The susceptibility to pentylenetetrazol (PTZ)-induced seizures during postnatal ontogeny [postnatal day (PN) 10–220] was investigated in two rat strains. The WAG\\/Rij strain, genetically prone for developing generalized absence epilepsy, and Wistar rats were tested and compared at PN 10, 26, 30, 70, 90, 125, and 220 on the PTZ-convulsive threshold. A subconvulsive dose of 25-mg\\/kg PTZ was administered every 15
I. A Klioueva; E. L. J. M van Luijtelaar; N. E Chepurnova; S. A Chepurnov
Properties of two pyrethroids was assessed using acute i.p. pentylenetetrazol (PTZ) administration and electrical kindling of the amygdale. he Type I pyrethroid, cismethrin (15 mg/kg, po), produced a 17% reduction in the threshold dosage of PTZ required to induce a seizure, while...
During drug development, seizure threshold tests are widely used to identify potential proconvulsant activity of investigational drugs. The most commonly used tests in this respect are the timed intravenous pentylenetetrazole (PTZ) infusion seizure test and the maximal electroshock seizure threshold (MEST) test in mice or rats. To our knowledge, no study is available in which proconvulsant drug activities in these models are directly compared, which prompted us to perform such experiments in male Wistar rats. Five drugs with reported proconvulsant activity were tested in the two models: d-amphetamine, chlorpromazine, caffeine, theophylline, and tramadol. Furthermore, the anticonvulsant drug phenobarbital was included in the experiments. While phenobarbital exerted anticonvulsant activity in both models, the five proconvulsant drugs markedly differed in their effects. In the dose range tested, d-amphetamine significantly lowered the PTZ seizure threshold but increased the MEST, caffeine and theophylline did not alter the PTZ seizure threshold but decreased the MEST, and tramadol reduced the PTZ threshold but increased the MEST. These marked differences between seizure threshold tests are most likely a consequence of the mechanisms underlying seizure induction in these tests. Our data indicate that using only one seizure threshold model during preclinical drug development may pose the risk that potential proconvulsant activity of an investigational drug is overseen. However, the label "proconvulsant" may be misleading if such activity only occurs at doses high above the therapeutic range, but the drug is not proconvulsant or even exerts anticonvulsant effects at lower, therapeutically relevant doses. PMID:22209701
Bankstahl, Marion; Bankstahl, Jens P; Bloms-Funke, Petra; Löscher, Wolfgang
Alterations in the NO pathway play an important role in the development of convulsive seizures via the glutamatergic and GABAergic systems in acute pentylenetetrazole (PTZ) seizure animals. We previously reported that the background NO levels under physiological conditions negatively regulate convulsive seizures, while excess NO levels under pathologic conditions positively regulate PTZ-induced convulsive seizures. In this study, the NO content in various brain regions after a single dose injection of PTZ was quantitatively and directly measured using the ex vivo X-band electron paramagnetic resonance method with an NO-trapping agent. Experimental data demonstrated the effects of NO on the convulsive seizure threshold: a 1.5-fold increase in the NO level in all brain regions compared to that observed in the control state showed proconvulsive properties without any involvement with nonconvulsive seizures. The distribution of the background NO content in the normal animals was higher in the temporal region of the cerebral cortex, including the amygdala, than in the hippocampus, cerebellum and other regions of the cerebral cortex. However, the levels of NO after the occurrence of acute PTZ-induced convulsive seizures significantly increased by more than 50% in all brain regions, thus suggesting that the NO levels in all brain regions contribute to PTZ-induced convulsions as a seizure threshold. In a pharmacological study, the inhibitor of neuronal NO synthase and antagonists of ionotropic glutamate receptors prevented PTZ-induced convulsions and excessive NO generation. In addition, therapeutic drugs, such as valproate and ethosuximide used to treat generalized seizures not only inhibited the increase in NO generation induced by PTZ, but also prevented both convulsive and nonconvulsive seizures caused by PTZ. We herein provide novel insight into the involvement of NO in PTZ-seizure susceptibility at the whole-animal level. PMID:23499834
Watanabe, Masatomo; Miyai, Asuka; Danjo, Sonoko; Nakamura, Yu; Itoh, Kouichi
The cognitive impairment seen in epileptics may be a consequence of either the underlying epileptogenic process alone or it could manifest on account of the use of antiepileptic drugs that cause cognitive impairment as an adverse effect or both. Thus, there is a need for drugs that can suppress epileptogenesis without contributing to or, if possible, by acting to prevent the development of cognitive impairment. Emblica officinalis, an Indian medicinal plant, has marked antioxidant property. The effect of seven days pretreatment of 300, 500 and 700 mg/kg doses of hydroalcoholic extract of E. officinalis (HAEEO) administered intraperitoneally to rats was evaluated on pentylenetetrazole (PTZ) induced seizures, cognitive deficit and oxidative stress markers viz malondialdehyde (MDA) and glutathione. The 500 and 700 mg/kg ip doses of HAEEO completely abolished the generalized tonic seizures and also improved the retention latency in passive avoidance task. Further, HAEEO dose-dependently ameliorated the oxidative stress induced by PTZ. These findings suggest the potential of HAEEO to be used as an adjuvant to treatment with antiepileptic drugs. PMID:20795364
Golechha, Mahaveer; Bhatia, Jagriti; Arya, Dharamvir Singh
Behavioral sensitization occurs after repeated administration of ?-opioid receptor agonists following a drug-free period. It seems that the changes in dopaminergic systems induced by ?-opioid receptor agonists play a crucial role in behavioral sensitization to opioids. Nitric oxide also plays a role in some behavioral effects of morphine, including sensitization to the locomotor-stimulating effect. This study investigated whether morphine sensitization appears in seizure threshold and the possible role of ?-opioid receptor and nitric oxide in this sensitization. Sensitization was produced by daily injections of morphine (0.1, 0.5, 1, 5, 15, or 30 mg/kg), followed by a 10-day washout period. Then the challenge test was performed using morphine (0.1, 0.5, 1, 5, 15, or 30 mg/kg) in different groups. To assess clonic seizure threshold, pentylenetetrazole (PTZ) was administered intravenously. Subcutaneous administration of morphine (0.1 and 0.5 mg/kg) induced sensitization in PTZ-induced clonic seizures in mice. Intraperitoneal administration of L-NAME (20 mg/kg), a nonselective inhibitor of nitric oxide synthase, or naltrexone (10 mg/kg), an opioid receptor antagonist, along with morphine inhibited morphine-induced sensitization in PTZ-induced seizure threshold. In conclusion, at low doses, morphine induces sensitization in PTZ-induced clonic seizures in mice probably as a result of the interaction with ?-receptors and nitric oxide. PMID:21419715
Shafaroodi, Hamed; Baradaran, Nazanin; Moezi, Leila; Dehpour, Siavash; Kabiri, Tina; Dehpour, Ahmad R
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. PMID:23376336
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
The effect of chronic perfusion of ammonia on the seizure threshold against pentylenetetrazol was studied. Ammonia plus sodium bicarbonate and saline (0.9%) was continuously administered to two groups of rats respectively. All animals were tested three times for seizure threshold, and were then decapitated and the brains removed for analysis of the amino acids. The results showed that the infusion
Kemal Arikan; Tamer Coskun; Bora Guvener; Oznur Oran
Cannabinoid system plays a pivotal role in the seizure threshold modulation which is mainly mediated through activation of the cannabinoid CB1 receptor. There is also several evidence of interaction between cannabinoid system and ?2-adrenoceptors in different paradigms. Using model of clonic seizure induced by intravenous pentylenetetrazole (PTZ) in male mice, we investigated whether ?2-adrenoceptors is involved in the effects of cannabinoids on the seizure threshold. Injection of the selective cannabinoid CB1 agonist ACEA (2mg/kg) significantly (P<0.01) increased the seizure threshold which was prevented by pretreatment with the selective CB1 antagonist AM251 (1mg/kg, i.p.). The highest doses of clonidine, a ?2 receptor agonist, (1 and 5mg/kg) showed anticonvulsant effects while yohimbine, a ?2 receptor antagonist, (0.01, 0.1, 1, and 10mg/kg) did not induce any significant effect on PTZ seizure threshold. Pretreatment with clonidine (0.1 and 0.5mg/kg) significantly reversed the anticonvulsant effect of ACEA (2mg/kg). Yohimbine (0.1, 1, and 10mg/kg) pretreatment of mice enhanced the clonic seizure threshold of ACEA (1mg/kg), significantly. Combination of non-effective doses of AM251 (0.1mg/kg) and clonidine (0.01mg/kg) showed additive effect in blocking the anticonvulsant effect of ACEA (2mg/kg). In conclusion, our findings demonstrated that ?2-adrenoceptors could be involved in the anticonvulsant properties of the specific cannabinoid CB1 agonist ACEA, suggesting that CB1 cannabinoid and ?2 receptors have functional interactions in modulation of clonic seizure threshold. PMID:23756131
Shafaroodi, Hamed; Moezi, Leila; Bahremand, Arsh; Dehpour, Ahmad Reza
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. PMID:24056205
Löscher, Wolfgang; Hoffmann, Katrin; Twele, Friederike; Potschka, Heidrun; Töllner, Kathrin
Activation of polyamine catabolism in transgenic mice through an overexpression of spermidine/spermine N(1)-acetyltransferase (SSAT) results in a massive overaccumulation of the diamine putrescine in most tissues including brain. Putrescine pool in transgenic animals was strikingly expanded in every six brain regions analyzed at present. Pons (23-fold), cerebellum (37-fold), cerebrum (34-fold), and hippocampus (16-fold) showed the greatest increases in putrescine levels. Moreover, the molar ratio of putrescine to spermidine was increased in the different brain regions of the transgenic animals on an average of nearly 40-fold. Upon an exposure of the animals to pentylenetetrazol (PTZ) infusions, a compound known to induce epilepsy-like seizure activity, the SSAT transgenic mice showed significantly elevated seizure threshold to both clonic and tonic convulsions in comparison with their syngenic littermates. This difference, however, disappeared when the animals were treated with ifenprodil prior to PTZ infusions. The latter compound acts as an antagonist of N-methyl-D-aspartate receptor by binding to the polyamine site of the receptor. Overexpression of SSAT likewise appeared to protect the transgenic animals from PTZ-induced neuron loss in the hippocampus. As putrescine is known to serve as a precursor to gamma-aminobutyric acid (GABA), we carried out (1)H NMR analyses the results of which revealed that the levels of the inhibitory amino acid GABA and its excitatory counterpart glutamate were indistinguishable in syngenic and transgenic animals in all brain regions analyzed. The present results suggest that the frequently observed enhanced accumulation of putrescine in response to brain insults belongs to neuroprotective measures rather than being a cause of the subsequent injury. PMID:14552906
Kaasinen, Selma K; Gröhn, Olli H J; Keinänen, Tuomo A; Alhonen, Leena; Jänne, Juhani
Febrile seizures (FSs) typically occur at the onset of fever and do not recur within the same febrile episode despite enduring or increased hyperthermia. Recurrent seizures during the same febrile episode are considered "complex," with potentially altered prognosis. A characterized immature rat model of FS was used to test the hypotheses that (1) a first FS influences the threshold temperature for subsequent ones, and (2) the underlying mechanisms involve the release and actions of the endogenous inhibitory hippocampal neuropeptide Y (NPY). Experimental FSs were induced two or three times, at 3- to 4-h intervals, and threshold temperatures measured. To determine the potential effects of seizure-induced endogenous NPY on thresholds for subsequent seizures, an antagonist of the major hippocampal NPY receptor (type 2) was infused prior to induction of the second seizure. As an indicator of NPY release, NPY expression was determined 4 and 24 h later. Threshold core and brain temperatures for hyperthermic seizures were consistent with those observed during human fever. Threshold temperatures for a second and third seizure were significantly and progressively higher than those required for the first. This "protective" effect involved induction of endogenous NPY because it was abolished by the NPY antagonist. In addition, NPY mRNA expression was increased in dentate gyrus, CA3 and CA1, after an experimental FS, consistent with peptide release. Collectively these data indicate that the absence of repetitive seizures during a febrile episode involves the inhibitory actions of endogenous NPY, suggesting that the signaling cascade triggered by this peptide might provide targets for therapeutic intervention. PMID:15800380
Dubé, Céline; Brunson, Kristen L; Eghbal-Ahmadi, Mariam; Gonzalez-Vega, Rebeca; Baram, Tallie Z
Summary Purpose To investigate whether STriatal Enriched protein tyrosine Phosphatase (STEP) influences ictogenesis. Methods STEP knockout mice were compared to wild-type (WT) mice in pilocarpine-induced seizures. Hippocampal slices were also prepared from these two mouse populations, allowing the examination of ictal-like stimulation in these slices using calcium imaging and electrophysiological recordings. Results To examine seizure thresholds, increasing doses of pilocarpine were administered to adult mice and seizures were scored behaviorally. Significantly fewer STEP knockout mice developed seizures that progressed to the stage of status epilepticus compared to WT mice. To examine potential differences in neural circuits that might account for this finding, seizure-like activity was induced in hippocampal slices. Electrical stimulation of the hippocampal-entorhinal cortex pathway in STEP knockout mice resulted in less activation of the dentate granule cell layer, but greater activation of the hilus in STEP knockouts, compared with heterozygous slices. Conclusions STEP deficiency is associated with higher seizure thresholds. The locus of these effects appears to include the dentate gyrus granule cell layer and hilus.
Aaron, Gloster; Briggs, Stephen; Walker, Jeffrey; Asik, Kemal; Lombroso, Paul; Naegele, Janice
Neuron restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor, has been reported to modulate neuronal excitability and acts as endogenous anticonvulsant in kainic acid-induced or kindling-evoked seizure activity. However, whether NRSF functions in pentylenetetrazol (PTZ)-induced seizure activity has never been studied. To investigate the role of endogenous NRSF in the epileptogenesis induced by PTZ, in our experiment, NRSF neuronal conditional knockout mice (NRSF cKO) were adopted, in which NRSF was specifically deleted in neurons by the Cre-loxP system. Seizure threshold for PTZ, including the dose-response convulsions and the threshold dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ that induced clonic and tonic seizures was significantly higher in NRSF cKO mice compared with the control. Similarly, the median lethal dose (LD(50)) of PTZ in NRSF cKO mice was also considerably higher than that of the control mice. These results revealed that NRSF cKO mice are of higher resistance to convulsions induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced seizure and provided new evidence for differential pathways in diverse types of seizure. PMID:22472570
Liu, Ming; Sheng, Zhejin; Cai, Lei; Zhao, Kai; Tian, Yu; Fei, Jian
In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5–50mg\\/kg) 30minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5,
Ali Lesani; Mehrak Javadi-Paydar; Tina Kabiri Khodadad; Alaleh Asghari-Roodsari; Mahyar Shirkhodaei; Abbas Norouzi; Ahmad Reza Dehpour
Sulfolane dosages that alter seizure susceptibility were determined using audiogenic (AG), pentylenetrazol (PTZ) and hippocampal afterdischarge (AD) seizure models. The presence of AG seizures and potentiation of PTZ seizures were investigated in rats injected IP with 0, 200, 400...
There are several lines of evidence that opioidergic and nitrergic systems could modulate the seizure threshold. We previously have shown that sildenafil had proconvulsant effects in a model of clonic seizure induced by pentylenetetrazole (PTZ) or bicuculline. In the present study, we examined whether the opioid system participates in the action of sildenafil on the PTZ-induced clonic seizures in mice. Sildenafil (1, 5, 10 and 20 mg/kg, i.p.) significantly decreased the seizure threshold in a dose-dependent manner, whereas morphine had both anticonvulsant and proconvulsant effects at low (0.5, 1, and 3 mg/kg, s.c.) and high (60 mg/kg, s.c.) doses. A sub-effective dose of sildenafil (5 mg/kg) combined with a dose of morphine (7.5 mg/kg) which was sub-effective for its proconvulsant effects significantly decreased the seizure threshold. Although naltrexone at 0.5 and 1 mg/kg had no effect on the seizure threshold, it significantly prevented both the proconvulsant effects of sildenafil as well as the anticonvulsant and proconvulsant effects of morphine on the PTZ-induced seizure thresholds. Our data suggested a role for opioidergic system in the proconvulsant effects of sildenafil on the PTZ-induced clonic seizures in mice. PMID:21377383
Montaser-Kouhsari, Laleh; Payandemehr, Borna; Gholipour, Taha; Ziai, Pouya; Nabavizadeh, Pooneh; Ghasemi, Abbas; Bahremand, Arash; Ghasemi, Mehdi; Dehpour, Ahmad Reza
We studied the effects of microinjected drugs and brainstem lesions on motor and limbic seizures in the kindling model of epilepsy. The duration of motor seizures was determined by timing the clonic and tonic movements of the extremities. The .duration of limbic seizures was determined by measuring afterdischarge recorded on the electroencephalogram. Bilateral microinjection of a y-aminobutyric acid (GABA) agonist,
MARC T. GALLOWAY; LEWIS C. RIGSBEE; CHEOLSU SHIN
The peptide angiotensin IV (Ang IV) influences seizure susceptibility in rat and mouse models. Indeed, Ang IV has been shown to protect rats from limbic seizures in the focal pilocarpine model. Moreover, both anticonvulsive and antiepileptogenic effects of Ang IV have been reported in the acute pentylenetetrazol (PTZ) and kindling model of generalized seizures in mice. It has been hypothesized that the latter effects on seizures could be established via a modulatory effect on dopamine receptors in the basal ganglia or via an indirect interaction between Ang IV and adenosine A1 receptors. However, a possible role for insulin-regulated aminopeptidase (IRAP), the high affinity binding site for Ang IV, has not been studied yet. To unequivocally unravel the involvement of IRAP in generalized seizure generation, we investigated the susceptibility of male IRAP wild-type (IRAP(+/+)) and knock-out (IRAP(-/-)) mice to PTZ-induced seizures. Challenging these mice intravenously with PTZ resulted in significantly increased thresholds for myoclonic twitch and generalized clonic seizures with loss of righting reflexes in IRAP(-/-) mice compared to their IRAP(+/+) littermates. These behavioural data were confirmed by video-electrocorticography monitoring. Our study shows that IRAP(-/-) mice are less sensitive to the development of PTZ-induced seizures and suggests that IRAP is involved in generalized seizure generation. PMID:21612947
Loyens, E; Schallier, A; Chai, S Y; De Bundel, D; Vanderheyden, P; Michotte, Y; Smolders, I
Exposing Sprague-Dawley rat pups to very low, sub-convulsant doses of domoic acid (DOM) during perinatal development has been previously shown to result in seizure-like activity in adulthood similar to partial complex epilepsy in humans, and to produce cellular and molecular changes in the dentate gyrus and area CA-3 of the hippocampus. To further these investigations we recorded electroencephalographical and behavioural activity in DOM and control rats following a normally sub-convulsant dose (25 mg/kg) of pentylenetetrazol. During this exposure, 50% of DOM-treated rats experienced a Stage V (tonic-clonic) seizure (X(2)((1))=5.33, P=0.021), indicating a lowering of generalized seizure threshold in these animals. In a separate experiment we explored focal seizure (afterdischarge) threshold as well as seizure propagation rates in treated rats, using a 25 consecutive day standard amygdala kindling paradigm. We report that the afterdischarge threshold for DOM-treated rats was significantly lower than controls (F((1,27))=7.117, P=0.013). No difference between groups was found in seizure progression as measured by afterdischarge duration, latency to first Stage V seizure, or latency to reach a fully kindled state (defined as five consecutive Stage V seizures). Timm staining to assess mossy fibre sprouting (MFS) in the hippocampus revealed a significant MFS increase relative to sham at the ventral level in both left and right inner molecular layer of the dentate gyrus for all DOM-treated animals, as well as in the dorsal stratum oriens of CA3 contralateral to electrode placement, and these increases were further enhanced by the kindling procedure. We conclude that perinatal exposure to subconvulsive doses of DOM results in permanent changes in neuronal excitability in the adult rat, as demonstrated by a lowering of both generalized seizure and focal afterdischarge threshold, and produces increased MFS following kindling. PMID:20600646
Gill, D A; Bastlund, J F; Watson, W P; Ryan, C L; Reynolds, D S; Tasker, R A
The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100-1000 ?g/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam required to elevate the threshold for seizure signs induced by intravenous PTZ were 500 and 100 ?g/kg, respectively, whereas the minimal intrapulmonary midazolam dose was 12.5 ?g/kg. Intratracheal midazolam caused a large increase in intravenous PTZ threshold 5 min after administration but the effect declined rapidly over 60 min and no antiseizure activity was evident at 120 min. The minimal intraperitoneal doses of midazolam required to elevate the threshold for seizure signs induced by intravenous picrotoxin and kainic acid were 100 and 2000 ?g/kg, respectively; the corresponding values for intratracheal midazolam were 25 and 100 ?g/kg, respectively. We conclude that midazolam is a highly effective anticonvulsant when administered by the intrapulmonary route. Midazolam is substantially more potent when delivered into the lung than when administered intraperitoneally or intravenously. Inhalation could be an alternative to other routes of administration for the delivery of midazolam to rapidly abort acute seizures. PMID:23774136
Dhir, Ashish; Zolkowska, Dorota; Rogawski, Michael A
The lung provides a portal of entry for drug delivery that could be used to administer anticonvulsant substances to prevent or abort seizures. Here, we demonstrate that intrapulmonary propofol hemisuccinate (PHS) rapidly confers seizure protection in various rodent chemoconvulsant models. Propofol is a powerful anticonvulsant substance at subanesthetic doses, but it is a viscous, water-immiscible oil that is not suitable for intrapulmonary administration. We found that PHS can be formulated as an aqueous solution that is well tolerated when instilled into the lung. High-dose intraperitoneally administered PHS induced loss-of-righting reflex in rats and mice. The onset of action of PHS was delayed in comparison with propofol, suggesting that conversion to propofol is required for activity. A lower dose of PHS (40 mg/kg i.p.) did not cause general anesthesia but protected against pentylenetetrazol (PTZ)-induced seizures in rats. Intrapulmonary administration of an aqueous PHS solution via a tracheal cannula at lower doses (5 and 10 mg/kg) conferred equivalent seizure protection without acute motor toxicity. In mice, intraperitoneal PHS (60-80 mg/kg) was associated with an elevation in PTZ, bicuculline, picrotoxin, and kainic acid seizure thresholds. Intratracheal PHS was markedly more potent, producing seizure threshold elevations at doses of 10 to 15 mg/kg. In the PTZ threshold model in mice, PHS was active at 5 min, maximally active at 10 min, and no longer active at 20 min. Intratracheal PHS also prolonged the onset of 4-aminopyridine-induced convulsions but did not affect the threshold for N-methyl-D-aspartate-induced convulsions. We conclude that intratracheal administration of an aqueous solution of PHS, a putative propofol prodrug, provides potent seizure protection of rapid onset and brief duration. Intrapulmonary PHS may be useful for preventing the spread of seizures or aborting seizure clusters without causing prolonged sedation. PMID:20837991
Dhir, Ashish; Zolkowska, Dorota; Murphy, Randall B; Rogawski, Michael A
In order to clarify the mechanisms involved in the susceptibility to GABA(A) antagonists-induced seizures in morphine dependent rats, we investigated how GABA(A) agonists modulate this vulnerability. Seizures were induced to animals by infusion of GABA(A) antagonists: pentylenetetrazole (PTZ), picrotoxin (PIC) and bicuculline (BIC). GABA(A) agonists, muscimol (MUS) and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP), were administered intravenous (i.v.) before antagonists. Morphine-dependence significantly decreased the PTZ threshold dose (19.16±1.89 versus 25.74±1.25mg/kg) while, it had no effect on PIC induced seizures. BIC doses for both threshold and tonic-clonic seizures induction were significantly lower in morphine dependent rats (0.10±0.01 and 0.12±0.02 versus 0.25±0.02 and 0.39±0.07mg/kg respectively). In morphine-dependence, although pre-treatment with MUS significantly increased the required dose of PTZ for seizures threshold, THIP significantly decreased the required dose of PTZ for tonic-clonic convulsion. Moreover, MUS pretreatment completely recovered the effect of morphine dependency on BIC seizure activity. The results suggest that the capability of GABA(A) agonists on modulation of propensity to seizures induced by different antagonists in morphine-dependence is dissimilar. Therefore, it seems that long-term morphine alters some properties of GABA system so that the responsive rate of GABA(A) receptors not only to its antagonists, but also to its agonists will change differently. PMID:21426916
Joukar, Siyavash; Atapour, Nafiseh; Kalantaripour, Tajpari; Bashiri, Hamideh; Shahidi, Alireza
Seizure is defined as "a strong shrinkage state of the skeletal muscle which is involuntary, and occurs spasmodically" and it is often accompanied by disturbance of consciousness. The typical disease which causes seizure is epilepsy. But there is many conditions causing seizure. Therefore, diagnosis of epilepsy should be careful. Seizure among eldery increases in an era of an aging population in Japan. The risk of recurrence of seizure or epilepsy in elderly is higher than that in youth. In considering of the treatment of seizure among elderly, differential diagnosis from various condition must be done. PMID:23855204
Saito, Ayumi; Terayama, Yasuo
Summary In view of previous reports of changes in seizure susceptibility in adult rats exposed to phenobarbital or diazepam as pups, we examined the effects of early-life exposure to lamotrigine and phenytoin, two commonly used antiepileptic drugs (AEDs), for their effect on seizure threshold in adult rats. We found that pups exposed to lamotrigine for six days during the second postnatal week had a significantly lower threshold for pentylenetetrazol-evoked seizures when tested as adults. In contrast, phenytoin exposure during the second postnatal week was without a significant effect on seizure threshold in adults. Seizure scores at threshold were comparable across all groups tested. The dose of lamotrigine used in our study (20 mg/kg) was below that required to cause developmental neuronal apoptosis, while the dose of phenytoin used (50 mg/kg) was above that required for developmental neurotoxicity. Thus, our findings suggest that neurodevelopmental alterations in seizure susceptibility may occur via mechanisms that are independent of those responsible for neural injury or teratogenesis. Our findings support the possibility that therapy with certain AEDs during pregnancy or infancy may alter seizure susceptibility later in life, a possibility that should be taken into account when examining early-life factors that contribute to seizure susceptibility in adulthood.
Forcelli, Patrick A.; Gale, Karen; Kondratyev, Alexei
In the present study, the effects of tamoxifen on pentylenetetrazole (PTZ)-induced repeated seizures and hippocampal neuronal damage in ovariectomized rats were investigated. Thirty seven virgin female Wistar rats were divided to: (1) control, (2) sham-PTZ, (3) sham-PTZ-tamoxifen (sham-PTZ-T), (4) Ovariectomized -PTZ (OVX-PTZ) and (5) OVX-PTZ-tamoxifen (OVX-PTZ-T) groups. The animals of groups 3 and 5 were injected by tamoxifen (10 mg/kg) on 7 consecutive days. After 7 days of tamoxifen injection, they also were then injected by tamoxifen 30 min prior each PTZ injection. PTZ (40 mg/kg) was injected on 6 consecutive days and the animal behaviors were observed for 60 min. The histological methods were then used to determine dark neurons in hippocampus. A significant decrease in the seizure score was seen in OVX-PTZ group compared to Sham-PTZ. The animals of OVX-PTZ-T group had a significant higher seizure score compared to OVX-PTZ group. The dark neurons in DG of OVX group were lower than sham group (p<0.01). The numbers of dark neurons in CA1 area of OVX-PTZ-T group was higher than OVX-PTZ group (p<0.05) compared to control, the numbers of dark neurons in CA3 area showed a significant increase in Sham-PTZ and OVX-PTZ group (p<0.05 and p<0.01 respectively). Dark neurons in OVX-PTZ-T group were higher than OVX-PTZ group (p<0.05). It is concluded that pretreatment of the ovariectomized rats by tamoxifen increased PTZ-induced seizure score and dark neurons. It might be suggested that tamoxifen has agonistic effects for estrogen receptors to change the seizure severity.
