alpinia officinarum , flumazenil (2 mg/kg, ip) and naloxone (5 mg/kg, ip) were also injected 5 minutes before Alpinia officinarum extract. Alpinia officinarum extract at the doses of 200 and 400 mg/kg prolonged the time of onset of seizure and decreased the duration of seizures compared to control (saline) group ( p < 0.05). At the dose of 600 mg/kg, percentage of seizure protection was 16.66%. Naloxone and flumazenil could suppress anticonvulsant effects of Alpinia officinarum . It seems that Alpinia officinarum could be a good candidate and be useful for seizure control and treatment, and in these effects, opioid and benzodiazepine receptors might probably be involved.

  6. Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats.

    PubMed

    Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

    2015-08-01

    To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment.

  7. Reflex seizures in Rett syndrome.

    PubMed

    Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

    2011-12-01

    Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

  8. Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure.

    PubMed

    Rizvi, Syed; Ladino, Lady Diana; Hernandez-Ronquillo, Lizbeth; Téllez-Zenteno, José F

    2017-07-01

    A single unprovoked seizure is a frequent phenomenon in the general population and the rate of seizure recurrence can vary widely. Individual risk prognostication is crucial in predicting patient outcomes and guiding treatment decisions. In this article, we review the most important risk factors associated with an increased likelihood of seizure recurrence after a single unprovoked seizure. In summary, the presence of focal seizure, nocturnal seizure, history of prior brain injury, family history of epilepsy, abnormal neurological exam, epileptiform discharges on electroencephalography and neuroimaging abnormalities, portend increased risk of seizure recurrence. Elucidation of these risk factors in patient assessment will augment clinical decision-making and may help determine the appropriateness of instituting anti-epilepsy treatment. We also discuss the Canadian model of single seizure clinics and the potential use to assess these patients. Copyright © 2017. Published by Elsevier Ltd.

  9. Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening.

    PubMed

    Siddiqui, Nadeem; Ahsan, Waquar

    2010-04-01

    Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED(50) values 23.9 mg/kg and 13.4 mg/kg respectively in MES screen and 178.6 mg/kg and 81.6 mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD(50)) and median lethal dose (LD(50)) much higher than the standard drugs. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  10. Differential Effects of High Dose Magnetic Seizure Therapy (MST) and Electroconvulsive Shock (ECS) on Cognitive Function

    PubMed Central

    Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.

    2008-01-01

    Background Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. Using a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6X seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5X seizure threshold. Methods Daily high-dose MST, ECS, and Sham (anesthesia-only) were administered for 4 weeks each in a within-subject cross-over design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results Subjects were slower to complete criterion tasks (p’s<0.0001) following ECS, compared to sham and high-dose MST. Moreover, time to task-completion following high-dose MST did not differ from sham. Out of 6 measures of accuracy, treatment effects were found in 4; in all of these, ECS, but not MST, fared worse than Sham. On all accuracy and time to completion measurements, subjects performed as well as following high-dose MST as did subjects from a previous study on moderate-dose MST. Conclusion These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS, and are in line with our previous studies. PMID:18262171

  11. Afebrile seizure subsequent to initial febrile seizure.

    PubMed

    Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

    2012-05-01

    Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

  12. Alfentanil anesthetic augmentation lengthens seizure duration in electroconvulsive therapy with older people.

    PubMed

    D'Cunha, Craig; Plakiotis, Christos; O'Connor, Daniel W

    2016-06-01

    Electroconvulsive therapy (ECT) prescription rates rise with age, making it important that treatments be made as effective and safe as possible (Plakiotis et al., 2012). Older people are vulnerable to post-treatment confusion and to subsequent deficits in attention, new learning, and autobiographical memory (Gardner and O'Connor, 2008). Strategies to minimize cognitive side-effects include unilateral electrode placement and stimulus dose titration whereby electrical charge is individually calibrated to seizure threshold (Sackeim et al., 2000). It remains the case, however, that threshold levels typically rise over the treatment course, leading to an increase both in delivered charge and the risk of adverse sequelae.

  13. Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy.

    PubMed

    Ramgopal, Sriram; Thome-Souza, Sigride; Jackson, Michele; Kadish, Navah Ester; Sánchez Fernández, Iván; Klehm, Jacquelyn; Bosl, William; Reinsberger, Claus; Schachter, Steven; Loddenkemper, Tobias

    2014-08-01

    Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy. Copyright © 2014. Published by Elsevier Inc.

  14. 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 ...

  15. The serotonin axis: Shared mechanisms in seizures, depression and SUDEP

    PubMed Central

    Richerson, George B.; Buchanan, Gordon F.

    2010-01-01

    Summary There is a growing appreciation that patients with seizures are also affected by a number of co-morbid conditions, including an increase in prevalence of depression (Kanner, 2009), sleep apnea (Chihorek et al, 2007), and sudden death (Ryvlin et al, 2006; Tomson et al, 2008). The mechanisms responsible for these associations are unclear. Here we discuss the possibility that underlying pathology in the serotonin (5-HT) system of epilepsy patients lowers the threshold for seizures, while also increasing the risk of depression and sudden death. We propose that post-ictal dysfunction of 5-HT neurons causes depression of breathing and arousal in some epilepsy patients, and this can lead to sudden unexpected death in epilepsy (SUDEP). We further draw parallels between SUDEP and sudden infant death syndrome (SIDS), which may share pathophysiological mechanisms, and which have both been linked to defects in the 5-HT system. PMID:21214537

  16. 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.

  17. Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

    PubMed

    Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

    2017-04-01

    Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

  18. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    NASA Astrophysics Data System (ADS)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  19. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2014-01-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.2–2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

  20. Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

    PubMed

    Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

    2016-03-01

    Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants.

    PubMed

    Singh, Paramdeep; Singh, Damanpreet; Goel, Rajesh K

    2016-07-01

    Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential. The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice. The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15 d post-treatment with phenytoin (25 mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15 mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35 mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry. The fraction showed marked antioxidant activity indicated by low IC50 values in DPPH (20.9 µg/mL), nitric oxide radical scavenging (195.2 µg/mL), and capacity of hydrogen peroxide scavenging (3.4 µg/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm. From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice.

  2. Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures.

    PubMed

    Maj, R; Fariello, R G; Pevarello, P; Varasi, M; McArthur, R A; Salvati, P

    1999-11-01

    PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drug (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation 1 day before drug treatment. PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose-dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose-related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

  3. Fibromyalgia and seizures.

    PubMed

    Tatum, William O; Langston, Michael E; Acton, Emily K

    2016-06-01

    The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described.

  4. 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.

  5. 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

  6. 7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions.

    PubMed

    Borowicz, K K; Luszczki, J; Kleinrok, Z; Czuczwar, S J

    2000-01-01

    The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and clonazepam, significantly reducing their ED50S against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor clonazepam, administered at their ED50S (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.

  7. Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

    PubMed

    Irmen, Friederike; Wehner, Tim; Lemieux, Louis

    2015-02-01

    Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  8. The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide.

    PubMed

    Shafaroodi, Hamed; Oveisi, Simin; Hosseini, Mahsa; Niknahad, Hossein; Moezi, Leila

    2015-07-01

    Aripiprazole is an antipsychotic drug which acts through dopamine and serotonin receptors. Aripiprazole was noted to have antiseizure effects in a study on mice, while it induced seizures in a few human case reports. Dopaminergic and serotonergic systems relate to nitric oxide, and aripiprazole also has effects on dopamine and serotonin receptors. This study investigated the effects of aripiprazole on seizures and the potential role of nitric oxide in the process. The following three models were examined to explore the role of aripiprazole on seizures in mice: 1 - pentylenetetrazole administered intravenously, 2 - pentylenetetrazole administered intraperitoneally, and 3 - electroshock. Aripiprazole administration delayed clonic seizure in intravenous and intraperitoneal pentylenetetrazole models. In the electroshock-induced seizure model, tonic seizure and mortality protection percent were increased after aripiprazole administration. In intraperitoneal administration of pentylenetetrazole, aripiprazole effects on clonic seizure latency were significantly decreased when l-NAME - a nonselective nitric oxide synthase (NOS) inhibitor, 7-nitroindazole - a selective neuronal NOS (nNOS) inhibitor, or aminoguanidine - a selective inducible NOS (iNOS) inhibitor was injected before aripiprazole administration. In the intravenous pentylenetetrazole method, administration of l-NAME or aminoguanidine inhibited aripiprazole effects on clonic seizure threshold. Aminoguanidine or l-NAME administration decreased aripiprazole-induced protection against tonic seizures and death in the electroshock model. In both intravenous and intraperitoneal seizure models, aripiprazole and l-arginine coadministration delayed the onset of clonic seizures. Moreover, it increased protection against tonic seizures and death in intraperitoneal pentylenetetrazole and electroshock models. In conclusion, the release of nitric oxide via iNOS or nNOS may be involved in anticonvulsant properties of

  9. Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

    PubMed

    Foote, F; Gale, K

    1983-11-25

    In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

  10. An EEG should not be obtained routinely after first unprovoked seizure in childhood.

    PubMed

    Gilbert, D L; Buncher, C R

    2000-02-08

    To quantify and analyze the value of expected information from an EEG after first unprovoked seizure in childhood. An EEG is often recommended as part of the standard diagnostic evaluation after first seizure. A MEDLINE search from 1980 to 1998 was performed. From eligible studies, data on EEG results and seizure recurrence risk in children were abstracted, and sensitivity, specificity, and positive and negative predictive values of EEG in predicting recurrence were calculated. Linear information theory was used to quantify and compare the expected information from the EEG in all studies. Standard test-treat decision analysis with a treatment threshold at 80% recurrence risk was used to determine the range of pretest recurrence probabilities over which testing affects treatment decisions. Four studies involving 831 children were eligible for analysis. At best, the EEG had a sensitivity of 61%, a specificity of 71%, and an expected information of 0.16 out of a possible 0.50. The pretest probability of recurrence was less than the lower limit of the range for rational testing in all studies. In this analysis, the quantity of expected information from the EEG was too low to affect treatment recommendations in most patients. EEG should be ordered selectively, not routinely, after first unprovoked seizure in childhood.

  11. Effect of sleep-wake reversal and sleep deprivation on the circadian rhythm of oxygen toxicity seizure susceptibility.

    NASA Technical Reports Server (NTRS)

    Dexter, J. D.; Hof, D. G.; Mengel, C. E.

    1972-01-01

    Albino Sprague-Dawley rats were exposed in a previously O2 flushed, CO2 free chamber. The exposure began with attainment of 60 psi (gauge) and the end point was the first generalized oxygen toxicity seizure. Animals were exposed to reversal diurnal conditions since weanlings until their sleep-wake cycles had completely reversed, and then divided into four groups of 20 based on the time of day exposed. The time of exposure to oxygen at high pressure prior to seizure was now significantly longer in the group exposed from 1900 to 2000 hr and a reversal of the circadian rhythm of oxygen toxicity seizure susceptibility was noted. Animals maintained on normal diurnal conditions were deprived of sleep on the day of exposure for the 12 hours prior to exposure at 1900 hr, while controls were allowed to sleep. There was no significant differences in the time prior to seizure between the deprived animals and the controls with an n = 40. Thus the inherent threshold in susceptibility to high-pressure oxygen seizures seems not to be a function of sleep itself, but of some biochemical/physiologic event which manifests a circadian rhythm.

  12. Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.

    PubMed

    Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat

    2015-10-01

    Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Delayed seizures after intracerebral haemorrhage

    PubMed Central

    Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

    2016-01-01

    Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1

  14. VEGF Receptor-2 (Flk-1) Overexpression in Mice Counteracts Focal Epileptic Seizures

    PubMed Central

    Nikitidou, Litsa; Kanter-Schlifke, Irene; Dhondt, Joke; Carmeliet, Peter; Lambrechts, Diether; Kokaia, Mérab

    2012-01-01

    Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1). VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg2+ via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity. PMID:22808185

  15. Seizures induced by music.

    PubMed

    Ogunyemi, A O; Breen, H

    1993-01-01

    Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

  16. Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats

    PubMed Central

    Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

    2015-01-01

    Aim: To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. Methods: For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Results: Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Conclusion: Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment. PMID:26095038

  17. Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

    PubMed

    Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

    2008-07-01

    Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

  18. Seizures and epilepsy in Alzheimer's disease.

    PubMed

    Friedman, Daniel; Honig, Lawrence S; Scarmeas, Nikolaos

    2012-04-01

    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. We performed a 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. 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. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. © 2011 Blackwell Publishing Ltd.

  19. Seizures and Teens: Using Technology to Develop Seizure Preparedness

    ERIC Educational Resources Information Center

    Shafer, Patricia O.; Schachter, Steven C.

    2007-01-01

    Most people learn about seizures from their doctors, but others know only what they have seen on television. Unfortunately, visits to doctor's office aren't long enough to learn all that is needed, and often times, doctors and nurses aren't available to teach this information. Seizures are often represented inaccurately and too dramatically on…

  20. mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

    PubMed Central

    Yang, Guo-Shuai; Zhou, Xiao-Yan; An, Xue-Fang; Liu, Xuan-Jun; Zhang, Yan-Jun; Yu, Dan

    2018-01-01

    Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke-induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)-1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT-1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT-1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)-mTOR and GLUT-1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT-1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia. The role of GLUT-1 in stroke-elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke-elicited seizures. PMID:29484389

  1. Behavioral and anticonvulsant effects of the standardized extract of Ficus platyphylla stem bark.

    PubMed

    Chindo, Ben A; Ya'U, Jamilu; Danjuma, Nuhu M; Okhale, Samuel E; Gamaniel, Karniyus S; Becker, Axel

    2014-06-11

    Decoctions of Ficus platyphylla Del.-Holl (Family: Moraceae) are used in Nigeria׳s folk medicine for the management of epilepsy and their efficacies are widely acclaimed among the rural communities of northern Nigeria. The aim of the study is to examine the behavioral and anticonvulsant properties of the standardized methanol extract of Ficus platyphylla (FP) stem bark, in order to scientifically describe its potential values in the management of convulsive disorders. High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the methanol extract were utilized and the intraperitoneal median lethal dose (LD50) determined in mice. The effects of FP were investigated on some murine models of behavior and its anticonvulsant effects studied on pentylenetetrazole (PTZ)-, strychnine (STN)-, picrotoxin (PCT)-, isoniazid (INH)-, aminophylline (AMI)- and maximal electroshock (MES)-induced seizures in mice. The intraperitoneal oral LD50 of FP was estimated to be 5000mg/kg. FP significantly reduced the locomotor activities including the total distance covered, speed, active time and rearing counts. It shortened the onset and prolonged the duration of diazepam-induced sleep, but had no effect on motor coordination on the rota-rod treadmill or beam-walking assay in mice at the doses tested. The extract protected the mice against PTZ- and STN-induced seizures and significantly delayed the latencies of myoclonic jerks and tonic seizures induced by all the standard convulsant agents (PTZ, PCT, INH, STN and AMI) used in this study, but failed to protect the mice against MES seizures at the doses tested. The HPLC fingerprint of the extract shows a spectrum profile characteristic of Ficus platyphylla, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids and tannins. Our study provides scientific evidence that FP may contain psychoactive principles with potential anticonvulsant properties, thus supporting further

  2. The anti-epileptogenic and cognition enhancing effect of novel 1-[4-(4-benzo [1, 3] dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea (BPPU) in pentylenetetrazole induced chronic rat model of epilepsy.

    PubMed

    Mishra, Chandra Bhushan; Kumari, Shikha; Siraj, Fouzia; Yadav, Rajesh; Kumari, Sweta; Tiwari, Ankit Kumar; Tiwari, Manisha

    2018-06-05

    Epilepsy is a chronic neurological disorder which affects 65 million worldwide population and characterized by recurrent seizure in epileptic patients. Recently, we reported a novel piperonylpiperazine derivative, BPPU "1-[4-(4-benzo [1,3]dioxol-5-ylmethyl-piperazin-1-yl)- phenyl]-3-phenyl-urea'' as a potent anticonvulsant agent. BPPU has shown excellent anticonvulsant activity in various in-vivo seizure models along with good anti-depressant activity. In this report, we have deeply examined the anti-epileptogenic potential of BPPU in pentylenetetrazole (PTZ) induced kindling model and BPPU effectively reduced seizure episodes in kindled animals upto 35 days. Further, neuroprotective potential of BPPU against PTZ induced neurodegeneration has also been evaluated in hippocampus as well as cortex region by histopathological and immunohistochemical studies. Epileptic patients generally suffer from a range of cognitive impairments. Therefore, the cognition enhancing effect of BPPU was also measured by using well known social recognition test, novel object recognition test, light/dark test and open field test in kindled rat model as well as scopolamine induced memory deficit mice model. Results indicated that BPPU successfully improved cognition deficits in both models. Thus, BPPU appeared as a potent anti-epileptic agent which has also capability to improve cognition decline associated with epilepsy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    PubMed Central

    2012-01-01

    Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested. PMID:22709243

  4. Frontal Lobe Seizures

    MedlinePlus

    ... cause of frontal lobe epilepsy remains unknown. Complications Status epilepticus. Frontal lobe seizures tend to occur in clusters and may provoke a dangerous condition called status epilepticus — in which seizure activity lasts much longer than ...

  5. The prevalence of thyrotoxicosis-related seizures.

    PubMed

    Song, Tae-Jin; Kim, Sun-Jung; Kim, Gyu Sik; Choi, Young-Chul; Kim, Won-Joo

    2010-09-01

    Central nervous system dysfunction, such as hyperexcitation, irritability, and disturbance of consciousness, may occur in patients with thyrotoxicosis. There are also a few case reports of seizures attributed to thyrotoxicosis. The objective of the present study was to determine the prevalence of seizures that appeared to be related to the thyrotoxic state in patients with thyrotoxicosis. We retrospectively determined the prevalence and clinical features of seizures in 3382 patients with hyperthyroidism. Among patients with seizures, we excluded those with other causes of seizures or a history of epilepsy. We did not exclude two patients in whom later work-up showed an abnormal magnetic resonance imaging, as their seizures resolved after they became euthyroid. Among the 3382 patients with hyperthyroidism, there were seven patients (0.2%) with seizures who met our criteria. Primary generalized tonic-clonic seizures occurred in four patients (57%), complex partial seizures with secondary generalized tonic-clonic seizures occurred in two patients (29%), and one patient had a focal seizure (14%). The initial electroencephalography (EEG) was normal in two patients (29%), had generalized slow activity in four patients (57%), and had diffuse generalized beta activity in one patient (14%). On magnetic resonance imaging, one patient had diffuse brain atrophy, and one had an old basal ganglia infarct. After the patients became euthyroid, the EEG was repeated and was normal in all patients. During follow-up periods ranging from 18 to 24 months, none of the patients had seizures. Hyperthyroidism is the precipitating cause of seizures in a small percentage of these patients. In these patients, the prognosis is good if they become euthyroid. The prevalence of thyrotoxicosis-related seizures reported here can be used in conjunction with the prevalence of thyrotoxicosis in the population to estimate the prevalence of thyrotoxicosis-related seizures in populations.

  6. NKCC1 up-regulation contributes to early post-traumatic seizures and increased post-traumatic seizure susceptibility.

    PubMed

    Wang, Fushun; Wang, Xiaowei; Shapiro, Lee A; Cotrina, Maria L; Liu, Weimin; Wang, Ernest W; Gu, Simeng; Wang, Wei; He, Xiaosheng; Nedergaard, Maiken; Huang, Jason H

    2017-04-01

    Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures. Many of the available anti-seizure drugs target gamma-aminobutyric acid (GABA A ) receptors. The inhibitory activity of GABA A receptor activation depends on low intracellular Cl - , which is achieved by the opposing regulation of Na + -K + -Cl - cotransporter 1 (NKCC1) and K + -Cl - -cotransporter 2 (KCC2). Up-regulation of NKCC1 in neurons has been shown to be involved in neonatal seizures and in ammonia toxicity-induced seizures. Here, we report that TBI-induced up-regulation of NKCC1 and increased intracellular Cl - concentration. Genetic deletion of NKCC1 or pharmacological inhibition of NKCC1 with bumetanide suppresses TBI-induced seizures. TGFβ expression was also increased after TBI and competitive antagonism of TGFβ reduced NKKC1 expression, ameliorated reactive astrocytosis, and inhibited seizures. Thus, TGFβ might be an important pathway involved in NKCC1 up-regulation after TBI. Our findings identify neuronal up-regulation of NKCC1 and its mediation by TGFβ, as a potential and important mechanism in the early post-traumatic seizures, and demonstrate the therapeutic potential of blocking this pathway.

  7. Mechanisms of Seizure Propagation in 2-Dimensional Centre-Surround Recurrent Networks

    PubMed Central

    Hall, David; Kuhlmann, Levin

    2013-01-01

    Understanding how seizures spread throughout the brain is an important problem in the treatment of epilepsy, especially for implantable devices that aim to avert focal seizures before they spread to, and overwhelm, the rest of the brain. This paper presents an analysis of the speed of propagation in a computational model of seizure-like activity in a 2-dimensional recurrent network of integrate-and-fire neurons containing both excitatory and inhibitory populations and having a difference of Gaussians connectivity structure, an approximation to that observed in cerebral cortex. In the same computational model network, alternative mechanisms are explored in order to simulate the range of seizure-like activity propagation speeds (0.1–100 mm/s) observed in two animal-slice-based models of epilepsy: (1) low extracellular , which creates excess excitation and (2) introduction of gamma-aminobutyric acid (GABA) antagonists, which reduce inhibition. Moreover, two alternative connection topologies are considered: excitation broader than inhibition, and inhibition broader than excitation. It was found that the empirically observed range of propagation velocities can be obtained for both connection topologies. For the case of the GABA antagonist model simulation, consistent with other studies, it was found that there is an effective threshold in the degree of inhibition below which waves begin to propagate. For the case of the low extracellular model simulation, it was found that activity-dependent reductions in inhibition provide a potential explanation for the emergence of slowly propagating waves. This was simulated as a depression of inhibitory synapses, but it may also be achieved by other mechanisms. This work provides a localised network understanding of the propagation of seizures in 2-dimensional centre-surround networks that can be tested empirically. PMID:23967201

  8. Seizure Prediction and its Applications

    PubMed Central

    Iasemidis, Leon D.

    2011-01-01

    Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous electrical activity, that may remain localized and/or spread and severely disrupt the brain’s normal multi-task and multi-processing function. Epileptic seizures are the hallmarks of such activity and had been considered unpredictable. It is only recently that research on the dynamics of seizure generation by analysis of the brain’s electrographic activity (EEG) has shed ample light on the predictability of seizures, and illuminated the way to automatic, prospective, long-term prediction of seizures. The ability to issue warnings in real time of impending seizures (e.g., tens of minutes prior to seizure occurrence in the case of focal epilepsy), may lead to novel diagnostic tools and treatments for epilepsy. Applications may range from a simple warning to the patient, in order to avert seizure-associated injuries, to intervention by automatic timely administration of an appropriate stimulus, for example of a chemical nature like an anti-epileptic drug (AED), electromagnetic nature like vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial direct current (TDC) or transcranial magnetic stimulation (TMS), and/or of another nature (e.g., ultrasonic, cryogenic, biofeedback operant conditioning). It is thus expected that seizure prediction could readily become an integral part of the treatment of epilepsy through neuromodulation, especially in the new generation of closed-loop seizure control systems. PMID:21939848

  9. Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

    PubMed

    Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

    2014-06-01

    Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

  10. Cannabidivarin is anticonvulsant in mouse and rat

    PubMed Central

    Hill, AJ; Mercier, MS; Hill, TDM; Glyn, SE; Jones, NA; Yamasaki, Y; Futamura, T; Duncan, M; Stott, CG; Stephens, GJ; Williams, CM; Whalley, BJ

    2012-01-01

    Background and Purpose Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. Experimental Approach The effect of CBDV (1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg2+-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50–200 mg·kg−1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays. Key Results CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg−1), audiogenic (≥50 mg·kg−1) and PTZ-induced seizures (≥100 mg·kg−1). CBDV (200 mg·kg−1) alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function. Conclusions and Implications These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti-epileptic in chronic epilepsy models. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http

  11. Improving staff response to seizures on the epilepsy monitoring unit with online EEG seizure detection algorithms.

    PubMed

    Rommens, Nicole; Geertsema, Evelien; Jansen Holleboom, Lisanne; Cox, Fieke; Visser, Gerhard

    2018-05-11

    User safety and the quality of diagnostics on the epilepsy monitoring unit (EMU) depend on reaction to seizures. Online seizure detection might improve this. While good sensitivity and specificity is reported, the added value above staff response is unclear. We ascertained the added value of two electroencephalograph (EEG) seizure detection algorithms in terms of additional detected seizures or faster detection time. EEG-video seizure recordings of people admitted to an EMU over one year were included, with a maximum of two seizures per subject. All recordings were retrospectively analyzed using Encevis EpiScan and BESA Epilepsy. Detection sensitivity and latency of the algorithms were compared to staff responses. False positive rates were estimated on 30 uninterrupted recordings (roughly 24 h per subject) of consecutive subjects admitted to the EMU. EEG-video recordings used included 188 seizures. The response rate of staff was 67%, of Encevis 67%, and of BESA Epilepsy 65%. Of the 62 seizures missed by staff, 66% were recognized by Encevis and 39% by BESA Epilepsy. The median latency was 31 s (staff), 10 s (Encevis), and 14 s (BESA Epilepsy). After correcting for walking time from the observation room to the subject, both algorithms detected faster than staff in 65% of detected seizures. The full recordings included 617 h of EEG. Encevis had a median false positive rate of 4.9 per 24 h and BESA Epilepsy of 2.1 per 24 h. EEG-video seizure detection algorithms may improve reaction to seizures by improving the total number of seizures detected and the speed of detection. The false positive rate is feasible for use in a clinical situation. Implementation of these algorithms might result in faster diagnostic testing and better observation during seizures. Copyright © 2018. Published by Elsevier Inc.

  12. Comparing maximum autonomic activity of psychogenic non-epileptic seizures and epileptic seizures using heart rate variability.

    PubMed

    Jeppesen, Jesper; Beniczky, Sándor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

    2016-04-01

    The semiology of psychogenic non-epileptic seizures (PNES) can resemble epileptic seizures, and differentiation between epileptic seizures with no EEG-correlate and PNES can be challenging even for trained experts. Therefore, there has been a search for a quantitative measure, other than EEG and semiology that could distinguish PNES from epileptic seizures. We used ECG to measure heart rate variability (HRV) in order to compare maximum autonomic activity of epileptic seizures and PNES. These comparisons could potentially serve as biomarkers for distinguishing these types of clinical episodes. Forty-nine epileptic seizures from 17 patients and 24 PNES from 7 patients with analyzable ECG were recorded during long-term video-EEG monitoring. Moving windows of 100 R-R intervals throughout each seizure were used to find maximum values of Cardiac Sympathetic Index (CSI) (sympathetic tonus) and minimum values of Cardiac Vagal Index (CVI), Root-Mean-Square-of-Successive-Differences (RMSSD) and HF-power (parasympathetic tonus). In addition, non-seizure recordings of each patient were used to compare HRV-parameters between the groups. The maximum CSI for epilepsy seizures were higher than PNES (P=0.015). The minimum CVI, minimum RMSSD and HF-power did not show significant difference between epileptic seizures and PNES (P=0.762; P=0.152; P=0.818). There were no statistical difference of non-seizure HRV-parameters between the PNES and epilepsy patients. We found the maximum sympathetic activity accompanying the epileptic seizures to be higher, than that during the PNES. However, the great variation of autonomic response within both groups makes it difficult to use these HRV-measures as a sole measurement in distinguishing epileptic seizures from PNES. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. 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.

  14. Early and late postoperative seizure outcome in 97 patients with supratentorial meningioma and preoperative seizures: a retrospective study.

    PubMed

    Zheng, Zhe; Chen, Peng; Fu, Weiming; Zhu, Junming; Zhang, Hong; Shi, Jian; Zhang, Jianmin

    2013-08-01

    We identified factors associated with early and late postoperative seizure control in patients with supratentorial meningioma plus preoperative seizures. In this retrospective study, univariate analysis and multivariate logistic regression analysis compared 24 clinical variables according to the occurrence of early (≤1 week) or late (>1 week) postoperative seizures. Sixty-two of 97 patients (63.9 %) were seizure free for the entire postoperative follow-up period (29.5 ± 11.8 months), while 13 patients (13.4 %) still had frequent seizures at the end of follow-up. Fourteen of 97 patients (14.4 %) experienced early postoperative seizures, and emergence of new postoperative neurological deficits was the only significant risk factor (odds ratio = 7.377). Thirty-three patients (34.0 %) experienced late postoperative seizures at some time during follow-up, including 12 of 14 patients with early postoperative seizures. Associated risk factors for late postoperative seizures included tumor progression (odds ratio = 7.012) and new permanent postoperative neurological deficits (odds ratio = 4.327). Occurrence of postoperative seizures in patients with supratentorial meningioma and preoperative seizure was associated with new postoperative neurological deficits. Reduced cerebral or vascular injury during surgery may lead to fewer postoperative neurological deficits and better seizure outcome.

  15. Seizures and Teens: The Practical Aspects of Managing Seizure Medications

    ERIC Educational Resources Information Center

    Shafer, Patricia Osborne; Israel, Beth

    2007-01-01

    Medications are the primary treatment for epilepsy, yet many teens and their families have problems managing seizure medicines. Fear of side effects, difficulties remembering to take medicines and figuring out how to take them are common challenges. Unfortunately, not taking medicine as prescribed can lead to breakthrough seizures, which in turn…

  16. Hyponatraemia and seizures after ecstasy use

    PubMed Central

    Holmes, S.; Banerjee, A.; Alexander, W.

    1999-01-01

    A patient presented to our unit with seizures and profound hyponatraemia after ingestion of a single tablet of ecstasy. The seizures proved resistant to therapy and ventilation on the intensive care unit was required. Resolution of the seizures occurred on correction of the metabolic abnormalities. The pathogenesis of seizures and hyponatraemia after ecstasy use is discussed. Ecstasy use should be considered in any young patient presenting with unexplained seizures and attention should be directed towards electrolyte levels, particularly sodium.


Keywords: ecstasy; seizures; hyponatraemia PMID:10396584

  17. Drosophila as a model for epilepsy: bss is a gain-of-function mutation in the para sodium channel gene that leads to seizures.

    PubMed

    Parker, Louise; Padilla, Miguel; Du, Yuzhe; Dong, Ke; Tanouye, Mark A

    2011-02-01

    We report the identification of bang senseless (bss), a Drosophila melanogaster mutant exhibiting seizure-like behaviors, as an allele of the paralytic (para) voltage-gated Na(+) (Na(V)) channel gene. Mutants are more prone to seizure episodes than normal flies because of a lowered seizure threshold. The bss phenotypes are due to a missense mutation in a segment previously implicated in inactivation, termed the "paddle motif" of the Na(V) fourth homology domain. Heterologous expression of cDNAs containing the bss(1) lesion, followed by electrophysiology, shows that mutant channels display altered voltage dependence of inactivation compared to wild type. The phenotypes of bss are the most severe of the bang-sensitive mutants in Drosophila and can be ameliorated, but not suppressed, by treatment with anti-epileptic drugs. As such, bss-associated seizures resemble those of pharmacologically resistant epilepsies caused by mutation of the human Na(V) SCN1A, such as severe myoclonic epilepsy in infants or intractable childhood epilepsy with generalized tonic-clonic seizures.

  18. Might astrocytes play a role in maintaining the seizure-prone state?

    PubMed

    Vessal, Mani; Dugani, Chandrasagar B; Solomon, Dianand A; McIntyre Burnham, W; Ivy, Gwen O

    2005-05-24

    The amygdala-kindling model is used to study complex partial epilepsy with secondary generalization. The present study was designed to (A) quantify astrocytic changes in the piriform cortex of amygdala-kindled subjects over time and (B) investigate the role that astrocytes might play in maintaining the seizure-prone state. In Study A, once the experimental subjects reached five stage 5 seizures, stimulation was stopped, and both kindled and control rats were allowed to survive for the interval appropriate to their group (7, 18, 30, or 90 days). Following each interval, the kindled and control animals were given 10 intraperitoneal injections of bromodeoxyuridine (BrdU) and sacrificed 24 h following the last injection. Significantly higher numbers of dividing astrocytes (identified by co-labeling for BrdU and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) were found in the kindled brains. All kindled groups had significantly higher numbers of double-labeled cells on the side contralateral to the stimulation site, except for those in the 90 day survival group. In Study B, rats were implanted with chemotrodes, were kindled as in Study A, and were subsequently infused with either saline or with L alpha-AA (to lesion astrocytes) during a further 25 stimulations (1/day). L alpha-AA infused rats had significantly diminished levels of behavioral seizures, higher after discharge thresholds, lower after discharge durations, and decreased numbers of double-labeled astrocytes in piriform cortex than did saline infused rats. Together, the data indicate that astrocytes may play a role in maintaining the seizure-prone state.

  19. Photogenic partial seizures.

    PubMed

    Hennessy, M J; Binnie, C D

    2000-01-01

    To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

  20. How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit.

    PubMed

    Jenssen, Sigmund; Gracely, Edward J; Sperling, Michael R

    2006-09-01

    More information is needed regarding how long seizures typically last, since this influences treatment decisions. Seizure type and other factors could influence seizure duration. Data were collected from a random sample of patients being evaluated with continuous video and scalp EEG. Seizure duration was defined as time from early sign of seizure (clinical or EEG) until the end of seizure on EEG. Seizures were categorized as simple partial (SPS), complex partial (CPS), secondarily generalized tonic-clonic (SGTCS), primary generalized tonic-clonic (PGTCS) and tonic (TS). SGTCS were divided into a complex partial part (SGTCS/CP) and a tonic-clonic part (SGTCS/TC). Median and longest duration of each seizure type in each individual were used. Comparisons of seizure types, first and last seizure, area of onset, and state of onset were performed. Five hundred seventy-nine seizures were recorded in 159 adult patients. Seizures with partial onset spreading to both hemispheres had the longest duration. SGTCS were unlikely to last more than 660 s, CPS more than 600 s, and SPS more than 240 s. PGTCS and TS had shorter durations, but the number of subjects with those two types was small. CPS did not differ in duration according to sleep state at onset nor side of origin. A working definition of status epilepticus in adults with cryptogenic or symptomatic epilepsy can be drawn from these data for purposes of future epidemiologic research. More information is needed for the idiopathic epilepsies and in children.

  1. Generalization of rapidly recurring seizures is suppressed in mice lacking glial cell line-derived neurotrophic factor family receptor alpha2.

    PubMed

    Nanobashvili, A; Kokaia, Z; Lindvall, O

    2003-01-01

    Recent experimental evidence indicates that neurotrophic factors play a role in the pathophysiology of epilepsy. The objective of this study was to explore whether signaling through one of the glial cell line-derived neurotrophic factor family receptors, GFRalpha2, influences the severity of kindling-evoked, rapidly recurring seizures and the subsequent development of permanent hyperexcitability. We applied the rapid kindling model to adult mice, using 40 threshold stimulations delivered with 5-min interval in the ventral hippocampus. Generalized seizures were fewer and developed later in response to kindling stimulations in mice lacking GFRalpha2. However, GFRalpha2 gene deletion did not influence the acquisition of the permanent abnormal excitability as assessed 4 weeks later. In situ hybridization revealed marked and dynamic changes of GFRalpha2 mRNA levels in several forebrain areas following the stimulus-evoked seizures. Our findings provide evidence that signaling through the GFRalpha2 receptor contributes to seizure generalization in rapid kindling.

  2. Characteristics of seizure-induced signal changes on MRI in patients with first seizures.

    PubMed

    Kim, Si Eun; Lee, Byung In; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Park, Kang Min; Kim, Hyung Chan; Lee, Joonwon; Bae, Soo-Young; Lee, Dongah; Kim, Sung Eun

    2017-05-01

    The aim of this study was to investigate the predictive factors and identify the characteristics of the seizure-induced signal changes on MRI (SCM) in patients with first seizures. We conducted a retrospective study of patients with first seizures from March 2010 to August 2014. The inclusion criteria for this study were patients with 1) first seizures, and 2) MRI and EEG performed within 24h of the first seizures. The definition of SCM was hyper-intensities in the brain not applying to cerebral arterial territories. Multivariate logistic regression was performed with or without SCM as a dependent variable. Of 431 patients with seizures visiting the ER, 69 patients met the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently significant variable predicting the presence of SCM in patients with first seizures. In addition, the topography of SCM was as follows; i) ipsilateral hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11), iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus (1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI exhibited unilateral cortical hyperperfusion with ipsilateral thalamic involvement reflecting unrestricted vascular territories. There is an association between epileptiform discharges and SCM. Additionally, the involvement of the unilateral cortex and ipsilateral thalamus in SCM and its hyperperfusion state could be helpful in differentiating the consequences of epileptic seizures from other pathologies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. 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.

  4. Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice.

    PubMed

    Hajek, Michael A; Buchanan, Gordon F

    2016-05-01

    Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death.

  5. Effect of central muscarinic receptors on passive-avoidance learning deficits induced by prenatal pentylenetetrazol kindling in male offspring.

    PubMed

    Pourmotabbed, A; Mahmoodi, G; Mahmoodi, S; Mohammadi-Farani, A; Nedaei, S E; Pourmotabbed, T; Pourmotabbed, T

    2014-10-24

    Occurrence of the epileptic seizures during gestation might affect the neurodevelopment of the fetus resulting in cognitive problems for the child later in life. We have previously reported that prenatal pentylenetetrazol (PTZ)-kindling induces learning and memory deficits in the children born to kindled mothers, later in life but the mechanisms involved in this processes are unknown. The cholinergic system plays a major role in learning and memory. The present study was performed to investigate the possible involvement of central muscarinic cholinergic receptors on learning and memory deficits induced by prenatal PTZ-kindling in male offspring. Pregnant Wistar rats were kindled by repetitive i.p. injection of 25mg/kg of PTZ on day 13 of their pregnancy. The effect of intracerebroventricular (ICV) microinjection of scopolamine and pilocarpine, muscarinic cholinergic receptors antagonist and agonist, respectively on passive-avoidance learning of pups were tested at 12weeks of age using shuttle-box apparatus. Our data showed that the retention latencies of pups that received scopolamine (2 or 3μg) were significantly reduced compared to those received normal saline (p<0.05). Interestingly, post training ICV administration of pilocarpine (2μg) retrieved pups' memory deficits (p<0.001). These results demonstrate for the first time, the importance of the central muscarinic cholinergic receptors in learning and memory deficits in pups born to kindled dams and suggest a central mechanism for the cognitive and memory dysfunction, associated with seizures during pregnancy. Copyright © 2014. Published by Elsevier Ltd.

  6. 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

  7. 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

  8. Seizures and Teens: When Seizures Aren't the Only Problem

    ERIC Educational Resources Information Center

    Kanner, Andres M.; Shafer, Patricia O.