Mansouri, Somaeh; Ataei, Mariam lale; Hosseini, Mahmoud
In this communication, the effect of acute treatment with lamotrigine (LTG) was investigated on release of main excitatory amino acids (EAA) such as glutamate (Glu) and aspartate (Asp) in the hippocampus of pentylenetetrazol (PTZ)-induced and PTZ-kindled freely moving rats using micro dialysis. The results show that, levels of Glu and Asp significantly increased in the rat hippocampus during the seizure/interical periods for PTZ-status epilepticus (SE) and PTZ-kindled epileptic (EP) rats. The levels of Glu and Asp increased more in EP rat hippocampus than in SE rat hippocampus. After administration of 20 mg/kg LTG, the levels of Glu and Asp significantly decreased in the SE and EP rat hippocampus. The results indicate that: (a) excitability of the PTZ-kindled epileptogenic model is higher than that of the status epilepticus model; (b) the modulation of LTG on the EAA neurotransmitters certainly plays an important role in antiepileptic efficacy, especially in PTZ-kindled epileptic model where the release of EAA was influenced more markedly by acute application of 20 mg/kg LTG. PMID:23229790
Deng, Yan; Wang, Minghuan; Wang, Wei; Ma, Chao; He, Nongyue
The high levels of taurine found in developing brain have led to postulates that taurine is involved in brain maturation. The authors have examined the effect of taurine on the chemoshock threshold of rats reared in the presence of the environmental toxin, lead. Within 24 h of giving birth, dams were placed on one of four regimens: Group P received 0.4% lead acetate in the drinking water; Group T received 3% taurine in drinking water; Group PT received both taurine and lead acetate; and Group C received distilled water. The pups were weaned at 21 days, but maintained on the same treatments. Pentylene tetrazole seizure thresholds were determined at 42 days. Thresholds in Group P were significantly depressed relative to Group C (56.0 mg/kg v 79.9 mg/kg). Taurine supplementation had no effect on threshold (T = 72.7 mg/kg). However, thresholds in Group PT were significantly higher than those of Group P (PT = 85.2 mg/kg). These data show that whereas taurine was without effect on the threshold of animals not stressed by exposure to lead, it had a protective effect on exposed animals. As human neonates are unable to synthesize taurine, the findings reinforce the concept of taurine being a conditionally essential nutrient in developing humans.
Huxtable, R.J.; Shindo, S.; Nakagawa, K.
In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5-50mg/kg) 30 minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5, and 10mg/kg), the nitric oxide precursor L-arginine (10, 30, and 60 mg/kg), and the nonspecific opioid receptor antagonist naloxone (0.1, 0.5, 1, and 5mg/kg) on the anticonvulsant effect of tramadol were investigated. Administration of tramadol (1mg/kg) increased the threshold for seizures induced with PTZ in a monophasic, dose-independent, and time-dependent manner. Acute administration of L-NAME (5 and 10mg/kg) inhibited the anticonvulsant effect of tramadol (1mg/kg), whereas L-arginine, in the noneffective dose range (30 and 60 mg/kg), potentiated the seizure threshold when co-administered with a subeffective dose of tramadol (0.5mg/kg). Naloxone partially and dose-independently antagonized the anticonvulsant effect of tramadol (1mg/kg). These results indicate that the anticonvulsant effect of tramadol is mediated by the nitric oxide pathway and also by classic opioid receptors. PMID:20880756
Lesani, Ali; Javadi-Paydar, Mehrak; Khodadad, Tina Kabiri; Asghari-Roodsari, Alaleh; Shirkhodaei, Mahyar; Norouzi, Abbas; Dehpour, Ahmad Reza
Cannabinoids and drugs that increase endocannabinoid levels inhibit neuronal excitability and restrain epileptic seizures through CB1 receptor activation. Nevertheless, the results have not been entirely consistent, since pro-convulsant effects have also been reported. The present study aimed to further investigate the effects of cannabinoid-related compounds on seizures induced by pentylenetetrazole (PTZ) in rats. Video-EEG recordings were used to determine both electrographic and behavioral thresholds to ictal activity. The animals received injections of WIN-55,212-2 (0.3-3 mg/kg, non-selective) or ACEA (1-4 mg/kg, CB1-selective), two synthetic cannabinoids, or URB-597 (0.3-3 mg/kg), an anandamide-hydrolysis inhibitor (FAAH enzyme inhibitor), followed by PTZ. Both WIN-55,212-2 (1 mg/kg) and ACEA (1-4 mg/kg) reduced the threshold for myoclonic seizures and enhanced epileptiform EEG activity, typical pro-convulsive effects. On the contrary, URB-597 (1 mg/kg) had an anti-convulsive effect, as it increased the threshold for the occurrence of minimal seizures and reduced EEG epileptiform activity. None of the drugs tested altered the tonic-clonic maximal seizure threshold. These data suggest that the effects of CB1 signaling upon seizure activity may depend on how this receptor is activated. Contrary to direct agonists, drugs that increase anandamide levels seem to promote an optimal tonus and represent a promising strategy for treating myoclonic seizures. PMID:23352737
Vilela, Luciano R; Medeiros, Daniel C; Rezende, Gustavo H S; de Oliveira, Antônio Carlos P; Moraes, Marcio F D; Moreira, Fabrício A
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 (60mg\\/kg, IP)-induced seizure rats treated with saline; PTZ-induced seizure rats pretreated with n-hexane, chloroform, ethyl acetate,
Gopalreddygari Visweswari; Kanchi Siva Prasad; Pandanaboina Sahitya Chetan; Valluru Lokanatha; Wudayagiri Rajendra
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.
Rakhade, S.N.; Fitzgerald, E.F.; Klein, P.M.; Zhou, C.; Sun, H; Huganir, R.L.; Jensen, F.E.
The seizure-inducing properties of two pyrethroids were assessed by pentylenetetrazol (PTZ) seizure models (repeated ip, sprathreshold ip, and iv), and electrical kindling of the amygdala. The efficacy of po versus ip routes of deltamethrin administration...
M. E. Gilbert S. K. Acheson C. M. Mack K. M. Crofton
In this paper, we present a cooperative stereo system based on two pant-tilt-zoom (PTZ) cameras that can localize a moving target in a complex environment. Given an approximate target position that can be estimated by a fixed camera with a wide field of view, two PTZ cameras with a large baseline are pointed toward the target in order to estimate precisely its position. The overall method is divided in three parts: offline construction of a look-up-table (LUT) of rectification matrices, use of the LUT in real time for computing the rectification transformations for arbitrary camera positions, and finally 3D target localization. A chain of homographic transformations are used for finding the matching between different pairs of wide baseline stereo images. The proposed stereo localization system has two advantages: improved localization on a partially occluded target and monitoring a large environment using only two PTZ cameras without missing significant information. Finally, through experimental results, we show that the proposed system is able to make required localization of targets with good accuracy.
Kumar, Sanjeev; Micheloni, Christian; Piciarelli, Claudio
Epilepsy is a complex neurological disorder manifested by recurrent episodes of convulsive seizures, loss of consciousness, and sensory disturbances. Pentylenetetrazole (PTZ)-induced kindling primarily represents a model of generalized epilepsy. The present study has been undertaken to evaluate the neuroprotective potential of hesperidin and its interaction with nitric oxide modulators against PTZ-induced kindling and associated cognitive dysfunction in mice. The experimental protocol comprised of eleven groups (n=6), where a subconvulsive dose of PTZ (40mg/kg, i.p.) had been administered every other day for a period of 12days, and seizure episodes were noted after each PTZ injection over a period of 30min. The memory performance tests were carried out on days 13 and 14 followed by the estimation of biochemical and mitochondrial parameters. Chronic administration of a subconvulsive dose of PTZ resulted in an increase in convulsive activity culminating in generalized clonic-tonic seizures, as revealed by a progressive increase in seizure score as well as alteration in antioxidant enzyme levels (lipid peroxidation, nitrite, glutathione, super oxide dismutase, and catalase) and mitochondrial complex (I, II, and IV) activities, whereas chronic treatment with hesperidin (200mg/kg) significantly attenuated these behavioral, biochemical, and mitochondrial alterations. Further, treatment with l-arginine (100mg/kg) or l-NAME (10mg/kg) in combination with hesperidin significantly modulated the protective effect of hesperidin which was significant as compared to their effects per se in PTZ-treated animals. Thus, the present study suggests a possible involvement of the NO-cGMP pathway in the neuroprotective effect of hesperidin in PTZ-kindled mice. PMID:23939034
Kumar, Anil; Lalitha, Sree; Mishra, Jitendriya
Vigabatrin is a rationally developed antiepileptic drug, which acts by increasing GABA levels in the brain by irreversibly inhibiting GABA degradation. However, its clinical use in epilepsy is restricted by severe side effects, including vision loss, which is thought to be a consequence of drug exposure of the retina and nonepileptic brain regions. Targeted delivery into brain regions involved in seizure generation and propagation would overcome this problem. Previous studies in rat models of seizures or epilepsy have shown that anticonvulsant effects can be achieved by bilateral microinjection of vigabatrin into the substantia nigra pars reticulata (SNr), a basal ganglia output structure that plays an important role in the modulation of seizures. In the present study, we compared the anticonvulsant efficacy of vigabatrin after systemic and intranigral administration in a rat model, in which seizure susceptibility can be determined by timed intravenous infusion of pentylenetetrazol (PTZ) before and after drug injection in individual animals. Furthermore, because the subthalamic nucleus (STN) plays a crucial role as a regulator of basal ganglia outflow by providing excitatory glutamatergic input into the two output nuclei of the basal ganglia, SNr and entopeduncular nucleus, we evaluated the effects of bilateral focal delivery of vigabatrin into the STN on PTZ seizure threshold. A significant increase in seizure threshold was observed following systemic (i.p.) administration of high (600 or 1200 mg/kg) doses of vigabatrin. Bilateral microinjection of vigabatrin (10 ?g) into either the anterior or posterior SNr also increased seizure threshold, but less markedly than systemic treatment. In contrast, focal delivery into the STN increased seizure threshold more markedly than either intranigral or systemic administration of vigabatrin. Furthermore, focal inhibition of STN was not associated with the severe adverse effects associated with systemic treatment. The data demonstrate that vigabatrin is an interesting substance for focal drug delivery in epilepsy and may be advantageous compared to more commonly evaluated compounds such as muscimol. PMID:22342648
Bröer, Sonja; Backofen-Wehrhahn, Bianca; Bankstahl, Marion; Gey, Laura; Gernert, Manuela; Löscher, Wolfgang
Background Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm.
Wills, Tiffany A.; Knapp, Darin J.; Overstreet, David H.; Breese, George R.
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. PMID:23819045
Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga
We investigated the anticonvulsant effect of acute Fuzi total alkaloid (FTA) in seizure induced by the GABAA-receptor antagonist pentylenetetrazole (PTZ). FTA significantly increased the seizure latency and decreased the mortality in PTZ-treated mice. Administration of PTZ increased c-Fos expression in the hippocampus, medial prefrontal cortex, and piriform cortex; and this PTZ-induced effect was inhibited by FTA in a dose-dependent manner. Furthermore, the effects of FTA on PTZ-induced seizure and c-Fos expression were reversed by the GABAA/benzodiazepine receptor-selective antagonist flumazenil. These findings suggest that the anticonvulsant effects of FTA may be related to modulation of GABAA-benzodiazepine receptor complex. PMID:24096829
Li, Bingjin; Tang, Fang; Wang, Liang; Liu, Lei; Zhao, Jing; Zhou, Yang; Wang, Yinuo; Song, Yunong; Li, Yuxin; Cui, Ranji
In this paper numerous alternative treatments in addition to pharmacological therapy are proposed for their use in epileptic patients. Epileptic animal models can play a crucial role in the performance evaluation of new therapeutic techniques. The objective of this research is to first develop various epileptic rat models; second, develop a portable wireless closed-loop seizure controller including on-line seizure detection and real-time electrical stimulation for seizure elimination; and third, apply the developed seizure controller to the animal models to perform on-line seizure elimination. The closed-loop seizure controller was applied to three Long-Evans rats with spontaneous spike-wave discharges (non-convulsive) and three Long-Evans rats with epileptiform activities induced by pentylenetetrazol (PTZ) injection (convulsive) for evaluation. The seizure detection accuracy is greater than 92% (up to 99%), and averaged seizure detection latency is less than 0.6 s for both spontaneous non-convulsive and PTZ-induced convulsive seizures. The average false stimulation rate is 3.1%. Near 30% of PTZ-induced convulsive seizures need more than two times of 0.5 s electrical stimulation for suppression and 90% of the non-convulsive seizures can be suppressed by only one 0.5 s electrical stimulation.
Liang, Sheng-Fu; Liao, Yi-Cheng; Shaw, Fu-Zen; Chang, Da-Wei; Young, Chung-Ping; Chiueh, Herming
The proconvulsive effect of the new generation of antidepressants remains controversial. The authors investigated in naïve rats the effect of chronic treatment with fluoxetine (FLX) on the convulsive threshold and on two parameters of the hippocampal glutamatergic neurotransmission: the in vitro glutamate release and the binding of [3H] MK801 to NMDA receptors. While the acute treatment with FLX provoked no change either in seizure susceptibility or in the glutamate release, the chronic treatment decreased the convulsive threshold in coincidence with an increment in the in vitro glutamate release. No significant effects on the binding of [3H] MK801 to NMDA receptors were found to be attributable to the FLX treatment. We also assessed the effect of the chronic treatment with FLX on the seizure threshold in rats exposed to an experimental model of depression, the learned helplessness paradigm (LH). While a decrease in the K+-stimulated glutamate release was observed in non treated LH animals, when they were chronically injected with FLX, no changes in the epileptic susceptibility and no increments in the glutamate release were found. Our results indicate that chronic treatment with FLX decreases the epileptic threshold in naïve but not in LH rats and that this effect correlates with the levels of the hippocampal glutamate release. PMID:15913874
Ferrero, Alejandro J; Cereseto, Marina; Reinés, Analía; Bonavita, Carla D; Sifonios, Laura L; Rubio, Modesto C; Wikinski, Silvia I
Cannabinoids have anti-convulsant effects in both in vivo and in vitro models of status epilepticus. Since the development of spontaneous seizures and neuronal vulnerability are age-dependent, we hypothesized that the anti-convulsant effects of cannabimimetics are also age-dependent. We administered a single injection of varied doses of (R+)WIN 55,212 (0.5, 1, 5 mg/kg) to postnatal (P) day 20 rats 90 min prior to induction of kainate (KA)-induced status epilepticus. The highest dose of (R+)WIN 55,212 (5 mg/kg) resulted in rapid onset of behavioral stupor, loss of balance, stiffening and immobility while standing on hind legs or laying flat in prone position; lower doses had minimal or no behavioral effect. After KA administration, seizure scores and electroencephalography (EEG) recordings were inversely related to (R+)WIN 55,212 dosage whereby higher doses were associated with high seizures scores and synchronous epileptiform activity and low doses with low seizure scores and diminished spiking in the EEG. Immunohistochemistry revealed a dose-dependent reduction in CB1 receptor expression with increasing concentrations of (R+)WIN 55,212 in presence or absence of KA seizures. Nissl and NeuN staining showed hippocampal injury was attenuated only when seizures were mild following low doses of WIN 55,212 (0.5, 1 mg/kg), consistent with the level of CB1 expression. Since low doses abolished seizures without psychotropic side-effects further study may facilitate a groundbreaking cannabamimetic therapeutic strategy to treat early-life seizures. Higher doses had adverse effects on behavior and failed to prevent seizures and protect CA1 neurons possibly due to inactivation or loss of CB1 receptors. PMID:22019959
Rudenko, V; Rafiuddin, A; Leheste, J R; Friedman, L K
The electromagnetic fields (EMF) have various behavioral and biological effects on human body. There are growing concerns about the consequences of exposure to EMF. However, some studies have shown beneficial effects of these waves on human. In this paper, we study the effect of acute, sub acute and long-term exposure to 50 Hz, 0.1 mT magnetic fields (MF) on the seizure induction threshold in mice. 64 mice are used and divided into four groups. Eight mice in any group were selected to be exposed to MF for specific duration and the others were used as a control group. The duration of the applied exposures was as follows: (1) 1 day (acute), (2) 3 days (sub acute), (3) 2 weeks (sub acute), (4) 1 month (long term). The mice were exposed 2 h for a day. After exposure, the pentylentetrazol (PTZ) is injected to the mice to induce seizure and the needed dose for the seizure induction threshold is measured. In the acute exposure, the threshold to induce seizure in the exposed and sham-exposed groups was 44.25 and 46.5 mg, respectively, while the difference was not significant (p value = 0.5). In the sub acute exposure (3 days), the mean amount of drug to induce seizure was 47.38 mg in the exposed and 43.88 mg in the sham-exposed groups, however, the difference was not significant (p value = 0.3). The results were 52.38 and 46.75 mg after 2 weeks of exposure which were not significantly different either (p value = 0.2). After 1 month of exposure to MF, the threshold for the induction of seizure was significantly increased (p value < 0.05). The mean dosage to induce seizure in the exposed and control group was 54.3 and 45.75 mg, respectively. However, considering the p value, the difference in the seizure induction threshold between the exposed and sham-exposed groups after acute and sub acute exposure was not significant, analyzing the effects of acute, sub acute and long-term exposures totally indicates that increasing the exposure time increases the seizure induction threshold. PMID:23055108
Fadakar, Kaveh; Saba, Valiallah; Farzampour, Shahrokh
Deep brain stimulation (DBS) is a critical therapeutic regimen for drug-resistant epilepsy. Our proposed method of assessing the neuromodulatory effects of DBS on seizure threshold and post-ictal activity is based on the principle that seizure build-up is always preceded by constantly changing EEG and field potential bursting levels. We use a novel measure of residual subband wavelet entropy (RSWE) to
C. B. Patel; D. L. Sherman; J. S. Paul; N. Zhang; M. A. Mirski
The seizure-inducing properties of two pyrethroids were assessed by pentylenetetrazol (PTZ) seizure models (repeated ip, suprathreshold ip, and iv), and electrical kindling of the amygdala. he efficacy of po versus ip routes of deltamethrin administration was compared using iv-PT...
1. c-fos mRNA expression and Fos protein expression were investigated by in situ hybridization and immunohistochemistry after 30 min of forced restraint stress or pentylenetetrazol (PTZ; 64 mg\\/kg, i.p.)-induced seizures.
Elaine Aparecida Del Bel; Maria Cristina Leite Silveira; Frederico Guilherme Graeff; Norberto Garcia-Cairasco; Francisco Silveira Guimarães
Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.
We report the effect of orally administered gabapentin (GBP) on pentylenetetrazole (PTZ)-induced seizure-like activity in adult zebrafish. Zebrafish were pretreated with vehicle or GBP using a novel method of precise oral administration, followed by an intraperitoneal administration of PTZ. Behavioral assessment was carried out using locomotion-based video-tracking analysis and seizure score assignment using visual observation. Cephalic field potential recordings of the zebrafish brain were conducted using an electrical data acquisition system. Orally administered GBP significantly suppressed the seizure-like locomotor activity and strong slow-wave (~3Hz) activity in the cephalic field potential caused by PTZ. This work is the first report of the activity of an orally delivered anticonvulsant in adult zebrafish. Our study provides behavioral and physiological evidence in support of an adult zebrafish model for studying seizures including excitotoxic brain injury and a novel in vivo framework for the evaluation of pharmacological modulators of epilepsy. PMID:23466252
Banote, Rakesh Kumar; Koutarapu, Srinivas; Chennubhotla, Keerthana Sarma; Chatti, Kiranam; Kulkarni, Pushkar
It has been widely suggested that oxidative stress products play an important role in the pathophysiology of epilepsy. Capparis ovata (C. ovata) may useful treatment of epilepsy because it contains antioxidant flavonoids. The current study was designed to determine the effects of C. ovata on lipid peroxidation, antioxidant levels and electroencephalography (EEG) records in pentylentetrazol (PTZ)-induced epileptic rats. Thirty-two rats were randomly divided into four groups. First group was used as control although second group was PTZ group. Oral 100 and 200 mg/kg C. ovata were given to rats constituting the third and fourth groups for 7 days before PTZ administration. Second, third and forth groups received 60 mg/kg PTZ for induction of epilepsy. Three hours after administration of PTZ, EEG records, brain cortex and blood samples were taken all groups. The lipid peroxidation levels of the brain cortex, number of spikes and epileptiform discharges of EEG were higher in PTZ group than in control and C. ovata group whereas they were decreased by C. ovata administration. Vitamin A, vitamin C, vitamin E and ?-carotene concentrations of brain cortex and latency to first spike of EEG were decreased by the PTZ administration although the brain cortex and plasma vitamin concentrations, and brain cortex and erythrocyte glutathione and glutathione peroxidase values were increased in PTZ + 100 and PTZ + 200 mg C. ovata groups. In conclusion, C. ovata administration caused protection against the PTZ-induced brain oxidative toxicity by inhibiting free radical and epileptic seizures, and supporting antioxidant redox system. PMID:23389657
Naz?ro?lu, Mustafa; Akay, Mehmet Berk; Çelik, Ömer; Y?ld?r?m, Muhammed ?kbal; Balc?, Erdinç; Yürekli, Vedat Ali
Myo-inositol (MI) and its isomers are used for the treatment of various neuropathological conditions. The purpose of the present research was to study anticonvulsant properties of MI and scyllo-inositol (SCI) on pentylenetetrazol (PTZ) induced seizures in rats. Half an hour after treatment with MI (30 mg/kg) or SCI (5 mg/kg) seizures were induced in Wistar rats with PTZ (60 mg/kg). Control animals were treated either by normal saline or mannitol (control polyol of the same molecular weight, 30 mg/kg), given at the same time interval before PTZ injection, as MI/SCI groups. The anticonvulsant effects of MI/SCI treatment were assessed by the latent period (the time from PTZ-injection to the onset of first seizures), and the duration and severity (score) of seizures. The mortality rate was also assessed. Both MI and SCI treatment significantly reduced the seizure score, seizure duration and increased the latent period. These data suggest for strong potential of MI and SCI as the agents of antiepileptic therapy. PMID:21074457
Nozadze, M; Mikautadze, E; Lepsveridze, E; Mikeladze, E; Kuchiashvili, N; Kiguradze, T; Kikvidze, M; Solomonia, R
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.
Doyle, Daniel D.; Black, Jonathan T.
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. PMID:20144879
Visweswari, Gopalreddygari; Prasad, Kanchi Siva; Chetan, Pandanaboina Sahitya; Lokanatha, Valluru; Rajendra, Wudayagiri
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. PMID:23684790
Bodda, Chiranjeevi; Tantra, Martesa; Mollajew, Rustam; Arunachalam, Jayamuruga P; Laccone, Franco A; Can, Karolina; Rosenberger, Albert; Mironov, Sergej L; Ehrenreich, Hannelore; Mannan, Ashraf U
Experimental prolonged febrile seizures (FS) lead to structural and molecular changes that promote hippocampal hyperexcitability and reduce seizure threshold to further convulsants. However, whether these seizures provoke later-onset epilepsy, as has been suspected in humans, has remained unclear. Pre- viously, intermittent EEGs with behavioural observations for motor seizures failed to demonstrate sponta- neous seizures in adult rats subjected to experimental
Celine Dube; Cristina Richichi; Roland A. Bender; Grace Chung; Brian Litt; Tallie Z. Baram
The aim of this study was to compare the outcomes associated with two differing right unilateral (RUL) electroconvulsive therapy (ECT) dosing protocols: 2-3X seizure threshold (2-3X ST) and fixed high dose (FHD) at 353 mC. A retrospective chart review was performed to compare patient outcomes during the implementation of two different dosing protocols: 2-3X ST from October 2000 to May 2001 and FHD from June 2001 to February 2002. A total of 56 patients received ECT under the 2-3X ST protocol, and 46 received ECT under the FHD protocol. In total, 13.6% of patients receiving ECT according to the 2-3X ST protocol received more than 12 ECT, whereas none of the FHD group received more than 12 ECT. The mean number of ECT per treatment course reduced significantly from 7.6 to 5.7 following the switch from the 2-3X ST protocol to the FHD protocol. There were no significant differences between the two groups in the incidence of adverse cognitive effects. ECT practitioners adhered to the 2-3X ST protocol for only 51.8% of ECT courses, with protocol adherence improving to 87% following introduction of the FHD protocol. Although this naturalistic retrospective chart survey had significant methodological limitations, it found that practitioners are more likely to correctly adhere to a fixed dose protocol, therefore, increasing its 'real world' effectiveness in comparison to titrated suprathreshold dosing techniques. The FHD protocol was associated with shorter courses of ECT than the 2-3X ST protocol, with no significant difference between the two protocols in clinically discernable adverse cognitive effects. PMID:16884443
Ward, Warren K; Lush, Pamela; Kelly, Marilyn; Frost, Aaron D J
Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the
Kang Chen; Ildiko Aradi; Niklas Thon; Mariam Eghbal-Ahmadi; Tallie Z. Baram; Ivan Soltesz
The complete nucleotide sequence of pTZ12, a chloramphenicol-resistance (CmR) plasmid (2517 bp) derived from Corynebacterium xerosis plasmid pTZ10, has been determined after propagation in Bacillus subtilis. The nucleotide sequence of pTZ12 suggests that a recombination event may have occurred naturally within the open reading frames for the Rep protein of pT181 (or a pT181-like plasmid) and pC221 (or a pC221-like plasmid). PMID:3110008
Aoki, T; Noguchi, N; Sasatsu, M; Kono, M
The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45-75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ-induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed. PMID:1751012
Ossenkopp, K P; Cain, D P
The anticonvulsant topiramate is effective in laboratory animals against maximal electroshock seizures, amygdala kindling, and spike-wave discharges and has demonstrated efficacy in humans for the treatment of complex partial seizures. However, its mechanism of action has yet to be clearly elucidated. When the chloride-sensitive fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used as a tool for estimating the effect of anticonvulsant
H. Steve White; S. Douglas Brown; Jose H Woodhead; Gwendolyn A Skeen; Harold H Wolf
Febrile seizures are the most common form of childhood seizures, occurring in 2 to 5% of children in the United States. Most febrile seizures are considered simple, although those with focal onset, prolonged duration, or that occur more than once within the same febrile illness are considered complex. Risk factors for a first febrile seizure, recurrence of febrile seizures, and development of future epilepsy are identifiable and varied. Children with febrile seizures encounter little risk of mortality and morbidity and have no association with any detectable brain damage. Recurrence is possible, but only a small minority will go on to develop epilepsy. Although antiepileptic drugs can prevent recurrent febrile seizures, they do not alter the risk of subsequent epilepsy. This has led to a changing view of how we approach the treatment of these common and largely benign seizures. This chapter will review the current understanding of the prognosis and management of febrile seizures. PMID:11918463
Shinnar, Shlomo; Glauser, Tracy A
Effects of repeated postnatal administration of caffeine (10 and 20mg\\/kg s.c. daily from P7 to P11) were studied in two models of epileptic seizures characterized by spike-and-wave EEG rhythm in 18- and 25-day-old rats. Rhythmic metrazol activity (RMA, model of human absences) was induced by low dose of pentylenetetrazol (PTZ, 20mg\\/kg or 40mg\\/kg, i.p.) and minimal clonic seizures (model of
Jana Tchekalarova; Hana Kubová; Pavel Mareš
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.