    2006-01-01

    Some teenagers with epilepsy only have to deal with seizures, which can be tough enough, but for other teens, seizures are not the only problem. Parents and caregivers often report changes in their teens' abilities to think clearly, learn in school, or remain focused in class. Mood and other behavioral problems may also be seen. It is critical…

  9. Seizures and Teens: Surgery for Seizures--What's It All About?

    ERIC Educational Resources Information Center

    Duchowny, Michael S.; Dean, Patricia

    2006-01-01

    Nearly 1 out of 2 children and teens with seizures may need to take medications throughout their lives. At least 25% will develop a condition called refractory epilepsy--meaning that their seizures do not respond to medical therapy. For these children and teens, non-drug therapies such as brain surgery are available that may offer a chance to…

  10. Seizures in Infants and Young Children.

    ERIC Educational Resources Information Center

    McBrien, Dianne M.; Bonthius, Daniel J.

    2000-01-01

    This article reviews the most frequent causes of seizure disorders in young children and the classification of different seizure types. It discusses current therapies, including alternatives to medication. Emergency response to seizures is covered a well as non-epileptic episodes that may resemble seizures. Epilepsy's potential impact on the…

  11. Seizure clusters: characteristics and treatment.

    PubMed

    Haut, Sheryl R

    2015-04-01

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

  12. 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.

  13. Setting the scene: definition of prolonged seizures, acute repetitive seizures, and status epilepticus. Do we know why seizures stop?

    PubMed

    Cross, J Helen

    2014-10-01

    Status epilepticus is recognised as an acute emergency requiring urgent intervention. The optimal timing of such an intervention during a prolonged seizure, and the reasons for such, have provided much discussion. For operational purposes, a definition of a prolonged seizure of ≥5 minutes requiring intervention appears justified. However, a definition of status epilepticus of ≥30 minutes should stand, with the proportion of seizures proceeding to this clinical state remaining small. The reasons for this may be inherent to an individual, but an understanding of the mechanisms underlying the predisposition may lead to improved management pathways in the future.

  14. 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

  15. 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

  16. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.

    PubMed

    Lutz, Beat

    2004-11-01

    Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.

  17. Reversible MRI lesions after seizures.

    PubMed

    Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

    1997-06-01

    After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

  18. Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei

    PubMed Central

    Feng, Li; Motelow, Joshua E.; Ma, Chanthia; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro

    2017-01-01

    The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

  19. Intraoperative seizures during craniotomy under general anesthesia.

    PubMed

    Howe, John; Lu, Xiaoying; Thompson, Zoe; Peterson, Gordon W; Losey, Travis E

    2016-05-01

    An acute symptomatic seizure is a clinical seizure occurring at the time of or in close temporal association with a brain insult. We report an acute symptomatic seizure occurring during a surgical procedure in a patient who did not have a prior history of epilepsy and who did not have a lesion associated with an increased risk of epilepsy. To characterize the incidence and clinical features of intraoperative seizures during craniotomy under general anesthesia, we reviewed cases where continuous EEG was acquired during craniotomy. Records of 400 consecutive cases with propofol as general anesthesia during craniotomy were reviewed. Demographic data, indication for surgery, clinical history, history of prior seizures, duration of surgery and duration of burst suppression were recorded. Cases where seizures were observed were analyzed in detail. Two out of 400 patients experienced intraoperative seizures, including one patient who appeared to have an acute symptomatic seizure related to the surgical procedure itself and a second patient who experienced two seizures likely related to an underlying diagnosis of epilepsy. This is the first report of an acute symptomatic seizure secondary to a neurosurgical procedure. Overall, 0.5% of patients monitored experienced seizures, indicating that intraoperative seizures are rare, and EEG monitoring during craniotomies is of low yield in detecting seizures. Copyright © 2016. Published by Elsevier Ltd.

  20. New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

    PubMed

    Radman, Thomas; Lisanby, Sarah H

    2017-04-01

    Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

  1. [Reflex seizures, cinema and television].

    PubMed

    Olivares-Romero, Jesús

    2015-12-16

    In movies and television series are few references to seizures or reflex epilepsy even though in real life are an important subgroup of total epileptic syndromes. It has performed a search on the topic, identified 25 films in which they appear reflex seizures. Most seizures observed are tonic-clonic and visual stimuli are the most numerous, corresponding all with flashing lights. The emotions are the main stimuli in higher level processes. In most cases it is not possible to know if a character suffers a reflex epilepsy or suffer reflex seizures in the context of another epileptic syndrome. The main conclusion is that, in the movies, the reflex seizures are merely a visual reinforcing and anecdotal element without significant influence on the plot.

  2. 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

    2017-08-15

    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.

  3. 19 CFR 162.22 - Seizure of conveyances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Seizure of conveyances. 162.22 Section 162.22... TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Seizures § 162.22 Seizure of conveyances. (a) General applicability. If it shall appear to any officer authorized to board conveyances and make seizures that there...

  4. Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

    PubMed Central

    Kundap, Uday P.; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq

    2017-01-01

    Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs. PMID:28824436

  5. Structural Exploration of Quinazolin-4(3H)-ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies.

    PubMed

    Ugale, Vinod G; Bari, Sanjay B

    2016-11-01

    Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED 50  = 23.5 mg/kg, MES, mice, i.p.; ED 50  = 32.6 mg/kg, scPTZ, mice, i.p.; ED 50  = 45.2 mg/kg, 6-Hz, mice, i.p.; TD 50  = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED 50  = 26.1 mg/kg, MES, mice, i.p.; ED 50  = 79.4 mg/kg, scPTZ, mice, i.p.; TD 50  = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Zebrafish-Based Discovery of Antiseizure Compounds from the Red Sea: Pseurotin A2 and Azaspirofuran A.

    PubMed

    Copmans, Daniëlle; Rateb, Mostafa; Tabudravu, Jioji N; Pérez-Bonilla, Mercedes; Dirkx, Nina; Vallorani, Riccardo; Diaz, Caridad; Pérez Del Palacio, José; Smith, Alan J; Ebel, Rainer; Reyes, Fernando; Jaspars, Marcel; de Witte, Peter A M

    2018-04-19

    In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A 2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model. Pseurotin A 2 and azaspirofuran A were identified as antiseizure hits, while their close chemical analogues were inactive. Besides, electrophysiological analysis from the zebrafish midbrain demonstrated that pseurotin A 2 and azaspirofuran A also ameliorate PTZ-induced epileptiform discharges. Next, to determine whether these findings translate to mammalians, both compounds were analyzed in the mouse 6 Hz (44 mA) psychomotor seizure model. They lowered the seizure duration dose-dependently, thereby confirming their antiseizure properties and suggesting activity against drug-resistant seizures. Finally, in a thorough ADMET assessment, pseurotin A 2 and azaspirofuran A were found to be drug-like. Based on the prominent antiseizure activity in both species and the drug-likeness, we propose pseurotin A 2 and azaspirofuran A as lead compounds that are worth further investigation for the treatment of epileptic seizures. This study not only provides the first evidence of antiseizure activity of pseurotins and azaspirofurans, but also demonstrates the value of the zebrafish model in (marine) natural product drug discovery in general, and for ASD discovery in particular.

  7. Glycolysis in energy metabolism during seizures.

    PubMed

    Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

    2013-05-15

    Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.

  8. Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

    PubMed

    Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

    2016-07-01

    Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Children with New Onset Seizures: A Prospective Study of Parent Variables, Child Behavior Problems, and Seizure Occurrence

    PubMed Central

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

    2015-01-01

    Objective 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, 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. Methods 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. Results 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 seizures group. Conclusions 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. PMID:26520879

  10. How do doctors in training react to seizures?

    PubMed

    Seneviratne, Udaya; Ma, Henry; Phan, Thanh G

    2016-01-01

    There are scant data on how doctors approach seizures in the acute setting. We sought to study (a) exposure to seizure disorders as well as relevant training and (b) reactions to seizures in the acute setting, among medical residents undergoing physician training. The exposure to and training on seizure disorders were assessed using a structured questionnaire first. Then, they were tested with 20 videos consisting of 10 epileptic seizures (ESs) and 10 psychogenic nonepileptic seizures (PNESs). After each video, we asked three questions to test (a) the diagnosis and the practice of administration of benzodiazepines to terminate the seizure, (b) the estimation of seizure duration, and (c) the practice of intubation. The accuracy of diagnosis was measured by the area under the summary receiver operating characteristics curve (AUC). The difference between true seizure duration and estimated duration was evaluated using paired-sample t-test. A total of 48 trainees participated in the study. The majority witnessed seizures in movies (37, 77.1%) and television (35, 72.9%). Only 12 (25%) received bedside teaching on seizure disorders. Their diagnostic accuracy of seizures was very poor (AUC=0.54). Participants significantly underestimated the duration of seizures. Thirty-five doctors made an illogical decision to intubate but not to terminate the seizure with intravenous benzodiazepine. The diagnostic accuracy of seizures is poor among trainees, and their estimates of seizure duration are unreliable. Our study highlights potential pitfalls in the acute management of seizures and the need for more training on seizure disorders. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  11. AMPA Receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures

    PubMed Central

    Lippman-Bell, Jocelyn J.; Rakhade, Sanjay N.; Klein, Peter M.; Obeid, Makram; Jackson, Michele C.; Joseph, Annelise; Jensen, Frances E.

    2013-01-01

    Summary Purpose To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mTOR pathway activation and long-term sequelae following neonatal seizures in rats, including later-life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits. Methods Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12h x 4 doses). 12h post-HS, we assessed mTOR activation marker phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS+V) or NBQX-treated post-HS rats (HS+N) versus littermate controls (C+V). Spontaneous seizure activity was compared between groups by epidural cortical electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was measured using Timm staining. Finally, we assessed behavior between P30-38. Key findings Post-seizure NBQX treatment significantly attenuated seizure-induced increases in p-P70S6K in the hippocampus (p<0.01) and cortex (p<0.001). While spontaneous recurrent seizures increased in adulthood in HS+V rats compared to controls (3.22±1seizures/hour; p=0.03), NBQX significantly attenuated later-life seizures (0.14±0.1 seizures/hour; p=0.046). HS+N rats showed less aberrant mossy fiber sprouting (115±8.0%) than vehicle-treated post-HS rats (174±10%, p=0.004), compared to controls (normalized to 100%). Finally, NBQX treatment prevented alterations in later-life social behavior; post-HS rats showed significantly decreased preference for a novel over a familiar rat (71.0±12 sec) compared to controls (99.0±15.6 sec; p<0.01), while HS+N rats showed social novelty preference similar to controls (114.3±14.1 sec). Significance Brief NBQX administration during the 48 hours post-seizure in P10 Long-Evans rats suppresses transient mTOR pathway activation and attenuates spontaneous recurrent seizures, social preference deficits and mossy fiber sprouting observed in

  12. Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

    PubMed

    Feng, Li; Motelow, Joshua E; Ma, Chanthia; Biche, William; McCafferty, Cian; Smith, Nicholas; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro; Blumenfeld, Hal

    2017-11-22

    The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

  13. 19 CFR 145.59 - Seizures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Seizures. 145.59 Section 145.59 Customs Duties U.S...) MAIL IMPORTATIONS Restricted and Prohibited Merchandise § 145.59 Seizures. (a) Articles prohibited and... handled by the Postal Service as specified in §§ 145.51 and 145.52. (b) Notification of seizure or...

  14. Genes, Seizures & Epilepsy

    ERIC Educational Resources Information Center

    Goldman, Alica M.

    2006-01-01

    The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…

  15. Nonlinear analysis of EEG for epileptic seizures

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

    Hively, L.M.; Clapp, N.E.; Daw, C.S.

    1995-04-01

    We apply chaotic time series analysis (CTSA) to human electroencephalogram (EEG) data. Three epoches were examined: epileptic seizure, non-seizure, and transition from non-seizure to seizure. The CTSA tools were applied to four forms of these data: raw EEG data (e-data), artifact data (f-data) via application of a quadratic zero-phase filter of the raw data, artifact-filtered data (g- data) and that was the residual after subtracting f-data from e-data, and a low-pass-filtered version (h-data) of g-data. Two different seizures were analyzed for the same patient. Several nonlinear measures uniquely indicate an epileptic seizure in both cases, including an abrupt decrease inmore » the time per wave cycle in f-data, an abrupt increase in the Kolmogorov entropy and in the correlation dimension for e-h data, and an abrupt increase in the correlation dimension for e-h data. The transition from normal to seizure state also is characterized by distinctly different trends in the nonlinear measures for each seizure and may be potential seizure predictors for this patient. Surrogate analysis of e-data shows that statistically significant nonlinear structure is present during the non-seizure, transition , and seizure epoches.« less

  16. 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

  17. 15 CFR 904.501 - Notice of seizure.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Notice of seizure. 904.501 Section 904... Seizure and Forfeiture Procedures § 904.501 Notice of seizure. Within 60 days from the date of the seizure, NOAA will serve the Notice of Seizure as provided in § 904.3 to the owner or consignee, if known or...

  18. [Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat].

    PubMed

    Sumi, T

    1993-03-01

    Kindling model has been regarded as an experimental model for partial seizure with secondary generalized convulsion in human epilepsy. A number of pharmacological studies have been carried out to evaluate antiepileptic effects of conventional anticonvulsants on kindled seizures, mainly using amygdala kindled model. However, it is known that hippocampus is a more important site for human temporal epilepsy. It should therefore be considered appropriate to evaluate effects of antiepileptic drugs, not only on amygdaloid- but also on hippocampal-kindled seizures. In the present study, effects of chronically administered phenobarbital (PB) on amygdaloid- and hippocampal-kindled seizures were investigated. In the first session, cats were orally administered 6 mg/kg of PB for 15 days to obtain the serum level between 15 micrograms/ml and 25 micrograms/ml (optimal level for human epileptic seizure), then stimulation was carried out once a day for the following five days with suprathreshold stimulation intensity (100 microA higher than generalized seizure triggering threshold). For evaluation of drug efficacy, duration of afterdischarge and seizure severity were determined. After the end of session 1, session 2 started with 12 mg/kg of PB for 35-50 micrograms/ml serum level (subtoxic level) and continued in the same manner as stated above. PB was proved to be more effective for hippocampal- than for amygdaloid-kindled seizures. Generalized convulsions were easily suppressed in the level of 15-25 micrograms/ml and afterdischarge was totally suppressed in 33% of cats in the level of 35-50 micrograms/ml in the hippocampal-kindled group. However, amygdaloid-kindled seizures were more resistant to PB. It was difficult to suppress generalized convulsion in the level of 15-25 micrograms/ml, and total suppression of afterdischarge was extremely rare even in the higher serum level in amygdaloid-kindled cats. In addition, cats requiring a smaller number of stimuli to the completion of

  19. Cerebral arteriovenous malformations and seizures: differential impact on the time to seizure-free state according to the treatment modalities.

    PubMed

    Hyun, Seung-Jae; Kong, Doo-Sik; Lee, Jung-Il; Kim, Jong-Soo; Hong, Seung-Chyul

    2012-06-01

    To determine the prognostic factors for the incidence and the outcome of seizure in patients with cerebral arteriovenous malformation (AVM) and to identify the time to seizure-free state according to the treatment modalities. Between 1995 and 2008, the multidisciplinary team at our institution treated 399 patients with cerebral AVMs. Treatment consisted of surgical resection, radiosurgery, and embolization, either alone or in combination. The median follow-up period was 6.0 years (range, 3.0-16.2 years). Eighty-six patients (21.5 %) experienced seizures before treatment. We investigated the variables associated with seizure incidence and seizure outcome and analyzed the outcomes of seizure among each treatment modality. After treatment, 60 (70 %) patients were seizure-free. Compared with 313 patients who did not experience seizures, we found that younger age (≤ 35 years), size ≥ 3 cm, and location of temporal lobe were associated with seizures (p < 0.05). Short seizure history, accompanying intracerebral hemorrhage, generalized tonic-clonic type seizure, deep-seated or infratentorial AVM, complete obliteration of AVM, and a favorable neurological outcome at 12 months were closely associated with Engel Class I outcomes (p < 0.05). Seizure-free outcomes after microsurgery, radiosurgery, or embolization were 78 %, 66 %, and 50 %, respectively. The overall annual bleeding rate was 1.0 % and 2.2 % in microsurgery-treated and radiosurgery-treated AVMs, respectively. In the surgery group, the median time to seizure-free status was 1.1 months (95 % CI, 0.7-1.2 months), whereas the radiosurgery group and embolization-alone group showed 20.5 months (95 % CI, 18.3-23.8 months), and 8.1 months (95 % CI, 6.0-13.5 months), respectively. A multidisciplinary team approach for cerebral AVMs achieved satisfactory seizure control results. Microsurgery led to the highest percentage of seizure-free outcomes and had the lowest annual bleeding rate, whereas radiosurgery had a higher

  20. Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats

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

    Yin Jinbo; Ma Yuxin; Yin Qing

    2007-03-30

    The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process andmore » explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after First PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression.« less

  1. Using trend templates in a neonatal seizure algorithm improves detection of short seizures in a foetal ovine model.

    PubMed

    Zwanenburg, Alex; Andriessen, Peter; Jellema, Reint K; Niemarkt, Hendrik J; Wolfs, Tim G A M; Kramer, Boris W; Delhaas, Tammo

    2015-03-01

    Seizures below one minute in duration are difficult to assess correctly using seizure detection algorithms. We aimed to improve neonatal detection algorithm performance for short seizures through the use of trend templates for seizure onset and end. Bipolar EEG were recorded within a transiently asphyxiated ovine model at 0.7 gestational age, a common experimental model for studying brain development in humans of 30-34 weeks of gestation. Transient asphyxia led to electrographic seizures within 6-8 h. A total of 3159 seizures, 2386 shorter than one minute, were annotated in 1976 h-long EEG recordings from 17 foetal lambs. To capture EEG characteristics, five features, sensitive to seizures, were calculated and used to derive trend information. Feature values and trend information were used as input for support vector machine classification and subsequently post-processed. Performance metrics, calculated after post-processing, were compared between analyses with and without employing trend information. Detector performance was assessed after five-fold cross-validation conducted ten times with random splits. The use of trend templates for seizure onset and end in a neonatal seizure detection algorithm significantly improves the correct detection of short seizures using two-channel EEG recordings from 54.3% (52.6-56.1) to 59.5% (58.5-59.9) at FDR 2.0 (median (range); p < 0.001, Wilcoxon signed rank test). Using trend templates might therefore aid in detection of short seizures by EEG monitoring at the NICU.

  2. Drosophila as a Model for Epilepsy: bss Is a Gain-of-Function Mutation in the Para Sodium Channel Gene That Leads to Seizures

    PubMed Central

    Parker, Louise; Padilla, Miguel; Du, Yuzhe; Dong, Ke; Tanouye, Mark A.

    2011-01-01

    We report the identification of bang senseless (bss), a Drosophila melanogaster mutant exhibiting seizure-like behaviors, as an allele of the paralytic (para) voltage-gated Na+ (NaV) channel gene. Mutants are more prone to seizure episodes than normal flies because of a lowered seizure threshold. The bss phenotypes are due to a missense mutation in a segment previously implicated in inactivation, termed the “paddle motif” of the NaV fourth homology domain. Heterologous expression of cDNAs containing the bss1 lesion, followed by electrophysiology, shows that mutant channels display altered voltage dependence of inactivation compared to wild type. The phenotypes of bss are the most severe of the bang-sensitive mutants in Drosophila and can be ameliorated, but not suppressed, by treatment with anti-epileptic drugs. As such, bss-associated seizures resemble those of pharmacologically resistant epilepsies caused by mutation of the human NaV SCN1A, such as severe myoclonic epilepsy in infants or intractable childhood epilepsy with generalized tonic-clonic seizures. PMID:21115970

  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. Synthesis and anticonvulsant activity of some substituted 1,2,4-thiadiazoles.