Huang, Xiaoxing; McMahon, John; Yang, Jun; Shin, Damian; Huang, Yunfei
The function of endogenous interleukin-1? (IL-1?) signaling in acute seizure activity was examined using transgenic mice harboring targeted deletions in the genes for either IL-1? (Il1b) or its signaling receptor (Il1r1). Acute epileptic seizure activity was modeled using two mechanistically distinct chemoconvulsants, kainic acid (KA) and pentylenetetrazole (PTZ). KA-induced seizure activity was more severe in homozygous null (-/-) Il1b mice compared to their wild-type (+/+) littermate controls, as indicated by an increase in the incidence of sustained generalized convulsive seizure activity. In the PTZ seizure model, the incidence of acute convulsive seizures was increased in both Il1b and Il1r1-/- mice compared to their respective +/+ littermate controls. Interestingly, the selective cyclooxygenase (COX)-2 inhibitor, rofecoxib, mimicked the effect of IL-1? deficiency on PTZ-induced convulsions in Il1r1+/+ but not -/- mice. Together, these results suggest that endogenous IL-1? possesses anticonvulsive properties that may be mediated by arachidonic acid metabolites derived from the catalytic action of COX-2. PMID:21856425
Claycomb, Robert J; Hewett, Sandra J; Hewett, James A
Background The effects of electromagnetic waves (EMWs) on humans and their relationship with various disorders have been investigated. We aimed to investigate the effects of exposure to different frequencies of EMWs in various durations in a mouse epilepsy model induced by pentylenetetrazole (PTZ). Material/Methods A total of 180 4-week-old male mice weighing 25–30 g were used in this study. Each experimental group consisted of 10 mice. They were exposed to 900, 700, 500, 300, and 100 MHz EMWs for 20 hours, 12 hours and 2 hours. Following electromagnetic radiation exposure, 60 mg/kg of PTZ was injected intraperitoneally to all mice. Each control was also injected with PTZ without any exposure to EMW. The latency of initial seizure and most severe seizure onset were compared with controls. Results The shortest initial seizure latency was noted in the 12-hour group, followed by the 700 MHz. The mean initial seizure latencies in the 2-hour EMW exposed group was significantly shorter compared to that in the 12- and 20-hour groups. There was no significant difference between 12- and 20-hour EMW exposed groups. There was a significant difference between control and 2- and 10-hour EMW exposed groups. No statistically significant differences were noted in mean latencies of the most severe seizure latency, following 20-, 12-, and 2- hour EMW exposed groups and control groups. Conclusions Our findings suggest that acute exposure to EMW may facilitate epileptic seizures, which may be independent of EMW exposure time. This information might be important for patients with epilepsy. Further studies are needed.
Cinar, Nilgun; Sahin, Sevki; Erdinc, Oguz O.
Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid. Sodium selenate treatment was then tested against three different rodent seizure models. Firstly the propensity of 6-Hz electrical corneal stimulation to induce seizures in adult mice was assessed following acute treatment with different doses of sodium selenate. Secondly, the number of seizures induced by pentylenetetrazole (PTZ) was quantified in rats following chronic sodium selenate treatment via drinking water. Finally, amygdala kindled rats were chronically treated with sodium selenate in drinking water and the length and the severity of the seizures evoked by stimulation of the amygdala recorded. The results demonstrated a dose-dependent protection of sodium selenate against 6-Hz stimulation induced seizures, and significant reduction in the total number of seizures following PTZ injection. Amygdala kindled rats chronically treated with sodium selenate had significantly shorter seizure duration compared controls, with more pronounced effects observed as the duration of treatment increased. The results of this study indicate that targeting hyperphosphorylated tau by treatment with sodium selenate has anti-seizure effects in a broad range of rodent models, and may represent a novel approach to treatment of patients with epilepsy. PMID:22182692
Jones, Nigel C; Nguyen, Thanh; Corcoran, Niall M; Velakoulis, Dennis; Chen, Tracy; Grundy, Robert; O'Brien, Terence J; Hovens, Christopher M
Complex Partial Seizures You are here: Home About Epilepsy Seizures Partial Seizures Complex Partial Seizures Email Print Twitter Facebook MySpace Delicous ... Complex Partial Seizures ] First Aid for Complex Partial Seizures Do not restrain the person. Remove dangerous objects ...
The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electro-encephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats. PMID:23098651
Szczurowska, E; Mareš, P
Opinion statement Seizures in neonates are common and often suggest a serious underlying brain injury such as hypoxia-ischemia, stroke, or hemorrhage.\\u000a There is a lack of evidence regarding optimal monitoring, evaluation, and treatment for newborns with seizures. Prolonged\\u000a video-electroencephalogram (EEG) is the gold standard for detecting seizures, whereas amplitude-integrated EEG may be a convenient\\u000a and useful screening tool. Evaluation involves a
Hannah C. Glass; Joseph E. Sullivan
Two new polyoxometalate (POM)-based metal-organic frameworks (MOFs) constructed from multinuclear silver-ptz cycle/belts, namely [Ag7(ptz)4(NO3)(H2O)][H4P2W18O62]·5H2O () and [Ag6(ptz)4(H2O)2][HPMo12O40]·3H2O () (ptzH = 5-(3-pyridyl)-1H-tetrazole), have been successfully synthesized under hydrothermal conditions via changing the polyoxoanions and adjusting the pH. Compound exhibits a 3D framework constructed from the Wells-Dawson [P2W18O62](6-) anion and a 2D layer based on two types of multinuclear Ag-ptz cycles. In compound , the 1D infinite multinuclear Ag-ptz belts consisting of repeated tetranuclear subunits [(Ag1)2(Ag2)2(ptz)4] are connected by Ag3 ions to form a 2D layer. The adjacent 2D layers are further linked by tetra-dentate Keggin [PMo12O40](3-) anions to construct a 3D framework. The structural analyses reveal that the different polyoxoanions have a great influence on the Ag(I)-ptz multinuclear cycle/belts and the whole structures. The influences of the pH and molar ratio of initial reactants in the hydrothermal process were also discussed. The electrochemical and photocatalytic properties of the title compounds have been studied in detail. PMID:23989233
Wang, Xiuli; Li, Na; Tian, Aixiang; Ying, Jun; Liu, Guocheng; Lin, Hongyan; Zhang, Juwen; Yang, Yang
The paper reports about the development of a software module that allows autonomous object detection, recognition and tracking in outdoor urban environment. The purpose of the project was to endow a commercial PTZ camera with object tracking and recognition capability to automate some surveillance tasks. The module can discriminate between various moving objects and identify the presence of pedestrians or
M. Lalonde; S. Foucher; L. Gagnon; E. Pronovost; M. Derenne; A. Janelle
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
Steven Yi; Hui Li
Traumatic brain injury (TBI) has been reported to increase seizure susceptibility and also contribute to the development of epilepsy. However, the mechanistic basis of the development of increased seizure susceptibility and epilepsy is not clear. Though there is substantial work done using rats, data are lacking regarding the use of mice in the fluid percussion injury (FPI) model. It is unclear if mice, like rats, will experience increased seizure susceptibility following FPI. The availability of a mouse model of increased seizure susceptibility after FPI would provide a basis for the use of genetically modified mice to study mechanism(s) of the development of post-traumatic epilepsy. Therefore, this study was designed to test the hypothesis that, mice subjected to a FPI develop increased seizure susceptibility to a subconvulsive dose of the chemoconvulsant, pentylenetetrazole (PTZ). Three groups of mice were used: FPI, sham, and naïve controls. On day 30 after FPI, mice from the three groups were injected with PTZ. The results showed that FPI mice exhibited an increased severity, frequency, and duration of seizures in response to PTZ injection compared with the sham and naïve control groups. Histopathological assessment was used to characterize the injury at 1, 3, 7, and 30?days after FPI. The results show that mice subjected to the FPI had a pronounced lesion and glial response that was centered at the FPI focus and peaked at 3?days. By 30?days, only minimal evidence of a lesion is observed, although there is evidence of a chronic glial response. These data are the first to demonstrate an early increase in seizure susceptibility following FPI in mice. Therefore, future studies can incorporate transgenic mice into this model to further elucidate mechanisms of TBI-induced increases in seizure susceptibility. PMID:23519723
Mukherjee, Sanjib; Zeitouni, Suzanne; Cavarsan, Clarissa Fantin; Shapiro, Lee A
Traumatic brain injury (TBI) has been reported to increase seizure susceptibility and also contribute to the development of epilepsy. However, the mechanistic basis of the development of increased seizure susceptibility and epilepsy is not clear. Though there is substantial work done using rats, data are lacking regarding the use of mice in the fluid percussion injury (FPI) model. It is unclear if mice, like rats, will experience increased seizure susceptibility following FPI. The availability of a mouse model of increased seizure susceptibility after FPI would provide a basis for the use of genetically modified mice to study mechanism(s) of the development of post-traumatic epilepsy. Therefore, this study was designed to test the hypothesis that, mice subjected to a FPI develop increased seizure susceptibility to a subconvulsive dose of the chemoconvulsant, pentylenetetrazole (PTZ). Three groups of mice were used: FPI, sham, and naïve controls. On day 30 after FPI, mice from the three groups were injected with PTZ. The results showed that FPI mice exhibited an increased severity, frequency, and duration of seizures in response to PTZ injection compared with the sham and naïve control groups. Histopathological assessment was used to characterize the injury at 1, 3, 7, and 30?days after FPI. The results show that mice subjected to the FPI had a pronounced lesion and glial response that was centered at the FPI focus and peaked at 3?days. By 30?days, only minimal evidence of a lesion is observed, although there is evidence of a chronic glial response. These data are the first to demonstrate an early increase in seizure susceptibility following FPI in mice. Therefore, future studies can incorporate transgenic mice into this model to further elucidate mechanisms of TBI-induced increases in seizure susceptibility.
Mukherjee, Sanjib; Zeitouni, Suzanne; Cavarsan, Clarissa Fantin; Shapiro, Lee A.
L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific /sup 3/H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of /sup 3/H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor.
Chang, Y.F.; Hargest, V.; Chen, J.S.
The anticonvulsant effects of adding a non-protective dose of vigabatrin (VGB) to increasing single doses of sodium valproate (VPA) against seizures induced by 110 mgkg(-1) of pentylenetetrazole (PTZ) or by 4.5 mgkg(-1) of picrotoxin (PIC) were compared in CD1 mice with those of VPA alone and vice versa. Neurotoxicity was evaluated by the rotarod test. The study also assessed changes in concentrations of anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate in the whole brain. VGB increased the potency ratio of VPA against PTZ (1.62, P < 0.05) but not against PIC (1.08, n.s.). VGB slightly decreased the neurotoxicity of VPA (0.93, n.s.) and the protective index of VPA was, therefore, increased from 1.93 to 3.34 for the PTZ model and from 1.40 to 1.61 for the PIC model. VGB did not modify brain concentrations of VPA, and increased brain GABA in relation to VPA alone. On the other hand, VGB did not achieve a complete protection neither against seizures induced by PTZ nor against seizures induced by PIC and a non-protective dose of VPA did not significantly modify the effects of increasing doses of VGB. In conclusion, the addition of a non-protective dose of VGB increased the anticonvulsants effects and the protective index of VPA in the PTZ model. A more than expected brain GABA increase together with the lack of a pharmacokinetic interaction support a pharmacodynamic basis for this interaction. PMID:15749465
Cuadrado, Antonio; Armijo, Juan A
Cyclooxygenase (COX) is reported to play a significant role in neurodegenerative and neuropsychiatric disorders, and may play a significant role in the pathogenesis of epilepsy. Various neurotransmitter abnormalities, especially of GABA and glutamate, have been reported to play a key role in the pathophysiology of epilepsy. The objective of the present study was to elucidate the effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced (80 mg/kg) convulsions in mice with possible mechanism of action. Various COX-inhibitors were administered 45 min prior to the PTZ administration. Onset, duration of clonic convulsions and percentage mortality/recovery were recorded. Pretreatment with COX-inhibitors aspirin (10 and 20 mg/kg, p.o.), naproxen (7 and 14 mg/kg, p.o.), nimesulide (1-5 mg/kg, p.o.) or rofecoxib (1-4 mg/kg, p.o.) dose-dependently showed protection against PTZ-induced convulsions. COX-2 inhibitors were more effective as compared to non-selective COX-inhibitors. Rofecoxib (1 mg/kg) or nimesulide (1 mg/kg) also enhanced the sub-protective effect of diazepam or muscimol showing GABAergic modulation of COX-2 inhibitors. COX-2 inhibitors also antagonized the effect of flumazenil (4 mg/kg)- against PTZ-induced convulsions further confirming the GABAergic mechanism. In conclusion, the results of the present study strongly suggest the possible role of cyclooxygenase isoenzymes in the pathophysiology of epilepsy and the use of COX-inhibitors as an adjuvant therapy in the treatment of epilepsy. PMID:16844276
Dhir, Ashish; Naidu, Pattipati S; Kulkarni, Shrinivas K
Although caffeine supplementation has a beneficial effect on people with neurological disorders, its implications for oxidative damage related to seizures are not well documented. Thus the aim of this study was to investigate the effects of two weeks caffeine supplementation (6mg/kg; p.o.) on seizures and neurochemical alterations induced by pentylenetetrazol (PTZ 60mg/kg i.p.). Statistical analyses showed that long-term rather than single dose caffeine administration decreased the duration of PTZ-induced seizures in adult male Wistar rats as recorded by cortical electroencephalographic (EEG) and behavioral analysis. The quantification of EEG recordings also revealed that caffeine supplementation protected against a wave increase induced by PTZ. Neurochemical analyses revealed that caffeine supplementation increased glutathione (GSH) content per se and protected against the increase in the levels of thiobarbituric acid reactive substances (TBARS) and oxidized diclorofluoresceine diacetate (DCFH-DA). Also, caffeine prevent the decrease in GSH content and Na(+), K(+)-ATPase activity induced by PTZ. Our data also showed that the infusion of L-buthionine sulfoximine (BSO; 3.2?mol/site i.c.v), an inhibitor of GSH synthesis, two days before injecting PTZ reversed the anticonvulsant effect caused by caffeine. BSO infusion also decreased GSH content and Na(+), K(+)-ATPase activity. However, it increased DCFH-DA oxidation and TBARS per se and reversed the protective effect of caffeine. Results presented in this paper support the neuroprotective effects of low long-term caffeine exposure to epileptic damage and suggest that the increase in the cerebral GSH content caused by caffeine supplementation may provide a new therapeutic approach to the control of seizure. PMID:23485558
Souza, Mauren Assis; Mota, Bibiana Castagna; Gerbatin, Rogério Rosa; Rodrigues, Fernanda Silva; Castro, Mauro; Fighera, Michele Rechia; Royes, Luiz Fernando Freire
To characterize the anticonvulsant effects and types of interactions exerted by mixtures of vigabatrin (VGB) and conventional antiepileptic drugs (valproate (VPA), ethosuximide (ESM), phenobarbital (PB), and clonazepam (CZP)) in pentylenetetrazole (PTZ)-induced seizures in mice, the isobolographic analysis for three fixed-ratio combinations of 1 : 3, 1 : 1, and 3 : 1 was used. The adverse-effect profile of the combinations
Jarogniew J Luszczki; Joanna Wojcik-Cwikla; Marta M Andres; Stanislaw J Czuczwar
Opinion statement \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a •Neonatal seizures are frequently manifested by subtle movements that are referable to brain stem structure, ie, nystagmus, conjugate eye movements, posturing, sucking movements, and so forth.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a •Electroencephalogram (EEG) confirmation of abnormal movements is essential in diagnosing seizures in the neonate.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a •Clinical seizure signs are often a clue to etiology.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a •Metabolic abnormalities must always be
Michael J. Painter; John Alvin
The present study was designed to evaluate the effects of age on the efficacy of the ketogenic diet in suppressing seizures evoked by tail-vein infusion of pentylenetetrazole (PTZ). Male rats of various ages were divided into three groups and fed one of three diets: (1) a calorie-restricted ketogenic diet, (2) a calorie-restricted normal (rodent chow) diet, or (3) a normal
Kristopher J. Bough; Ritu Valiyil; Frederick T. Han; Douglas A. Eagles
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 Ca2+-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
Toru Matsu-ura; Yoshiyuki Konishi; Tsutomu Aoki; Jose R Naranjo; Katsuhiko Mikoshiba; Taka-aki Tamura
Epilepsy, which is one of the most common neurological disorders, involves the occurrence of spontaneous and recurrent seizures that alter the performance of the brain and affect several sensory and behavioral functions. Oxidative damage has been associated with post-seizure neuronal injury, thereby increasing an individual's susceptibility to the occurrence of neurodegenerative disorders. The present study investigated the possible anticonvulsive and neuroprotective effects of organic and conventional yerba mate (Ilex paraguariensis), a plant rich in polyphenols, on pentylenetetrazol (PTZ)-induced seizures in Wistar rats. The behavioral and polyphenolic profiles of the yerba mate samples were also evaluated. Infusions of yerba mate (50mg/kg) or distilled water were given to rats for fifteen days by oral gavage. On the 15th day the animals were subjected to open field test, and exploratory behavior was assessed. Subsequently, 60mg/kg PTZ (i.p.) was administered, and animals were observed for the appearance of convulsions for 30min. Latency for the first seizure, tonic-clonic and generalized seizures time, frequency of seizures and mortality induced by PTZ were recorded. The animals were then sacrificed, and the cerebellum, cerebral cortex and hippocampus were quickly removed and frozen to study the neuroprotective effects of yerba mate. The oxidative damage in lipids and proteins, nitric oxide levels, the activities of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat) and non-enzymatic cellular defense (sulfhydryl protein) were quantified in all the tissues. The results showed that organic and conventional yerba mate infusions were able to reduce the frequency of seizures when compared to the PTZ group. Besides, organic yerba mate infusion decreases the tonic-clonic seizures time in relation to the PTZ group. It was also shown that organic and conventional yerba mate infusions reduced the oxidative damage in lipids and proteins and nitric oxide levels and prevented the decrease in Sod and Cat activities and sulfhydryl protein content when compared to the PTZ group in all the CNS tissues assayed. Organic and conventional yerba mate commercial samples did not change the behavior (locomotion, exploration or anxiety) of the treated animals. In both organic and conventional infusions, the presence of the polyphenols rutin, chlorogenic acid and their acyl derivatives were detected, which could be associated with the biological effects observed. These data indicate that yerba mate may provide new perspectives for the development of therapeutic approaches with natural compounds in the pharmaceutical area, both to reduce the convulsions' frequency and to minimize the neuronal damage associated with recurrent seizures. PMID:23270878
Branco, Cátia Dos Santos; Scola, Gustavo; Rodrigues, Adriana Dalpicolli; Cesio, Verónica; Laprovitera, Mariajosé; Heinzen, Horacio; Dos Santos, Maitê Telles; Fank, Bruna; de Freitas, Suzana Cesa Vieira; Coitinho, Adriana Simon; Salvador, Mirian
The analysis of epileptic seizures is typically performed by visual inspection, limited by interrater variation. Our aim was to differentiate seizures characterized by automatisms with an objective, quantitative movement analysis. In part 1 of this study we found parameters (extent and speed of movement of the wrist and trunk) separating seizures with predominant proximal (hyperkinetic, n=10) and distal (automotor, n=10) limb automatisms (P<0.002). For each movement parameter we used the lowest value recorded for a hyperkinetic seizure in part 1 as the cutoff parameter in part 2 on a consecutive sample of 100 motor seizures. As in part 1, the difference between hyperkinetic and non-hyperkinetic seizures was highly significant (<0.001). When all movement parameters were above the threshold, a hyperkinetic seizure was identified with a probability of 80.8%, but the probability for a non-hyperkinetic seizure to have all parameters above the threshold was only 0.02%. PMID:21458386
Rémi, Jan; Cunha, João P Silva; Vollmar, Christian; Topçuo?lu, Özgür Bilgin; Meier, Alexander; Ulowetz, Steffen; Beleza, Pedro; Noachtar, Soheyl
|This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…
This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…
Background: Adverse drug reactions are important determinants of inpatient and outpatient morbidity. Thiocolchicoside is a semisynthetic derivate of naturally occurring colchicoside, which is largely used in humans as a centrally acting muscle relaxant. Epileptic seizures after thiocolchicoside intake have been reported in individuals with a history of epilepsy, acute brain injury or possible blood–brain barrier disruption. Case report: We report the case of a 66-year-old male patient presenting a sudden epileptic seizure temporally related to the intake of thiocolchicoside for muscle contracture and pain. The probably causes of the seizures were thiocolchicoside intake and cerebral microhemorrhages attributed to cerebral amyloid angiopathy. Discussion: Drugs only rarely cause focal seizures. Our case indicates that thiocolchicoside can precipitate seizures in predisposed patients, and that its use should be avoided in patients with brain diseases (and therefore lower seizure thresholds) or blood–brain barrier disruption. This information should be provided in the drug package insert.
Giavina-Bianchi, Pedro; Giavina-Bianchi, Mara; Tanno, Luciana Kase; Ensina, Luis Felipe Chiaverini; Motta, Antono Abilio; Kalil, Jorge
The paper reports about the development of a software module that allows autonomous object detection, recognition and tracking in outdoor urban environment. The purpose of the project was to endow a commercial PTZ camera with object tracking and recognition capability to automate some surveillance tasks. The module can discriminate between various moving objects and identify the presence of pedestrians or vehicles, track them, and zoom on them, in near real-time. The paper gives an overview of the module characteristics and its operational uses within the commercial system.
Lalonde, M.; Foucher, S.; Gagnon, L.; Pronovost, E.; Derenne, M.; Janelle, A.
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.
Yi, Steven; Li, Hui
Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models. PMID:23801192
Aguiar, Carlos Clayton Torres; Almeida, Anália Barbosa; Araújo, Paulo Victor Pontes; Vasconcelos, Germana Silva; Chaves, Edna Maria Camelo; do Vale, Otoni Cardoso; Macêdo, Danielle Silveira; Leal, Luzia Kalyne Almeida Moreira; de Barros Viana, Glauce Socorro; Vasconcelos, Silvânia Maria Mendes
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 (Ca(2+)) 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
Baxendale, Sarah; Holdsworth, Celia J; Meza Santoscoy, Paola L; Harrison, Michael R M; Fox, James; Parkin, Caroline A; Ingham, Philip W; Cunliffe, Vincent T
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. PMID:12531529
Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki
Citalopram, a selective serotonin reuptake inhibitor (SSRI), is frequently used in the treatment of major depressive disorders. In addition to its antidepressant features, citalopram shows some anticonvulsive properties at lower doses, whereas higher doses, ingested in cases of suicide, have been associated with seizures. Moreover, some reports support the enhancing effect of morphine on different responses of SSRIs such as analgesic and anticonvulsant properties. Although the exact mechanisms of these additive effects are not yet fully understood, 5-HT(3) receptor has recently been shown to play an important role in the central effects of SSRIs and morphine. In this regard, we used a model of clonic seizures induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether morphine and citalopram exhibit additive anticonvulsant effects and, if so, whether this effect is mediated through modulation of 5-HT(3) receptors. In our study, citalopram at lower doses (0.5 and 1 mg/kg, ip) significantly increased the seizure threshold (P<0.01) and at a higher dose (50 mg/kg) had proconvulsive effects. Moreover, morphine at low and noneffective doses had additive effects on the anticonvulsive properties of citalopram. This additive effect was prevented by pretreatment with low and noneffective doses of tropisetron (a 5-HT(3) receptor antagonist) and augmented by 1-(m-chlorophenyl)-biguanide (mCPBG, a 5-HT(3) receptor agonist). Moreover, low doses of morphine (0.1 and 0.5 mg/kg) alone or in combination with potent doses of 5-HT(3) receptor agonist or antagonist could not alter the proconvulsive properties of citalopram at higher dose (50 mg/kg), ruling out the contribution of 5-HT(3) to this effect. In summary, our findings demonstrate that 5-HT(3) receptor mediates the additive anticonvulsant properties of morphine and low-dose citalopram. This could constitute a new approach to augmenting the efficacy and curtailing the adverse effects of citalopram. PMID:21531632
Bahremand, Arash; Payandemehr, Borna; Rahimian, Reza; Ziai, Pouya; Pourmand, Naghmeh; Loloee, Sogol; Ebrahimi, Ali; Ghasemi, Abbas; Fakhfouri, Gohar; Ghasemi, Mehdi; Dehpour, Ahmad Reza
Differential operators can detect significant changes in signals. This has been utilized to enhance the contrast of the seizure signatures in depth EEG or ECoG. We have actually taken normalized exponential of absolute value of single or double derivative of epileptic ECoG. This in short we call differential filtering. Windowed variance operation has been performed to automatically detect seizure onset on differentially filtered signal. A novel method for determining the duration of seizure has also been proposed. Since all operations take only linear time, the whole method is extremely fast. Seven empirical parameters have been introduced whose patient specific thresholding brings down the rate of false detection to a bare minimum. Results of implementation of the methods on the ECoG data of four epileptic patients have been reported with an ROC curve analysis. High value of the area under the ROC curve indicates excellent detection performance. PMID:22104594
We compared the effects of adding a non-protective dose of valproate (VPA) to increasing single doses of felbamate (FBM) with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by 14 mg kg(-1) of 4-aminopyridine (4-AP) and by 110 mg kg(-1) of pentylenetetrazole (PTZ), and neurotoxicity by the rotarod test. The study also assessed changes in concentrations of anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate in the whole brain. VPA increased the potency ratio of FBM against 4-AP (1.94, P<0.05) but not against PTZ. VPA increased the neurotoxicity of FBM (3.30, P<0.05) and the protective index of FBM was, therefore, reduced from 12.0 to 7.0 for the 4-AP model and from 11.8 to 5.2 for the PTZ model; VPA reduced brain FBM, and increased brain GABA in relation to FBM monotherapy. On the other hand, FBM increased the potency ratio of VPA against 4-AP (1.60, P<0.05) but not against the PTZ, and had no effect on the rotarod model. Therefore, the protective index increased from 1.1 to 1.6 for the 4-AP model and decreased from 1.9 to 1.7 for the PTZ model. FBM did not change brain VPA, and changes in brain GABA and glutamate were not clearly related to anticonvulsant effects. In conclusion, although the addition of a low dose of FBM to VPA was beneficial in the 4-AP model, the addition of a low dose of VPA to FBM was not; both combinations were disadvantageous in the PTZ model. This interaction appears to be pharmacodynamic because a pharmacokinetic mechanism was discarded. PMID:12798671
Cuadrado, Antonio; Amat, Gaspar; Armijo, Juan A
|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…
Shafer, Patricia Osborne
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…
Shafer, Patricia Osborne
The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby these mutations produce seizures is unknown. Three mutations of the alpha(4) subunit of the neuronal nicotinic acetylcholine receptor (nAChR) have been identified in autosomal dominant nocturnal frontal lobe epilepsy. In vitro studies of two mutations suggest an alteration of receptor function resulting in decreased ion channel current flow. We investigated the response of alpha(4) nAChR subunit knockout mice to the gamma-aminobutyric acid (GABA) receptor antagonists; pentylenetetrazole (PTZ) and bicuculline (BIC), the glutamate receptor agonist kainic acid (KA), the glycine receptor antagonist strychnine and the K(+) channel blocker 4-aminopyridine (4-AP). Mutant (Mt) mice had a greater sensitivity to PTZ and BIC, with an increase in major motor seizures and seizure-related deaths. Furthermore, Mt mice were more sensitive to KA and strychnine, but the effects were much smaller compared to those seen with the GABA receptor antagonists. Paradoxically, Mt mice appeared to be relatively protected from 4-AP-induced major motor seizures and death. The results show that a functional deletion of the alpha(4) nAChR subunit in vivo is associated with a major increase in sensitivity to GABA receptor blockers. PMID:12213259
Wong, John Y F; Ross, Shelley A; McColl, Craig; Massalas, Jim S; Powney, Emma; Finkelstein, David I; Clark, Malcolm; Horne, Malcolm K; Berkovic, Samuel F; Drago, John
In spite of the availability of new antiepileptic drugs a considerable number of epilepsy patients still have pharmacoresistant seizures, and thus there is a need for novel approaches. Acetyl-l-carnitine (ALCAR), which delivers acetyl units to mitochondria for acetyl-CoA production, has been shown to improve brain energy homeostasis and protects against various neurotoxic insults. To our knowledge, this is the first study of ALCAR's effect on metabolism in pentylenetetrazole (PTZ) kindled mice. ALCAR or the commonly used antiepileptic drug valproate, was added to the drinking water of mice for 25days, and animals were injected with PTZ or saline three times a week during the last 21 days. In order to investigate ALCAR's effects on glucose metabolism, mice were injected with [1-(13)C]glucose 15 min prior to microwave fixation. Brain extracts from cortex and the hippocampal formation (HF) were studied using (1)H and (13)C NMR spectroscopy and HPLC. PTZ kindling caused glucose hypometabolism, evidenced by a reduction in both glycolysis and TCA cycle turnover in both brain regions investigated. Glutamatergic and GABAergic neurons were affected in cortex and HF, but the amount of glutamate was only reduced in HF. Slight astrocytic involvement could be detected in the cortex. Interestingly, the dopamine content was increased in the HF. ALCAR attenuated the PTZ induced reduction in [3-(13)C]alanine and the increase in dopamine in the HF. However, TCA cycle metabolism was not different from that seen in PTZ kindled animals. In conclusion, even though ALCAR did not delay the kindling process, it did show some promising ameliorative effects, worthy of further investigation. PMID:22709675
Smeland, Olav B; Meisingset, Tore W; Sonnewald, Ursula
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.