    PubMed

    Gupta, Arun; Mishra, Pradeep; Pandeya, S N; Kashaw, Sushil K; Kashaw, Varsha; Stables, James P

    2009-03-01

    A series of new substituted 1,2,4-thiadiazoles were synthesized by appropriate route and screened for anticonvulsant, neurotoxic and sedative-hypnotic activity. The structures of the synthesized compounds were confirmed by IR spectroscopy, (13)C NMR and elemental (nitrogen and sulphur) analysis. After i.p. injection of the compounds to mice or rate at doses of 30, 100, and 300 mg/kg, body weights were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models after 0.5 and 4 h. Rotorod method and phenobarbitone-induced hypnosis potentiation study were employed to examine neurotoxicity and sedative-hypnotic activity, respectively. All the compounds except 4g showed protection against MES screen after 0.5 h. Compounds 3a-c, 4a-c were active at 100 mg/kg dose i.p., whereas remaining compounds showed activity at 300 mg/kg. All 14 compounds except 3g showed neurotoxicity at 100 and 300 mg/kg after 0.5 h. Compounds 3b and 4b showed NT after 4 h. Two compounds 3b and 4g showed significant (p<0.05) percentage increase in sleeping time i.e. 67% and 59%, respectively. It may be concluded that the synthesized compounds were potent against MES-induced seizures than ScPTZ induced and showed low potency as sedative-hypnotic agent which is advantageous.

  5. 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.

  6. Neonatal Seizures: Advances in Mechanisms and Management

    PubMed Central

    Glass, Hannah C.

    2013-01-01

    Synopsis Seizures occur in approximately 1–5 per 1,000 live births, and are among the most common neurologic conditions managed by a neonatal neurocritical care service. There are several, age-specific factors that are particular to the developing brain, which influence excitability and seizure generation, response to medications, and impact of seizures on brain structure and function. Neonatal seizures are often associated with serious underlying brain injury such as hypoxia-ischemia, stroke or hemorrhage. Conventional, prolonged, continuous video-electroencephalogram (cEEG) is the gold standard for detecting seizures, whereas amplitude-integrated EEG (aEEG) is a convenient and useful bedside tool. Evaluation of neonatal seizures involves a thorough search for the etiology of the seizures, and includes detailed clinical history, routine chemistries, neuroimaging (and preferably magnetic resonance imaging, MRI), and specialized testing such as screening for inborn errors of metabolism if no structural cause is identified and seizures persist after correction of transient metabolic deficits. Expert opinion supports rapid medical treatment to abolish electrographic seizures, however the relative risk versus benefit for aggressive medical treatment of neonatal seizures is not known. While there is increasing evidence to support a harmful effect of seizures on the developing brain, there is also evidence that commonly used medications are potentially neurotoxic in animal models. Newer agents appear less harmful, but data are lacking regarding optimal dosing and efficacy. PMID:24524454

  7. Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures: an individual participant data review.

    PubMed

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

    2016-04-28

    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). This review is one in a series of Cochrane reviews investigating pair-wise monotherapy comparisons. This is the latest updated version of the review first published in 2001 and updated in 2013. To review the time to withdrawal, remission and first seizure of phenytoin compared to valproate when used as monotherapy in people with partial onset seizures or generalised tonic-clonic seizures (with or without other generalised seizure types). We searched the Cochrane Epilepsy Group's Specialised Register (19 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 4), MEDLINE (1946 to 19 May 2015), SCOPUS (19 February 2013), ClinicalTrials.gov (19 May 2015), and WHO International Clinical Trials Registry Platform ICTRP (19 May 2015). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. Randomised controlled trials (RCTs) 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 participant data (IPD) review. Outcomes were time to: (a) withdrawal of allocated treatment (retention time); (b) achieve 12-month remission (seizure-free period); (c) achieve six-month remission (seizure-free period); and (d) first seizure (post-randomisation). We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and the generic inverse variance method to obtain the overall pooled HR and 95% CI. IPD were available for 669 individuals out of 1119 eligible individuals

  8. Seizures in the alcoholic patient.

    PubMed

    Young, G P

    1990-11-01

    The First International Symposium on Alcohol and Seizures (September 1988, Washington, DC) convened experts from North America and Europe to discuss the basic and clinical research findings in this field. Most of the observations communicated at this symposium are included in this article. Emergency physicians are familiar with the alcoholic patient who presents during or after a seizure(s). This familiarity must not obscure the fact that a significant minority of these patients will have an underlying process that can cause morbidity or mortality if the unsuspecting physician does not have an organized and methodic approach to the evaluation and management of the seizing alcoholic patient. Status epilepticus should be evaluated and treated in a similar fashion, whether or not the patient is an alcoholic. Otherwise, almost without exception, there are nuances and controversies with respect to the evaluation and management of the alcoholic patient with a seizure(s), from the indications for CT scan, to the proper role of sedatives and anticonvulsants, and the need for admission. The emergency physician must remain a patient advocate. The great majority of alcoholic patients with seizures who require admission can be treated satisfactorily at the hospital of presentation.

  9. A Discriminative Approach to EEG Seizure Detection

    PubMed Central

    Johnson, Ashley N.; Sow, Daby; Biem, Alain

    2011-01-01

    Seizures are abnormal sudden discharges in the brain with signatures represented in electroencephalograms (EEG). The efficacy of the application of speech processing techniques to discriminate between seizure and non-seizure states in EEGs is reported. The approach accounts for the challenges of unbalanced datasets (seizure and non-seizure), while also showing a system capable of real-time seizure detection. The Minimum Classification Error (MCE) algorithm, which is a discriminative learning algorithm with wide-use in speech processing, is applied and compared with conventional classification techniques that have already been applied to the discrimination between seizure and non-seizure states in the literature. The system is evaluated on 22 pediatric patients multi-channel EEG recordings. Experimental results show that the application of speech processing techniques and MCE compare favorably with conventional classification techniques in terms of classification performance, while requiring less computational overhead. The results strongly suggests the possibility of deploying the designed system at the bedside. PMID:22195192

  10. [Epilepsy and psychic seizures].

    PubMed

    Fukao, Kenjiro

    2006-01-01

    Various psychic symptoms as ictal manifestation have been found in epileptic patients. They are classified as psychic seizures within simple partial seizures, and subclassified into affective, cognitive, dysmnesic seizures and so on, although the subclassification is not yet satisfactory and almost nothing is known about their relationships with normal brain functions. In this presentation, the speaker picked ictal fear, déjà vu and out-of-body experience (OBE) from them and suggested that studies on these symptoms could uniquely contribute to the progress of cognitive neuroscience, presenting some results from the research and case study that he had been engaged in. Psychic seizures are prone to be missed or misdiagnosed unless psychiatrists with sufficient knowledge and experience on epilepsy care would not treat them, because they are subjective symptoms that are diverse and subtle, while they have some characteristics as ictal symptoms.

  11. Automatic Seizure Detection in Rats Using Laplacian EEG and Verification with Human Seizure Signals

    PubMed Central

    Feltane, Amal; Boudreaux-Bartels, G. Faye; Besio, Walter

    2012-01-01

    Automated detection of seizures is still a challenging problem. This study presents an approach to detect seizure segments in Laplacian electroencephalography (tEEG) recorded from rats using the tripolar concentric ring electrode (TCRE) configuration. Three features, namely, median absolute deviation, approximate entropy, and maximum singular value were calculated and used as inputs into two different classifiers: support vector machines and adaptive boosting. The relative performance of the extracted features on TCRE tEEG was examined. Results are obtained with an overall accuracy between 84.81 and 96.51%. In addition to using TCRE tEEG data, the seizure detection algorithm was also applied to the recorded EEG signals from Andrzejak et al. database to show the efficiency of the proposed method for seizure detection. PMID:23073989

  12. Studies of stimulus parameters for seizure disruption using neural network simulations.

    PubMed

    Anderson, William S; Kudela, Pawel; Cho, Jounhong; Bergey, Gregory K; Franaszczuk, Piotr J

    2007-08-01

    A large scale neural network simulation with realistic cortical architecture has been undertaken to investigate the effects of external electrical stimulation on the propagation and evolution of ongoing seizure activity. This is an effort to explore the parameter space of stimulation variables to uncover promising avenues of research for this therapeutic modality. The model consists of an approximately 800 mum x 800 mum region of simulated cortex, and includes seven neuron classes organized by cortical layer, inhibitory or excitatory properties, and electrophysiological characteristics. The cell dynamics are governed by a modified version of the Hodgkin-Huxley equations in single compartment format. Axonal connections are patterned after histological data and published models of local cortical wiring. Stimulation induced action potentials take place at the axon initial segments, according to threshold requirements on the applied electric field distribution. Stimulation induced action potentials in horizontal axonal branches are also separately simulated. The calculations are performed on a 16 node distributed 32-bit processor system. Clear differences in seizure evolution are presented for stimulated versus the undisturbed rhythmic activity. Data is provided for frequency dependent stimulation effects demonstrating a plateau effect of stimulation efficacy as the applied frequency is increased from 60 to 200 Hz. Timing of the stimulation with respect to the underlying rhythmic activity demonstrates a phase dependent sensitivity. Electrode height and position effects are also presented. Using a dipole stimulation electrode arrangement, clear orientation effects of the dipole with respect to the model connectivity is also demonstrated. A sensitivity analysis of these results as a function of the stimulation threshold is also provided.

  13. 27 CFR 478.152 - Seizure and forfeiture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Seizure and forfeiture... Exemptions, Seizures, and Forfeitures § 478.152 Seizure and forfeiture. (a) Any firearm or ammunition... demonstrated by clear and convincing evidence, shall be subject to seizure and forfeiture, and all provisions...

  14. 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.

  15. 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.

  16. Phenobarbitone, neonatal seizures, and video-EEG

    PubMed Central

    Boylan, G; Rennie, J; Pressler, R; Wilson, G; Morton, M; Binnie, C

    2002-01-01

    Aims: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. Methods: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20–40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. Results: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. Conclusion: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal. PMID:11978746

  17. 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.

  18. 50 CFR 12.11 - Notification of seizure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Notification of seizure. 12.11 Section 12... SEIZURE AND FORFEITURE PROCEDURES Preliminary Requirements § 12.11 Notification of seizure. Except where the owner or consignee is personally notified or seizure is made pursuant to a search warrant, the...

  19. AMPA receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures.

    PubMed

    Lippman-Bell, Jocelyn J; Rakhade, Sanjay N; Klein, Peter M; Obeid, Makram; Jackson, Michele C; Joseph, Annelise; Jensen, Frances E

    2013-11-01

    To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mammalian target of rapamycin (mTOR) pathway activation and long-term sequelae following neonatal seizures in rats, including later-life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits. Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12 h × 4 doses). Twelve hours post-HS, we assessed mTOR activation marker phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS + V) or NBQX-treated post-HS rats (HS + N) versus littermate controls (C + V). Spontaneous seizure activity was compared between groups by epidural cortical electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was measured using Timm staining. Finally, we assessed behavior between P30 and P38. Postseizure NBQX treatment significantly attenuated seizure-induced increases in p-p70S6K in the hippocampus (p < 0.01) and cortex (p < 0.001). Although spontaneous recurrent seizures increased in adulthood in HS + V rats compared to controls (3.22 ± 1 seizures/h; p = 0.03), NBQX significantly attenuated later-life seizures (0.14 ± 0.1 seizures/h; p = 0.046). HS + N rats showed less aberrant mossy fiber sprouting (115 ± 8.0%) than vehicle-treated post-HS rats (174 ± 10%, p = 0.004), compared to controls (normalized to 100%). Finally, NBQX treatment prevented alterations in later-life social behavior; post-HS rats showed significantly decreased preference for a novel over a familiar rat (71.0 ± 12 s) compared to controls (99.0 ± 15.6 s; p < 0.01), whereas HS + N rats showed social novelty preference similar to controls (114.3 ± 14.1 s). Brief NBQX administration during the 48 h postseizure in P10 Long-Evans rats suppresses transient mTOR pathway activation and attenuates spontaneous recurrent seizures, social preference deficits, and mossy

  20. 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.

  1. Review-of-systems questionnaire as a predictive tool for psychogenic nonepileptic seizures.

    PubMed

    Robles, Liliana; Chiang, Sharon; Haneef, Zulfi

    2015-04-01

    Patients with refractory epilepsy undergo video-electroencephalography for seizure characterization, among whom approximately 10-30% will be discharged with the diagnosis of psychogenic nonepileptic seizures (PNESs). Clinical PNES predictors have been described but in general are not sensitive or specific. We evaluated whether multiple complaints in a routine review-of-system (ROS) questionnaire could serve as a sensitive and specific marker of PNESs. We performed a retrospective analysis of a standardized ROS questionnaire completed by patients with definite PNESs and epileptic seizures (ESs) diagnosed in our adult epilepsy monitoring unit. A multivariate analysis of covariance (MANCOVA) was used to determine whether groups with PNES and ES differed with respect to the percentage of complaints in the ROS questionnaire. Tenfold cross-validation was used to evaluate the predictive error of a logistic regression classifier for PNES status based on the percentage of positive complaints in the ROS questionnaire. A total of 44 patients were included for analysis. Patients with PNESs had a significantly higher number of complaints in the ROS questionnaire compared to patients with epilepsy. A threshold of 17% positive complaints achieved a 78% specificity and 85% sensitivity for discriminating between PNESs and ESs. We conclude that the routine ROS questionnaire may be a sensitive and specific predictive tool for discriminating between PNESs and ESs. Published by Elsevier Inc.

  2. Design, synthesis and anticonvulsant activity of new hybrid compounds derived from N-phenyl-2-(2,5-dioxopyrrolidin-1-yl)-propanamides and -butanamides.

    PubMed

    Kamiński, Krzysztof; Rapacz, Anna; Filipek, Barbara; Obniska, Jolanta

    2016-07-01

    The focused library of 21 new N-phenyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamide, and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives as potential new hybrid anticonvulsant agents was synthesized. These hybrid molecules were obtained as close analogs of previously described N-benzyl derivatives and fuse the chemical fragments of clinically relevant antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, as well as in the six-Hertz (6Hz) model of pharmacoresistant limbic seizures. Applying the rotarod test, the acute neurological toxicity was determined. The broad spectra of activity across the preclinical seizure models in mice (ip) displayed compounds 4, 5, 11, and 19. The most favorable anticonvulsant properties demonstrated 4 (ED50 MES=96.9mg/kg, ED50scPTZ=75.4mg/kg, ED50 6Hz=44.3mg/kg) which showed TD50=335.8mg/kg in the rotarod test that yielded satisfying protective indexes (PI MES=3.5, PI scPTZ=4.4, PI 6Hz=7.6). Consequently, compound 4 revealed comparable or better safety profile than model antiepileptic drugs (AEDs): ethosuximide, lacosamide, and valproic acid. In the in vitro assays, compound 4 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and diltiazem site of L-type calcium channels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. 19 CFR 162.92 - Notice of seizure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Notice of seizure. 162.92 Section 162.92 Customs... (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Civil Asset Forfeiture Reform Act § 162.92 Notice of seizure. (a) Generally. Customs will send written notice of seizure as provided in this section to all known interested...

  4. Multi-modal intelligent seizure acquisition (MISA) system--a new approach towards seizure detection based on full body motion measures.

    PubMed

    Conradsen, Isa; Beniczky, Sandor; Wolf, Peter; Terney, Daniella; Sams, Thomas; Sorensen, Helge B D

    2009-01-01

    Many epilepsy patients cannot call for help during a seizure, because they are unconscious or because of the affection of their motor system or speech function. This can lead to injuries, medical complications and at worst death. An alarm system setting off at seizure onset could help to avoid hazards. Today no reliable alarm systems are available. A Multi-modal Intelligent Seizure Acquisition (MISA) system based on full body motion data seems as a good approach towards detection of epileptic seizures. The system is the first to provide a full body description for epilepsy applications. Three test subjects were used for this pilot project. Each subject simulated 15 seizures and in addition performed some predefined normal activities, during a 4-hour monitoring with electromyography (EMG), accelerometer, magnetometer and gyroscope (AMG), electrocardiography (ECG), electroencephalography (EEG) and audio and video recording. The results showed that a non-subject specific MISA system developed on data from the modalities: accelerometer (ACM), gyroscope and EMG is able to detect 98% of the simulated seizures and at the same time mistakes only 4 of the normal movements for seizures. If the system is individualized (subject specific) it is able to detect all simulated seizures with a maximum of 1 false positive. Based on the results from the simulated seizures and normal movements the MISA system seems to be a promising approach to seizure detection.

  5. Emergency Management of Seizures in the School Setting

    ERIC Educational Resources Information Center

    O'Dell, Christine; O'Hara, Kathryn; Kiel, Sarah; McCullough, Kathleen

    2007-01-01

    Effective seizure management in the school setting is a critical issue for students with seizures, as well as their parents, classmates, and school personnel. The unpredictable nature of seizures and the potential outcomes of experiencing a seizure in school are sources of anxiety for students with seizures. The ability to respond appropriately to…

  6. Seizures in hospitalized cocaine users.

    PubMed

    Choy-Kwong, M; Lipton, R B

    1989-03-01

    We reviewed the records of 283 cocaine abusers consecutively admitted to a municipal hospital, and identified eight patients (2.8%) who presented with seizures. Four (1.4%) had focal or generalized seizures temporally associated with cocaine use. Based on these four cases and five previous reports, we conclude that although seizures are relatively rare in hospitalized cocaine users, they are provoked by all major routes of administration, and may be partial or generalized.

  7. Seizures

    MedlinePlus

    ... of seizures. Some have mild symptoms without shaking. Considerations It may be hard to tell if someone ... Epilepsy Fever (particularly in young children ) Head injury Heart disease Heat illness ( heat intolerance ) High fever Phenylketonuria ( PKU ), ...

  8. Is slack an intrinsic seizure terminator?

    PubMed

    Igelström, Kajsa M

    2013-06-01

    Understanding how epileptic seizures are initiated and propagated across large brain networks is difficult, but an even greater mystery is what makes them stop. Failure of spontaneous seizure termination leads to status epilepticus-a state of uninterrupted seizure activity that can cause death or permanent brain damage. Global factors, like changes in neuromodulators and ion concentrations, are likely to play major roles in spontaneous seizure cessation, but individual neurons also have intrinsic active ion currents that may contribute. The recently discovered gene Slack encodes a sodium-activated potassium channel that mediates a major proportion of the outward current in many neurons. Although given little attention, the current flowing through this channel may have properties consistent with a role in seizure termination.

  9. Partial psychic seizures and brain organization.

    PubMed

    Ardila, A; Montañes, P; Bernal, B; Serpa, A; Ruiz, E

    1986-08-01

    This research was an attempt to determine the cerebral areas involved in focal epileptic seizures accompanied by psychic manifestations. Six types of partial seizures involving psychic symptomatology and phonatory seizures were included in the study. Sixty-one clinical records of focal epilepsy, which had been revealed by means of a CT-scan examination, were analyzed and a subsample of 25 patients with psychic symptoms was selected. The scans taken of the lesions were transferred to a six-level standard template built for this purpose. Subsequently, templates of patients with the same type of seizures were superimposed. The critical zones for the seven types of seizures studied are presented. A clear correlation was found between these results and our present knowledge of functional brain organization.

  10. 8 CFR 280.21 - Seizure of aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Seizure of aircraft. 280.21 Section 280.21... OF FINES § 280.21 Seizure of aircraft. Seizure of an aircraft under the authority of section 239 of... than the amount of the fine which may be imposed. If seizure of an aircraft for violation of section...

  11. 8 CFR 1280.21 - Seizure of aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Seizure of aircraft. 1280.21 Section 1280... REGULATIONS IMPOSITION AND COLLECTION OF FINES § 1280.21 Seizure of aircraft. Seizure of an aircraft under the... that its value is less than the amount of the fine which may be imposed. If seizure of an aircraft for...

  12. Clustering of spontaneous recurrent seizures separated by long seizure-free periods: An extended video-EEG monitoring study of a pilocarpine mouse model.

    PubMed

    Lim, Jung-Ah; Moon, Jangsup; Kim, Tae-Joon; Jun, Jin-Sun; Park, Byeongsu; Byun, Jung-Ick; Sunwoo, Jun-Sang; Park, Kyung-Il; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Kim, Manho; Jeon, Daejong; Chu, Kon; Lee, Sang Kun

    2018-01-01

    Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring. A seizure cluster was defined as the occurrence of one or more seizures per day for at least three consecutive days and at least five seizures during the cluster period. We analyzed the cluster duration, seizure-free period, cluster interval, and numbers of seizures within and outside the seizure clusters. The video-EEG monitoring began 84.5±33.7 days after the induction of SE and continued for 53.7±20.4 days. Every mouse displayed seizure clusters, and 97.0% of the seizures occurred within a cluster period. The seizure clusters were followed by long seizure-free periods of 16.3±6.8 days, showing a cyclic pattern. The SRSs also occurred in a grouped pattern within a day. We demonstrate that almost all seizures occur in clusters with a cyclic pattern in the chronic stage of a mouse pilocarpine-induced epilepsy model. The seizure-free periods between clusters were long. These findings should be considered when performing in vivo studies using this animal model. Furthermore, this model might be appropriate for studying the unrevealed mechanism of ictogenesis.

  13. Lacosamide monotherapy for partial onset seizures.

    PubMed

    Lattanzi, Simona; Cagnetti, Claudia; Foschi, Nicoletta; Provinciali, Leandro; Silvestrini, Mauro

    2015-04-01

    To evaluate the 1-year efficacy and safety of oral lacosamide as conversion monotherapy in adult patients with partial onset seizures with or without generalization. We prospectively followed-up consecutive patients converted to lacosamide monotherapy after 1-year seizure freedom on lacosamide add-on therapy and withdrawal of the concurrent antiepileptic drug (AED). Seizure occurrence, treatment compliance and drug toxicity were assessed every 3 months up to 1 year. The study outcomes were the retention rate of lacosamide as single AED and the seizure freedom under lacosamide monotherapy at 1 year from withdrawal of background AED. The safety variable was the prevalence of lacosamide related adverse events (AEs). Among the 58 included patients, at 1 year from withdrawal of background medication, 37 (63.8%) retained lacosamide as single AED and 32 (55.2%) were free from seizure occurrence under lacosamide monotherapy throughout the entire follow-up. The history of less than three lifetime AEDs turned out to be significant predictor of seizure freedom (adjusted OR = 6.38, 95% CI 1.85-21.98, p = 0.003). Twelve (20.8%) subjects reported mild to moderate AEs, with the commonest being drowsiness, dizziness, and headache. Conversion to lacosamide monotherapy could be effective and well tolerated in selected adults patients with partial onset seizures who had achieved seizure freedom during lacosamide add-on therapy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.

    PubMed

    Sakkaki, Sophie; Gangarossa, Giuseppe; Lerat, Benoit; Françon, Dominique; Forichon, Luc; Chemin, Jean; Valjent, Emmanuel; Lerner-Natoli, Mireille; Lory, Philippe

    2016-02-01

    T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection. Copyright © 2015. Published by Elsevier Ltd.

  15. Dissociation in patients with dissociative seizures: relationships with trauma and seizure symptoms.

    PubMed

    Pick, S; Mellers, J D C; Goldstein, L H

    2017-05-01

    This study aimed to extend the current understanding of dissociative symptoms experienced by patients with dissociative (psychogenic, non-epileptic) seizures (DS), including psychological and somatoform types of symptomatology. An additional aim was to assess possible relationships between dissociation, traumatic experiences, post-traumatic symptoms and seizure manifestations in this group. A total of 40 patients with DS were compared with a healthy control group (n = 43), matched on relevant demographic characteristics. Participants completed several self-report questionnaires, including the Multiscale Dissociation Inventory (MDI), Somatoform Dissociation Questionnaire-20, Traumatic Experiences Checklist and the Post-Traumatic Diagnostic Scale. Measures of seizure symptoms and current emotional distress (Hospital Anxiety and Depression Scale) were also administered. The clinical group reported significantly more psychological and somatoform dissociative symptoms, trauma, perceived impact of trauma, and post-traumatic symptoms than controls. Some dissociative symptoms (i.e. MDI disengagement, MDI depersonalization, MDI derealization, MDI memory disturbance, and somatoform dissociation scores) were elevated even after controlling for emotional distress; MDI depersonalization scores correlated positively with trauma scores while seizure symptoms correlated with MDI depersonalization, derealization and identity dissociation scores. Exploratory analyses indicated that somatoform dissociation specifically mediated the relationship between reported sexual abuse and DS diagnosis, along with depressive symptoms. A range of psychological and somatoform dissociative symptoms, traumatic experiences and post-traumatic symptoms are elevated in patients with DS relative to healthy controls, and seem related to seizure manifestations. Further studies are needed to explore peri-ictal dissociative experiences in more detail.

  16. Electronic and structural aspects of spin transitions observed by optical microscopy. The case of [Fe(ptz)6](BF4)2.

    PubMed

    Chong, Christian; Mishra, Haritosh; Boukheddaden, Kamel; Denise, Stéphane; Bouchez, Guillaume; Collet, Eric; Ameline, Jean-Claude; Naik, Anil D; Garcia, Yann; Varret, François

    2010-02-11

    The colorimetric analysis of images recorded with an optical microscope during the onset of the spin crossover transformation allows monitoring separately the involved electronic and structural aspects, through the separation of resonant absorption and scattering effects. Complementary information can also be obtained by using the polarized modes of the microscope. These potentialities are illustrated by the observation of [Fe(ptz)(6)](BF(4))(2) single crystals during the onset of the thermal transitions in the 110-140 K range. We characterized the interplay between the electronic (HS <--> LS) and structural (order <--> disorder) transformations. Elastic stresses and mechanical effects (hopping, self-cleavage) generated by the volume change upon electronic transition are also illustrated, with their impact on the photoswitching properties of the crystals.

  17. [Research advances in circadian rhythm of epileptic seizures].

    PubMed

    Yang, Wen-Qi; Li, Hong

    2017-01-01

    The time phase of epileptic seizures has attracted more and more attention. Epileptic seizures have their own circadian rhythm. The same type of epilepsy has different seizure frequencies in different time periods and states (such as sleeping/awakening state and natural day/night cycle). The circadian rhythm of epileptic seizures has complex molecular and endocrine mechanisms, and currently there are several hypotheses. Clarification of the circadian rhythm of epileptic seizures and prevention and administration according to such circadian rhythm can effectively control seizures and reduce the adverse effects of drugs. The research on the circadian rhythm of epileptic seizures provides a new idea for the treatment of epilepsy.

  18. Generalized tonic-clonic seizure

    MedlinePlus

    ... lasts for 1 hour or longer (called the post-ictal state) Loss of memory (amnesia) about the seizure episode Headache Weakness of 1 side of the body for a few minutes to a few hours following seizure (called Todd paralysis) Exams and Tests The doctor will perform a physical exam. This ...

  19. Treating seizures in Creutzfeldt-Jakob disease.

    PubMed

    Ng, Marcus C; Westover, M Brandon; Cole, Andrew J

    2014-01-01

    Seizures are known to occur in Creutzfeldt-Jakob disease (CJD). In the setting of a rapidly progressive condition with no effective therapy, determining appropriate treatment for seizures can be difficult if clinical morbidity is not obvious yet the electroencephalogram (EEG) demonstrates a worrisome pattern such as status epilepticus. Herein, we present the case of a 39-year-old man with CJD and electrographic seizures, discuss how this case challenges conventional definitions of seizures, and discuss a rational approach toward treatment. Coincidentally, our case is the first report of CJD in a patient with Stickler syndrome.

  20. Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures.

    PubMed

    Kay, Lara; Reif, Philipp S; Belke, Marcus; Bauer, Sebastian; Fründ, Detlef; Knake, Susanne; Rosenow, Felix; Strzelczyk, Adam

    2015-09-01

    To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring. Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ. In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p = 0.009). Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic

  1. 15 CFR 904.501 - Notice of seizure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS CIVIL PROCEDURES Seizure and Forfeiture Procedures § 904.501 Notice of seizure. Within 60 days from the date of the seizure...

  2. Do oral contraceptives increase epileptic seizures?

    PubMed

    Reddy, Doodipala Samba

    2017-02-01

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

  3. 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.

  4. Seizure disorders in Systemic Lupus Erythematosus

    PubMed Central

    Hanly, John G.; Urowitz, Murray B.; Su, Li; Gordon, Caroline; Bae, Sang-Cheol; Sanchez-Guerrero, Jorge; Romero-Diaz, Juanita; Wallace, Daniel J; Clarke, Ann E.; Ginzler, E.M.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Petri, M.; Fortin, Paul R.; Gladman, D. D.; Bruce, Ian N.; Steinsson, Kristjan; Dooley, M.A.; Khamashta, Munther A.; Alarcón, Graciela S.; Fessler, Barri J.; Ramsey-Goldman, Rosalind; Manzi, Susan; Zoma, Asad A.; Sturfelt, Gunnar K.; Nived, Ola; Aranow, Cynthia; Mackay, Meggan; Ramos-Casals, Manuel; van Vollenhoven, R.F.; Kalunian, Kenneth C.; Ruiz-Irastorza, Guillermo; Lim, Sam; Kamen, Diane L.; Peschken, Christine A.; Inanc, Murat; Theriault, Chris; Thompson, Kara; Farewell, Vernon

    2015-01-01

    Objective To describe the frequency, attribution, outcome and predictors of seizures in SLE Methods The Systemic Lupus International Collaborating Clinics (SLICC) performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)) and neuropsychiatric events were recorded at enrollment and annually. Lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrollment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 mental (MCS) and physical (PCS) component summary scores. Statistical analyses included Cox and linear regressions. Results The cohort was 89.4% female with a mean follow up of 3.5±2.9 years. 75/1631 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR(CI):1.97 (1.07–3.63); p=0.03) and lower education status (1.97 (1.21–3.19); p<0.01). Higher damage scores (without NP variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46–10.55)); SDI=2 or 3:1.57 (0.32–7.65); SDI≥4:7.86 (0.89–69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78(76%)) in the absence of anti-seizure drugs. There was no significant impact on the MCS or PCS scores. Anti-malarial drugs in absence of immunosuppressive agents were associated with reduced seizure risk (0.07(0.01–0.66); p=0.03). Conclusion Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Anti-malarial drugs were associated with a protective effect. PMID:22492779

  5. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  6. Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials.

    PubMed

    Kerr, Wesley T; Janio, Emily A; Le, Justine M; Hori, Jessica M; Patel, Akash B; Gallardo, Norma L; Bauirjan, Janar; Chau, Andrea M; D'Ambrosio, Shannon R; Cho, Andrew Y; Engel, Jerome; Cohen, Mark S; Stern, John M

    2016-08-01

    The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=-0.9, p=0.38). Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. 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.

  8. A systematic review of suggestive seizure induction for the diagnosis of psychogenic nonepileptic seizures.

    PubMed

    Popkirov, Stoyan; Grönheit, Wenke; Wellmer, Jörg

    2015-09-01

    Suggestive seizure induction is a widely used method for diagnosing psychogenic nonepileptic seizures (PNES). Despite seven decades of multidisciplinary research, however, there is still no unified protocol, no definitive agreement on the ethical framework and no consensus on diagnostic utility. This systematic review surveys the evidence at hand and addresses clinically relevant aspects of suggestive seizure induction. In addition to its use for facilitating the diagnostic process, its mechanism of action and utility in elucidating the psychopathology of PNES will be discussed. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. Maternal knowledge of acute seizures.

    PubMed

    Asiri, Nawal A; Bin Joubah, Mohammed A; Khan, Samar M; Jan, Mohammed M

    2015-10-01

    To study maternal knowledge -of, and behavior during acute seizures. A cross sectional study conducted from September 2013 to January 2014 included consecutive mothers presenting at the Pediatric Neurology Clinics of King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. A structured 30-item questionnaire was designed to examine their demographics, knowledge, and behavior on acute seizures. A total of 92 mothers were interviewed and 41% witnessed at least one acute seizure in their affected child (range 1-15 years, mean 4.5). Up to 26% felt not knowledgeable at all regarding the acute care and management of seizure. Mothers with higher education (college or university degree) were more likely to feel very knowledgeable (19% versus 11%, p=0.02). Only 10% were aware of an antiepileptic drug that could be used at home to stop prolonged seizures, and 35% mentioned that they would wait for 15 minutes before taking the child to the emergency department. Most mothers (93%) wanted more information. Those who felt strongly regarding that (66%), were more likely to be younger (<27 years) (p=0.01), and have at least 3 out of 7 mismanagement decisions (p=0.003). Maternal level of knowledge and behavior during acute seizures needs improvement. Many mothers have significant misinformation, negative behavior, and poor management practices. Increased awareness and educational programs are needed.

  10. Does remifentanil improve ECT seizure quality?

    PubMed

    Gálvez, Verònica; Tor, Phern-Chern; Bassa, Adriana; Hadzi-Pavlovic, Dusan; MacPherson, Ross; Marroquin-Harris, Mincho; Loo, Colleen K

    2016-12-01

    Studies have reported that co-adjuvant remifentanil can enhance electroconvulsive therapy (ECT) seizure quality, putatively by allowing a reduction in the dosage of the main anaesthetic agents, as the latter have anticonvulsant properties. However, whether remifentanil also has direct effects on ECT seizure quality, and by implication, treatment efficacy, is unknown. This is the first study examining the effect of adjuvant remifentanil on ECT seizure quality when the dose of conventional anaesthesia remained unchanged. A total of 96 ECT sessions (from 36 patients) were retrospectively analysed. Subjects received ECT with and without remifentanil (1 µg/kg), while the dose of thiopentone (3-5 mg/kg) or propofol (1-2 mg/kg) was unchanged. Seizure quality indices (time to slow wave activity or TSLOW, amplitude, regularity, stereotypy, post-ictal suppression) and duration were assessed through a structured rating scale by a single trained blinded rater. Linear mixed-effects models with random subject effects analysed the effect of remifentanil on seizure parameters, controlling for other variables that can affect seizure quality or duration. Remifentanil was given in 47.9 % of the ECT sessions. Co-adjuvant remifentanil had no effects on any of the seizure quality parameters analysed [TSLOW (E = -0.21, p > 0.1), amplitude (E = 0.08, p > 0.5), regularity (E = -0.05, p > 0.5), stereotypy (E = -0.02, p > 0.5), suppression (E = -0.3, p > 0.05)] or on seizure duration (E = -0.25, p > 0.1). While adjuvant remifentanil may be a useful strategy for reducing anaesthetic dosage in ECT, present evidence suggests that remifentanil does not have intrinsic properties that enhance ECT seizures.

  11. ATPergic signalling during seizures and epilepsy.

    PubMed

    Engel, Tobias; Alves, Mariana; Sheedy, Caroline; Henshall, David C

    2016-05-01

    Much progress has been made over the last few decades in the identification of new anti-epileptic drugs (AEDs). However, 30% of epilepsy patients suffer poor seizure control. This underscores the need to identify alternative druggable neurotransmitter systems and drugs with novel mechanisms of action. An emerging concept is that seizure generation involves a complex interplay between neurons and glial cells at the tripartite synapse and neuroinflammation has been proposed as one of the main drivers of epileptogenesis. The ATP-gated purinergic receptor family is expressed throughout the brain and is functional on neurons and glial cells. ATP is released in high amounts into the extracellular space after increased neuronal activity and during chronic inflammation and cell death to act as a neuro- and gliotransmitter. Emerging work shows pharmacological targeting of ATP-gated purinergic P2 receptors can potently modulate seizure generation, inflammatory processes and seizure-induced brain damage. To date, work showing the functional contribution of P2 receptors has been mainly performed in animal models of acute seizures, in particular, by targeting the ionotropic P2X7 receptor subtype. Other ionotropic P2X and metabotropic P2Y receptor family members have also been implicated in pathological processes following seizures such as the P2X4 receptor and the P2Y12 receptor. However, during epilepsy, the characterization of P2 receptors was mostly restricted to the study of expressional changes of the different receptor subtypes. This review summarizes the work to date on ATP-mediated signalling during seizures and the functional impact of targeting the ATP-gated purinergic receptors on seizures and seizure-induced pathology. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The number of seizures needed in the EMU

    PubMed Central

    Struck, Aaron F.; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon

    2016-01-01

    Summary Objective The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Methods Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Results Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. Significance These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for

  13. Unsupervised EEG analysis for automated epileptic seizure detection

    NASA Astrophysics Data System (ADS)

    Birjandtalab, Javad; Pouyan, Maziyar Baran; Nourani, Mehrdad

    2016-07-01

    Epilepsy is a neurological disorder which can, if not controlled, potentially cause unexpected death. It is extremely crucial to have accurate automatic pattern recognition and data mining techniques to detect the onset of seizures and inform care-givers to help the patients. EEG signals are the preferred biosignals for diagnosis of epileptic patients. Most of the existing pattern recognition techniques used in EEG analysis leverage the notion of supervised machine learning algorithms. Since seizure data are heavily under-represented, such techniques are not always practical particularly when the labeled data is not sufficiently available or when disease progression is rapid and the corresponding EEG footprint pattern will not be robust. Furthermore, EEG pattern change is highly individual dependent and requires experienced specialists to annotate the seizure and non-seizure events. In this work, we present an unsupervised technique to discriminate seizures and non-seizures events. We employ power spectral density of EEG signals in different frequency bands that are informative features to accurately cluster seizure and non-seizure events. The experimental results tried so far indicate achieving more than 90% accuracy in clustering seizure and non-seizure events without having any prior knowledge on patient's history.

  14. Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

    PubMed

    Di Gennaro, Giancarlo; Casciato, Sara; Quarato, Pier Paolo; Mascia, Addolorata; D'Aniello, Alfredo; Grammaldo, Liliana G; De Risi, Marco; Meldolesi, Giulio N; Romigi, Andrea; Esposito, Vincenzo; Picardi, Angelo

    2015-01-01

    To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. Types of Seizures Affecting Individuals with TSC

    MedlinePlus

    ... Cannabis you can review. *New Terms for Seizure Classifications The International League Against Epilepsy has approved a ... seizures. This new system will make diagnosis and classification of seizures easier and more accurate. Learn more ...

  16. Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

    PubMed Central

    Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

    2010-01-01

    We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

  17. Predictability of uncontrollable multifocal seizures - towards new treatment options

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus; Dickten, Henning; Porz, Stephan; Helmstaedter, Christoph; Elger, Christian E.

    2016-04-01

    Drug-resistant, multifocal, non-resectable epilepsies are among the most difficult epileptic disorders to manage. An approach to control previously uncontrollable seizures in epilepsy patients would consist of identifying seizure precursors in critical brain areas combined with delivering a counteracting influence to prevent seizure generation. Predictability of seizures with acceptable levels of sensitivity and specificity, even in an ambulatory setting, has been repeatedly shown, however, in patients with a single seizure focus only. We did a study to assess feasibility of state-of-the-art, electroencephalogram-based seizure-prediction techniques in patients with uncontrollable multifocal seizures. We obtained significant predictive information about upcoming seizures in more than two thirds of patients. Unexpectedly, the emergence of seizure precursors was confined to non-affected brain areas. Our findings clearly indicate that epileptic networks, spanning lobes and hemispheres, underlie generation of seizures. Our proof-of-concept study is an important milestone towards new therapeutic strategies based on seizure-prediction techniques for clinical practice.

  18. 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

  19. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats.