Chowdhury, Bimalendu; Bhattamisra, Subrat K.; Das, Mangala C.
The objective of this study was to delineate the clinical and video-electroencephalographic (EEG) manifestations of children with complex partial seizures with a predominant “hyperkinetic” presentation. Certain types of partial seizures can be difficult to differentiate from nonepileptic seizures because of their intense motor presentation and, at times, lack of alteration of consciousness. Based on a published semiologic seizure classification, this
Arie Weinstock; Pierre Giglio; Susan L. Kerr; Patricia K. Duffner; Michael E. Cohen
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.
Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid (PUFA) which has been found to have anticonvulsant properties. Our group has previously reported in a pilot study that the acute administration of subcutaneous (s.c.) DHA increases seizure latencies in the maximal pentylenetetrazole (PTZ) seizure test, however it loses its effect at higher doses. The purpose of the present experiments was (1) to confirm that DHA loses its effect at higher doses, (2) to correlate the anticonvulsant properties of DHA with DHA levels in the different lipid pools of serum and (3) to evaluate whether an anticonvulsant dose of DHA resulted in an increase in DHA release from the brain phospholipids following induction of seizure. In the first experiment, male Wistar rats were injected s.c. with 200, 300, 400 or 600 mg/kg of DHA, or 400mg/kg oleic acid (OA, isocaloric control), and seizure tested with the maximal PTZ test 1h post injection (Experiment 1). In a second experiment, subjects received either: (1) an effective dose of DHA (400mg/kg), (2) a higher, non-effective dose (600 mg/kg; based on the findings of Experiment 1), or (3) OA (400mg/kg). Subjects were sacrificed 1h post injection and blood was collected for fatty acid analysis (Experiment 2). In the third experiment, subjects were injected with either the effective dose of DHA (400mg/kg) or OA (400mg/kg). One hour post lipid injection, animals received either PTZ or saline, and animals were euthanized via microwave fixation. Brain were extracted and unesterified fatty acid concentrations were measured (Experiment 3). Experiment 1 confirmed that DHA loses its effects at higher doses in the maximal PTZ test. The 400mg/kg dose was maximally effective but effects were lost at 600 mg/kg. Experiment 2 showed that only the unesterified DHA pool in serum was statistically increased by an acute injection of s.c. DHA (P<0.05, as compared to OA), whereas esterified DHA pools were unchanged (P>0.05). Curiously, unesterified DHA levels were similar in both the 400mg/kg and 600 mg/kg dosage groups. Experiment 3 showed that an anticonvulsant dose of DHA (400mg/kg) did not increase DHA release from brain phospholipids following seizure induction (P>0.05). In conclusion, DHA has anticonvulsant properties when injected s.c., but these properties are lost at higher doses. The anticonvulsant effects of DHA are accompanied by increased levels of unesterified DHA in the serum, but not in increased DHA release from brain phospholipids. PMID:22285511
Trépanier, Marc-Olivier; Taha, Ameer Y; Mantha, Rebecca L; Ciobanu, Flaviu A; Zeng, Qiudi H; Tchkhartichvili, George M; Domenichiello, Anthony F; Bazinet, Richard P; Burnham, W M
Ultrafine SnO2 powder was made with grain size down to 20 nm. Such powder was introduced into the textured growth of Y1+xBa2Cu3O7+? (YBCO) superconductors. Crystalline inclusions, which were cubic in shape and from micrometer to submicrometer in size, were found trapped inside such grown YBCO superconductors. Determined by energy dispersive spectroscopy (EDS), and further confirmed by X-ray diffraction, the composition of the inclusions was Y2Ba5(Sn3-y- zCuyPtz)Ox. This Sn-based phase belongs to double perovskite structures. They were not trapped uniformly inside the YBa2Cu3O7-? (123), possibly caused by the agglomeration of the SnO2 powder at the very beginning. Nevertheless, it is possible for fine Sn-based inclusions down to a few hundred nanometers to be trapped inside the 123. The addition of the ultrafine SnO2 to YBCO textured superconductors without Pt did not seem to affect the size of Y2BaCuO5 (211) particles. For comparison, Y2Sn2O7 was also introduced to YBCO textured superconductor. In this case, the so-called ? phase YBa3Sn2-xCuxO9-? was found.
He, Z. H.; Wu, M. Z.; Bruchlos, G.; Xiong, X. M.; Luo, Y. Y.; Gawalek, W.
\\u000a Abstract\\u000a Although pathophysiologically distinct, syncope and seizures share clinical characteristics which may make diagnosis difficult.\\u000a Adding to diagnostic complexity are the facts that seizures and syncope may coexist in the same patient, syncope may be associated\\u000a with seizure-like motor manifestations, and seizures may be complicated by cardiac arrhythmia and syncope. Combined EEG\\/ECG\\u000a telemetry is sometimes necessary to establish the correct
Jeffrey W. Britton; Eduardo Benarroch
|This paper examines the practice of search and seizure from a legal perspective. All issues concerning lawful or unlawful search and seizure, whether in a public school or otherwise, are predicated upon the Fourth Amendment to the United States Constitution. The terms "search,""seizure,""probable cause,""reasonable suspicion," and "exclusionary…
Murray, Kenneth T.
Adverse effects to antipsychotics are varied, frequently intolerable, often serious and sometimes fatal in clinical practice. Seizures are one of these adverse effects. Almost all first and second generation antipsychotics elicit dose-dependent lowering of seizure threshold, indicating increased seizure risk at higher drug dosages. The adverse event of zotepine induced seizure is published in few case reports. We report the occurrence of myoclonic seizure progressing to generalized tonic-clonic seizures with zotepine along with clear temporal association of dose dependent modulation evident in this case.
Khairkar, Praveen; Gupta, Neha; Varma, Sushil Kumar
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. PMID:16823386
Uzbay, Tayfun I; Kayir, Hakan; Ceyhan, Mert
Seizures may frequently occur during tuberculous meningitis. We describe a patient with an apparent generalised tonic-clonic seizure, initially not associated with any magnetic resonance imaging (MRI) abnormality, which was the presenting symptom of tuberculous meningitis. Follow-up MRI, performed after gadolinium administration, showed signs of meningeal involvement. Seizures may be the presenting symptoms of tuberculous meningitis even in the absence of evident intracerebral lesions on MRI. Therefore, contrast-enhanced brain MRI should be performed in the diagnostic workup for each first seizure, especially in patients with a clinical suspicion of CNS infectious disease. The term "heraldic seizure", indicating a subset of acute symptomatic seizures presenting at the onset of a brain/systemic injury or preceding the full clinical manifestation of a cerebral insult, may be helpful to classify these seizures retrospectively, based initially on unknown aetiology. PMID:22940820
Brigo, Francesco; Ausserer, Harald; Zuccoli, Giulio; Tezzon, Frediano; Nardone, Raffaele
Male Wistar rat pups were weaned at 20 days of age and placed on either a control diet or a ketogenic diet containing medium-chain triglyceride (MCT) oil. After 10 days on the diets, they were subjected to one of four seizure tests—maximal electric shock, threshold electroconvulsive shock, threshold pentylenetetrazol, or maximal pentylenetetrazol. After testing, subjects were sacrificed and blood samples
Paaladinesh Thavendiranathan; Antonio Mendonca; Cynthia Dell; Sergei S. Likhodii; Kathy Musa; Costa Iracleous; Stephen C. Cunnane; W. McIntyre Burnham
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. PMID:22236820
Knowles, Byron Don; Pleacher, Michael D
Febrile seizures (FS), as a multifactorial and genetic disease, are the most common type of convulsive event in infants and young children. Their genetic basis, however, remains elusive. To investigate the genetic mechanisms involved in FS and to identify novel susceptibility genes, we developed two new strains of rats that are hyperthermia-prone (HP, lower seizure threshold) and hyperthermia-resistant (HR, higher seizure threshold) using an established model of hyperthermia-induced seizures combined with selective breeding process. With each subsequent generation, the morbidity of the FS gradually increased in the HP group and gradually decreased in the HR group. Changes in seizure susceptibility between the two genotypes were investigated using kainic acid (KA)-induced seizures and electroencephalography (EEG). The HP rats had a greater seizure severity compared with the HR rats. Our findings may be a significant step toward discovering the genetic mechanisms involved in FS and may elucidate the pathogenesis of this disorder. PMID:23948396
Xu, Jian; Fan, Yuanteng; Li, Liang; Qiu, Yanyan; Wang, Zhongcheng; Han, Song; Yin, Jun; Liu, Wanhong; Peng, Biwen; He, Xiaohua
In this study, we present five cases of seizures following withdrawal of flunitrazepam, lorazepam, or triazolam, representing 3% of a sample consisting of 153 patients dependent on benzodiazepines. Both abrupt cessation of benzodiazepine intake and high-dose use seem to be critical for the appearance of seizures. Pharmacological features, such as short elimination half-life and high potency, might explain the higher risk of seizures observed in these patients. PMID:8773293
Martínez-Cano, H; Vela-Bueno, A; de Iceta, M; Pomalima, R; Martínez-Gras, I
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. PMID:23223299
Rakhade, Sanjay N; Fitzgerald, Erin F; Klein, Peter M; Zhou, Chengwen; Sun, Hongyu; Huganir, Richard L; Hunganir, Richard L; Jensen, Frances E
A multi-threshold element is one in which several thresholds are used to separate the true inputs from the false inputs. Many circuit elements and configurations can be described by this model. An approach, based on conventional single-threshold threshold elements, is developed for the analysis and synthesis of multithreshold threshold elements. It is shown that the basic properties of such elements
Donald R. Haring
The patent application relates to epileptic seizure warning system based on pattern recognition principles. The system is embodied in a small self-contained device which can be carried in a pocket of a person subject to grand mal seizures, to monitor the ...
S. S. Viglione V. A. Ordon W. B. Martin C. C. Kesler
Seizures and intracranial hemorrhage are possible medical diseases that any obstetrician may encounter. This article reviews the cause, treatment, and medical management in pregnancy for seizures and intracranial hemorrhage, and how the two can overlap into preeclampsia or eclampsia. This article also highlights some challenging management issues from the obstetrician's perspective. PMID:23466140
Wilson, Karen L; Alexander, James M
Epilepsy affects 0.5% to 1% of the population and can cause focal, partial, generalized, and absence seizures and several unusual types. Seizure disorders often begin in childhood and are treated with a variety of pharmacologic or surgical interventions for those refractory to medical therapy. Functional imaging, with both PET and single-photon emission CT (SPECT), has been highly useful in the
Andrew B. Newberg; Abass Alavi
Prolactin secretion after tonic-clonic seizures (10 patients), complex partial seizures (five) and non-epileptic attacks (three) was studied in a group of children aged between 0.3 and 14 years. Seven patients with other subcategories of seizure disorders were also studied. Eight children with tonic-clonic seizures exhibited post ictal concentrations of prolactin greater than 500 mU/l. One of the children, who responded on one occasion, did not do so on another. Three children with complex partial seizures had post ictal prolactin concentrations greater than 500 mU/l, while in two the increased values were more modest (390 mU/l and 420 mU/l). The timing of the peak post ictal prolactin concentration varied from less than 20 minutes to a prolonged plateau for three hours. Other seizure types--simple partial with motor signs (2), absence seizure (1), myoclonic seizure (1), minor epileptic status (3) (with one exception), and non-epileptic attacks (3) were not associated with post ictal concentrations greater than 500 mU/l.
Bye, A M; Nunn, K P; Wilson, J
The fourth amendment to the Constitution has two basic clauses. The first, the reasonableness clause, protects the people against unreasonable searches and seizures. The second, the warrant clause, sets forth conditions under which a warrant may issue. Searches and seizures made pursuant to a warrant are, quite obviously, governed by the commands of the warrant clause. However, the effect of
Mack Allen Player
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…
Goldman, Alica M.
Stimulants are an effective treatment frequently prescribed for attention-deficit–hyperactivity disorder (ADHD), but they commonly are believed to lower the threshold for seizures. Although several studies have revealed that stimulants do not exacerbate well-controlled epilepsy, there is a paucity of data about seizure risk in nonepileptic children treated with stimulants. Two hundred thirty-four children (179 males, 9.1 ± 3.6 years of
Sarah A Hemmer; Joseph F Pasternak; Steven G Zecker; Barbara L Trommer
In this communication, the effect of acute treatment with lamotrigine (LTG) and topiramate (TPM) was investigated on release of the main excitatory amino acids (EAA) such as glutamate (Glu) and aspartate (Asp) in the hippocampus of pentylenetetrazol (PTZ)-kindled freely moving rats using microdialysis. The results showed that the level of Glu and Asp significantly decreased in the PTZ-kindled epileptic (EP) rat hippocampus after the 20 mg/kg LTG or 40 mg/kg TPM administration. But LTG gave rise to a better result than TPM in controlling EAA release. PMID:23858978
Deng, Yan; Wang, Minghuan; Jiang, Li; Ma, Chao; Xi, Zhijiang; Li, Xiaolong; He, Nongyue
The objective of this study was to delineate the clinical and video-electroencephalographic (EEG) manifestations of children with complex partial seizures with a predominant "hyperkinetic" presentation. Certain types of partial seizures can be difficult to differentiate from nonepileptic seizures because of their intense motor presentation and, at times, lack of alteration of consciousness. Based on a published semiologic seizure classification, this type of seizures can be described as "hyperkinetic," characterized by intense motor activity involving the extremities and trunk. We report five children diagnosed with hyperkinetic seizures by video-EEG monitoring. All patients were referred for video-EEG evaluation because of an initial suspicion of pseudoseizures. Presented in this study is a review of the patients' clinical data, including video-EEG evaluation. There were three boys and two girls; the mean age at presentation was 10 +/- 3 years. In four patients, there was a history of behavioral disorder, with two patients carrying a diagnosis of attention-deficit hyperactivity disorder (ADHD). One girl had significant developmental delay and an abnormal neurologic examination. Brain magnetic resonance imaging was normal in three patients and abnormal in two. The semiology of the seizures consisted of stereotypic intense motor activity, mainly upper extremity flailing and kicking. Screaming and shouting were noted in three cases, and intense fear was present in two patients. The hyperkinetic ictal activity progressed to tonic-clonic seizures in two patients. Seizures occurred out of sleep or on awakening in four patients. The interictal EEG activity was normal in one patient and revealed a continuous generalized slowing and slowing of the posterior dominant rhythm in two patients. One of the latter patients had interictal epileptiform activity in the frontal and midline regions. An intermittent rhythmic slow activity of the left hemisphere with superimposed bifrontal sharp waves was noted in the fifth patient. The ictal EEG revealed profuse superimposed electromyographic (EMG) activity in all patients, making some of the EEG interpretation difficult to analyze, particularly a longitudinal bipolar montage. However, with digital manipulation of the ictal EEG data, such as changes in EEG sensitivity, application of fast frequency filters, and use of different EEG montages, it was possible to discern an ictal EEG pattern or postictal slowing following the diffuse EMG artifact in all patients. On clinical follow-up, adequate seizure control was achieved in three patients. Based on the clinical history, one patient was diagnosed with autosomal dominant nocturnal frontal lobe epilepsy. Diagnosis of hyperkinetic seizures can be difficult because of the similarity of the clinical manifestations with nonepileptic events such as certain parasomnias and pseudoseizures. Video-EEG is the most effective way of diagnosing this type of seizure. PMID:13677576
Weinstock, Arie; Giglio, Pierre; Kerr, Susan L; Duffner, Patricia K; Cohen, Michael E
Over the last decade, the search for a method able to reliably predict seizures hours in advance has been largely replaced by a more realistic goal of very early detection of seizure onset which would allow therapeutic or warning devices to be triggered prior to the onset of disabling clinical symptoms. We explore in this article the steps along the pathway from data acquisition to closed loop applications that can and should be considered to design the most efficient early seizure detection. Microelectrodes, high-frequency oscillations, high sampling rate, high-density arrays, and modern analysis techniques are all elements of the recording and detection process that in combination with modeling studies can provide new insights into the dynamics of seizure onsets. Each of these step needs to be considered if one wants to implement improved detection devices that will favorably impact the quality of life of patients.
Jouny, Christophe C.; Franaszczuk, Piotr J.; Bergey, Gregory K.
Based on medicine for the public lecture represented in October 1990 at NIH. Discusses seizure disorders--causes, effects, treatment, and research. Includes graphic illustrations and b-roll, as well as interview with doctor.
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The differential diagnoses of epileptic seizures depend on the different semiologies of the respective seizures. Patient history and history of witnesses are of foremost importance in the differentiation. When seizures recur, they are more easily distinguished than single seizures. Diagnostic methods like EEG and eventually EEG video monitoring will help in the differentiation when clinical information and patient history do not allow a clear diagnosis. We present the most common differential diagnoses and their differences compared to epileptic seizures. PMID:22237650
Rémi, J; Noachtar, S
\\u000a Clinical evidence, in particular the wide use of theophylline as a bronchodilator, suggests that methylxanthines can cause\\u000a seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure\\u000a exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by their antagonizing\\u000a the brain’s own anticonvulsant adenosine. Recent evidence
Unilateral exposure of 21-day-old mice to doorbell sound induces unilateral seizure susceptibility to subsequent sound. However, this unilateral component of sound-induced seizures, as well as the inhibitory effect of repetitious sound, appear only in these older mice as susceptibility to audiosensitization is declining. Unilateralîty and audiosensitization have separate ontogenetic patterns, and thus involve separate mechanisms. Ether anesthesia eliminates the inhibitory
W. B. Iturrian; H. D. Johnson
Often the power to use a cryptosystem has to be shared. In threshold schemes, t-out-of-l have the power to regenerate a secret key (while less than t have not). However threshold schemes cannot be used directly in many applications, such as threshold signatures in which t-out-of-l have to co-sign a message. A normal threshold scheme would require the shareholders to
Experimental prolonged febrile seizures (FS) lead to structural and molecular changes that promote hippocampal hyperexcitability and reduce seizure threshold to further convulsants. However, whether these seizures provoke later-onset epilepsy, as has been suspected in humans, has remained unclear. Previously, intermittent EEGs with behavioural observations for motor seizures failed to demonstrate spontaneous seizures in adult rats subjected to experimental prolonged FS during infancy. Because limbic seizures may be behaviourally subtle, here we determined the presence of spontaneous limbic seizures using chronic video monitoring with concurrent hippocampal and cortical EEGs, in adult rats (starting around 3 months of age) that had sustained experimental FS on postnatal day 10. These subjects were compared with groups that had undergone hyperthermia but in whom seizures had been prevented (hyperthermic controls), as well as with normothermic controls. Only events that fulfilled both EEG and behavioural criteria, i.e. electro-clinical events, were considered spontaneous seizures. EEGs (over 400 recorded hours) were normal in all normothermic and hyperthermic control rats, and none of these animals developed spontaneous seizures. In contrast, prolonged early-life FS evoked spontaneous electro-clinical seizures in 6 out of 17 experimental rats (35.2%). These seizures consisted of sudden freezing (altered consciousness) and typical limbic automatisms that were coupled with polyspike/sharp-wave trains with increasing amplitude and slowing frequency on EEG. In addition, interictal epileptiform discharges were recorded in 15 (88.2%) of the experimental FS group and in none of the controls. The large majority of hippocampally-recorded seizures were heralded by diminished amplitude of cortical EEG, that commenced half a minute prior to the hippocampal ictus and persisted after seizure termination. This suggests a substantial perturbation of normal cortical neuronal activity by these limbic spontaneous seizures. In summary, prolonged experimental FS lead to later-onset limbic (temporal lobe) epilepsy in a significant proportion of rats, and to interictal epileptifom EEG abnormalities in most others, and thus represent a model that may be useful to study the relationship between FS and human temporal lobe epilepsy. PMID:16446281
Dubé, Céline; Richichi, Cristina; Bender, Roland A; Chung, Grace; Litt, Brian; Baram, Tallie Z
Repeated subconvulsant doses of the GABA antagonist drugs picrotoxin (5 mg\\/kg), pentylenetetrazol (PTZ) (30 mg\\/kg), and bicuculline (3.5 mg\\/kg), were given IP once daily to rats. Picrotoxin produced rapid kindling to full seizures in about 5 days, PTZ produced sporadic myoclonic seizures after 17 days whereas bicuculline only produced occasional mild jerking. Following these treatments, seizure thresholds to these drugs
David J. Nutt; Philip J. Cowen; Celia C. Batts; David G. Grahame-Smith; A. Richard Green
Early developmental exposure to caffeine in rats results in decreased susceptibility to certain chemically-induced seizures in the adult. To determine whether this effect first appears in adulthood or is present during preceding developmental stages, we exposed neonatal rats to caffeine and determined seizure thresholds in animals 28, 42 and 70–90 days of age. Rats were unhandled or received either vehicle
Summary. The nootropic drug piracetam was investigated in various experimental models of epilepsy. Generally, piracetam exhibits no or only moderate anticonvulsant properties against generalized tonic or clonic seizures. However, in many cases it did increase the anticonvulsant effectiveness of conventional antiepileptics, as shown in the maximal electroshock seizure (MES) threshold test, the traditional MES test or in DBA\\/2 mice. A
W. Fischer; H. Kittner; R. Regenthal; E. Russo; G. De Sarro
Seizures and epilepsy in children are common. They are caused by a variety of causes ranging from genetic to neuro -infections. History and actual observation or/video are very important to differentiate true seizure from non-epileptic event. A correct classification of seizure and epilepsy helps to decide need to treat, choice of anti-epileptic drugs (AED) and prognostication. Except for few seizure types, in majority of seizure types regular AED are started after second confirmed seizure. Goal of treatment is seizure control with minimal side effects and ensuring quality of life. With appropriate mono - therapy, about 70 % patients become seizure free and can be easily treated in community. An orderly approach to classify seizure type, holistic management and timely referral of intractable epilepsy will help in improving care of children with epilepsy. PMID:24048876
Seizures induced by fever (febrile seizures) are the most common type of pathological brain activity in infants and children. These febrile seizures and their potential contribution to the mechanisms of limbic (temporal lobe) epilepsy have been a topic of major clinical and scientific interest. Key questions include the mechanisms by which fever generates seizures, the effects of long febrile seizures on neuronal function and the potential contribution of these seizures to epilepsy. This review builds on recent advances derived from animal models and summarizes our current knowledge of the mechanisms underlying febrile seizures and of changes in neuronal gene expression and function that facilitate the enduring effects of prolonged febrile seizures on neuronal and network excitability. The review also discusses the relevance of these findings to the general mechanisms of epileptogenesis during development and points out gaps in our knowledge, including the relationship of animal models to human febrile seizures and epilepsy. PMID:17897728
Dubé, Céline M; Brewster, Amy L; Richichi, Cristina; Zha, Qinqin; Baram, Tallie Z
Fluoxetine, a selective serotonin reuptake inhibitor, is known to increase the cortical content of allopregnanolone (ALLO) without altering the level of other neurosteroids. In contrast to the proconvulsant effect of many antidepressants, fluoxetine exhibits anticonvulsant effects. The present study was undertaken to examine the role of ALLO in the anticonvulsant action of fluoxetine against pentylenetetrazole (PTZ)-induced seizures in mice. Prior administration of GABA(A) receptor agonist muscimol or neurosteroid ALLO or progesterone, a precursor of ALLO or neurosteroidogenic drugs like FGIN 1-27, an agonist at the mitochondrial diazepam binding inhibitor receptor (MDR) or metyrapone, an 11beta-hydroxylase inhibitor, significantly potentiated the anticonvulsant effect of fluoxetine. In contrast, the effect of fluoxetine was counteracted by inhibition of the neurosteroid biosynthesis using drugs like 5alpha-reductase inhibitor, finasteride; 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane; 3alpha-hydroxysteroid dehydrogenase inhibitor, indomethacin; MDR antagonist, PK 11195; or the GABA(A) receptor antagonist, bicuculline. Further, bilateral adrenalectomy had no significant effect on the anticonvulsant action of fluoxetine, suggesting negligible contribution from peripheral steroidogenesis. The anticonvulsant effect of fluoxetine was partially abolished in 5,7-DHT treated mice, indicating that the effect may also, in part, be dependent on serotonergic transmission. Thus, our data indicate that increased synthesis of ALLO in CNS is a major factor that ultimately leads to anticonvulsant effects of fluoxetine against PTZ-induced seizures. PMID:15364024
Ugale, Rajesh Ramesh; Mittal, Nutan; Hirani, Khemraj; Chopde, Chandrabhan Tukaram
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) is associated in some kindreds with mutations in the genes encoding the alpha 4 or beta 2 subunits of the neuronal nicotinic acetylcholine receptor (nAChR). Functional characterisation of the described ADNFLE mutations in oocyte preparations has produced conflicting results, with some studies suggesting hypofunction but others showing increased ligand sensitivity or delayed desensitisation. Knockout mice were studied to investigate extreme hypofunction of alpha 4 nAChRs in vivo. Mutant (Mt) and control mice underwent epidural electroencephalographic (EEG) recording for 2 h in the untreated state and for 1 h following administration of the gamma-amino butyric acid (GABA) antagonist, pentylenetetrazole (PTZ, 80 mg/kg). No spontaneous seizures occurred and no EEG differences were observed between the genotypes in drug naïve mice. Following PTZ, however, Mt mice showed markedly increased mortality compared to controls (85 vs 30%, P<0.001). Mts also had a greater number of generalised clonic seizures in the first 40 min following injection. In the same period, the EEGs of Mt mice showed an excess of spikes (P=0.033), multi-spike complexes (P=0.002) and continuous fast activity (P=0.017) compared to controls. These findings demonstrate that intact alpha 4 nAChR subunits provide significant in vivo protection against the proconvulsant effects of GABA antagonism. PMID:12623222
McColl, C D; Horne, M K; Finkelstein, D I; Wong, J Y F; Berkovic, S F; Drago, J
A dynamical analogy supported by five scale-free statistics (the Gutenberg-Richter distribution of event sizes, the distribution of interevent intervals, the Omori and inverse Omori laws, and the conditional waiting time until the next event) is shown to exist between two classes of seizures (“focal” in humans and generalized in animals) and earthquakes. Increments in excitatory interneuronal coupling in animals expose the system’s dependence on this parameter and its dynamical transmutability: moderate increases lead to power-law behavior of seizure energy and interevent times, while marked ones to scale-free (power-law) coextensive with characteristic scales and events. The coextensivity of power law and characteristic size regimes is predicted by models of coupled heterogeneous threshold oscillators of relaxation and underscores the role of coupling strength in shaping the dynamics of these systems.