    PubMed

    Saberi, Mehdi; Rezvanizadeh, Alireza; Bakhtiarian, Azam

    2008-08-22

    The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (P<0.05). These changes were more significant with higher doses (120 or 180 mg/kg) for ADD (P<0.01) and S5D (P<0.001). Vitex at the dose of 120 mg/kg, induced significant increment in S4L (P<0.05). This effect was more prominent at the dose of 180 mg/kg (P<0.001). The latter dose could significantly reduce seizure stage (P<0.01) and most of the animals did not show S5. These results indicate that Vitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.

  20. A new model to study sleep deprivation-induced seizure.

    PubMed

    Lucey, Brendan P; Leahy, Averi; Rosas, Regine; Shaw, Paul J

    2015-05-01

    A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB(9ed4)), and in an adult temperature sensitive seizure mutant seizure (sei(ts1)) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB(9ed4) flies was also assessed. Laboratory. Drosophila melanogaster. Sleep deprivation. Sleep deprivation increased seizure susceptibility in adult sesB(9ed4)/+ and sei(ts1) mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB(9ed4)/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB(9ed4)/+ became adults. These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. © 2015 Associated Professional Sleep Societies, LLC.

  1. Pre-stroke seizures: A nationwide register-based investigation.

    PubMed

    Zelano, Johan; Larsson, David; Kumlien, Eva; Åsberg, Signild

    2017-07-01

    The relationship between cerebrovascular disease and seizures is clearly illustrated by poststroke epilepsy. Seizures can also be the first manifestation of cerebrovascular disease and case-control studies have demonstrated that seizures carry an increased risk of subsequent stroke. Thus, seizures could serve as a marker for vascular risk that merits intervention, but more data is needed before proper trials can be conducted. The occurrence of pre-stroke seizures has not been assessed on a national scale. We asked what proportion of strokes in middle-aged and elderly patients was preceded by seizures. All patients over 60 years of age with first-ever stroke in 2005-2010 (n=92,596) were identified in the Swedish stroke register (Riksstroke) and cross-sectional data on a history of a first seizure or epilepsy diagnosis in the ten years preceding stroke were collected from national patient registers with mandatory reporting. 1372 patients (1.48%) had a first seizure or epilepsy diagnosis registered less than ten years prior to the index stroke. The mean latency between seizure and stroke was 1474days (SD 1029 days). Seizures or epilepsy preceded 1.48% of strokes in patients >60years of age. Based on recent national incidence figures, 5-20% of incident cases of seizures or epilepsy after 60 years of age could herald stroke, depending on age group. These proportions are of a magnitude that merit further study on how to reduce the risk of stroke in patients with late-onset seizures or epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. Neuronal Ensemble Synchrony during Human Focal Seizures

    PubMed Central

    Ahmed, Omar J.; Harrison, Matthew T.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.

    2014-01-01

    Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40–60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50–100 ms level. In addition, transient fine synchrony occurred primarily during the initial ∼20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (∼80 Hz) gamma-band and during high-frequency oscillations (∼130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons. PMID:25057195

  3. A Novel Signal Modeling Approach for Classification of Seizure and Seizure-Free EEG Signals.

    PubMed

    Gupta, Anubha; Singh, Pushpendra; Karlekar, Mandar

    2018-05-01

    This paper presents a signal modeling-based new methodology of automatic seizure detection in EEG signals. The proposed method consists of three stages. First, a multirate filterbank structure is proposed that is constructed using the basis vectors of discrete cosine transform. The proposed filterbank decomposes EEG signals into its respective brain rhythms: delta, theta, alpha, beta, and gamma. Second, these brain rhythms are statistically modeled with the class of self-similar Gaussian random processes, namely, fractional Brownian motion and fractional Gaussian noises. The statistics of these processes are modeled using a single parameter called the Hurst exponent. In the last stage, the value of Hurst exponent and autoregressive moving average parameters are used as features to design a binary support vector machine classifier to classify pre-ictal, inter-ictal (epileptic with seizure free interval), and ictal (seizure) EEG segments. The performance of the classifier is assessed via extensive analysis on two widely used data set and is observed to provide good accuracy on both the data set. Thus, this paper proposes a novel signal model for EEG data that best captures the attributes of these signals and hence, allows to boost the classification accuracy of seizure and seizure-free epochs.

  4. Change in illness perception is associated with short-term seizure burden outcome following video-EEG confirmation of psychogenic nonepileptic seizures.

    PubMed

    Chen, David K; Majmudar, Shirine; Ram, Aarthi; Rutherford, Holly C; Fadipe, Melissa; Dunn, Callie B; Collins, Robert L

    2018-04-27

    We aimed to evaluate whether potential changes in the patient's illness perception can significantly influence short-term seizure burden following video-electroencephalography (EEG) confirmation/explanation of psychogenic nonepileptic seizures (PNES). Patients with PNES were dichotomized to two groups based on a five-point Symptom Attribution Scale: (a) those who prior to diagnosis perceived their seizures to be solely ("5") or mainly ("4") physical in origin (physical group) and (b) the remainder of patients with PNES (psychological group). The physical group (n=32), psychological group (n=40), and group with epilepsy (n=26) also completed the Brief Illness Perception Questionnaire (BIPQ) prior to diagnosis, and were followed up at 3months as well as at 6months postdiagnosis. At 3months postdiagnosis, the physical group experienced significantly greater improvement in seizure intensity (p=0.002) and seizure frequency (p=0.016) when compared with the psychological group. The physical group was significantly more likely to have modified their symptom attribution toward a greater psychological role to their seizures (p=0.002), and their endorsement on the BIPQ item addressing "consequences" (How much do your seizures affect your life?) was significantly less severe (p'=0.014) when compared with that of the psychological group and the group with epilepsy. At 6months postdiagnosis, the physical group continued to experience significantly greater improvement in seizure intensity (p=0.007) while their seizure frequency no longer reached significant difference (p=0.078) when compared with the psychological group. The physical group continued to be significantly more likely to have modified their symptom attribution toward a greater psychological role to their seizures (p=0.005), and their endorsement on the BIPQ item addressing "consequences" remained significantly less severe (p'=0.037) when compared with the psychological group and the group with epilepsy. Among

  5. A New Model to Study Sleep Deprivation-Induced Seizure

    PubMed Central

    Lucey, Brendan P.; Leahy, Averi; Rosas, Regine; Shaw, Paul J.

    2015-01-01

    Background and Study Objectives: A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Design: Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB9ed4), and in an adult temperature sensitive seizure mutant seizure (seits1) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB9ed4 flies was also assessed. Setting: Laboratory. Participants: Drosophila melanogaster. Interventions: Sleep deprivation. Measurements and Results: Sleep deprivation increased seizure susceptibility in adult sesB9ed4/+ and seits1 mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB9ed4/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB9ed4/+ became adults. Conclusions: These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. Citation: Lucey BP, Leahy A, Rosas R, Shaw PJ. A new model to study sleep deprivation-induced seizure. SLEEP 2015;38(5):777–785. PMID:25515102

  6. The number of seizures needed in the EMU.

    PubMed

    Struck, Aaron F; Cole, Andrew J; Cash, Sydney S; Westover, M Brandon

    2015-11-01

    The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery. Wiley Periodicals, Inc. © 2015

  7. Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

    PubMed

    Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K; Dehaen, Wim; de Witte, Peter A M; Esguerra, Camila V

    2013-01-01

    In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

  8. Insights from Zebrafish and Mouse Models on the Activity and Safety of Ar-Turmerone as a Potential Drug Candidate for the Treatment of Epilepsy

    PubMed Central

    Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K.; Dehaen, Wim; de Witte, Peter A. M.; Esguerra, Camila V.

    2013-01-01

    In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application. PMID:24349101

  9. 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.

  10. Febrile seizures: a population-based study.

    PubMed

    Dalbem, Juliane S; Siqueira, Heloise H; Espinosa, Mariano M; Alvarenga, Regina P

    2015-01-01

    To determine the prevalence of benign febrile seizures of childhood and describe the clinical and epidemiological profile of this population. This was a population-based, cross-sectional study, carried out in the city of Barra do Bugres, MT, Brazil, from August 2012 to August 2013. Data were collected in two phases. In the first phase, a questionnaire that was previously validated in another Brazilian study was used to identify suspected cases of seizures. In the second phase, a neurological evaluation was performed to confirm diagnosis. The prevalence was 6.4/1000 inhabitants (95% CI: 3.8-10.1). There was no difference between genders. Simple febrile seizures were found in 88.8% of cases. A family history of febrile seizures in first-degree relatives and history of epilepsy was present in 33.3% and 11.1% of patients, respectively. The prevalence of febrile seizures in Midwestern Brazil was lower than that found in other Brazilian regions, probably due to the inclusion only of febrile seizures with motor manifestations and differences in socioeconomic factors among the evaluated areas. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. Why are seizures rare in rapid eye movement sleep? Review of the frequency of seizures in different sleep stages.

    PubMed

    Ng, Marcus; Pavlova, Milena

    2013-01-01

    Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.

  12. Forecasting seizures in dogs with naturally occurring epilepsy.

    PubMed

    Howbert, J Jeffry; Patterson, Edward E; Stead, S Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W Douglas; Litt, Brian; Worrell, Gregory A

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-70 Hz), and high-gamma (70-180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring.

  13. Periictal activity in cooled asphyxiated neonates with seizures.

    PubMed

    Major, Philippe; Lortie, Anne; Dehaes, Mathieu; Lodygensky, Gregory Anton; Gallagher, Anne; Carmant, Lionel; Birca, Ala

    2017-04-01

    Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming. We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events. Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence. This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. 19 CFR 162.21 - Responsibility and authority for seizures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Responsibility and authority for seizures. 162.21...; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Seizures § 162.21 Responsibility and authority for seizures. (a) Seizures by Customs officers. Property may be seized, if available, by any...

  15. Tranexamic acid–associated seizures: Causes and treatment

    PubMed Central

    Lecker, Irene; Wang, Dian‐Shi; Whissell, Paul D.; Avramescu, Sinziana; Mazer, C. David

    2015-01-01

    Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26 PMID:26580862

  16. Do foods precipitate seizures? A cross-cultural comparison.

    PubMed

    Asadi-Pooya, Ali A; Sperling, Michael R

    2007-11-01

    It has been reported that a common belief of the families of the patients with epilepsy in Iran is that foods provoke seizures. Our aim in the present study was to ascertain whether a culturally different population of patients with epilepsy in the United States believe that foods precipitate seizures. Adults aged 18 and older with epilepsy were recruited in either the inpatient epilepsy monitoring unit or the outpatient epilepsy clinic at Thomas Jefferson University from September to December 2006. Patients completed a questionnaire asking their age, sex, education, seizure control, and beliefs about the relationship between foods and seizures. One hundred ninety-three patients participated, with a mean age of 40.3 +/- 16. Only 11 (5.7%) patients reported foods as a precipitating factor for seizures. The difference between the results of the Iranian study, in which 55.2% of the families of children with epilepsy reported a relationship between specific foods and seizures, and the present results is significant (P=0.0001). The perception of foods as a seizure precipitant differs greatly between a Middle Eastern country (Iran) and a Western country (United States). This discordance suggests that cultural factors may play a large role in the perception of probable precipitating factors related to seizures. Some commonly reported seizure precipitants may represent cultural beliefs, and this raises a question as to whether foods truly precipitate seizures.

  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. First seizure while driving (FSWD)--an underestimated phenomenon?

    PubMed

    Pohlmann-Eden, Bernd; Hynick, Nina; Legg, Karen

    2013-07-01

    Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD). Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence. The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour. FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

  19. Epileptic Seizures Prediction Using Machine Learning Methods

    PubMed Central

    Usman, Syed Muhammad

    2017-01-01

    Epileptic seizures occur due to disorder in brain functionality which can affect patient's health. Prediction of epileptic seizures before the beginning of the onset is quite useful for preventing the seizure by medication. Machine learning techniques and computational methods are used for predicting epileptic seizures from Electroencephalograms (EEG) signals. However, preprocessing of EEG signals for noise removal and features extraction are two major issues that have an adverse effect on both anticipation time and true positive prediction rate. Therefore, we propose a model that provides reliable methods of both preprocessing and feature extraction. Our model predicts epileptic seizures' sufficient time before the onset of seizure starts and provides a better true positive rate. We have applied empirical mode decomposition (EMD) for preprocessing and have extracted time and frequency domain features for training a prediction model. The proposed model detects the start of the preictal state, which is the state that starts few minutes before the onset of the seizure, with a higher true positive rate compared to traditional methods, 92.23%, and maximum anticipation time of 33 minutes and average prediction time of 23.6 minutes on scalp EEG CHB-MIT dataset of 22 subjects. PMID:29410700

  20. Levetiracetam for Treatment of Neonatal Seizures

    PubMed Central

    Abend, Nicholas S.; Gutierrez-Colina, Ana M.; Monk, Heather M.; Dlugos, Dennis J.; Clancy, Robert R.

    2011-01-01

    Neonatal seizures are often refractory to treatment with initial antiseizure medications. Consequently, clinicians turn to alternatives such as levetiracetam, despite the lack of published data regarding its safety, tolerability, or efficacy in the neonatal population. We report a retrospectively identified cohort of 23 neonates with electroencephalographically confirmed seizures who received levetiracetam. Levetiracetam was considered effective if administration was associated with a greater than 50% seizure reduction within 24 hours. Levetiracetam was initiated at a mean conceptional age of 41 weeks. The mean initial dose was 16 ± 6 mg/kg and the mean maximum dose was 45 ± 19 mg/kg/day. No respiratory or cardiovascular adverse effects were reported or detected. Levetiracetam was associated with a greater than 50% seizure reduction in 35% (8 of 23), including seizure termination in 7. Further study is warranted to determine optimal levetiracetam dosing in neonates and to compare efficacy with other antiseizure medications. PMID:21233461

  1. Characteristics of people with self-reported stress-precipitated seizures.

    PubMed

    Privitera, Michael; Walters, Michael; Lee, Ikjae; Polak, Emily; Fleck, Adrienne; Schwieterman, Donna; Haut, Sheryl R

    2014-12-01

    Stress is the most common patient-reported seizure precipitant. We aimed to determine mood and epilepsy characteristics of people who report stress-precipitated seizures. Sequential patients at a tertiary epilepsy center were surveyed about stress as a seizure precipitant. We asked whether acute (lasting minutes-hours) or chronic (lasting days-months) stress was a seizure precipitant, whether stress reduction had been tried, and what effect stress reduction had on seizure frequency. We collected information on antiepileptic drugs, history of depression and anxiety disorder, prior or current treatment for depression or anxiety, and scores on the Neurological Disorders Depression Inventory (NDDI-E) and Generalized Anxiety Disorders-7 (GAD-7) instruments, which are administered at every visit in our Epilepsy Center. We also asked whether respondents thought that they could predict their seizures to determine if stress as a seizure precipitant was correlated with seizure self-prediction. Two hundred sixty-six subjects were included: 219 endorsed stress as a seizure precipitant [STRESS (+)] and 47 did not [STRESS (-)]. Among STRESS (+) subjects, 85% endorsed chronic stress as a seizure precipitant, and 68% endorsed acute stress as a seizure precipitant. In STRESS (+) subjects, 57% had used some type of relaxation or stress reduction method (most commonly yoga, exercise and meditation), and, of those who tried, 88% thought that these methods improved seizures. Among STRESS (-) subjects, 25% had tried relaxation or stress reduction, and 71% thought that seizures improved. Although univariate analysis showed multiple associations with stress as a seizure precipitant, in the multivariable logistic regression, only the GAD-7 score was associated with STRESS (+) (OR = 1.18 [1.03-1.35], p = 0.017). Subjects who reported stress as a seizure precipitant were more likely to report an ability to self-predict seizures (p < 0.001). Stress-precipitated seizures are commonly reported

  2. Forecasting Seizures in Dogs with Naturally Occurring Epilepsy

    PubMed Central

    Stead, S. Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H.; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W. Douglas; Litt, Brian; Worrell, Gregory A.

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. PMID:24416133

  3. 50 CFR 12.5 - Seizure by other agencies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Seizure by other agencies. 12.5 Section 12... SEIZURE AND FORFEITURE PROCEDURES General Provisions § 12.5 Seizure by other agencies. Any authorized... the laws listed in § 12.2 will, if so requested, deliver such seizure to the appropriate Special Agent...

  4. 27 CFR 447.63 - Seizure and forfeiture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Seizure and forfeiture. 447.63 Section 447.63 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS... IMPLEMENTS OF WAR Penalties, Seizures and Forfeitures § 447.63 Seizure and forfeiture. Whoever knowingly...

  5. Mozart K.448 listening decreased seizure recurrence and epileptiform discharges in children with first unprovoked seizures: a randomized controlled study.

    PubMed

    Lin, Lung-Chang; Lee, Mei-Wen; Wei, Ruey-Chang; Mok, Hin-Kiu; Yang, Rei-Cheng

    2014-01-13

    Increasing numbers of reports show the beneficial effects of listening to Mozart music in decreasing epileptiform discharges as well as seizure frequency in epileptic children. There has been no effective method to reduce seizure recurrence after the first unprovoked seizure until now. In this study, we investigated the effect of listening to Mozart K.448 in reducing the seizure recurrence rate in children with first unprovoked seizures. Forty-eight children who experienced their first unprovoked seizure with epileptiform discharges were included in the study. They were randomly placed into treatment (n = 24) and control (n = 24) groups. Children in the treatment group listened to Mozart K.448 daily before bedtime for at least six months. Two patients in the treatment group were excluded from analysis due to discontinuation intervention. Finally, forty-six patients were analyzed. Most of these patients (89.1%) were idiopathic in etiology. Seizure recurrence rates and reduction of epileptiform discharges were compared. The average follow-up durations in the treatment and control groups were 18.6 ± 6.6 and 20.1 ± 5.1 months, respectively. The seizure recurrence rate was estimated to be significantly lower in the treatment group than the control group over 24 months (37.2% vs. 76.8%, p = 0.0109). Significant decreases in epileptiform discharges were also observed after 1, 2, and 6 months of listening to Mozart K.448 when compared with EEGs before listening to music. There were no significant differences in gender, mentality, seizure type, and etiology between the recurrence and non-recurrence groups. Although the case number was limited and control music was not performed in this study, the study revealed that listening to Mozart K.448 reduced the seizure recurrence rate and epileptiform discharges in children with first unprovoked seizures, especially of idiopathic etiology. We believe that Mozart K.448 could be a promising alternative treatment in patients with

  6. Effects of seizure severity and seizure freedom on the health-related quality of life of an African population of people with epilepsy.

    PubMed

    Fawale, Michael B; Owolabi, Mayowa O; Ogunniyi, Adesola

    2014-03-01

    This study aimed at determining the effects of seizure severity and seizure freedom on health-related quality of life (HRQOL) of people with epilepsy (PWE) in the presence of perceived stigma in a sub-Saharan African culture. Health-related quality of life was assessed using QOLIE-31 in 93 consecutive adults (56 males and 37 females) with epilepsy. They were stratified into seizure-free, low-moderate seizure severity, and high seizure severity groups based on the seizure type and the number of seizures in the previous 6months. Other illness variables and sociodemographic variables were also obtained. A 3-item perceived stigma scale was administered. A modified QOLIE-31 (excluding the epilepsy-specific items) was given to 102 age- and sex-matched healthy controls. There was moderate negative correlation between seizure severity and mean total HRQOL score as well as scores on the Seizure Worry (p=.000), Overall Quality of Life (p=.000), and Social Function (p=.001) subscales of QOLIE-31. Overall, the healthy control subjects had a higher mean HRQOL score compared with the PWE put together (71.0+11.1 vs 64.2±13.6, p=.001). However, there was no difference in the mean HRQOL score between the seizure-free individuals and the healthy controls (p=.270). Seizure severity was associated with HRQOL independent of perceived stigma on a multiple regression analysis. This study provides evidence that seizure severity relates to health-related quality of life in an inverse, graded manner and independent of perceived stigma. Seizure-free people with epilepsy can have quality of life comparable with healthy individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. The new patient with a first seizure.