Osorio, Ivan; Frei, Mark G.; Sornette, Didier; Milton, John; Lai, Ying-Cheng
Early life exposure to opiates may affect neuropathological conditions, such as epilepsy, during adulthood. We investigated whether neonatal morphine exposure affects pentylenetetrazol (PTZ)-induced seizures in adulthood. Male rats were subcutaneously injected with morphine or saline on postnatal days 8-14. During adulthood, each rat was assigned to 1 of the following 10 sub-groups: saline, nicotine (0.1, 0.5, or 1??g), atropine (0.25 or 1??g), oxotremorine M (0.1 or 1??g), or mecamylamine (2 or 8??g). An intrahippocampal infusion of the indicated compound was administered 30?min before seizure induction (80mg/kg PTZ). Compared with the saline/oxotremorine (1??g), saline/saline, and morphine/saline groups, the morphine/oxotremorine (1??g) group showed a significantly increased latency to the first epileptic behavior. The duration of tonic-clonic seizures was significantly lower in the morphine/oxotremorine (1??g) group compared to the saline/saline and morphine/saline groups. The severity of seizure was significantly decreased in the morphine/atropine (1??g) group than in the saline/atropine (1??g). Seizure severity was also decreased in the morphine/mecamylamine (2??g) group than in the saline/mecamylamine (2??g) group. Latency for death was significantly lower in the morphine/mecamylamine (2??g) group compared with the saline/mecamylamine (2??g) group. Mortality rates in the morphine/atropine (1??g) and morphine/mecamylamine (2??g) groups were significantly lower than those in the saline/atropine (1??g) and saline/mecamylamine (2??g) groups, respectively. Chronic neonatal morphine administration attenuated PTZ-induced seizures, reduced the mortality rate, and decreased the impact of the hippocampal cholinergic system on seizures and mortality rate in adult rats. Neonatal morphine exposure induces changes to ?-receptors that may lead to activation of GABAergic neurons in the hippocampus. This pathway may explain the anti-convulsant effects of morphine observed in our study. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 9999: XX-XX, 2013. PMID:23775703
Saboory, Ehsan; Gholami, Morteza; Zare, Samad; Roshan-Milani, Shiva
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…
The present study examined the ovarian hormonal regulation of seizure susceptibility in prenatally morphine- and saline-exposed adult female rats in the flurothyl seizure model in vivo, and in low-magnesium-induced epileptiform activity in brain slices, in vitro. All females were ovariohysterectomized (OVX); some received either estrogen (E) or progesterone (P) replacement, while others were injected with E + P sequentially. In prenatally saline-treated control females, there was an increase in the flurothyl-induced clonic seizure threshold (anticonvulsant effect) in the presence of both hormones (E + P) compared to OVX controls. In morphine-exposed females, there was an increase in the flurothyl-induced clonic seizure threshold after an E injection alone while there was a reduced tonic--clonic seizure threshold in the presence of both hormones (E + P) compared to the hormone treatment-matched group of saline-exposed females. In control females, in low magnesium medium in vitro, the development of two types of epileptiform activity (seizure-like events and status of short discharges) was not affected by the different hormonal conditions. However, prenatal morphine exposure suppressed the development of both types of epileptiform activity in the E-injected females compared to the E-injected, control females. The present data demonstrate that the anticonvulsant effects of P on seizure susceptibility requires the presence of E. Furthermore, prenatal morphine exposure alters ovarian steroid hormone-regulated seizure susceptibility. PMID:9689475
Velísek, L; Velísková, J; Moshé, S L; Vathy, I
Presents a six-step model to help teachers develop curriculum related to the Fourth Amendment (search and seizure). The model focuses on determining values and attitudes, defining valid and unreasonable search and seizure, recognizing a valid warrant, and using film to teach about search and seizure. Journal available from the American Bar…
Kelly, Cynthia A.
Abstract—Current epileptic seizure “prediction” algorithms are generally based on the knowledge of seizure occurring time and analyze the electroencephalogram,(EEG) recordings retro- spectively. It is then obvious that, although these analyses provide evidence of brain activity changes prior to epileptic seizures, they cannot be applied to develop implantable devices for diagnostic and therapeutic purposes. In this paper, we describe an adaptive
Leon D. Iasemidis; Deng-Shan Shiau; Wanpracha Chaovalitwongse; J. Chris Sackellares; Panos M. Pardalos; Jose C. Principe; Paul R. Carney; Awadhesh Prasad; Balaji Veeramani; Konstantinos Tsakalis
Clinical reports have shown that some antihistamines, such as ketotifen, occasionally produced seizures, especially in pre-school age children or young patients with epilepsy. The purpose of this study was to investigate whether olopatadine, one of the most efficacious antihistamines, promotes seizures induced by electroshocks in young rats. We investigated the seizures induced by electroshock using increasing-current delivery in 3- or 4-week-old rats, and found that the threshold-current of tonic extensor seizures was elevated with age in weeks in the vehicle-treatment groups. While caffeine decreased the threshold-current in every age group of rats, pentylenetetrazole, a ?-aminobutyric acid (GABA)(A) receptor antagonist, significantly decreased them only in 4-week-old rats. On the other hand, ketotifen decreased them only in 3-weeks-old rats. In the 3-week-old rats, neither olopatadine nor fexofenadine had any effect on the threshold-currents of tonic extensor seizures. These results showed that histaminergic neuro-transmission in the brain plays a crucial role in inhibiting seizures in rats soon after weaning, but is no longer effective in rats as they approach sexual maturation. In addition, unlike ketotifen, olopatadine, as well as fexofenadine, do not promote the occurrence of seizures in infant rats. PMID:22687403
Yamada, Koji; Takizawa, Fumitake; Tamura, Tadafumi; Kanda, Tomoyuki
Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system.
Carney, Paul R.; Myers, Stephen; Geyer, James D.
This study compared psychiatric factors and diagnoses in patients with pseudoepileptic seizures and genuine seizures. A semistructured interview identified psychiatric diagnosis and the presence of psychiatric factors associated with conversion phenomena. Twenty-five subjects with medically refractory seizures were interviewed and followed prospectively until a definitive diagnosis of pseudoepileptic or genuine seizures was made by neurologists using video-EEG telemetry. Four factors help to identify patients with pseudoepileptic seizures: a psychiatric diagnosis of either somatization disorder or personality disorder, the presence of a childhood loss, or the presence of a model for seizure symptoms. These findings can aid clinicians in identifying patients who would benefit from referral to a video-EEG telemetry diagnostic unit. PMID:7950348
Eisendrath, S J; Valan, M N
Epileptic seizures are reported to occur frequently in Rett syndrome (RS). We evaluated the hypothesis that many events classified as seizures in RS represent other paroxysmal, non-epileptic events; thus, the overall incidence of seizures in RS is overestimated. We conducted video\\/polygraphic\\/EEG monitoring sessions (8–120 h duration) in 82 RS females (ages 2–30 years). Fifty-five patients (67%) had a history of
Daniel G Glaze; Rebecca J Schultz; James D Frost
Febrile seizures are the most common seizures in childhood. They have been observed in 2-5% of children before the age of 5, but in some populations this figure may increase to 15%. It is a common cause of pediatric hospital admissions and cause of anxiety for parents. Febrile seizures could be the first manifestation of epilepsy. About 13% of epileptic patients have a history of febrile seizure, and 30% have had recurrent febrile seizures. Their phenotypic characteristics allow, in the majority of cases, a classification of the seizure, an elaboration of a prognosis and to assume a specific therapeutic attitude. It is possible to describe a spectrum according to their severity, from the benign simple seizure to the more complex, febrile seizure plus, Dravet'syndrome, and FIRES. During the past decade, molecular genetic studies have contributed to the identification of genetic factors involved in febrile seizure and related disorders, making the necessity of a careful follow up of these patients in order to detect risk factors earlier. We have reviewed the medical literature to update current knowledge of febrile seizures, their prognosis and their relation to new epileptic syndromes. PMID:24072053
Moreno de Flagge, Noris
BACKGROUND First seizures are common, with one in 20 people suffering a seizure at some time in their life. OBJECTIVE 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. DISCUSSION Seizures are classified into generalised and partial (arising from a focal
Purpose: To investigate the seizure precipitants in children with intractable epilepsy, and to determine any distinctive clinical features contributing to seizures in these patients. Methods: A questionnaire and seizure diary prepared by the parents of the patients. Demographic and seizure data were reviewed. Results: Of 120 patients with intractable epilepsy, 74 (62%) had one (n=43), two (n=23), or three seizure
Peng-Cheng Fang; Yung-Jung Chen; Inn-Chi Lee
\\u000a Seizures are a nonspecific neurological manifestation of cerebral dysfunction and not indicative of any particular disease\\u000a processes or pathology. As such, the evaluation and treatment of seizures in transplant patients generally follow the same\\u000a clinical approach as for other patients. A seizure in a transplant patient is commonly unanticipated and entirely unexplained.\\u000a The effects can be substantial with aspiration, loss
Tarek Zakaria; Eelco F. M. Wijdicks; Greg A. Worrell
Hypersexual behavior was induced in adult male cats by repeatedly evoked limbic system seizures. Accentuation of Dopaminergic\\u000a activity with drugs was used to facilitate development of the seizure induced hypersexuality. Hypersexuality consisted of\\u000a biting knap of neck, mounting, thrusting and coital intromission. The gradual development and eventual disappearance of hypersexuality\\u000a was correlated with the progressive prolongation of the seizures in
O. J. Andy
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.
Iasemidis, Leon D.
This is a case study presented by the University of Pittsburgh Department of Pathology in which a 24-day-old baby is failing to thrive and experiencing seizures. Visitors are given the microscopic description, with images, the results of the postmortem examination, and are given the opportunity to diagnose the patient. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to use to introduce or test student learning in pediatric pathology.
Lyons, Valerie; Dickman, Paul S.
|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…
Shafer, Patricia Osborne; Israel, Beth
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…
Shafer, Patricia O.; Schachter, Steven C.
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…
Shafer, Patricia Osborne; Israel, Beth
Objective In patients with spontaneous intracerebral hemorrhage (ICH), the risk factors for seizure and the effect of prophylactic anticonvulsants are not well known. This study aimed to determine the risk factor for seizures and the role for prophylactic anticonvulsants after spontaneous ICH. Methods Between 2005 and 2010, 263 consecutive patients with spontaneous ICH were retrospectively assessed with a mean follow-up of 19.5 months using medical records, updated clinical information and, when necessary, direct patient contact. The seizures were classified as early (within 1 week of ICH) or late (more than 1 week after ICH). The outcomes were measured with the Glasgow Outcome Scale at discharge and the modified Rankin Scale (mRS) at both 2 weeks and discharge. Results Twenty-two patients (8.4%; 9 patients with early seizures and 13 patients with late seizures) developed seizures after spontaneous ICH. Out of 263 patients, prophylactic anticonvulsants were administered in 216 patients. The prophylactic anticonvulsants were not associated with a reduced risk of early (p=0.094) or late seizures (p=0.326). Instead, the factors associated with early seizure were cortical involvement (p<0.001) and younger age (60 years or less) (p=0.046). The risk of late seizure was increased by cortical involvement (p<0.001) and communicating hydrocephalus (p=0.004). The prophylactic anticonvulsants were associated with a worse mRS at 2 weeks (p=0.024) and at last follow-up (p=0.034). Conclusion Cortical involvement may be a factor for provoked seizures. Although the incidence of early seizures tended to decrease in patients prescribed prophylactic anticonvulsants, no statistical difference was found.
Woo, Kwang-Moo; Cho, Keun-Tae
Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). In this study, we show that GA inhibits Na+,K+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances-TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 micromol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na+,K+-ATPase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na+,K+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance ex vivo. In addition, GM1 (50-200 microM) protected against Na+,K+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 micromol/striatum) seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na+,K+-ATPase and GABA(A) receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1. PMID:16516483
Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider; Fiorenza, Natália Gindri; Frussa-Filho, Roberto; Petry, João Carlos; Coelho, Rafael Correa; Mello, Carlos Fernando
... OMIM Genetic disorder catalog Conditions > Benign familial neonatal seizures (often shortened to BFNS ) On this page: Description ... May 2011 What is BFNS? Benign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures ...
Endogenous cannabinoid ligands and cannabinoid CB1 receptor agonists have been shown to exert anticonvulsant effects in various experimental models of epilepsy. The purpose of this study was to determine the effects of arachidonyl-2'-chloroethylamide (ACEA-a highly selective cannabinoid CB1 receptor agonist) on the protective action of clonazepam, ethosuximide, phenobarbital, and valproate against pentylenetetrazole (PTZ)-induced clonic seizures in mice. To ascertain any pharmacokinetic contribution of ACEA to the observed interactions between tested drugs, free (non-protein bound) plasma and total brain concentrations of the antiepileptic drugs were estimated. Additionally, acute adverse-effect profiles of the combination of ACEA and different classical antiepileptic drugs (clonazepam, ethosuximide, phenobarbital and valproate) with respect to motor performance, long-term memory and skeletal muscular strength were measured. Results indicated that ACEA (10mg/kg, i.p.) co-administered with phenylmethylsulfonyl fluoride (PMSF-a substance protecting ACEA against degradation by the fatty-acid hydrolase; 30mg/kg, i.p.) significantly potentiated the anticonvulsant activity of ethosuximide, phenobarbital and valproate in the mouse PTZ-induced clonic seizure model by reducing their median effective doses (ED(50) values) from 122.8mg/kg to 71.7mg/kg (P<0.01; for ethosuximide), from 13.77mg/kg to 5.26mg/kg (P<0.05; for phenobarbital), and from 142.7mg/kg to 87.3mg/kg (P<0.05; for valproate), respectively. In contrast, ACEA (10mg/kg, i.p.) in combination with PMSF (30mg/kg, i.p.) had no impact on the protective action of clonazepam against PTZ-induced seizures in mice. However, ACEA (10mg/kg)+PMSF (30mg/kg) considerably increased free plasma and total brain concentrations of ethosuximide and valproate in mice suggesting a pharmacokinetic nature of interaction between drugs. In contrast, free plasma and total brain concentrations of clonazepam and phenobarbital remained unchanged after ACEA+PMSF administration and thus, indicating pharmacodynamic interactions. Moreover, none of the examined combinations of ACEA (10mg/kg, i.p.)+PMSF (30mg/kg, i.p.) with clonazepam, ethosuximide, phenobarbital, and valproate (at their ED(50) values from the PTZ-induced seizure test) affected motor coordination in the chimney test, long-term memory in the passive avoidance task, and muscular strength in the grip-strength test in mice, indicating no possible acute adverse effects in animals. In conclusion, pharmacodynamic enhancement of the anticonvulsant potency of phenobarbital by ACEA+PMSF is worthy of recommendation for further clinical settings. Pharmacokinetic interactions of ACEA+PMSF with ethosuximide and valproate seem to be responsible for a significant suppression of PTZ-induced seizures in mice. The combination of ACEA+PMSF with clonazepam seems to be neutral from a preclinical viewpoint. PMID:22789660
Andres-Mach, Marta; Zolkowska, Dorota; Barcicka-Klosowska, Beata; Haratym-Maj, Agnieszka; Florek-Luszczki, Magdalena; Luszczki, Jarogniew J
SUMMARY Neural stimulation can reduce the frequency of seizures in persons with epilepsy, but rates of seizure-free outcome are low. Vagus nerve stimulation prevents seizures by continuously activating noradrenergic projections from the brainstem to the cortex. Cortical norepinephrine then increases GABAergic transmission and increases seizure threshold. Another approach, responsive nervous stimulation, prevents seizures by reactively shocking the seizure onset zone in precise synchrony with seizure onset. The electrical shocks abort seizures before they can spread and manifest clinically. The goal of this study was to determine whether a hybrid platform in which brainstem activation triggered in response to impending seizure activity could prevent seizures. We chose the zebrafish as a model organism for this study because of its ability to recapitulate human disease, in conjunction with its innate capacity for tightly controlled high-throughput experimentation. We first set out to determine whether electrical stimulation of the zebrafish hindbrain could have an anticonvulsant effect. We found that pulse train electrical stimulation of the hindbrain significantly increased the latency to onset of pentylenetetrazole-induced seizures, and that this apparent anticonvulsant effect was blocked by noradrenergic antagonists, as is also the case with rodents and humans. We also found that the anticonvulsant effect of hindbrain stimulation could be potentiated by reactive triggering of single pulse electrical stimulations in response to impending seizure activity. Finally, we found that the rate of stimulation triggering was directly proportional to pentylenetetrazole concentration and that the stimulation rate was reduced by the anticonvulsant valproic acid and by larger stimulation currents. Taken as a whole, these results show that that the anticonvulsant effect of brainstem activation can be efficiently utilized by reactive triggering, which suggests that alternative stimulation paradigms for vagus nerve stimulation might be useful. Moreover, our results show that the zebrafish epilepsy model can be used to advance our understanding of neural stimulation in the treatment of epilepsy.
Pineda, Ricardo; Beattie, Christine E.; Hall, Charles W.
A previously non-epileptic 17-year-old patient presented with 2 generalized epileptic seizures, which occurred at 6 months of interval, following the oral intake of 200-250 mg of tramadol. Urine analysis showed only the product and its metabolites. Epileptic seizures induced by tramadol and high risk factors are described and discussed. PMID:14710027
Koussa, S; Rizk, T; Tohmé, A
\\u000a At the present time, the conventional management of seizures includes a trial of multiple medications, followed by consideration\\u000a of surgical ablation of part of the brain. Since seizures are related to paroxysmal depolarization shifts, more specific therapies\\u000a are possible. These include the use of electrical stimulation to the brain.
This case report describes a patient who developed a seizure with single-pulse transcranial magnetic stimulation during motor threshold estimation. The patient had no history of seizures in the past and no gross neurologic deficits. The only possible seizure-provoking factors were modest doses of lithium and chlorpromazine, which the patient was on, and family history of seizure in a brother. This report aims to highlight the fact that single-pulse transcranial magnetic stimulation may provoke a seizure even in the absence of gross neurologic abnormality. PMID:16127313
Tharayil, Biju Sunny; Gangadhar, B N; Thirthalli, Jagadisha; Anand, L
The substantia nigra pars reticulata (SNR) plays an important age- and sex-specific role in control of clonic seizures. Its involvement in control of tonic-clonic seizures is contradictory. We investigated the role of the SNR in the tonic-clonic seizures induced in male, female and neonatally castrated male rats using flurothyl. In adult female rats, vaginal impedance determined the changes in progesterone/estrogen ratio. Rats at various postnatal ages received infusions of muscimol or vehicle in the SNRanterior or SNRposterior. Furthermore, in 15-day-old (P15) and adult male rats, ZAPA (a GABA(A) receptor agonist) or AP7 (an NMDA receptor antagonist) was infused. The developmental profile of tonic-clonic seizure threshold differed between male and female rats possibly due to early postnatal testosterone surge in male rats. On the other hand, changing estrogen/progesterone ratio in cycling adult female rats had no effect on seizure threshold. Intranigral muscimol had proconvulsant effects on tonic-clonic seizures only in immature rats, and this effect was dependent on the perinatal testosterone surge. ZAPA had anticonvulsant effects in P15 rats but was not effective in adult rats. Only AP7 had anticonvulsant effects in both adult and P15 rats. Results indicate that thresholds for flurothyl-induced tonic-clonic seizures develop under the control of postnatal testosterone. Although GABAergic inhibition in the SNR affects tonic-clonic seizures in developing rats, only the NMDA antagonist had consistent anticonvulsant effects throughout development. PMID:16730708
Velísek, Libor; Velísková, Jana; Giorgi, Filippo S; Moshé, Solomon L
Vaccine administration is the second leading cause of febrile seizures (FS). FS occurrence in children is a serious concern because it leads to public apprehension of vaccinations. This review discusses the clinical implications of FS, its potential link to vaccinations and its impact on official recommendations for vaccinations in children. Vaccines such as the pertussis antigen-containing vaccine, the measles-containing vaccine and the influenza vaccine have been linked to FS. However, FS events are very rare and are not usually associated with downstream complications or severe neurologic diseases. Considering their significant health benefits, vaccinations have not been restricted in the pediatric population. Nevertheless, vaccine-induced FS could be a problem, particularly in genetically predisposed children. Therefore, post-marketing surveillance studies are required to accurately assess the incidence of FS and identify individuals who are particularly susceptible to FS after vaccination. PMID:23984960
Principi, Nicola; Esposito, Susanna
Bupropion is a relatively new and popular medication with seizures as its major side effect. This drug can produce seizures with an overdose. The purpose of this investigation was to determine the relative importance of this medication as the etiology of new-onset seizures relative to other drugs and new-onset seizures in general. The study design was a retrospective case series.
Gene R Pesola; Jagannadha Avasarala
Background Increasing evidence suggests seizures cause blood–brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. Methods Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3–15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood–brain barrier permeability. Results We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. Conclusions Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.
Treating patients with psychiatric problems can present numerous challenges for clinicians. The deliberate self-ingestion of antidepressants is one such challenge frequently encountered in hospitals throughout the United States. This review focuses on 1) the classes of antidepressants, their pharmacologic properties, and some of the proposed mechanism(s) for antidepressant overdose-induced seizures; 2) the evidence for seizures caused by antidepressants in overdose; 3) management strategies for patients who have intentionally or unintentionally overdosed on an antidepressant, or who have experienced an antidepressant overdose-induced seizure. PMID:23688690
Judge, Bryan S; Rentmeester, Landen L
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
Ayoubian, L; Lacoma, H; Gotman, J
Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.
Rodgers, Krista M.; Hutchinson, Mark R.; Northcutt, Alexis; Maier, Steven F.; Watkins, Linda R.
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 EE...
L. M. Hively N. E. Clapp C. S. Daw W. F. Lawkins M. L. Eisenstadt
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…
McBrien, Dianne M.; Bonthius, Daniel J.
The study objective was to assess the applicability and reliability of the semiological seizure classification in children with epilepsy in outpatient clinics. Ninety patients (age range, 2-16 years) who experienced clinical seizures during prolonged video-electroencephalogram (EEG) monitoring were evaluated. Semiological seizure classification was performed, first based on history obtained from parents of the patient during outpatient follow-up visits and then based on video EEG-monitoring. Kappa statistics (kappa) were used to evaluate the consistency of the two rounds of semiological seizure classification. Classification based on history yielded the following distribution: simple motor seizures (66.3%), aura (28%), complex motor seizures (15.8%), special seizures (15.8%), dialeptic seizures (9.3%), and autonomic seizures (3.7%). Classification based on video EEG-monitoring yielded a different distribution: simple motor seizures (55.7%), complex motor seizures (26.9%), automotor seizures (26.9%), aura (23%), dialeptic seizures (22.1%), special seizures (9.6%), and autonomic seizures (1.9%). Negative myoclonic seizures (kappa = 1, P = 0.000) and hypermotor seizures (kappa = 0.85, P = 0.000) had excellent consistency; somatosensory aura (kappa = 0.26, P = 0.012) and automotor seizures (kappa = 0.28, P = 0.004) had the lowest consistency. The families or doctors often defined simple motor seizures (decrease of 10.6% from before to after monitoring, kappa = 0.44); the proportion of complex motor seizures changed rather from before to after monitoring (11.1%, kappa = 0.33). Generally, parents can describe seizures quite well. We suggest that semiological seizure classification is a reliable method applicable for everyday use during outpatient visits, especially if seizure semiology is evaluated individually for each component or if the semiological seizure classification is modified or refined for some seizure components (tonic, clonic, versive, conscious, automotor seizures). PMID:17437905
Hirfanoglu, Tugba; Serdaroglu, Ayse; Cansu, Ali; Bilir, Erhan; Gucuyener, Kivilcim
Investigation of changes in the hippocampal EEG produced by GABAergic and cholinergic substances delivered into the medial septum region was performed in awake rabbits. Changes in the threshold of seizure discharges in the hippocampus evoked by perforant path stimulation (model of acute epilepsy) were also examined. Injections of GABAA receptor antagonist picrotoxin or agonist of cholinergic receptors carbacholine in low doses induced an increase in the power of delta- and theta modulation and appearance of 7-12-Hz oscillations. The threshold of hippocampal seizure afterdischarges decreased. In higher doses, these substances evoked 7-15-Hz oscillations followed by seizures. GABAA receptor agonist muscimol and muscarinic receptor antagonist scopolamine decreased the power of the theta rhythm and increased the seizure threshold. Picrotoxin or carbacholine injected after muscimol or scopolamine, respectively, did not evoke seizures. Thus, we have shown the possibility to control hippocampal activity by local changes in the GABAergic and cholinergic systems of the medial septum region. PMID:17432318
Kichigina, V F; Butuzova, M V; Sinel'nikova, V V
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
Timothy Spellman; Angel V Peterchev; Sarah H Lisanby
Assessment of treatment strategies in febrile seizures should be based on short- and long-term outcomes, with and without acute, intermittent, or chronic medical intervention, as well as short- and long-term side effects. Febrile seizures are a benign condition with a normal neurological, motor, intellectual, and cognitive long-term outcome and have a low risk of later epilepsy in most cases. Even
Finn Ursin Knudsen
Background Epilepsy is a chief communal health problem. Antiepileptic drugs only provide symptomatic treatment. Walnut Kernels (WK) have high concentrations of phenolic compounds, which have beneficial effects on human health because of their antioxidant and anti-atherogenic properties. The present study was designed to evaluate the efficacy of WK supplementation for the prevention of experimental epilepsy in male rats. Methods Wistar adult male rats were divided into three groups: a control group (PTZ injection, fed with ordinary food), experimental group (PTZ injection, fed with WK) and a sham group (no PTZ injection, only for histological studies). Pentylenetetrazole (PTZ) was administered after the prescribed time. Results WKs displayed anti-epileptogenic properties, and WK supplementation was associated with increased seizure threshold and reduced mortality in the experimental group versus controls. Conclusion Use of WK may be helpful in prevention of PTZ-induced seizure and its further neurodegeneration in male rats.
Asadi-Shekaari, Majid; Kalantaripour, Taj Pari; Nejad, Fatemeh Arab; Namazian, Elaheh; Eslami, Azam
Observability of a dynamical system requires an understanding of its state—the collective values of its variables. However, existing techniques are too limited to measure all but a small fraction of the physical variables and parameters of neuronal networks. We constructed models of the biophysical properties of neuronal membrane, synaptic, and microenvironment dynamics, and incorporated them into a model-based predictor-controller framework from modern control theory. We demonstrate that it is now possible to meaningfully estimate the dynamics of small neuronal networks using as few as a single measured variable. Specifically, we assimilate noisy membrane potential measurements from individual hippocampal neurons to reconstruct the dynamics of networks of these cells, their extracellular microenvironment, and the activities of different neuronal types during seizures. We use reconstruction to account for unmeasured parts of the neuronal system, relating micro-domain metabolic processes to cellular excitability, and validate the reconstruction of cellular dynamical interactions against actual measurements. Data assimilation, the fusing of measurement with computational models, has significant potential to improve the way we observe and understand brain dynamics.
Ullah, Ghanim; Schiff, Steven J.
This study investigated the anticonvulsant activity of a new phthalazine tetrazole derivative, QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), in the mouse maximal electroshock (MES) seizure model. The neurotoxicity of QUAN-0808 was investigated using the rotarod neurotoxicity test in mice. QUAN-0808 exhibited higher activity (median effective dose, ED(50) = 6.8 mg/kg) and lower neurotoxicity (median toxic dose, TD(50) = 456.4 mg/kg), resulting in a higher protective index (PI = 67.1) compared with carbamazepine (PI = 6.4). In addition, QUAN-0808 exhibited significant oral anticonvulsant activity (ED(50) = 24 mg/kg) against MES-induced seizure with low neurotoxicity (TD(50) > 4500 mg/kg) in mice, resulting in a PI value of more than 187.5. QUAN-0808 was also tested in chemically induced animal models of seizure (pentylenetetrazole [PTZ], isoniazid [ISO], thiosemicarbazide [THIO] and 3-mercaptopropionic acid [3-MP]) to further investigate the anticonvulsant activity; QUAN-0808 produced significant anticonvulsant activity against seizures induced by ISO, THIO and 3-MP. PMID:20508282
Sun, Xian-Yu; Wei, Cheng-Xi; Deng, Xian-Qing; Sun, Zhi-Gang; Quan, Zhe-Shan
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 findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT. PMID:19225453
Spellman, Timothy; Peterchev, Angel V; Lisanby, Sarah H
Seizure prediction has proven to be difficult in clinically realistic environments. Is it possible that fluctuations in cortical firing could influence the onset of seizures in an ictal zone? To test this, we have now used neural network simulations in a computational model of cortex having a total of 65,536 neurons with intercellular wiring patterned after histological data. A spatially distributed Poisson driven background input representing the activity of neighboring cortex affected 1% of the neurons. Gamma distributions were fit to the interbursting phase intervals, a non-parametric test for randomness was applied, and a dynamical systems analysis was performed to search for period-1 orbits in the intervals. The non-parametric analysis suggests that intervals are being drawn at random from their underlying joint distribution and the dynamical systems analysis is consistent with a nondeterministic dynamical interpretation of the generation of bursting phases. These results imply that in a region of cortex with abnormal connectivity analogous to a seizure focus, it is possible to initiate seizure activity with fluctuations of input from the surrounding cortical regions. These findings suggest one possibility for ictal generation from abnormal focal epileptic networks. This mechanism additionally could help explain the difficulty in predicting partial seizures in some patients. PMID:22169211
Anderson, William S; Azhar, Feraz; Kudela, Pawel; Bergey, Gregory K; Franaszczuk, Piotr J
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.