    PubMed

    King, Mark

    2003-04-01

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

  8. Tranexamic acid-associated seizures: Causes and treatment.

    PubMed

    Lecker, Irene; Wang, Dian-Shi; Whissell, Paul D; Avramescu, Sinziana; Mazer, C David; Orser, Beverley A

    2016-01-01

    Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients. © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  9. Neonatal Seizures: An Update on Mechanisms and Management

    PubMed Central

    Jensen, Frances E.

    2010-01-01

    The lifespan risk of seizures is highest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the last several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. Here we provide an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifying some of the recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment. PMID:19944840

  10. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-12-01

    We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character.

  11. 27 CFR 555.166 - Seizure or forfeiture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Seizure or forfeiture. 555... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Unlawful Acts, Penalties, Seizures and Forfeitures § 555.166 Seizure or forfeiture. Any explosive materials involved or used or intended to be used...

  12. Temporal seizure focus and status epilepticus are associated with high-sensitive troponin I elevation after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-09-01

    Postictal elevation of high-sensitive troponin I (TNI), a highly specific biomarker for myocardial ischemia, has been reported. We aimed at evaluating its association of high-sensitive troponin I (TNI) with seizure type and focus, as well as vascular risk factors. TNI was measured in 247 patients admitted to our clinic via the emergency room with an acute epileptic seizure. TNI control measurements were performed in 61.5% of cases. All patients underwent electroencephalography and cerebral imaging. Seizure focus - when possible - was determined using results from these examinations as well as clinical data. Of 247 patients, 133 (53.8%) were men, the mean age was 59 ± 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05 ± 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus and temporal seizure focus were significantly associated with TNI elevation in multivariate analysis. In 21 (13.8%) of the patients with TNI control measurement, TNI was continuously elevated. Higher age and temporal seizure focus were significantly associated with continuously high TNI. Coronary heart disease and vascular risk factors were significantly associated with high TNI only in univariate analysis. No patient had a symptomatic myocardial ischemia. Postictal TNI elevation is relatively common in older patients with status epilepticus or temporal seizure focus. These data support the concept of relevant and possibly dangerous ictal effects on cardiac function especially in temporal lobe seizures. Although the risk of manifest postictal myocardial infarction seems to be very low, selected patients could profit from closer monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Instantaneous frequency based newborn EEG seizure characterisation

    NASA Astrophysics Data System (ADS)

    Mesbah, Mostefa; O'Toole, John M.; Colditz, Paul B.; Boashash, Boualem

    2012-12-01

    The electroencephalogram (EEG), used to noninvasively monitor brain activity, remains the most reliable tool in the diagnosis of neonatal seizures. Due to their nonstationary and multi-component nature, newborn EEG seizures are better represented in the joint time-frequency domain than in either the time domain or the frequency domain. Characterising newborn EEG seizure nonstationarities helps to better understand their time-varying nature and, therefore, allow developing efficient signal processing methods for both modelling and seizure detection and classification. In this article, we used the instantaneous frequency (IF) extracted from a time-frequency distribution to characterise newborn EEG seizures. We fitted four frequency modulated (FM) models to the extracted IFs, namely a linear FM, a piecewise-linear FM, a sinusoidal FM, and a hyperbolic FM. Using a database of 30-s EEG seizure epochs acquired from 35 newborns, we were able to show that, depending on EEG channel, the sinusoidal and piecewise-linear FM models best fitted 80-98% of seizure epochs. To further characterise the EEG seizures, we calculated the mean frequency and frequency span of the extracted IFs. We showed that in the majority of the cases (>95%), the mean frequency resides in the 0.6-3 Hz band with a frequency span of 0.2-1 Hz. In terms of the frequency of occurrence of the four seizure models, the statistical analysis showed that there is no significant difference( p = 0.332) between the two hemispheres. The results also indicate that there is no significant differences between the two hemispheres in terms of the mean frequency ( p = 0.186) and the frequency span ( p = 0.302).

  14. Effect of root-extracts of Ficus benghalensis (Banyan) in memory, anxiety, muscle co-ordination and seizure in animal models.

    PubMed

    Panday, Dipesh Raj; Rauniar, G P

    2016-11-03

    Ficus benghalensis L. (Banyan) is a commonly found tree in Eastern Nepal. Its different plant parts are used for various neurological ailments. This study was performed in mice to see its effects in various neuropharmacological parameters. Passive-avoidance (memory), Open-field (anxiety), Pentobarbital-induced Sleep potentiation (sleep), Rota-rod (muscle-co-ordination), Pentylenetetrazol-Induced and Maximal Electroshock Seizure Tests were performed. Sample size was calculated using G*Power 3.1.9.2. Aqueous root extracts (Soxhlet method) of Ficus benghalensis 100 mg/kg and 200 mg/kg with negative and positive controls were used. The experimental results were represented as Mean ± SD. P-value was set at <0.05. Oneway analysis of variance (ANOVA) or Mann-Whitney U test was appropriately used. Passive-avoidance test showed 200 mg/kg group spent significantly less. Time (0.00s + 0.00s) in shock-zone than Normal Saline-group (9.67 s + 14.36 s, P = 0.000) or Diazepam-group (41.07 s + 88.24 s, P = 0.000). Open-field test showed 200 mg/kg group spent significantly longer Time (24.77 s + 12.23 s) in central-square than either Normal Saline group (15.08 s + 6.81 s, P = 0.000) or Diazepam-group (15.32 s + 5.12 s, P = 0.000). In Rota-rod test, 200 mg/kg group fell off the rod significantly (P = 0.000) earlier (33.01 s + 43.61 s) than both Normal Saline (>120 s) and Diazepam (62.07 s + 43.83 s) PTZ model showed that 100 mg/kg significantly (P = 0.004) delayed seizure-onset (184.40s + 36.36 s) compared to Normal Saline (101.79 s + 22.81 s), however, in MES model 200 mg/kg significantly (P = 0.000) prolonged tonic hind-limb extension (17.57 s + 2.15 s) compared to Normal Saline (13.55 s + 2.75 s) or Phenytoin (00.00s + 00.00s). Aerial roots of Ficus benghalensis have memory-enhancing, anxiolytic, musclerelaxant, and seizure-modifying effect.

  15. Immediate, early and late seizures after primary intracerebral hemorrhage.

    PubMed

    Qian, Cheng; Löppönen, Pekka; Tetri, Sami; Huhtakangas, Juha; Juvela, Seppo; Turtiainen, Hanna-Maria E; Bode, Michaela K; Hillbom, Matti

    2014-05-01

    Seizures after primary intracerebral hemorrhage (PICH) are significant and treatable complications, but the factors predicting immediate, early and late seizures are poorly known. We investigated characteristics and outcome with special reference to occurrence and timing of a first seizure among consecutive subjects with PICH. A population-based study was conducted in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h after admission), early (1-14 days) and late (>2 weeks) seizures were considered separately. Out of a total of 935 ICH patients, 51 had immediate, 21 early and 58 late seizures. The patients with seizures were significantly younger than the others and more often had a subcortical hematoma location (p<0.05). Lifestyle factors did not differ between the groups. The risk factors for immediate seizures in multivariable analysis were a low Glasgow coma scale score (GCS) on admission, subcortical location and age inversely (p<0.01). The only independent risk factor for early seizures was subcortical location (p<0.001), whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma evacuation (p<0.05) independently predicted late seizures. Immediate and early seizures predicted infectious complications (p<0.05). Patients with subcortical hematoma and of younger age are at risk for immediate seizures after primary ICH irrespective of hematoma size. Patients with immediate and early seizures more often had infectious complications. Surgery increases the risk of a late seizure after ICH. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty.

    PubMed

    Popkirov, Stoyan; Jungilligens, Johannes; Grönheit, Wenke; Wellmer, Jörg

    2017-08-01

    Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0±12.9years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force report's utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic ("negative") VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 14 CFR 13.17 - Seizure of aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Seizure of aircraft. 13.17 Section 13.17... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Legal Enforcement Actions § 13.17 Seizure of aircraft. (a) Under... officer, or a Federal Aviation Administration safety inspector, authorized in an order of seizure issued...

  18. High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring

    PubMed Central

    Girotto, Fernando; Scott, Lucas; Avchalumov, Yosef; Harris, Jacqueline; Iannattone, Stephanie; Drummond-Main, Chris; Tobias, Rose; Bello-Espinosa, Luis; Rho, Jong M.; Davidsen, Jörn; Teskey, G. Campbell; Colicos, Michael A.

    2013-01-01

    Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold. In vitro, acute application of folic acid or its metabolite 4Hfolate to neurons induced hyper-excitability and bursting. Cultured neuronal networks which develop in the presence of a low concentration (50 nM) of 4Hfolate had reduced capacity to stabilize their network dynamics after a burst of high-frequency activity, and an increase in the frequency of mEPSCs. Networks reared in the presence of the folic acid metabolite 5M4Hfolate developed a spontaneous, distinctive bursting pattern, and both metabolites produced an increase in synaptic density. PMID:23492951

  19. Seizure Freedom in Children With Pathology-Confirmed Focal Cortical Dysplasia.

    PubMed

    Mrelashvili, Anna; Witte, Robert J; Wirrell, Elaine C; Nickels, Katherine C; Wong-Kisiel, Lily C

    2015-12-01

    We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. We performed a single-center retrospective study of children ≤ 18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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.

  1. Efficacy of Pregabalin in Childhood Refractory Partial Seizure

    PubMed Central

    Zamani, Gholamreza; Tavasoli, Alireza; Zare-Shahabadi, Ameneh; Rezaei, Nima; Ahmadvand, Alireza

    2014-01-01

    Objective: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. Methods: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. Conclusion: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures. PMID:25793053

  2. Predictors of seizure occurrence in children undergoing pre-surgical monitoring.

    PubMed

    Harini, Chellamani; Singh, Kanwaljit; Takeoka, Masanori; Parulkar, Isha; Bergin, Ann Marie; Loddenkemper, Tobias; Kothare, Sanjeev V

    2013-10-01

    Long-Term-Monitoring (LTM) is a valuable tool for seizure localization/lateralization among children with refractory-epilepsy undergoing pre-surgical-monitoring. The aim of this study was to examine the factors predicting occurrence of single/multiple seizures in children undergoing pre-surgical monitoring in the LTM unit. Chart review was done on 95 consecutive admissions on 92 children (40 females) admitted to the LTM-unit for pre-surgical workup. Relationship between occurrence of multiple (≥ 3) seizures and factors such as home seizure-frequency, demographics, MRI-lesions/seizure-type and localization/AED usage/neurological-exam/epilepsy-duration was evaluated by logistic-regression and survival-analysis. Home seizure-frequency was further categorized into low (up-to 1/month), medium (up-to 1/week) and high (>1/week) and relationship of these categories to the occurrence of multiple seizures was evaluated. Mean length of stay was 5.24 days in all 3 groups. Home seizure frequency was the only factor predicting the occurrence of single/multiple seizures in children undergoing presurgical workup. Other factors (age/sex/MRI-lesions/seizure-type and localization/AED-usage/neurological-exam/epilepsy-duration) did not affect occurrence of single/multiple seizures or time-to-occurrence of first/second seizure. Analysis of the home-seizure frequency categories revealed that 98% admissions in high-frequency, 94% in the medium, and 77% in low-frequency group had at-least 1 seizure recorded during the monitoring. Odds of first-seizure increased in high vs. low-frequency group (p=0.01). Eighty-nine percent admissions in high-frequency, 78% in medium frequency, versus 50% in low-frequency group had ≥ 3 seizures. The odds of having ≥ 3 seizures increased in high-frequency (p=0.0005) and in medium-frequency (p=0.007), compared to low-frequency group. Mean time-to-first-seizure was 2.7 days in low-frequency, 2.1 days in medium, and 2 days in high-frequency group. Time-to-first-seizure

  3. SEIZURE PREDICTION: THE FOURTH INTERNATIONAL WORKSHOP

    PubMed Central

    Zaveri, Hitten P.; Frei, Mark G.; Arthurs, Susan; Osorio, Ivan

    2010-01-01

    The recently convened Fourth International Workshop on Seizure Prediction (IWSP4) brought together a diverse international group of investigators, from academia and industry, including epileptologists, neurosurgeons, neuroscientists, computer scientists, engineers, physicists, and mathematicians who are conducting interdisciplinary research on the prediction and control of seizures. IWSP4 allowed the presentation and discussion of results, an exchange of ideas, an assessment of the status of seizure prediction, control and related fields and the fostering of collaborative projects. PMID:20674508

  4. 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.

  5. Diagnostic implications of review-of-systems questionnaires to differentiate epileptic seizures from psychogenic seizures.

    PubMed

    Kerr, Wesley T; Janio, Emily A; Braesch, Chelsea T; Le, Justine M; Hori, Jessica M; Patel, Akash B; Barritt, Sarah E; Gallardo, Norma L; Bauirjan, Janar; Chau, Andrea M; Hwang, Eric S; Davis, Emily C; Torres-Barba, David; Cho, Andrew Y; Engel, Jerome; Cohen, Mark S; Stern, John M

    2017-04-01

    Early and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool. Our dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities. On average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p<0.001). The prospective accuracy to differentiate PNES from ES was not significantly higher than naïve assumption that all patients had ES (76% vs 70%, p>0.1). This analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consistency of RoSQ responses was neither

  6. Seizure Forecasting from Idea to Reality. Outcomes of the My Seizure Gauge Epilepsy Innovation Institute Workshop

    PubMed Central

    French, Jaqueline A.; Fureman, Brandy E.

    2017-01-01

    Abstract The Epilepsy Innovation Institute (Ei2) is a new research program of the Epilepsy Foundation designed to be an innovation incubator for epilepsy. Ei2 research areas are selected based on community surveys that ask people impacted by epilepsy what they would like researchers to focus on. In their 2016 survey, unpredictability was selected as a top issue regardless of seizure frequency or severity. In response to this need, Ei2 launched the My Seizure Gauge challenge, with the end goal of creating a personalized seizure advisory system device. Prior to moving forward, Ei2 convened a diverse group of stakeholders from people impacted by epilepsy and clinicians, to device developers and data scientists, to basic science researchers and regulators, for a state of the science assessment on seizure forecasting. From the discussions, it was clear that we are at an exciting crossroads. With the advances in bioengineering, we can utilize digital markers, wearables, and biosensors as parameters for a seizure-forecasting algorithm. There are also over a thousand individuals who have been implanted with ambulatory intracranial EEG recording devices. Pairing up peripheral measurements to brain states could identify new relationships and insights. Another key component is the heterogeneity of the relationships indicating that pooling findings across groups is suboptimal, and that data collection will need to be done on longer time scales to allow for individualization of potential seizure-forecasting algorithms. PMID:29291239

  7. Acute Symptomatic Seizures Caused by Electrolyte Disturbances

    PubMed Central

    Nardone, Raffaele; Brigo, Francesco

    2016-01-01

    In this narrative review we focus on acute symptomatic seizures occurring in subjects with electrolyte disturbances. Quite surprisingly, despite its clinical relevance, this issue has received very little attention in the scientific literature. Electrolyte abnormalities are commonly encountered in clinical daily practice, and their diagnosis relies on routine laboratory findings. Acute and severe electrolyte imbalances can manifest with seizures, which may be the sole presenting symptom. Seizures are more frequently observed in patients with sodium disorders (especially hyponatremia), hypocalcemia, and hypomagnesemia. They do not entail a diagnosis of epilepsy, but are classified as acute symptomatic seizures. EEG has little specificity in differentiating between various electrolyte disturbances. The prominent EEG feature is slowing of the normal background activity, although other EEG findings, including various epileptiform abnormalities may occur. An accurate and prompt diagnosis should be established for a successful management of seizures, as rapid identification and correction of the underlying electrolyte disturbance (rather than an antiepileptic treatment) are of crucial importance in the control of seizures and prevention of permanent brain damage. PMID:26754778

  8. Self-injury and incontinence in psychogenic seizures.

    PubMed

    Peguero, E; Abou-Khalil, B; Fakhoury, T; Mathews, G

    1995-06-01

    Two patients who incurred significant injuries during psychogenic seizures prompted us to do a telephone survey of self-injury and incontinence in 102 consecutive patients diagnosed with psychogenic seizures by EEG-closed-circuit TV (EEG-CCTV) monitoring. Seventy-three patients (or a close family member or friend) were reached by telephone and responded to our survey. During typical attacks of psychogenic seizures, 40% reported injuries, 44% reporting tongue biting, and 44% reported urinary incontinence. Suicide attempts were reported by 32% and were more common in those with self-injury and urinary incontinence. We compared the results of patients with psychogenic seizures with those of 30 patients with refractory epilepsy documented by ictal recordings, using a similar telephone survey. Injuries of all types were more commonly reported by epilepsy patients. Burn injuries were reported only by patients with epilepsy. Suicide attempts were more commonly reported by the psychogenic seizure group. Self-injury and incontinence are commonly reported by psychogenic seizure patients. In view of their significant association with suicide attempts, they may indicate an underlying depression.

  9. Detection of convulsive seizures using surface electromyography.

    PubMed

    Beniczky, Sándor; Conradsen, Isa; Wolf, Peter

    2018-06-01

    Bilateral (generalized) tonic-clonic seizures (TCS) increase the risk of sudden unexpected death in epilepsy (SUDEP), especially when patients are unattended. In sleep, TCS often remain unnoticed, which can result in suboptimal treatment decisions. There is a need for automated detection of these major epileptic seizures, using wearable devices. Quantitative surface electromyography (EMG) changes are specific for TCS and characterized by a dynamic evolution of low- and high-frequency signal components. Algorithms targeting increase in high-frequency EMG signals constitute biomarkers of TCS; they can be used both for seizure detection and for differentiating TCS from convulsive nonepileptic seizures. Two large-scale, blinded, prospective studies demonstrated the accuracy of wearable EMG devices for detecting TCS with high sensitivity (76%-100%). The rate of false alarms (0.7-2.5/24 h) needs further improvement. This article summarizes the pathophysiology of muscle activation during convulsive seizures and reviews the published evidence on the accuracy of EMG-based seizure detection. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  10. Revising the Rule Of Three For Inferring Seizure Freedom

    PubMed Central

    Westover, M. Brandon; Cormier, Justine; Bianchi, Matt T.; Shafi, Mouhsin; Kilbride, Ronan; Cole, Andrew J.; Cash, Sydney S.

    2011-01-01

    Summary Purpose How long after starting a new medication must a patient go without seizures before they can be regarded as seizure free? A recent ILAE task force proposed using a “Rule of Three” as an operational definition of seizure freedom, according to which a patient should be considered seizure-free following an intervention after a period without seizures has elapsed equal to three times the longest pre-intervention inter-seizure interval over the previous year. This rule was motivated in large part by statistical considerations advanced in a classic 1983 paper by Hanley and Lippman-Hand. However, strict adherence to the statistical logic of this rule generally requires waiting much longer than recommended by the ILAE task force. Therefore, we set out to determine whether an alternative approach to the Rule of Three might be possible, and under what conditions the rule may be expected to hold or would need to be extended. Methods Probabilistic modeling and application of Bayes’ rule. Key Findings We find that an alternative approach to the problem of inferring seizure freedom supports using the Rule of Three in the way proposed by the ILAE in many cases, particularly in evaluating responses to a first trial of anti-seizure medication, and to favorably-selected epilepsy surgical candidates. In cases where the a priori odds of success are less favorable, our analysis requires longer seizure-free observation periods before declaring seizure freedom, up to six times the average pre-intervention insterseizure interval. The key to our approach is to take into account not only the time elapsed without seizures but also empirical data regarding the a priori probability of achieving seizure freedom conferred by a particular intervention. Significance In many cases it may be reasonable to consider a patient seizure free after they have gone without seizures for a period equal to three times the pre-intervention inter-seizure interval, as proposed on pragmatic

  11. 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

  12. 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.