Friedman, Daniel; Honig, Lawrence S.; Scarmeas, Nikolaos
Martin Luther's diseases are well documented, because he used to discuss them freely in his letters. There is also a wealth of evidence through reports by his friends. Most of his diseases were common and well known to the contemporary physicians, who accordingly interpreted them correctly: bladder stones, chronic constipation, hemorrhoids. Luther's death obviously was due to a coronary thrombosis. During the last 19 years of his life, in addition to these "natural diseases", Luther also suffered from recurring attacks of a peculiar symptomatology. Luther himself and his friends considered these seizures to be no "natural disease", but Satan punching his flesh, and he compared them to St. Paul's disease (2. Cor. 12). The first of these attacks occurred on July 6, 1527, when Luther was 43 years of age. It began with a roaring tinnitus in his left ear, which increased dramatically and seemed to occupy the left half of his head. Then a state of sickness and collapse followed, however, consciousness was retained throughout the whole period. After a night's rest all the symptoms had subsided, except the tinnitus, which, from that day on, continued for all the following years in varying intensity. Similar attacks with increase of the tinnitus and vertigo as the leading symptoms, seized Luther at irregular intervals and distressed him extremely. Former investigators of Luther's diseases interpreted these attacks as manifestations of a psychiatric disorder and a chronic inflammatory disease of the middle ear. The present detailed study reveals that it was a typical case of Menière's disease of the left ear manifesting itself more than 330 years before Menière's classical observation. PMID:2529669
Combining the use of some antiepileptic drugs (AEDs) in patients with epilepsy can result in interactions of a pharmacodynamic or pharmacokinetic character. To quantify the profile of interactions between tiagabine (TGB) and gabapentin (GBP), two novel AEDs influencing the GABAergic neurotransmitter system, an isobolographic analysis was performed in the maximal electroshock seizure threshold (MEST), pentylenetetrazole (PTZ)-induced seizure and chimney tests
Jarogniew J. Luszczki; Stanislaw J. Czuczwar
In mammals, odorants are detected by a large family of receptors that are each expressed in just a small subset of olfactory sensory neurons (OSNs). Here we describe a strain of transgenic mice engineered to express an octanal receptor in almost all OSNs. Remarkably, octanal triggered a striking and involuntary phenotype in these animals, with passive exposure regularly inducing seizures. Octanal exposure invariably resulted in widespread activation of OSNs but interestingly seizures only occurred in 30–40% of trials. We hypothesized that this reflects the need for the olfactory system to filter strong but slowly-changing backgrounds from salient signals. Therefore we used an olfactometer to control octanal delivery and demonstrated suppression of responses whenever this odorant is delivered slowly. By contrast, rapid exposure of the mice to octanal induced seizure in every trial. Our results expose new details of olfactory processing and provide a robust and non-invasive platform for studying epilepsy.
Nguyen, Minh Q.; Ryba, Nicholas J. P.
In mammals, odorants are detected by a large family of receptors that are each expressed in just a small subset of olfactory sensory neurons (OSNs). Here we describe a strain of transgenic mice engineered to express an octanal receptor in almost all OSNs. Remarkably, octanal triggered a striking and involuntary phenotype in these animals, with passive exposure regularly inducing seizures. Octanal exposure invariably resulted in widespread activation of OSNs but interestingly seizures only occurred in 30-40% of trials. We hypothesized that this reflects the need for the olfactory system to filter strong but slowly-changing backgrounds from salient signals. Therefore we used an olfactometer to control octanal delivery and demonstrated suppression of responses whenever this odorant is delivered slowly. By contrast, rapid exposure of the mice to octanal induced seizure in every trial. Our results expose new details of olfactory processing and provide a robust and non-invasive platform for studying epilepsy. PMID:22848650
Nguyen, Minh Q; Ryba, Nicholas J P
Summary: The objective of the present work was to study cerebral energy metabolism at threshold levels of hypoxia, i.e., degrees of hypoxia that abolish cerebral electrical activity, in the “normal” and in the epileptic brain. Seizures were induced by intravenous bicuculline and cerebral oxygen availability was reduced by a combination of lowered Po2 and reduced blood pressure to give a
G. Blennow; B. Nilsson; B. K. Siesj
Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach
H. Honar; K. Riazi; H. Homayoun; H. Sadeghipour; N. Rashidi; M. R. Ebrahimkhani; N. Mirazi; A. R. Dehpour
...S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Seizures Â§ 162.21 Responsibility and authority for seizures. (a) Seizures by Customs...
Tramadol (Ultram) is a new analgesic agent with a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of neurotransmitter (serotonin, norepinephrine) re-uptake. Although it has proven to be a safe and effective agent for the control of pain, adverse effects can occur with its use. I report the occurrence of seizure activity after the inadvertent administration of 4 mg/kg of tramadol to a child. Previous reports of seizure activity after tramadol administration are reviewed and the treatment of this problem is discussed. PMID:9258310
Tobias, J D
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.
Johnson, Ashley N.; Sow, Daby; Biem, Alain
The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Departmen...
G. W. Bohnert L. Smith
Febrile seizures are the most common seizure type in young children. Whether they induce death of hippocampal and amyg- dala neurons and consequent limbic (temporal lobe) epilepsy has remained controversial, with conflicting data from prospec- tive and retrospective studies. Using an appropriate-age rat model of febrile seizures, we investigated the acute and chronic effects of hyperthermic seizures on neuronal integrity
Zsolt Toth; Xiao-Xin Yan; Suzie Haftoglou; Charles E. Ribak; Tallie Z. Baram
Background and Purpose: Though there have been many reports on poststroke seizures, there is still much we do not know about them. Using a large cohort of stroke patients we analyzed the characteristics of the seizure(s) and the rate and factors involved in seizure recurrence. Methods: Out of the 3,205 patients admitted for a first-ever stroke to our department between
Sophie Berges; Thierry Moulin; Eric Berger; Laurent Tatu; Denis Sablot; Bruno Challier; Lucien Rumbach
The theory is discussed of presently available threshold logic circuits, and an analysis of threshold functions is presented. An operational threshold gate adding circuit in TTL technology is described, and the difficulty of improving logic in complex cir...
C. Vader J. W. M. Wasser
The program represents the second phase in the Development of MOS threshold logic. Studies were made previously, indicating the limitations and applications of MOS threshold gates. Now, threshold gates were integrated for use in parallel array multipliers...
D. Hampel K. J. Prost N. Scheinberg
This Survey is designed to assist lawyers and judges who must argue and resolve search and seizure issues in Washington State. The Survey summarizes the controlling state and federal cases on search and seizure law and uses as an additional reference W. LAFAVE, Search and Seizure: A Treatise on the Fourth Amendment (1978). Washington courts are likely to analyze future
Justice Robert F. Utter
|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…
Hollingsworth, Jan Carter
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…
Hollingsworth, Jan Carter
Patients with partial seizures aged 1 week to 19 years (n = 175) were included in several prospective vigabatrin studies at the hospital Saint Vincent de Paul. A decrease in seizure frequency of over 50% was achieved in 70% of patients, with 30% becoming seizure free, and only 6% experiencing an increase. Tuberous sclerosis gave the best response (85%), tumors
Rima C. Nabbout; Catherine Chiron; John Mumford; Caroline Dumas; Olivier Dulac
Dogs with spontaneous occurring epilepsy with partial seizures express symptomatology resembling what is found in humans with partial epileptic seizures. Questionnaires on clinical signs from 70 dogs, with a confirmed diagnosis of epilepsy with partial seizures with or without secondary generalization, were reviewed in order to characterize and classify clinical signs of partial seizure activity in dogs and compare them to partial seizure phenomenology in humans. Signs of partial seizure activity were distributed into three categories: motor signs, autonomic signs and paroxysms of behavioral signs. Motor signs were described in 48 dogs (69%), autonomic signs in 16 dogs (23%) and paroxysms of behavioral signs in 56 dogs (80%). The majority of dogs expressed signs from more than one group. Sixty-one dogs (87%) had partial seizures with secondary generalization. Nine dogs (13%) had partial seizures without secondary generalization. The study shows a remarkable resemblance between the seizure phenomenology expressed in humans and canines with partial epileptic seizures. PMID:15451018
Berendt, M; Gredal, H; Alving, J
Zolpidem is an imidazopiridine with hypnotic properties. Compared to benzodiazepines, zolpidem has a mechanism of action that is thought to reduce the risk of dependence or abuse. However, in the past 10 years, several cases of zolpidem abuse, dependence and withdrawal reactions have been described in the litterature. Here, we describe a case of dependence and withdrawal seizure. PMID:19777922
Pitchot, W; Ansseau, M
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.
Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh
Temporal lobe seizures in humans correlate with stereotyped electrophysiological patterns that can be reproduced in animal models to study the cellular and network changes responsible for ictogenesis. Seizure-like discharges that mimic seizure patterns in humans were induced in the entorhinal cortex of the in vitro isolated guinea pig brain by 3-min arterial applications of the GABA(A) receptor antagonist bicuculline. The onset of seizure is characterized by a paradoxical interruption of firing for several seconds in principal neurons coupled with both enhanced interneuronal firing and increased extracellular potassium (Gnatkovsky et al. 2008). The evolution of action potential features from firing break to excessive and synchronous activity associated with the progression of seizure itself is analyzed here. We utilized phase plot analysis to characterize action potential features of entorhinal cortex neurons in different phases of a seizure. Compared with preictal action potentials, resumed spikes in layer II-III neurons (n = 17) during the early phase of the seizure-like discharge displayed 1) depolarized threshold, 2) lower peak amplitude, 3) depolarized voltage of repolarization and 4) decelerated depolarizing phase, and 5) spike doublettes. Action potentials in deep-layer principal cells (n = 8) during seizure did not show the marked feature changes observed in superficial layer neurons. Action potential reappearance correlated with an increase in extracellular potassium. High-threshold, slow-action potentials similar to those observed in the irregular firing phase of a seizure were reproduced in layer II-III neurons by direct cortical application of a highly concentrated potassium solution (12-24 mM). We propose that the generation of possibly nonsomatic action potentials by increased extracellular potassium represents a crucial step toward reestablish firing after an initial depression in an acute model of temporal lobe seizures. Resumed firing reengages principal neurons into seizure discharge and promotes the transition toward the synchronized burst firing that characterizes the late phase of a seizure. PMID:21676935
Trombin, Federica; Gnatkovsky, Vadym; de Curtis, Marco
It is agreed that 1% of the general population is afflicted with epilepsy and close to 30% of epilepsy patients are intractable to medications. In spite of a recent increase in the number of new medications that are available on the market, many patients continue to have seizures or their seizures are controlled at the expense of intolerable side effects. Resection epilepsy surgery is an alternative; however, not every intractable patient is a good candidate for this surgery. Additionally, it is only offered to a small fraction of these patients due to the lack of an adequate number of comprehensive epilepsy programs and financial support for such surgeries. Vagus nerve stimulation (VNS) is a novel adjunctive therapy that has recently become commercially available for intractable epilepsy. It is indicated as an add-on treatment for seizures of partial onset with or without secondary generalization in patients 12 years of age or older. The VNS system is comprised of a battery generator that delivers regular intermittent electrical stimuli programmed via menu-driven software and an interrogating wand. The generator is implanted in the left upper chest and connected to the left cervical vagus nerve via a pair of semi-circular helical electrodes wound around the vagus nerve and wires tunneled under the skin. Surgery is normally completed within 2 h under general anesthesia and the patient can go home within a few hours postoperatively. Experiments in humans began in 1988 with two single-blind pilot studies that demonstrated the feasibility and safety of this unconventional therapy. Following these studies, two multicenter, active-control, parallel, double-blind protocols showed a statistically significant reduction in partial onset seizures with reasonable and well-tolerated side effects. Adverse events related to VNS included voice alteration and a tingling sensation in the throat during stimulation only and a decrease in intensity over several weeks. Coughing during stimulation occurred normally when therapy was initiated and shortness of breath occurred mainly during exertion. Long-term follow-up suggests that reduction in seizure frequency and intensity is maintained over time. VNS is a novel adjunctive anti-epilepsy therapy that offers patients a better-tolerated option than medications in general and that is less invasive and extensive than resection surgery. Its efficacy may compare to novel potent anti-epilepsy drugs; however, VNS does not replace resection epilepsy surgery in selected patients in whom chances of seizure-free results are high (70-90%). PMID:11036181
Uthman, B M
Febrile seizures occurring during childhood have been shown to interfere with the development of cognitive functions. However, an alteration of the developing sensory systems might also result from febrile seizures. In order to test this hypothesis, seizures were induced by hyperthermia in Long Evans rats on postnatal day 10. Extracellular single neuron recordings were carried out from postnatal days 15 to 30 and at adulthood. The response of neurons in the primary visual cortex to drifting sinusoidal gratings was recorded in anaesthetized rats. As soon as postnatal day 15, the neurons of rats having experienced a hyperthermic seizure showed significantly lower optimal spatial frequencies (SF), broader directional and temporal bandwidths, as well as higher contrast thresholds than did neurons recorded in normal rats. At adulthood, significantly broader spatial bandwidths and lower optimal temporal frequencies (TF) were obtained from neurons of rats subjected to hyperthermia. These results suggest that febrile seizures during infancy could affect the development of spatio-temporal receptive field properties of neurons in primary visual cortex. Such alterations of a sensory system might contribute to the cognitive deficits associated with early-onset febrile seizures. PMID:20955763
Prévost, F; Costa, M; Carmant, L; Lepore, F; Guillemot, J-P
Peroxisomes are organelles responsible for multiple metabolic pathways including the biosynthesis of plasmalogens and the oxidation of branched-chain as well as very-long-chain fatty acids (VLCFAs). Peroxisomal disorders (PDs) are heterogeneous groups of diseases and affect many organs with varying degrees of involvement. Even pathogenetically distinct PDs share some common symptoms. However, several PDs have uniquely characteristic clinical findings. The durations of survival in PDs are also variable. Infants with PDs are usually presented with developmental delay, visual and hearing impairment. Generalized hypotonia is present in severe cases. Epileptic seizures are also a common characteristic of patients with certain PDs. Nonetheless, the classification and evolution of epilepsy in PDs have not been elucidated in detail. Here, we review the relevant literatures and provide an overview of PDs with particular emphasis on the characteristics of seizures in infants. PMID:21397417
Liang, Jao-Shwann; Lu, Jyh-Feng
Neurons respond to numerous factors in their environment that influence their survival and function during development and in the mature brain. Among these factors, the neurotrophins have been shown to support neuronal survival and function, acting primarily through the Trk family of receptor tyrosine kinases. However, recent studies have established that the uncleaved neurotrophin precursors, the proneurotrophins, can be secreted and induce apoptosis via the p75 neurotrophin receptor, suggesting that the balance of secreted mature and proneurotrophins has a critical impact on neuronal survival or death. Epileptic seizures elicit increases in both proneurotrophin secretion and p75NTR expression, shifting the balance of these factors toward signaling cell death. This review will discuss the evidence that this ligand-receptor system plays an important role in neuronal loss following seizures.
Friedman, Wilma J.
The potential role of genetic factors in the etiology of posttraumatic and alcohol-associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first-degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcohol-associated seizures had a rate ratio of 2.45 [95% confidence interval (CI) 1.41-4.25], whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64-2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92-3.20 CI). Among probands with alcohol-associated seizures, the rate ratio of 2.05 for patients with alcohol-related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcohol-related seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures. PMID:8112257
Schaumann, B A; Annegers, J F; Johnson, S B; Moore, K J; Lubozynski, M F; Salinsky, M C
Background Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. Methodology/Principal Findings By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. Conclusion/Significance Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy.
Balseanu, Adrian Tudor; Pop, Oltin Tiberiu; Streba, Costin; Toescu, Emil; Popa-Wagner, Aurel
We present the concept of threshold collaborative unitary transformation or threshold quantum cryptography, which is a kind of quantum version of threshold cryptography. Threshold quantum cryptography states that classical shared secrets are distributed to several parties and a subset of them, whose number is greater than a threshold, collaborates to compute a quantum cryptographic function, while keeping each share secretly inside each party. The shared secrets are reusable if no cheating is detected. As a concrete example of this concept, we show a distributed protocol (with threshold) of conjugate coding.
Tokunaga, Yuuki [NTT Information Sharing Platform Laboratories, NTT Corporation, 1-1 Hikari-no-oka, Yokosuka, Kanagawa 239-0847 (Japan); Division of Materials Physics, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531 (Japan); Okamoto, Tatsuaki [NTT Information Sharing Platform Laboratories, NTT Corporation, 1-1 Hikari-no-oka, Yokosuka, Kanagawa 239-0847 (Japan); Imoto, Nobuyuki [Division of Materials Physics, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531 (Japan)
Supplementary motor area seizures may present with bilateral tonic-clonic movements with no loss of consciousness and no postictal confusion, and patients may be erroneously thought to have psychogenic nonepileptic seizures. We describe the rapid emergence of alpha activity in the immediate postictal period in patients with supplementary motor area seizures as an additional confounding factor that may lead to the erroneous diagnosis of nonepileptic seizures in these patients. We present two cases of patients with intractable supplementary motor area seizures investigated with video/EEG monitoring. Their postictal EEG records revealed an immediate postictal recovery of alpha activity, mimicking the pattern seen with psychogenic nonepileptic seizures. Prolonged video/EEG monitoring is mandatory in establishing the diagnosis of supplementary motor area seizures and in distinguishing this condition from nonepileptic seizures. PMID:20537596
Adamolekun, Bola; Foreman, Adam
Seizures consisting of a tonic followed by a clonic phase have rarely been described in neonates and are not included in the current classifications of neonatal seizures. Our video archive of 105 neonates with seizures or suspected seizures revealed six neonates with such tonic clonic or tonic myoclonic sequences. Two of those neonates had pyridoxine dependent seizures. The other four
Bernhard Schmitt; Gabriele Wohlrab; Thomas Sander; Ortrud K. Steinlein; Beatrice Latal Hajnal
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…
O'Dell, Christine; O'Hara, Kathryn; Kiel, Sarah; McCullough, Kathleen
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.
Zaveri, Hitten P.; Frei, Mark G.; Arthurs, Susan; Osorio, Ivan
Febrile seizures are the most common form of childhood seizures, affecting 2–5% of all children and usually appearing between\\u000a 3 months and 5 years of age. Despite its predominantly benign nature, a febrile seizure (FS) is a terrifying experience for\\u000a most parents. The condition is perhaps one of the most prevalent causes of admittance to pediatric emergency wards worldwide.\\u000a FS, defined as
The association between seizures and blood pressure elevation remains a common medical emergency encountered in the setting\\u000a of an intensive care unit. Syndromes such as preeclampsia or eclampsia, hypertensive encephalopathy, and posterior leukoencephalopathy\\u000a commonly present with seizures. The primary treatment goal is to reduce the arterial blood pressure. In most cases, seizure\\u000a control is thus achieved, but unique medications, such
Errol Gordon; Michel T. Torbey
Pallister-Killian syndrome (PKS) is a congenital disorder attributed to supernumerary isochromosome 12p mosaicism. Craniofacial dysmorphism, learning impairment and seizures are considered cardinal features. However, little is known regarding the seizure and epilepsy patterns in PKS. To better define the prevalence and spectrum of seizures in PKS, we studied 51 patients (39 male, 12 female; median age 4 years and 9 months; age range 7 months to 31 years) with confirmed 12p tetrasomy. Using a parent-based structured questionnaire, we collected data regarding seizure onset, frequency, timing, semiology, and medication therapy. Patients were recruited through our practice, at PKS Kids family events, and via the PKS Kids website. Epilepsy occurred in 27 (53%) with 23 (85%) of those with seizures having seizure onset prior to 3.5 years of age. Mean age at seizure onset was 2 years and 4 months. The most common seizure types were myoclonic (15/27, 56%), generalized convulsions (13/27, 48%), and clustered tonic spasms (similar to infantile spasms; 8/27, 30%). Thirteen of 27 patients with seizures (48%) had more than one seizure type with 26 out of 27 (96%) ever having taken antiepileptic medications. Nineteen of 27 (70%) continued to have seizures and 17/27 (63%) remained on antiepileptic medication. The most commonly used medications were: levetiracetam (10/27, 37%), valproic acid (10/27, 37%), and topiramate (9/27, 33%) with levetiracetam felt to be "most helpful" by parents (6/27, 22%). Further exploration of seizure timing, in-depth analysis of EEG recordings, and collection of MRI data to rule out confounding factors is warranted. PMID:23169688
Candee, Meghan S; Carey, John C; Krantz, Ian D; Filloux, Francis M
Theoretically, gene therapy techniques offer an attractive alternative treatment option for intractable, focal epilepsies. Although logical gene therapy targets include excitatory and inhibitory receptors, variable viral vector tropism interjects an uncertainty as to the direction of change, seizure suppression, or seizure sensitization. To circumvent this therapeutic liability, adeno-associated virus (AAV) vectors have been constructed where the gene product is constitutively secreted from the transduced cell. Using AAV vectors, the fibronectin secretory signal sequence (FIB) was placed in front of the coding sequence for green fluorescent protein or the active portion of the neuroactive peptide galanin (GAL). Subsequent studies showed that these vectors supported expression and constitutive secretion of these gene products from transfected cells in vitro. More importantly, upon transduction in vivo, AAV-FIB-GAL vectors significantly attenuated focal seizure sensitivity, and this seizure attenuation could be controlled in vivo by using a tetracycline-regulated promoter. The expression and constitutive secretion of green fluorescent protein, or the expression of GAL alone, exerted no effect on focal seizure sensitivity. Moreover, unilateral infusion of the AAV-FIB-GAL vectors into the hippocampus prevented kainic acid-induced hilar cell death. With regard to limbic seizures, bilateral infusion of AAV-FIB-GAL vectors into the piriform cortex prevented both behavioral and localized electrographic seizure activity after the peripheral administration of kainic acid. Also, when rats were electrically kindled to class V seizure activity, subsequent infusion of AAV-FIB-GAL proved capable of significantly elevating the seizure initiation threshold. Thus, these studies clearly demonstrate the anti-seizure effectiveness of AAV vector-mediated expression and constitutive secretion of galanin. PMID:19332324
McCown, Thomas J
This study addressed some of the controversial issues surrounding the anticonvulsant effect of phenytoin, and the predictive validity of the guinea-pig kindling model for the screening of anticonvulsant drugs. Following an intraperitoneal injection of either 50 or 75 mg/kg phenytoin, we analysed plasma concentrations of phenytoin at various time intervals. Behavioural toxicity was assessed at 0.5 h postinjection using quantitative locomotor tests, as well as scores on a sedation/muscle relaxation rating index. The anticonvulsant efficacy of phenytoin was evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD) and behavioural seizure severity at three phases of kindling: non-kindled, kindling acquisition (early and late) and kindled (50+ ADs). ADD and seizure severity were also measured in response to both threshold and suprathreshold kindling stimulation. Plasma levels of phenytoin corresponded to the human therapeutic range at the time of behavioural testing and kindling. Phenytoin did not exert significant adverse effects in guinea-pigs on both the behavioural tests and rating index. Phenytoin increased ADT in non-kindled and kindled guinea-pigs and effectively reduced ADD and seizure severity, indicating that the guinea-pig model correctly predicted phenytoin's anticonvulsant effect. Phenytoin produced reliable anticonvulsant activity in the guinea-pig at threshold stimulation but a somewhat reduced efficacy on seizure severity at suprathreshold stimulation intensities. Kindling in the guinea-pig is a valid model of human partial seizures. PMID:11685400
Gilbert, T H; Bharadia, V; Teskey, G C
Intellectual disability occurs as an isolated X-linked trait and as a component of recognizable X-linked syndromes in the company of somatic, metabolic, neuromuscular, or behavioral abnormalities. Seizures accompany intellectual disability in almost half of these X-linked disorders. The spectrum of seizures found in the X-linked intellectual disability syndromes is broad, varying in time of onset, type of seizure, and response to anticonvulsant therapy. The majority of the genes associated with XLID and seizures have now been identified.
Stevenson, Roger E.; Holden, Kenton R.; Rogers, R. Curtis; Schwartz, Charles E.
Studies of febrile seizures have been driven by two major enigmas: first, how these most common of human seizures are generated by fever has not been known. Second, epidemiological studies have linked prolonged febrile seizures with the development of temporal lobe epilepsy, yet whether long or recurrent febrile seizures cause temporal lobe epilepsy has remained unresolved. To investigate these questions, a model of prolonged (complex) febrile seizures was developed in immature rats and mice, permitting mechanistic examination of the potential causal relationships of fever and seizures, and of febrile seizures and limbic epilepsy. Although the model relied on hyperthermia, it was discovered that the hyperthermia-induced secretion of endogenous fever mediators including interleukin-1beta, which contributed to the generation of these 'febrile' seizures. In addition, prolonged experimental febrile seizures provoked epilepsy in a third of the animals. Investigations of the mechanisms of this epileptogenesis demonstrated that expression of specific ion (HCN) channels and of endocannabinoid signaling, may be involved. These may provide novel drug targets for intervention in the epileptogenic process. PMID:19232478
Dubé, Céline M; Brewster, Amy L; Baram, Tallie Z
While the majority of children with febrile seizures have an excellent prognosis, a small percentage are later discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures. PMID:19000675
Dubé, Céline M; Zhou, Jun-Li; Hamamura, Mark; Zhao, Qian; Ring, Alex; Abrahams, Jennifer; McIntyre, Katherine; Nalcioglu, Orhan; Shatskih, Tatiana; Baram, Tallie Z; Holmes, Gregory L
Flumazenil is a new drug indicated for the reversal of the sedative effects of benzodiazepines mediated at the benzodiazepine-receptor site. Worldwide sources to date have disclosed 43 cases of seizures related, at least temporally, to the intravenous administration of flumazenil. There was no apparent relationship between the dose of flumazenil and the development of seizures, which occurred at doses ranging from 0.2 to 10.0 mg. The seizures were not considered to be a toxic effect of flumazenil, but many of them probably were due to an unmasking of the anticonvulsant effect of the previously used benzodiazepine or to a severe benzodiazepine-withdrawal syndrome. Eighteen (42%) of the patients had ingested overdoses of cyclic antidepressants, which were considered responsible for the seizures. In addition to patients with concurrent cyclic antidepressant poisoning, high-risk populations include patients who have been treated with benzodiazepines for a seizure disorder or an acute convulsive episode, patients with concurrent major sedative-hypnotic drug withdrawal, patients who have recently been treated with repeated doses of parenteral benzodiazepines, and overdose patients with myoclonic jerking or seizure activity before flumazenil administration. To minimize the likelihood of a seizure, it is recommended that flumazenil not be administered to patients who have used benzodiazepines for the treatment of seizure disorders or to patients who have ingested drugs (eg, cyclic antidepressants, cocaine, lithium, methylxanthines, isoniazid, propoxyphene, monoamine oxidase inhibitors, buproprion HCl, and cyclosporine) that place them at risk for the development of seizures. PMID:1611650
Spivey, W H
Fever can provoke "febrile" seizures (FS). Because complex FS may promote development of temporal lobe epilepsy, understanding their mechanisms is clinically important. Using an immature rodent model and transgenic technology, we examined the role of interleukin-1beta, (IL-1beta), a pyrogenic, proinflammatory cytokine, in FS. IL-1beta receptor-deficient mice were resistant to experimental FS. This resistance appeared independent of genetic background and was attributed to lack of IL-1beta signaling, because exogenous cytokine reduced seizure threshold in wild-type but not receptor-deficient mice independent of strain. In addition, high IL-1beta doses induced seizures only in IL-1beta receptor-expressing mice. These data indicate that IL-1beta signaling contributes critically to fever-induced hyperexcitability underlying FS, constituting a potential target for their prevention. PMID:15622539
Dubé, Celine; Vezzani, Annamaria; Behrens, Marga; Bartfai, Tamas; Baram, Tallie Z
Supplementary motor area seizures may present with bilateral tonic–clonic movements with no loss of consciousness and no postictal confusion, and patients may be erroneously thought to have psychogenic nonepileptic seizures. We describe the rapid emergence of alpha activity in the immediate postictal period in patients with supplementary motor area seizures as an additional confounding factor that may lead to the
Bola Adamolekun; Adam Foreman
An automatic threshold circuit to establish a threshold that is a specified number of db above the input's rms frequency weighted noise value is described. The input is compared with the feedback threshold value, the result of which is coupled to a limite...
J. H. Bumgardner
|Threshold concepts can be identified for any discipline and provide a framework for linking student learning to curricular design. Threshold concepts represent a transformed understanding of a discipline, without which the learner cannot progress and are therefore pivotal in learning in a discipline. Although threshold concepts have been…
Osteogenesis imperfecta (OI) is a group of hereditary disorders most often due to an anomaly of collagen biosynthesis. Divers clinical manifestations are reported. Neurological manifestations are exceptional. A 40-year-old man with a history of multiple bone fractures was admitted for a generalized tonic-clonic seizure. There was no metabolic disorder, the patient however complained of bilateral shoulder pain. Standard radiography and shoulder MRI revealed bilateral humeral fractures. The electroencephalogram and the brain MRI showed no abnormalities. He was given valproate acid and eight months later was free of crises. Search for an etiological favored the diagnosis of Lobstein disease. PMID:17878811
Boughammoura-Bouatay, A; Chebel, S; Aissi, M; Koubaa, M; Frih-Ayed, M
Seizurogenic chemicals include a variety of toxic agents, including chemical warfare agents, toxic industrial chemicals, and natural toxins. Chemical weapons such as sarin and VX, and pesticides such as parathion and carbaryl cause hyperstimulation of cholinergic receptors and an increase in excitatory neurotransmission. Glutamatergic hyperstimulation can occur after exposure to excitatory amino acid toxins such as the marine toxin domoic acid. Other pesticides such as lindane and strychnine do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory GABA and glycine synapses. In this paper, chemicals that cause seizures by a variety of molecular mechanisms and pathways are discussed. PMID:23085523
Jett, David A
Recent research in seizure anticipation has shown that 'pre-seizure states' can he detected several minutes in advance from analysis of EEG time series. This time frame would allow development and testing of specific seizure prevention techniques. Thus, t...
...Part 233 Inspection Service Authority; Seizure and Forfeiture AGENCY: Postal Service...Service's rules and regulations regarding the seizure and forfeiture of property from four sections...governing practical issues regarding the seizure, custody, inventory, appraisal,...
The circadian pattern of seizures in people with epilepsy (PWE) was first described two millennia ago. However, these phenomena have not received enough scientific attention, possibly due to the lack of promising hypotheses to address the interaction between seizure generation and a physiological clock. To propose testable hypotheses at the molecular level, interactions between circadian rhythm, especially transcription factors governing clock genes expression, and the mTOR (mammalian target of rapamycin) signaling pathway, the major signaling pathway in epilepsy, will be reviewed. Then, two closely related hypotheses will be proposed: (1) Rhythmic activity of hyperactivated mTOR signaling molecules results in rhythmic increases in neuronal excitability. These rhythmic increases in excitability periodically exceed the seizure threshold, displaying the behavioral seizures. (2) Oscillation of neuronal excitability in SCN modulates the rhythmic excitability in the hippocampus through subiculum via long-range projections. Findings from published results, their implications, and proposals for new experiments will be discussed. These attempts may ignite further discussion on what we still need to learn about the rhythmicity of spontaneous seizures.
A Matlab®-based software package, EPILAB, was developed for supporting researchers in performing studies on the prediction of epileptic seizures. It provides an intuitive and convenient graphical user interface. Fundamental concepts that are crucial for epileptic seizure prediction studies were implemented. This includes, for example, the development and statistical validation of prediction methodologies in long-term continuous recordings. Seizure prediction is usually based on electroencephalography (EEG) and electrocardiography (ECG) signals. EPILAB is able to process both EEG and ECG data stored in different formats. More than 35 time and frequency domain measures (features) can be extracted based on univariate and multivariate data analysis. These features can be post-processed and used for prediction purposes. The predictions may be conducted based on optimized thresholds or by applying classifications methods such as artificial neural networks, cellular neuronal networks, and support vector machines. EPILAB proved to be an efficient tool for seizure prediction, and aims to be a way to communicate, evaluate, and compare results and data among the seizure prediction community. PMID:21763347
Teixeira, C A; Direito, B; Feldwisch-Drentrup, H; Valderrama, M; Costa, R P; Alvarado-Rojas, C; Nikolopoulos, S; Le Van Quyen, M; Timmer, J; Schelter, B; Dourado, A
Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracranial EEG (iEEG) to distinguish nonictal versus ictal states; (ii) modeling the dynamics of these statistics in each state and the state transitions; you can remove this word if there is no room. (iii) developing an optimal control-based “quickest detection” (QD) strategy to estimate the transition times from nonictal to ictal states from sequential iEEG measurements. The QD strategy minimizes a cost function of detection delay and false positive probability. The solution is a threshold that non-monotonically decreases over time and avoids responding to rare events that normally trigger false positives. We applied QD to four drug resistant epileptic patients (168 hour continuous recordings, 26–44 electrodes, 33 seizures) and achieved 100% sensitivity with low false positive rates (0.16 false positive/hour). This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.
Santaniello, Sabato; Burns, Samuel P.; Golby, Alexandra J.; Singer, Jedediah M.; Anderson, William S.; Sarma, Sridevi V.
Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracranial EEG (iEEG) to distinguish nonictal versus ictal states; (ii) modeling the dynamics of these statistics in each state and the state transitions; you can remove this word if there is no room. (iii) developing an optimal control-based "quickest detection" (QD) strategy to estimate the transition times from nonictal to ictal states from sequential iEEG measurements. The QD strategy minimizes a cost function of detection delay and false positive probability. The solution is a threshold that non-monotonically decreases over time and avoids responding to rare events that normally trigger false positives. We applied QD to four drug resistant epileptic patients (168 hour continuous recordings, 26-44 electrodes, 33 seizures) and achieved 100% sensitivity with low false positive rates (0.16 false positive/hour). This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID:22078519
Santaniello, Sabato; Burns, Samuel P; Golby, Alexandra J; Singer, Jedediah M; Anderson, William S; Sarma, Sridevi V
(Full text is available at http://www.manu.edu.mk/prilozi). Seizures have been reported with tramadol monotherapy in animal and human studies, both at recommended and high doses. After tramadol abuse or overdose, neurotoxicity is speculated to be related to the reuptake inhibition of serotonin and norepinephrine, rather than its opioid effects. THE AIM OF THIS STUDY is to show three unusual cases of seizures provoked by tramadol. Case reports: A 56 year-old female was hospitalized with intensive lumbosacral pain. Because the standard therapy with non steroid anti-inflammatory drugs and diazepam did not show enough pain release, Tramadol ampoules were applied. Fifteen minutes later generalized tonic clonic seizure was noticed. A 24 year-old female was admitted to the Toxicology Clinic, one hour after ingestion of 1000 mg Tramadol (20 pills of 50 mg) in a suicide attempt. Five hours later generalized tonic clonic seizure was noticed. A 27 year-old male was hospitalized for detoxification procedure with bup-renorphine. The patient was a more than four years heroin abuser, and in the last two years he mixed the heroin with high doses of tramadol. 16 hours later, after application of the first 2 mg of Buprenorphine, generalized tonic clonic seizure was noticed. Conclusion: Tramadol prescription, use and abuse are connected with the risk of developing seizures. The neurotoxicity of tramadol commonly manifests as seizures. Key words: tramadol, use/abuse, seizures. PMID:22983066
Bekjarovski, N; Chaparoska, D; Radulovikj-Bekjarovska, S
In "New Jersey v. T.L.O." the U.S. Supreme Court held that the prohibitions of the Fourth Amendment regarding unreasonable searches and seizures apply to student searches and seizures conducted by public school officials. However, the Court said the legality of a search should depend upon "reasonableness, under the circumstances" rather than…
Lincoln, Eugene A.
This monograph attempts to provide clear understanding of the standards presented by the Supreme Court in "New Jersey v. T.L.O." relative to search and seizure in public schools, and suggests practical ways of applying search and seizure law to situations in the school setting. ("T.L.O." are the initials of the anonymous student.) After an…
Rossow, Lawrence F.
Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists.
Robinson, Prema; Garza, Armandina; Weinstock, Joel; Serpa, Jose A.; Goodman, Jerry Clay; Eckols, Kristian T.; Firozgary, Bahrom; Tweardy, David J.
Recognizing possible seizure disorders, medication side-effects, behavioral and cognitive effects of seizures, and their treatments are important skills for school psychologists because they affect 500,000 United States school-aged children attending regular education. A knowledgeable school professional serves a critical role in integrating…
Sachs, Henry T.; Barrett, Rowland P.
Between October 1990 and November 1991 data were collected on the frequency, causes, and nature of epileptic seizures in children admitted to the paediatric ward at Kilifi District Hospital, Kenya, from a defined study area. During this period, 1324 children were studied, of whom 15·8% had seizures as part of their illness. Malaria was by far the commonest cause of
C. M. Waruiru; C. R. J. C. Newton; D. Forster; L. New; P. Winstanley; I. Mwangi; V. Marsh; M. Winstanley; R. W. Snow; K. Marsh
|In "New Jersey v. T.L.O." the U.S. Supreme Court held that the prohibitions of the Fourth Amendment regarding unreasonable searches and seizures apply to student searches and seizures conducted by public school officials. However, the Court said the legality of a search should depend upon "reasonableness, under the circumstances" rather than…
Lincoln, Eugene A.
A 37-year-old female presented following a witnessed generalised tonic clonic seizure while washing her car. Witnesses reported the patient hit her head on the car bumper upon falling. She was investigated for a cause of a second seizure with blood tests, CT and MR brain which were normal. On day 3 of her admission she was still unable to walk
Imran Satia; Lynsey Goodwin; Salem Madi; Hisham Hamdalla
This report describes studies of anticonvulsants for the organophosphorus (OP) nerve agent soman: a basic research effort to understand how different pharmacological classes of compounds influence the expression of seizure produced by soman in rats, and a drug screening effort to determine whether clinically useful antiepileptics can modulate soman-induced seizures in rats. Electroencephalographic (EEG) recordings were used in these studies.
Tsung-Ming Shih; John H. McDonough; Irwin Koplovitz
Seizures and seizure-like activity may occur in patients experiencing aneurysmal subarachnoid hemorrhage. Treatment of these events with prophylactic antiepileptic drugs remains controversial. An electronic literature search was conducted for English language articles describing the incidence and treatment of seizures after aneurysmal subarachnoid hemorrhage from 1980 to October 2010. A total of 56 articles were included in this review. Seizures often occur at the time of initial presentation or aneurysmal rebleeding before aneurysm treatment. Seizures occur in about 2% of patients after invasive aneurysm treatment, with a higher incidence after surgical clipping compared with endovascular repair. Non-convulsive seizures should be considered in patients with poor neurological status or deterioration. Seizure prophylaxis with antiepileptic drugs is controversial, with limited data available for developing recommendations. While antiepileptic drug use has been linked to worse prognosis, studies have evaluated treatment with almost exclusively phenytoin. When prophylaxis is used, 3-day treatment seems to provide similar seizure prevention with better outcome compared with longer-term treatment. PMID:21751102
Lanzino, Giuseppe; D'Urso, Pietro Ivo; Suarez, Jose
The population incidence of psychogenic nonepileptic seizures (PNES) may be only 4% that of epilepsy, but many patients with PNES have a tendency to seek medical attention, and PNES make up a larger share of the workload of neurologists and emergency and general physicians. Although a great number of publications describe how PNES can be distinguished from epileptic seizures, it
Markus Reuber; Christian E. Elger
The Fourth Amendment to the U.S. Constitution protects the people of the United States from unreasonable searches and seizures. On first reading, these protections seem clearly defined. The amendment was meant to protect Americans from the kinds of random searches and seizures that the colonists experienced under British colonial rule. Under…
Staros, Kari; Williams, Charles F.
Complementary and alternative medicine (CAM) is increasingly being used for a multitude of medical problems, one of them being seizures. This article discusses the prevalence of CAM use for seizures and epilepsy. Evidence-based data regarding CAM for epilepsy are presented as well as potential safety concerns regarding ephedra and cannabis use. PMID:17701869
Sirven, Joseph I
There is meager information in the literature regarding the characteristics and risk factors for injuries caused during epileptic seizures in adults. Previous studies focused mainly on specific types of injuries incurred, and only few explored associated risk factors. A questionnaire regarding lifetime seizures and their traumatic consequences was administered to 298 consecutive epileptic patients and their caretakers or relatives. Ninety-one
MiriamY Neufeld; Tali Vishne; Vladimir Chistik; AmosD Korczyn
This article provides an overview of the latest knowledge and understanding of childhood febrile seizures. This review also discusses childhood febrile seizure occurrence, health services utilization and treatment costs. Parental reactions associated with its occurrence and how healthcare providers can assist parents with dealing effectively with this potentially frightening and anxiety-producing event are also discussed.
Jones, Tonia; Jacobsen, Steven J.
|This monograph attempts to provide clear understanding of the standards presented by the Supreme Court in "New Jersey v. T.L.O." relative to search and seizure in public schools, and suggests practical ways of applying search and seizure law to situations in the school setting. ("T.L.O." are the initials of the anonymous student.) After an…
Rossow, Lawrence F.
To evaluate the possible age-related differences in the behavioral effects of zolpidem, a widely used hypnotic, we compared\\u000a the effects of zolpidem on the locomotor activity and on the seizure threshold for pentylenetetrazole (PTZ) and picrotoxin\\u000a (given by i.v. infusion) between adult (3 months) and aged (13 months) mice. Zolpidem (10 mg\\/kg) produced similar enhancements\\u000a of the seizure threshold in adult and aged
Danka Peri?i?; Josipa Vlaini?; Dubravka Švob Štrac
During the 2010-2011 influenza season, the Centers for Disease Control and Prevention and the Food and Drug Administration conducted enhanced vaccine safety monitoring for possible febrile seizures in all trivalent influenza vaccine (TIV) products in the United States using the Vaccine Adverse Event Reporting System (VAERS). We used Empirical Bayesian data mining techniques to assess disproportionate reporting after TIV and reviewed febrile seizure reports in children aged <5 years. On November 23, 2010, the combination of the coding term "febrile convulsion" and the Fluzone(®) TIV product exceeded a predetermined threshold in the VAERS database. By December 10, we confirmed 43 reports of febrile seizure following TIV in children aged 6-23 months. Clinical features of most reports were consistent with typical uncomplicated febrile seizures, and all children recovered. Further epidemiologic assessment of a possible association between TIV and febrile seizures was undertaken in a separate, population-based vaccine safety monitoring system. PMID:22361303
Leroy, Z; Broder, K; Menschik, D; Shimabukuro, T; Martin, D
Pyridoxine-dependent seizures is a rare cause of recurrent seizures in neonatal period and resistant to most of the antiepileptic medications, but respond to administration of pyridoxine. We report a male infant who had neonatal seizures which were initially responsive to anticonvulsants and later became unresponsive and presented at 45 days of life with seizures. These seizures were not responding to any anticonvulsant but responded to pyridoxine. After discharge parents inadvertently stopped pyridoxine and the infant presented with seizures once again. These seizures were promptly controlled with readministration of pyridoxine confirming the diagnosis of pyridoxine-dependant seizures. PMID:24027745
Murty, V S S Yerramilli; Kishore, M S S; Patel, Manisha R
Pyridoxine-dependent seizures is a rare cause of recurrent seizures in neonatal period and resistant to most of the antiepileptic medications, but respond to administration of pyridoxine. We report a male infant who had neonatal seizures which were initially responsive to anticonvulsants and later became unresponsive and presented at 45 days of life with seizures. These seizures were not responding to any anticonvulsant but responded to pyridoxine. After discharge parents inadvertently stopped pyridoxine and the infant presented with seizures once again. These seizures were promptly controlled with readministration of pyridoxine confirming the diagnosis of pyridoxine-dependant seizures.
Murty, V.S.S. Yerramilli; Kishore, M.S.S.; Patel, Manisha R.
We conducted a study of the risk of idiopathic incident seizures among users of tramadol derived from data present in the General Practice Research Database based in the United Kingdom for 1994-1996. We used a nested case-control study design, comparing risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol using a 90-day follow-up. Among the 10,916 subjects, we identified 17 cases of idiopathic seizures, 11 of which were definite and 6 possible. None of the patients was exposed to tramadol alone in the prior 90 days. Eight patients were exposed to opiates, five to both tramadol and opiates, three to other analgesics, and one to no analgesics. We found no increased risk of idiopathic incident seizures associated with exposure to tramadol alone. Thus seizures seem rarely attributable to the agent. PMID:9620111
Jick, H; Derby, L E; Vasilakis, C; Fife, D
An epileptic seizure is reported in a 38-year-old woman, known to be an epileptic patient. Although she was under antiepileptic treatment and had well-controlled epilepsy, she developed a typical generalised tonic-clonic seizure and remained unconscious for 45 minutes following ingestion of a number of cakes containing an unknown quantity of fennel essential oil. Involuntary diarrhoea accompanied her epileptic seizure. This reported case recalls the fact that fennel essential oil can induce seizures and that this oil should probably be avoided by patients with epilepsy. Labelling of products with fennel essential oil should refer to the risk of seizures, particularly for patients with epilepsy. An awareness programme should involve all stakeholders affected by this issue. PMID:21865126
Skalli, Souad; Soulaymani Bencheikh, Rachida
Gastroesophageal reflux disease can have variable manifestations including regurgitation, irritability, arching, choking, and apnea. The disorder is also frequently mistaken for seizures (Sandifer syndrome). We report 6 patients in whom the opposite phenomenon occurred: their seizures were mistaken for gastroesophageal reflux disease. Six of 77 patients (6.8%) with gelastic seizures and epilepsy symptomatic of hypothalamic hamartomas were noted to be misdiagnosed with gastroesophageal reflux disease in infancy. As is typical in these patients, gelastic seizures were not diagnosed until months, or often years, later. Delayed diagnosis of hypothalamic hamartomas can lead to a potentially deleterious syndrome involving refractory epilepsy, developmental problems, and precocious puberty. Gelastic seizures should be considered among the conditions that can mimic reflux symptoms. PMID:17475990
Sweetman, Laura L; Ng, Yu-Tze; Kerrigan, John F
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.
Abend, Nicholas S.; Gutierrez-Colina, Ana M.; Monk, Heather M.; Dlugos, Dennis J.; Clancy, Robert R.
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.
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
A seizure prediction algorithm is proposed that combines novel multivariate EEG features with patient-specific machine learning. The algorithm computes the eigenspectra of space-delay correlation and covariance matrices from 15-s blocks of EEG data at multiple delay scales. The principal components of these features are used to classify the patient's preictal or interictal state. This is done using a support vector machine (SVM), whose outputs are averaged using a running 15-minute window to obtain a final prediction score. The algorithm was tested on 19 of 21 patients in the Freiburg EEG data set who had three or more seizures, predicting 71 of 83 seizures, with 15 false predictions and 13.8 h in seizure warning during 448.3 h of interictal data. The proposed algorithm scales with the number of available EEG signals by discovering the variations in correlation structure among any given set of signals that correlate with seizure risk. PMID:23041171
Williamson, James R; Bliss, Daniel W; Browne, David W; Narayanan, Jaishree T
Sudden Unexpected Death in Epilepsy (SUDEP) is the most common cause of epilepsy related mortality in treatment resistant epilepsy. Most SUDEPs occur after one or more seizure(s) during sleep. Nocturnal seizures may go unrecognized. Respiratory depression in the peri-ictal period is one of the primary potential causes of SUDEP. Ictal and postictal apnea is often overlooked because it is not routinely assessed, but appears common and has been a recent focus of SUDEP research. We report a 37 year-old man who had central apnea as the initial manifestation of partial complex seizures associated with oxygen desaturation. This important pathophysiological consequence of a nocturnal complex seizure was identified by respiratory monitoring during a combined video EEG and sleep study. Diagnostic and therapeutic implications are discussed. PMID:22726818
Nadkarni, Mangala A; Friedman, Daniel; Devinsky, Orrin
Current therapeutic options for treatment of neonatal seizures, such as phenobarbital and phenytoin lack efficacy, and are potentially harmful to the developing brain. Topiramate appears to be effective as both an anti-seizure and neuroprotective agent in animal models of newborn brain injury. Though topiramate is commonly used as an add-on agent in newborns, its use in this population has not yet been reported. We performed a retrospective cohort study of clinical topiramate use in newborns with acute symptomatic seizures that were refractory to standard agents. In four of six identified newborns, there was apparent reduction or no further seizures, and none of the children experienced side effects that resulted in discontinuation of the drug, either during the hospital admission or after discharge home. Prospective studies evaluating the safety and efficacy of topiramate for both seizures and neuroprotection will be important to determine whether this medication deserves widespread use in clinical practice.
Glass, Hannah C.; Poulin, Chantal; Shevell, Michael I.
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., genetic rat models, 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
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
We retrospectively identified 49 cases of recreational drug-induced seizures in 47 patients seen at the San Francisco General Hospital between 1975 and 1987. Most patients experienced a single generalized tonic-clonic seizure associated with acute drug intoxication, but 7 patients had multiple seizures and 2 patients developed status epilepticus. The recreational drugs implicated were cocaine (32 cases), amphetamine (11), heroin (7), and phencyclidine (4). A combination of drugs was responsible in 11 cases. Seizures occurred independent of the route of administration, and occurred in both first-time and chronic abusers. Ten patients (21%) reported having had prior seizures, all with a close temporal association with drug abuse. Other than 1 patient who developed prolonged status epilepticus that caused a fixed neurologic deficit, most patients had no obvious short-term neurologic sequelae. PMID:2788249
Alldredge, B K; Lowenstein, D H; Simon, R P
This is a case study presented by the University of Pittsburgh Department of Pathology which presents a 43 year old man with a "seizure" of dizziness associated with difficulty in walking and performing simple movements. Visitors are provided with patient history along with neuroimaging and microscopic description, including images, and are given the opportunity to diagnose the patient. A "Final Diagnosis" section provides a discussion of the findings as well as references. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to use to introduce or test student learning in neuropathology.
The International Classification of Epileptic Seizures is the most widely used, but an alternative system based purely on ictal symptoms and signs has been proposed: the semiological classification. Our objective was to compare the two in a sample of patients evaluated at epilepsy centers. We collected 78 consecutive patients evaluated in outpatient epilepsy clinics who subsequently underwent noninvasive video-EEG monitoring at three centers. Patients with pseudoseizures were excluded. Seizures were first classified based on information obtained during clinic visits, and again after video-EEG monitoring. Each time, seizures were classified using both the International Classification and the semiological classification. Eventual epilepsy syndrome diagnosis was based on all the clinical data, video-EEG monitoring, and other independent tests including imaging studies. Sixty-six (87%) patients were classified as having 'complex partial seizures' in the International Classification. Using the semiological classification, these same 66 patients were classified as follows: automotor (34), dialeptic (17), hypermotor (13), hypomotor (2). Seizure classification changed between initial 'clinic-based' data and the 'monitoring-based' classification in 27 cases using the ILAE, vs. six using the semiological classification. Seizure classification tended to change significantly between pre- and post-monitoring using the ILAE but not the semiological classification. The term complex partial seizure included multiple categories of the semiological classification, and was very nonspecific. The semiological classification may be better suited for everyday clinic use, since it is based solely on clinical characteristics. PMID:11466019
Benbadis, S R; Thomas, P; Pontone, G
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).
Mesbah, Mostefa; O'Toole, John M.; Colditz, Paul B.; Boashash, Boualem
The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Department of Energy (DOE) Global Initiatives for Proliferation Prevention (GIPP) grant to the Kansas City Plant (KCP), Argonne National Laboratory (ANL), and Pacific Northwest National Laboratory (PNNL) to partner with Flint Hills Scientific, LLC, Lawrence, KS and Biophysical Laboratory Ltd (BIOFIL), Sarov, Russia to develop a method to help control epileptic seizures.
Smith, LaCurtise; Bohnert, George W.
The evaluation of episodic seizure-like symptoms is a common challenge in the neurologist's daily routine. The clinical signs (semiology) are the most important puzzle pieces to distinguish epileptic seizures from other episodic entities. Due to the often far-reaching health and social consequences of the diagnosis of epilepsy, the early and rigorous assessment of episodic symptoms by means of the patient history is important. This assessment is based on knowledge of the association of certain semiologies with epileptic syndromes and brain regions; however, certain limitations and pitfalls have to be considered. Typical propagation pathways of seizure activity determine the serial occurrence of semiological features and provide supplementary information. PMID:23756821
Gellner, A-K; Fritsch, B
We examined potential clinical and pathologic correlates of seizures among the 3,291 children in the Childhood Brain Tumor Consortium database. Fourteen percent had seizures prior to their hospitalization for a brain tumor. Among children who had a supratentorial tumor, seizures occurred in 22% of those less than 14 years of age. The prevalence of seizures increased to 68% of older
Floyd H. Gilles; Eugene Sobel; Alan Leviton; E. Tessa Hedley-Whyte; C. Jane Tavare; Lester S. Adelman; Raymond A. Sobel
The effect of pregnancy on seizure frequency was monitored prospectively in 136 pregnancies of 122 epileptic women. Pregnancy did not influence the seizure frequency in 68 pregnancies (50%). In 50 pregnancies (37%) the number of seizures increased during pregnancy or puerperium. The seizure frequency decreased in 18 pregnancies (13%). In 34 out of 50 pregnancies (68%) the increase was associated
D Schmidt; R Canger; G Avanzini; D Battino; C Cusi; G Beck-Mannagetta; S Koch; D Rating; D Janz
In clinical practice, a classification of seizures based on clinical signs and symptoms leads to an improved understanding of epilepsy-related issues and therefore strongly contributes to a better patient care. The inverse problem involves inferring the anatomical brain localization of a seizure from the scalp surface EEG, a concept we apply here to correlate seizure origin with seizure semiology. The
Andrea O. Rossetti; Peter W. Kaplan
Data from experimental models provide evidence that both prolonged and brief seizures can cause irreversible impairment in spatial and emotional learning and memory. Factors related to the severity of the behavioral impairments include genetic background, age at the time of the epileptogenic insult, extent of brain lesion, location of seizure focus, seizure duration, seizure number, brain reserve, and environmental and
Katarzyna Majak; Asla Pitkänen
Seizures are common in the neonatal period and represent a most distinctive signal of neurological disease. Seizures in newborns are associated with an increased risk of neurodevelopmental impairment, including cerebral palsy, mental retardation and epilepsy and mortality. Controversy still exists concerning diagnosis and treatment of neonatal seizures. Furthermore the question, regarding the potential detrimental effect of neonatal seizures on the
L. G. M. van Rooij
Objective: To report clinical and EEG features in 5 adults with unusual., fast rhythmic discharges accompanying absence seizures.Design and methods: The 5 patients presented with uncontrolled seizures. All had EEG-video monitoring with recorded seizures. Video seizures were reviewed and ictal as well as interictal epileptiform activity was analyzed. The patients were followed up after appropriate therapy for a minimum of
Toufic Fakhoury; Bassel Abou-Khalil
Overview. Simple febrile seizures that occur in children ages 6 months to 5 years are common events with few adverse outcomes. Those who advocate therapy for this disorder have been concerned that such seizures lead to additional febrile seizures, to epilepsy, and perhaps even to brain injury. Moreover, they note the potential for such seizures to cause parental anxiety. We
Robert J. Baumann
The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. Despite its clinical relevance, the potential of ECT to identify mouse epilepsy models in genetic studies has not been thoroughly assessed. We adopted the ECT test to screen the progeny of ethylnitrosourea treated male C57BL\\/6J mice. In
Yan Yang; Barbara J. Beyer; James F. Otto; T P OBrien; Verity A. Letts; H. Steve White; Wayne N. Frankel
|Bayesian estimation of a threshold time (hereafter simply threshold) for the receipt of impulse signals is accomplished given the following: 1) data, consisting of the number of impulses received in a time interval from zero to one and the time of the largest time impulse; 2) a model, consisting of a uniform probability density of impulse time…
Gustafson, S. C.; Costello, C. S.; Like, E. C.; Pierce, S. J.; Shenoy, K. N.