  13. Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

    PubMed

    Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

    2008-01-01

    Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

  14. 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.

  15. Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

    PubMed

    Leclercq, Karine; Kaminski, Rafal M

    2015-08-01

    Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks

  16. Rapidly Learned Identification of Epileptic Seizures from Sonified EEG

    PubMed Central

    Loui, Psyche; Koplin-Green, Matan; Frick, Mark; Massone, Michael

    2014-01-01

    Sonification refers to a process by which data are converted into sound, providing an auditory alternative to visual display. Currently, the prevalent method for diagnosing seizures in epilepsy is by visually reading a patient’s electroencephalogram (EEG). However, sonification of the EEG data provides certain advantages due to the nature of human auditory perception. We hypothesized that human listeners will be able to identify seizures from EEGs using the auditory modality alone, and that accuracy of seizure identification will increase after a short training session. Here, we describe an algorithm that we have used to sonify EEGs of both seizure and non-seizure activity, followed by a training study in which subjects listened to short clips of sonified EEGs and determined whether each clip was of seizure or normal activity, both before and after a short training session. Results show that before training subjects performed at chance level in differentiating seizures from non-seizures, but there was a significant improvement of accuracy after the training session. After training, subjects successfully distinguished seizures from non-seizures using the auditory modality alone. Further analyses using signal detection theory demonstrated improvement in sensitivity and reduction in response bias as a result of training. This study demonstrates the potential of sonified EEGs to be used for the detection of seizures. Future studies will attempt to increase accuracy using novel training and sonification modifications, with the goals of managing, predicting, and ultimately controlling seizures using sonification as a possible biofeedback-based intervention for epilepsy. PMID:25352802

  17. An Incredible Tool for Tracking Seizure Activity

    ERIC Educational Resources Information Center

    Hollingsworth, Jan Carter

    2007-01-01

    Eric Schumacher knows all too well the trials and tribulations of tracking seizures and daily activities in the ongoing attempt to gain seizure control. Diagnosed with epilepsy in his teens, he is now bringing a new and innovative tool to the market that could help countless people with epilepsy gain better control over their seizures and thus…

  18. Early follow-up data from seizure diaries can be used to predict subsequent seizures in same cohort by borrowing strength across participants

    PubMed Central

    Hall, Charles B.; Lipton, Richard B.; Tennen, Howard; Haut, Sheryl R.

    2014-01-01

    Accurate prediction of seizures in persons with epilepsy offers opportunities for both precautionary measures and preemptive treatment. Previously identified predictors of seizures include patient-reported seizure anticipation, as well as stress, anxiety, and decreased sleep. In this study, we developed three models using 30 days of nightly seizure diary data in a cohort of 71 individuals with a history of uncontrolled seizures to predict subsequent seizures in the same cohort over a 30-day follow-up period. The best model combined the individual’s seizure history with that of the remainder of the cohort, resulting in 72% sensitivity for 80% specificity, and 0.83 area under the receiver operating characteristic curve. The possibility of clinically relevant prediction should be examined through electronic data capture and more specific and more frequent sampling, and with patient training to improve prediction. PMID:19138755

  19. 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.

  20. Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients.

    PubMed

    Kim, Jiha; Kim, Chi Heon; Chung, Chun Kee

    2014-08-01

    Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures. Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N = 20) and a sporadic group (N = 26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel's classification. After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p = 0.025). Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.

  1. Comparative sensitivity of quantitative EEG (QEEG) spectrograms for detecting seizure subtypes.

    PubMed

    Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

    2018-02-01

    To assess the sensitivity of Persyst version 12 QEEG spectrograms to detect focal, focal with secondarily generalized, and generalized onset seizures. A cohort of 562 seizures from 58 patients was analyzed. Successive recordings with 2 or more seizures during continuous EEG monitoring for clinical indications in the ICU or EMU between July 2016 and January 2017 were included. Patient ages ranged from 5 to 64 years (mean = 36 years). There were 125 focal seizures, 187 secondarily generalized and 250 generalized seizures from 58 patients analyzed. Seizures were identified and classified independently by two epileptologists. A correlate to the seizure pattern in the raw EEG was sought in the QEEG spectrograms in 4-6 h EEG epochs surrounding the identified seizures. A given spectrogram was interpreted as indicating a seizure, if at the time of a seizure it showed a visually significant departure from the pre-event baseline. Sensitivities for seizure detection using each spectrogram were determined for each seizure subtype. Overall sensitivities of the QEEG spectrograms for detecting seizures ranged from 43% to 72%, with highest sensitivity (402/562,72%) by the seizure detection trend. The asymmetry spectrogram had the highest sensitivity for detecting focal seizures (117/125,94%). The FFT spectrogram was most sensitive for detecting secondarily generalized seizures (158/187, 84%). The seizure detection trend was the most sensitive for generalized onset seizures (197/250,79%). Our study suggests that different seizure types have specific patterns in the Persyst QEEG spectrograms. Identifying these patterns in the EEG can significantly increase the sensitivity for seizure identification. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. 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

  3. Ambulatory Seizure Monitoring: From Concept to Prototype Device.

    PubMed

    Myers, Mark H; Threatt, Madeline; Solies, Karsten M; McFerrin, Brent M; Hopf, Lindsey B; Birdwell, J Douglas; Sillay, Karl A

    2016-07-01

    The brain, made up of billions of neurons and synapses, is the marvelous core of human thought, action and memory. However, if neuronal activity manifests into abnormal electrical activity across the brain, neural behavior may exhibit synchronous neural firings known as seizures. If unprovoked seizures occur repeatedly, a patient may be diagnosed with epilepsy. The scope of this project is to develop an ambulatory seizure monitoring system that can be used away from a hospital, making it possible for the user to stay at home, and primary care personnel to monitor a patient's seizure activity in order to provide deeper analysis of the patient's condition and apply personalized intervention techniques. The ambulatory seizure monitoring device is a research device that has been developed with the objective of acquiring a portable, clean electroencephalography (EEG) signal and transmitting it wirelessly to a handheld device for processing and notification. This device is comprised of 4 phases: acquisition, transmission, processing and notification. During the acquisition stage, the EEG signal is detected using EEG electrodes; these signals are filtered and amplified before being transmitted in the second stage. The processing stage encompasses the signal processing and seizure prediction. A notification is sent to the patient and designated contacts, given an impending seizure. Each of these phases is comprised of various design components, hardware and software. The experimental findings illustrate that there may be a triggering mechanism through the phase lock value method that enables seizure prediction. The device addresses the need for long-term monitoring of the patient's seizure condition in order to provide the clinician a better understanding of the seizure's duration and frequency and ultimately provide the best remedy for the patient.

  4. Seizure precipitants (triggering factors) in patients with epilepsy.

    PubMed

    Ferlisi, Monica; Shorvon, Simon

    2014-04-01

    adult epilepsy clinic population: (a) to identify the frequency of seizure precipitants (triggering factors) and their relative frequency in those with psychiatric disorders, and in those in remission or with active epilepsy, differences in frequency with regard to gender, seizure duration, number of drugs taken; (b) to determine which precipitants patients most commonly report; and (c) to identify differences in the distribution of precipitants among generalized, temporal, and extratemporal epilepsies. Consecutive patients attending a tertiary-care epilepsy clinic were prospectively and an open personal interview to identify and characterize seizure precipitants. Information about the epilepsy and clinical characteristics of patients was collected during the interview and from medical records. Of 104 patients, 97% cited at least one precipitant. Stress, sleep deprivation, and fatigue were the most frequently reported precipitants. Patients with psychological comorbidities reported a greater percentage of seizures with seizure precipitants. Patients with idiopathic generalized epilepsy seemed to be more sensitive to seizures during awakening and sleep deprivation, patients with extratemporal epilepsy reported more frequent seizures during sleep. There were no differences in frequency or type of seizure precipitants with regard to gender, seizure duration or frequency, and the number of antiepileptic drugs taken. The findings may have implications for the better management of epilepsy by increasing a focus on nonpharmacological therapy. The implications of the findings for nosology and causation of epilepsy are also briefly discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Does Naloxone Prevent Seizure in Tramadol Intoxicated Patients?

    PubMed Central

    Eizadi-Mood, Nastaran; Ozcan, Dilek; Sabzghabaee, Ali Mohammad; Mirmoghtadaee, Parisa; Hedaiaty, Mahrang

    2014-01-01

    Background: Tramadol poisoning has increased in recent years. Seizure is one of the side-effects of tramadol toxicity. There is a controversy about possible preventive effect of naloxone in tramadol poisoning induced seizure. Therefore, this study was performed to compare seizure incidence in tramadol poisoning patients who received and did not receive naloxone, as an opioid antagonist. Methods: This study involved prospective data collection followed by retrospective analysis on 104 tramadol poisoning patients who were admitted in a referral poisoning center. The incidences of seizure were compared between patients received naloxone and those did not. Outcome was considered as survived without or with complications and death. Logistic Regression analysis was used to determine the effects of different variables on seizure incidence. Results: 70 (67.3%) of the patients were men. The mean age of the patients was 26.3 ± 9 years old. 18.3% of the patients received naloxone in their treatment period. Seizure incidence was significantly higher among tramadol poisoning patients who did not receive naloxone compare with those received naloxone (14.1% vs. 5.1%). Among different variable studied, age had a significant effect on predicting of seizure (odds ratio = 2.09; 95% of confidence interval: 1.82-2.26; P value, 0.004). Conclusions: Although the seizure incidence was lower in patients with tramadol poisoning who received naloxone, the logistic regression did not support the preventive effect of naloxone on seizure in tramadol poisoning cases. PMID:24829714

  6. 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.

  7. Increasing Epilepsy Awareness in Schools: A Seizure Smart Schools Project.

    PubMed

    Brook, Heather A; Hiltz, Cynthia M; Kopplin, Vicki L; Lindeke, Linda L

    2015-08-01

    A high prevalence of epilepsy diagnoses and seizure events among students was identified at a large Midwestern school district. In partnership with the Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was conducted to provide education and resources to staff caring for school children with seizures. School nurses (N = 26) were trained as seizure management educators and instructed staff in 21 schools on seizure awareness and response. School nurses utilized new seizure management resources, a procedural guideline, and care plan updates. The majority of school nurses rated the resources and training interventions as "very helpful." School nurse confidence in managing students with seizures increased, seizure action plan use increased, and 88% of children's records with new seizure diagnoses had completed documentation. School nurses played vital roles in increasing seizure awareness as educators and care managers. EFMN is using this project as an exemplar for expanding its Seizure Smart Schools program. © The Author(s) 2015.

  8. Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis.

    PubMed

    Zhu, Hongyan; Zhao, Yuxiao; Wu, Hao; Jiang, Nan; Wang, Ziyi; Lin, Weide; Jin, Jiahui; Ji, Yonghua

    2016-12-01

    Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ). A prominent, seizure intensity-dependent increase of Nav1.6 expression in reactive astrocytes was observed in ipsilateral hippocampus of post-SE rats, reaching the peak at 21 days after SE, a time point during the latent stage of epileptogenesis. However, Nav1.6 with low expression level was selectively expressed in the hippocampal neurons rather than astrocytes in PTZ-kindled animals. This seizure-related increase of a VGSCs subtype in reactive astrocytes after SE may represent a new mechanism for signal communication between neuron and glia in the course of epileptogenesis, facilitating the neuronal hyperexcitability.

  9. Seizure Recognition and Observation: A Guide for Allied Health Professionals.

    ERIC Educational Resources Information Center

    Epilepsy Foundation of America, Landover, MD.

    Intended for allied health professionals, this guide provides information on seizure recognition and classification to help them assist the patient, the family, and the treating physician in obtaining control of epileptic seizures. A section on seizure recognition describes epilepsy and seizures, covering seizure classification and the causes of…

  10. 43 CFR 3.16 - Seizure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Seizure. 3.16 Section 3.16 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.16 Seizure. Any object of antiquity taken, or collection made, on lands owned or controlled by the United States, without...

  11. Multifunctional Hybrid Compounds Derived from 2-(2,5-Dioxopyrrolidin-1-yl)-3-methoxypropanamides with Anticonvulsant and Antinociceptive Properties.

    PubMed

    Abram, Michał; Zagaja, Mirosław; Mogilski, Szczepan; Andres-Mach, Marta; Latacz, Gniewomir; Baś, Sebastian; Łuszczki, Jarogniew J; Kieć-Kononowicz, Katarzyna; Kamiński, Krzysztof

    2017-10-26

    The focused set of new pyrrolidine-2,5-diones as potential broad-spectrum hybrid anticonvulsants was described. These derivatives integrate on the common structural scaffold the chemical fragments of well-known antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. Such hybrids demonstrated effectiveness in two of the most widely used animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure models. Compound 33 showed the highest anticonvulsant activity in these models (ED 50 MES = 79.5 mg/kg, ED 50 6 Hz = 22.4 mg/kg). Compound 33 was also found to be effective in pentylenetetrazole-induced seizure model (ED 50 PTZ = 123.2 mg/kg). In addition, 33 demonstrated effectiveness by decreasing pain responses in formalin-induced tonic pain, in capsaicin-induced neurogenic pain, and notably in oxaliplatin-induced neuropathic pain in mice. The pharmacological data of stereoisomers of compound 33 revealed greater anticonvulsant activity by R(+)-33 enantiomer in both MES and 6 Hz seizure models.

  12. Seizures presenting as apnoea.

    PubMed Central

    Navelet, Y; Wood, C; Robieux, I; Tardieu, M

    1989-01-01

    Between the ages of 3 and 6 months a baby boy presented with repeated, non-specific episodes of cyanosis, apnoea, bradycardia, and abnormal movements of the limbs. The episodes were severe and required resuscitation and several admissions to hospital. Initial investigations showed only signs of oesophagitis. Despite treatment of the oesophagitis the symptoms recurred, and electroencephalography and polygraphy eventually showed evidence of minor seizures. Severe epilepsy with tonic-clonic seizures developed when he was 6 months old. PMID:2705798

  13. Bursts of seizures in long-term recordings of human focal epilepsy

    PubMed Central

    Karoly, Philippa J.; Nurse, Ewan S.; Freestone, Dean R.; Ung, Hoameng; Cook, Mark J.; Boston, Ray

    2017-01-01

    Summary Objective We report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies. Methods Chronic ambulatory intracranial EEG data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to non-burst events to evaluate event dispersion, duration and dynamics. Results Bursts of seizures were present in six of fifteen patients, and detections were consistent over long term monitoring (> 2 years). Seizures within bursts are highly overdispersed compared to non-burst seizures. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multi-modal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive pre-ictal dynamics compared to clinical seizures. Significance We have previously hypothesized that there are distinct physiological pathways underlying short and long duration seizures. Here we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics. PMID:28084639

  14. Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

    PubMed

    Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2017-07-01

    In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Role of oxidative stress in epileptic seizures

    PubMed Central

    Shin, Eun-Joo; Jeong, Ji Hoon; Chung, Yoon Hee; Kim, Won-Ki; Ko, Kwang-Ho; Bach, Jae-Hyung; Hong, Jau-Shyong; Yoneda, Yukio; Kim, Hyoung-Chun

    2013-01-01

    Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. However, much evidence suggests that oxidative stress does not always have the same pattern in all seizures models. Thus, this review provides an overview aimed at achieving a better understanding of this issue. We summarize work regarding seizure models (i.e., genetically epilepsy-prone rats, kainic acid, pilocarpine, pentylenetetrazol, and trimethyltin), oxidative stress as an etiologic factor in epileptic seizures (i.e., impairment of antioxidant systems, mitochondrial dysfunction, involvement of redox-active metals, arachidonic acid pathway activation, and aging), and antioxidant strategies for seizure treatment. Combined, this review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment. PMID:21672578

  16. Functional Neuroimaging of Spike-Wave Seizures

    PubMed Central

    Motelow, Joshua E.; Blumenfeld, Hal

    2013-01-01

    Generalized spike-wave seizures are typically brief events associated with dynamic changes in brain physiology, metabolism, and behavior. Functional magnetic resonance imaging (fMRI) provides a relatively high spatio-temporal resolution method for imaging cortical-subcortical network activity during spike-wave seizures. Patients with spike-wave seizures often have episodes of staring and unresponsiveness which interfere with normal behavior. Results from human fMRI studies suggest that spike-wave seizures disrupt specific networks in the thalamus and fronto-parietal association cortex which are critical for normal attentive consciousness. However, the neuronal activity underlying imaging changes seen during fMRI is not well understood, particularly in abnormal conditions such as seizures. Animal models have begun to provide important fundamental insights into the neuronal basis for fMRI changes during spike-wave activity. Work from these models including both fMRI and direct neuronal recordings suggest that, like in humans, specific cortical-subcortical networks are involved in spike-wave, while other regions are spared. Regions showing fMRI increases demonstrate correlated increases in neuronal activity in animal models. The mechanisms of fMRI decreases in spike-wave will require further investigation. A better understanding of the specific brain regions involved in generating spike-wave seizures may help guide efforts to develop targeted therapies aimed at preventing or reversing abnormal excitability in these brain regions, ultimately leading to a cure for this disorder. PMID:18839093

  17. Intravenous Carbamazepine for Adults With Seizures.

    PubMed

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  18. Variable-Threshold Threshold Elements,

    DTIC Science & Technology

    A threshold element is a mathematical model of certain types of logic gates and of a biological neuron. Much work has been done on the subject of... threshold elements with fixed thresholds; this study concerns itself with elements in which the threshold may be varied, variable- threshold threshold ...elements. Physical realizations include resistor-transistor elements, in which the threshold is simply a voltage. Variation of the threshold causes the

  19. Factors associated with ambulance requests for febrile seizures.

    PubMed

    Sakai, Rie; Marui, Eiji

    2008-08-01

    The objective of this study was to determine factors associated with ambulance requests for febrile seizures. This study retrospectively investigated medical records of patients who visited the Emergency Care Unit at Tokyo Metropolitan Toshima Hospital in the 5-year period after April 2001. Subjects' basic characteristics (e.g., age and sex), medical history of febrile seizures, sibling and parental medical history of febrile seizures, and distance from hospital were investigated. In total, 310 subjects used ambulances, and 106 came to the hospital without requesting ambulances. The results of binomial logistic analysis indicated that factors associated with ambulance requests included patient's and parents' medical history of febrile seizures. Increasing awareness of febrile seizures and provision of a general public educational campaign are possible strategies to help decrease unnecessary ambulance requests. However, a medical history of febrile seizures among siblings revealed no association, indicating the need to conduct repeated early-stage interventions.

  20. Orgasm-induced seizures: male studied with ictal electroencephalography.

    PubMed

    Sengupta, Anshuman; Mahmoud, Ali; Tun, Shwe Z; Goulding, Peter

    2010-06-01

    Reflex seizures can occur in response to a variety of stimuli, both sensory and emotional. Common triggers include light and music; however, in a growing number of case reports, the phenomenon of sexual activity triggering epileptic seizures is described. The majority of these case reports have been in women so far, and most have been found to localise to the right cerebral hemisphere on interictal electroencephalography (EEG). We report the case of a 34-year-old male with orgasm-induced seizures, recorded on ictal EEG. This gentleman's electrophysiology localised his seizure focus to the left cerebral hemisphere, making his case atypical in comparison with the majority of previous reports. Orgasm-induced seizures are an increasingly well-described phenomenon and we suggest that this should be taken into account when assessing patients with possible reflex seizures. Copyright 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.