We consider the problem of threshold secret sharing in groups with hierarchical structure. In such settings, the secret is shared among a group of participants that is partitioned into levels. The access structure is then determined by a sequence of threshold requirements: a subset of participants is authorized if it has at least k0 members from the highest level, as
Seizure response and alerting behaviour may spontaneously develop in dogs living with children or adults with epilepsy. Some\\u000a dogs can also be reliably trained to respond and anticipate seizures. We describe the case of a dog, not previously trained\\u000a for assistance work, showing complex seizure response behaviour. This is the first release of a home video recording of a\\u000a dog
Lidia Di Vito; Ilaria Naldi; Barbara Mostacci; Laura Licchetta; Francesca Bisulli; Paolo Tinuper
Intramuscular (i.m.) administration ofdiazepam in a dose of 10 mg/kg and adrenaline in a dose of 0.2 mg/kg prevents generalized clonic-tonic pentylenetetrazol (PTZ) seizures in 75-80 % of rats, but only in 35-40 % of rats it prevents local clonic PTZ seizures. In the above mentioned dose, diazepam causes a strong sedation, but adrenaline does not cause a sedative effects. The combined administration of diazepam and adrenaline in threshold independently ineffective doses prevents both clonic-tonic and clonic PTZ seizures in 80 % of rats without a sedation development. The basis for mechanism of potentiation of anticonvulsant action of diazepam is the stimulation of gastric mucosa afferents by adrenaline. PMID:22650067
Serdiuk, S E; Gmiro, V E
A survey regarding the management of the child with febrile seizures was mailed to 10,000 child neurologists, pediatricians, family and general practitioners. The response rate varied by specialty, and overall slightly more than half the physicians respon...
D. G. Hirtz Y. J. Lee J. H. Ellenberg K. B. Nelson
There is clinical need to extend the understanding of epilepsy and to find novel approaches to treat this condition. Bang-sensitive (bs) Drosophila mutants, which exhibit reduced thresholds for seizure, offer an attractive possibility to combine tractable genetics, electrophysiology, and high-throughput screening. However, despite these advantages, the precise electrophysiological aberrations that contribute to seizure have not been identified in any bs mutant. Because of this, the applicability of Drosophila as a preclinical model has not yet been established. In this study, we show that electroshock of bs slamdance (sda) larvae was sufficient to induce extended seizure-like episodes. Whole cell voltage-clamp recordings from identified motoneurons (termed aCC and RP2) showed synaptic currents that were greatly increased in both amplitude and duration. Current-clamp recordings indicated that these inputs produced longer-lived plateau depolarizations and increased action potential firing in these cells. An analysis of voltage-gated currents in these motoneurons, in both first and third instar larvae, revealed a consistently increased persistent Na(+) current (I(Nap)) and a reduced Ca(2+) current in first instar larvae, which appeared normal in older third instar larvae. That increased I(Nap) may contribute to seizure-like activity is indicated by the observation that feeding sda larvae the antiepileptic drug phenytoin, which was sufficient to reduce I(Nap), rescued both seizure-like episode duration and synaptic excitation of motoneurons. In contrast, feeding of either anemone toxin, a drug that preferentially increases I(Nap), or phenytoin to wild-type larvae was sufficient to induce a bs behavioral phenotype. Finally, we show that feeding of phenytoin to gravid sda females was sufficient to both reduce I(Nap) and synaptic currents and rescue the bs phenotype in their larval progeny, indicating that a heightened predisposition to seizure may arise as a consequence of abnormal embryonic neural development. PMID:21451059
Marley, Richard; Baines, Richard A
INTRODUCTION: Seizures with or without trauma may cause fractures that occur commonly in epileptic seizures. Fracture risk is less reported in non-epileptic seizures. Some metabolic conditions leading to a decrease in bone mineral density may cause fractures secondary to non-epileptic seizure. CASE PRESENTATION: We describe two cases of non-traumatic acetabular and vertebrae fractures following seizures without history of epilepsy. They
Koussay Ach; Ines Slim; Sihem Ajmi; Molka Chaieb; Amel Beizig; Larbi Chaieb
Most seizures stop spontaneously; however, the molecular mechanisms that terminate seizures remain unknown. Observations that seizures reduced brain pH and that acidosis inhibited seizures indicate that acidosis halts epileptic activity. Because acid-sensing ion channel 1a (ASIC1a) is exquisitely sensitive to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a, which would terminate seizures. Disrupting mouse ASIC1a
Adam E Ziemann; Mikael K Schnizler; Gregory W Albert; Meryl A Severson; Matthew A Howard III; Michael J Welsh; John A Wemmie
For many neurologists, seizures in critically ill patients represent a difficult problem. Etiology can be elusive because\\u000a of the complexity of the environment, and treatment decisions can be compromised by the paucity of evidence-based guidelines.\\u000a Emerging data support a higher than previously thought incidence of nonconvulsive epileptic activity in this patient population,\\u000a which is another important consideration. Although a seizure
Panayiotis N. Varelas; Marek A. Mirski
Although cases of Vitamin D-deficient Rickets have declined since the Industrial Revolution, certain populations remain at risk. Risk factors for developing vitamin D-deficient Rickets include breast-feeding without formula or vitamin supplementation, very dark skin and inadequate exposure to sunlight. We describe a case of Rickets in a breastfed infant with dark skin who presented with hypocalcemic seizures. The pathophysiology of Rickets is briefly described along with the emergency management of infants presenting with hypocalcemic seizure. PMID:15707811
Bellazzini, Marc A; Howes, David S
Objectives: To determine the risk of epileptic seizures due to a brain arteriovenous malformation (AVM) or cavernous malformation (CM). Methods: In a prospective population-based study of new diagnoses of AVMs (n = 229) or CMs (n = 139) in adults in Scotland in 1999–2003, we used annual medical records surveillance, general practitioner follow-up, and patient questionnaires to quantify the risk of seizures between clinical presentation and AVM/CM treatment, last follow-up, or death. Results: The 5-year risk of first-ever seizure after presentation was higher for AVMs presenting with intracranial hemorrhage or focal neurologic deficit (ICH/FND: n = 119; 23%, 95% confidence interval [CI] 9%–37%) than for incidental AVMs (n = 40; 8%, 95% CI 0%–20%), CMs presenting with ICH/FND (n = 38; 6%, 95% CI 0%–14%), or incidental CMs (n = 57; 4%, 95% CI 0%–10%). For adults who had never experienced ICH/FND, the 5-year risk of epilepsy after first-ever seizure was higher for CMs (n = 23; 94%, 95% CI 84%–100%) than AVMs (n = 37; 58%, 95% CI 40%–76%; p = 0.02). Among adults who never experienced ICH/FND and presented with or developed epilepsy, there was no difference in the proportions achieving 2-year seizure freedom over 5 years between AVMs (n = 43; 45%, 95% CI 20%–70%) and CMs (n = 35; 47%, 95% CI 27%–67%). Conclusions: AVM-related ICH confers a significantly higher risk of a first-ever seizure compared to CMs or incidental AVMs. Adults with a CM have a high risk of epilepsy after a first-ever seizure but achieve seizure freedom as frequently as those with epilepsy due to an AVM.
Josephson, C.B.; Leach, J.-P.; Duncan, R.; Roberts, R.C.; Counsell, C.E.
Objective: To investigate the presenting characteristics of new-onset afebrile seizures in infants (age 1–24 months) and the yield of neuroimaging. Methods: Prospective data were obtained from a standardized evaluation and management plan mandated by a critical care pathway. A total of 317 infants presented with new-onset afebrile seizures between 2001 and 2007. EEG was performed on 90.3%, head CT was obtained on 94%, and MRI was obtained on 57.4%. Results: We found half of the infants had partial features to their seizures, yet evidence for primary generalized seizures was rare. The majority had more than 1 seizure upon presentation. Seizures in this age group tended to be brief, with 44% lasting less than 1 minute. EEG abnormalities were found in half. One-third of CTs were abnormal, with 9% of all CTs requiring acute medical management. Over half of MRIs were abnormal, with cerebral dysgenesis being the most common abnormality (p < 0.05). One-third of normal CTs had a subsequent abnormal MRI—only 1 resulted in altered medical management. Conclusions: Infantile seizures are usually brief, but commonly recurrent, and strong consideration should be made for inpatient observation. Acute imaging with CT can alter management in a small but important number of infants. Due to the superior yield, strong consideration for MRI should be given for all infants, as primary generalized seizures are rare, and there is a high rate of cerebral dysgenesis. GLOSSARY ED = emergency department; ILAE = International League Against Epilepsy; IRB = Institutional Review Board.
Hsieh, D T.; Chang, T; Tsuchida, T N.; Vezina, L G.; Vanderver, A; Siedel, J; Brown, K; Berl, M M.; Stephens, S; Zeitchick, A; Gaillard, W D.
Seizures may occur after orthotopic liver transplantation. Antiepileptic drugs (AEDs) are used to treat these seizures, but the immunosuppressant regimen also may be altered. Levetiracetam is an attractive treatment because of its efficacy, lack of hepatic enzyme induction, and its rapid attainment of serum levels. Treatment with levetiracetam is efficacious, and levetiracetam-treated patients require significantly lower doses of immunosuppressant medications to achieve an equivalent antirejection effect. PMID:15781837
Glass, G A; Stankiewicz, J; Mithoefer, A; Freeman, R; Bergethon, P R
Epilepsy is associated with significantly increased morbidity and mortality from a variety of causes. Patients with epilepsy\\u000a have approximately two to three times the risk of death from any cause compared with persons without epilepsy. Seizures may\\u000a cause significant trauma, drowning, and accidental injury. Many of the deaths in persons with epilepsy are directly related\\u000a to seizures, accidents and injuries
Maromi Nei; Ritu Bagla
Febrile seizures are the most common form of childhoodseizures,affecting2-5%of allchildrenandusually appearing between 3 months and 5 years of age. Despite its predominantly benign nature, a febrile seizure (FS) is a terrifying experience for most parents. The condition is perhaps one of the most prevalent causes of admittance to pediatric emergency wards worldwide. FS, defined as either simple or complex, may
The population incidence of psychogenic nonepileptic seizures (PNES) may be only 4% that of epilepsy, but many patients with PNES have a tendency to seek medical attention, and PNES make up a larger share of the workload of neurologists and emergency and general physicians. Although a great number of publications describe how PNES can be distinguished from epileptic seizures, it usually takes several years to arrive at this diagnosis, and three-quarters of patients (with no additional epilepsy) are treated with anticonvulsants initially. However, the management of PNES as epileptic seizures can lead to significant iatrogenic harm. Moreover, the failure to recognize the psychological cause of the disorder detracts from addressing associated psychopathology and enhances secondary somatization processes. This review provides an overview of studies of the diagnosis, etiology, treatment, and prognosis of PNES. Physicians should always consider PNES in the differential diagnosis of a seizure disorder. If a diagnosis of PNES is possible, or a diagnosis of epilepsy in doubt, a clear diagnostic categorization should be sought. This should involve the assessment of the patient by a physician versed in the diagnosis of seizure disorders and, in many cases, the documentation of a typical seizure by video-EEG. Outcome may be improved if the diagnosis is more actively sought, made earlier, and communicated more convincingly. PMID:12791321
Reuber, Markus; Elger, Christian E
Most intellectually normal children with focal epilepsy have partial complex or focal with secondary generalization seizures without a precise epilepsy syndrome. Their long-term outcome is largely unknown. Cases were identified from the population-based Nova Scotia Childhood Epilepsy cohort. Those eligible had seizure onset at 1 month to 16 years between 1977 and 1985, normal intelligence, ?10 years of follow-up, only focal seizures and no benign epilepsy syndromes. There were 108 patients with partial complex with or without secondary generalization as the only seizure type(s) throughout (partial complex group) and 80 with secondary generalization as the only seizure type (secondary generalization group). Average age ± standard deviation at onset was 7.3 ± 4.5 years and follow-up was 27.9 ± 5.4 years. At follow-up, 57% of the partial complex group were in remission versus 81% of the secondary generalization group (P = 0.001). The partial complex group was more likely to be intractable or have undergone epilepsy surgery (36% versus 5%, P = 0.000). In the partial complex group, 28% had <5 years seizure free versus 5% in the secondary generalized group (P = 0.000). More patients in the partial complex group had undergone mental health assessments (59% versus 32%, P = 0.000), and 33% had a psychiatric diagnosis versus 15% in the secondary generalized group (P = 0.004). More patients with partial complex seizures had specific learning disorders (63% versus 45%, P = 0.03). Seven markers of poor social outcome were more common in patients with partial complex seizures (>2 markers: 34% versus 10%, P = 0.000). During 25-30 years of follow-up, >50% of intellectually normal patients with childhood-onset partial complex seizures had difficult-to-control seizures and learning and psychiatric/social problems. Most with secondary generalized seizures only had remission and better academic and psychiatric/social outcomes. PMID:23378221
Camfield, Carol S; Camfield, Peter R
In most situations, the signer is generally a single person. However, when the message is written on behalf of an organization, a valid message may require the approval or consent of several persons. Threshold signature is a solution to this problem. Generally speaking, as an authority which can be trusted by all members does not exist, a threshold signature scheme without a trusted party appears more attractive. Following some ideas of the classical Shamir’s threshold signature scheme, a quantum threshold group signature one is proposed. In the proposed scheme, only t or more of n persons in the group can generate the group signature and any t - 1 or fewer ones cannot do that. In the verification phase, any t or more of n signature receivers can verify the message and any t - 1 or fewer receivers cannot verify the validity of the signature.
Yang, Yuguang; Wen, Qiaoyan
Ashwagandharishta, an Ayurvedic classical formulation, is the remedy for Apasmara (epilepsy), Murchha (syncope), Unmada (psychosis), etc. Recent studies in animal models have shown that n-3 PUFAs can raise the threshold of epileptic seizures. The indigenous medicinal plant, called Atasi (Linum usitatissimum Linn.) in Ayurveda, or flax seed, is the best plant source of omega-3 fatty acids. The present study is designed to investigate whether Ashwagandharishta and Atasi taila (flax seed oil) protect against maximal electroshock (MES) seizures in albino rats. Further, a possible protective role of flax seed oil as an adjuvant to Ashwagandharishta in its anticonvulsant activity has also been evaluated in the study. MES seizures were induced for rats and seizure severity was assessed by the duration of hind limb extensor phase. Phenytoin was used as the standard antiepileptic drug for comparison. Both flax seed oil and Ashwagandharishta significantly decreased convulsion phase. Pre-treatment with flax seed oil exhibited significant anticonvulsant activity by decreasing the duration of tonic extensor phase. Contrary to the expectations, pre-treatment with flax seed oil as an adjuvant to Ashwagandharishta failed to decrease the tonic extensor phase; however, it significantly decreased the flexion phase (P < 0.001) and duration of the convulsions (P < 0.05). Both the drugs exhibited an excellent anti-post-ictal depression effect and complete protection against mortality. PMID:23049195
Tanna, Ila R; Aghera, Hetal B; Ashok, B K; Chandola, H M
Hyponatremia leading to seizures is well described in children. Hyponatremia is defined as a serum sodium of less than 135 mEq/L and can be acute or chronic. The seizure threshold in hyponatremia is markedly increased at a level of 125 mEq/L or less. Hyponatremia is one of the most common electrolyte disturbances and occurs in both the inpatient and outpatient setting. The 3 types of hyponatremia are hypovolemic, euvolemic, and hypervolemic. The diagnosis is made through serologic and urinary laboratory studies. We present the case of a 2-year-old girl with recurrent hyponatremic seizures, who was resuscitated twice within a short period at our institution. Her hyponatremia coupled with the seizures was initially thought to be secondary to salt-wasting renal disease, adrenal insufficiency, or even syndrome of inappropriate antidiuretic hormone secretion. The case took an interesting twist, which led us to conclude that this was an uncommon yet not unheard of form of child abuse. PMID:23128655
Barber, Gary A; Whitefield, Julia S
We consider the problem of threshold secret sharing in groups with hierarchical structure. In such settings, the secret is\\u000a shared among a group of participants that is partitioned into levels. The access structure is then determined by a sequence\\u000a of threshold requirements: a subset of participants is authorized if it has at least k0 0 members from the highest level,
|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…
Kanner, Andres M.; Shafer, Patricia O.
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…
Duchowny, Michael S.; Dean, Patricia
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…
Kanner, Andres M.; Shafer, Patricia O.
This study evaluated the incidence, prevalence, and clinical features of seizures in a pedigreed captive colony of baboons. The association of seizures with subspecies, age, sex, and various clinical features was assessed. Records for 1527 captive, pedigreed baboons were reviewed, and 3389 events were identified in 1098 baboons. Of these events, 1537 (45%) represented witnessed seizures, whereas the remaining 1852 presented with craniofacial trauma or episodic changes in behavior that were suggestive, but not diagnostic, of seizure activity. Seizures were generalized myoclonic or tonic–clonic, with two thirds of the events witnessed in the morning. Seizure onset occurred in adolescence (age, 5 y), with an average of 3 seizures in a lifetime. The incidence and prevalence of seizures were 2.5% and 26%, respectively, whereas the prevalence of recurrent seizures (that is, epilepsy) was 15%. Seizures were more prevalent in male baboons, which tended to present with earlier onset and more seizures over a lifetime than did female baboons. Seizures were equally distributed between the subspecies; age of onset and seizure recurrences did not differ significantly between subspecies. Clinical features including age of onset, characteristics, and diurnal presentation of seizures in baboons suggested similarities to juvenile myoclonic epilepsy in humans. Facial trauma may be useful marker for epilepsy in baboons, but its specificity should be characterized.
Szabo, C Akos; Knape, Koyle D; Leland, M Michelle; Cwikla, Daniel J; Williams-Blangero, Sarah; Williams, Jeff T
Under conditions that isolate rod vision, increment thresholds were measured on black bars of various widths, and compared to the increment threshold measured on a homogeneously illuminated field without the bar. Thresholds were found to be elevated in th...
D. Y. Teller
The authors report a patient with Lennox-Gastaut syndrome who was a fraternal twin. The twins encountered myoclonic seizures at the age of 4 years, but the seizures in the other patient were controlled very quickly without intellectual development damage. With the disease evolving, other characteristic seizures of Lennox-Gastaut syndrome appeared and failed to be controlled by multiple antiepileptic drugs, so levetiracetam was added on. At this time, frequent partial seizures from the left occipital and posterior temporal regions occurred, which always intermixed with atypical absence seizures in a single ictal event. To control the status epilepticus, levetiracetam was withdrawn immediately, and clonazepam, midazolam, and corticotropin in turn were used. The partial seizures were gradually alleviated. The results obtained in this study suggest that there might be some correlative mechanisms between partial seizures and atypical absence seizures in a single event. There is a temporal relationship between the occurrence of partial seizures and the introduction of levetiracetam. PMID:18984844
Yang, Zhixian; Liu, Xiaoyan; Qin, Jiong; Zhang, Yuehua; Bao, Xinhua; Xiong, Hui
Background: Tramadol is a synthetic analgesic. Seizures have been reported in patients receiving this drug. In this study we evaluated the correlation between tramadol consumption and seizure occurrence. Methods: Twenty-eight subjects with a history of tramadol consumption and seizure were studied. Electroencephalograms (EEG) were performed in the first 24 hours and again one week later. Subjects were followed up for a mean of 18 months after the initial attack. Results: In the 28 subjects, 26 (92.8%) were males and 2 (7.2%) were females. The mean age of the subjects was 28.4 years. Thirteen patients had abused more than 400 mg/day of tramadol. Sixteen subjects concomitantly used other drugs. The seizures occurred within the first 24 hours of tramadol intake in 25 of the subjects. The first EEG was abnormal in 12 cases, but the second EEG was abnormal in only one case. Neuroimaging of only one subject displayed patchy white matter lesions. Conclusion: In conclusion, the neurotoxicity of tramadol commonly manifests as generalized tonic clonic seizures most frequently within 24 hours after tramadol intake and was more common in subjects concomitantly consuming alcohol, illicit drugs, anti-psychotics, or anti-depressants.
Boostani, Reza; Derakhshan, Siavash
Background: Tramadol is a synthetic analgesic. Seizures have been reported in patients receiving this drug. In this study we evaluated the correlation between tramadol consumption and seizure occurrence. Methods: Twenty-eight subjects with a history of tramadol consumption and seizure were studied. Electroencephalograms (EEG) were performed in the first 24 hours and again one week later. Subjects were followed up for a mean of 18 months after the initial attack. Results: In the 28 subjects, 26 (92.8%) were males and 2 (7.2%) were females. The mean age of the subjects was 28.4 years. Thirteen patients had abused more than 400 mg/day of tramadol. Sixteen subjects concomitantly used other drugs. The seizures occurred within the first 24 hours of tramadol intake in 25 of the subjects. The first EEG was abnormal in 12 cases, but the second EEG was abnormal in only one case. Neuroimaging of only one subject displayed patchy white matter lesions. Conclusion: In conclusion, the neurotoxicity of tramadol commonly manifests as generalized tonic clonic seizures most frequently within 24 hours after tramadol intake and was more common in subjects concomitantly consuming alcohol, illicit drugs, anti-psychotics, or anti-depressants. PMID:24009919
Boostani, Reza; Derakhshan, Siavash
Over 40 missense mutations in the human SCN1A sodium channel gene are linked to an epilepsy syndrome termed genetic epilepsy with febrile seizures plus (GEFS+). Inheritance of GEFS+ is dominant but the underlying cellular mechanisms remain poorly understood. Here we report knock-in of a GEFS+ SCN1A mutation (K1270T) into the Drosophila sodium channel gene, para, causes a semi-dominant temperature-induced seizure phenotype. Electrophysiological studies of GABAergic interneurons in the brains of adult GEFS+ flies reveal a novel cellular mechanism underlying heat-induced seizures: the deactivation threshold for persistent sodium currents reversibly shifts to a more negative voltage when the temperature is elevated. This leads to sustained depolarizations in GABAergic neurons and reduced inhibitory activity in the central nervous system. Further, our data indicate a natural temperature-dependent shift in sodium current deactivation (exacerbated by mutation) may contribute to febrile seizures in GEFS+ and perhaps normal individuals.
Sun, Lei; Gilligan, Jeff; Staber, Cynthia; Schutte, Ryan J.; Nguyen, Vivian; O'Dowd, Diane K.; Reenan, Robert
The involvement of alpha(2) noradrenergic receptors during amygdala 'massed' stimulation (MS) was examined in rats that were selectively bred to be seizure-prone (Fast) or seizure-resistant (Slow) to amygdala kindling. The selective alpha(2) noradrenergic agonist guanfacine, or the antagonist idazoxan, was intraperitoneally injected during the MS procedure to study subsequent changes in afterdischarge (AD) threshold, AD duration and behavioral seizure expression. These measurements were again assessed weekly for 2 weeks after the MS treatment. Daily kindling began immediately thereafter. Following 6 stage-5 once daily convulsive seizures, guanfacine or idazoxan were re-administered. With idazoxan, the Slow rats expressed greater numbers of convulsive seizures and longer AD durations compared to guanfacine or saline controls during MS treatment. This pro-convulsive property of idazoxan was absent in Fast rats. By contrast, Fast rats showed enhanced convulsive expression in the presence of guanfacine. In the fully kindled rat, idazoxan and guanfacine differentially impacted seizure duration and severity in the Slow rats, but again not in the Fast rats. These data suggest that some aspect(s) of the alpha(2) noradrenergic system in the Fast and Slow rats are dissimilar and the mechanisms by which these receptors govern seizure genesis and propagation may be genetically controlled and distinct. PMID:17027042
Shin, Rick S; McIntyre, Dan C
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.
Girotto, Fernando; Scott, Lucas; Avchalumov, Yosef; Harris, Jacqueline; Iannattone, Stephanie; Drummond-Main, Chris; Tobias, Rose; Bello-Espinosa, Luis; Rho, Jong M.; Davidsen, Jorn; Teskey, G. Campbell; Colicos, Michael A.
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
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
The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases.
Rossignol, Rodrigue; Faustin, Benjamin; Rocher, Christophe; Malgat, Monique; Mazat, Jean-Pierre; Letellier, Thierry
Summary Purpose Focal seizures are thought to reflect simultaneous activation of a large population of neurons within a discrete region of pathological brain. Resective surgery targeting this focus is an effective treatment in carefully selected patients, but not all. While in vivo recordings of single-neuron (i.e., “unit”) activity in patients with epilepsy have a long history, no studies have examined long–term firing rates leading into seizures and the spatial relationship of unit activity with respect to the seizure onset zone. Methods Microelectrode arrays recorded action potentials from neurons in mesial temporal structures (often including contralateral mesial temporal structures) in seven patients with mesial temporal lobe epilepsy. Key Findings Only 7.6% of microelectrode recordings showed increased firing rates prior to seizure onset and only 32.4% of microelectrodes showed any seizure-related activity changes. Surprisingly, firing rates on the majority of microelectrodes (67.6%) did not change throughout the seizure, including some microelectrodes located within the seizure onset zone. Furthermore, changes in firing rate prior to and at seizure onset were observed on microelectrodes located outside the seizure onset zone and even in contralateral mesial temporal lobe. These early changes varied from seizure to seizure, demonstrating the heterogeneity of ensemble activity underlying the generation of focal seizures. Increased neuronal synchrony was primarily observed only following seizure onset. Significance These results suggest that cellular correlates of seizure initiation and sustained ictal discharge in mesial temporal lobe epilepsy involve a small subset of the neurons within and outside the seizure onset zone. These results further suggest that the “epileptic ensemble or network” responsible for seizure generation are more complex and heterogeneous than previously thought and that future studies may find mechanistic insights and therapeutic treatments outside the clinical seizure onset zone.
Bower, Mark R.; Stead, Matt; Meyer, Fredric B.; Marsh, W. Richard; Worrell, Gregory A.
In spite of its universal acceptance, the international classification of epileptic seizures suffers from certain limitations. The fundamental divisions between partial and generalized seizures on the one hand, and between partial simple and complex seizures on the other, are not always practical, nor useful. The terminology is often cumbersome, and does not contain essential localizing information. Finally, the seizure classification is sometimes dependent on ancillary testing, particularly the EEG. We propose a different seizure classification, which answers the above shortcomings of the international classification, and which has been used for years in major epilepsy centers. In this system, the seizure classification is based exclusively on seizure symptomatology. The terms are generally more concise than those of the international classification, and yet convey more precise information. For example, the term left visual aura-->automotor seizure-->generalized tonic clonic seizure would be equivalent to simple partial seizure with visual symptom evolving into complex partial seizure evolving into generalized tonic clonic seizure. The international classification is longer and omits essential later-alizing information. This classification is easy to apply, and can be an extremely useful complement to the international seizure classification, especially for centers whose emphasis is on surgical treatment of epilepsy. PMID:8684356
Benbadis, S; Lüders, H
Neurocysticercosis is the commonest cause for adult onset of seizures in developing countries, and is relatively uncommon in Singapore. However, with the influx of foreign workers from developing countries, we need to consider it as a differential diagnosis in our approach to adult-onset seizures in this group of patients. We describe a neurocysticercosis occurring in a 22-year-old Indian man who presented with a single episode of generalised tonic-clonic seizures. Magnetic resonance imaging of the brain showed a well-defined, hypointense lesion in the cortical and subcortical regions of the left frontal lobe with adjacent vasogenic oedema. Following contrast administration, a well-defined ring enhancement was noted, with suggestion of some internal enhancement. Imaging findings were suggestive of neurocysticercosis. Follow-up magnetic resonance imaging of the brain two weeks after treatment showed lesion resolution. PMID:18581006
Foo, S S; Selvan, V S; Clarke, M J; Shen, E J E
The effect of exercise on seizure frequency is uncertain. While some investigators have reported an increase in the normal background frequency of EEGs after exercise, other investigators believe that exercise increases EEG epileptiform activity in the recovery period following exercise. We asked all patients over a two month period at our outpatient Epilepsy Clinic to complete a questionnaire regarding their exercise habits. Those who were not otherwise healthy, were non-compliant with their medications, or whose blood levels were not therapeutic were eliminated from the analysis. Utilizing the complex Chi-square method, it was determined that patients who participated in some form of exercise had significantly fewer seizures than those who did not exercise (p less than 0.05). Conclusions from this brief study indicate the need for a more comprehensive trial, including EEGs, biochemical studies, and fitness evaluations, to determine the effects of an exercise program on seizure frequency. PMID:2769084
Denio, L S; Drake, M E; Pakalnis, A
We present a male infant with hemifacial seizures refractory to antiepileptic medication. Hemifacial spasms around the left eye were frequent during wakefulness and sleep since birth. He also had mild psychomotor retardation. Magnetic resonance imaging (MRI) revealed a large tumor in the left middle cerebellar peduncle. Ictal single photon emission computed tomography (SPECT) and ictal (18)F-fluorodeoxyglucose [(18)F-FDG] positron emission tomography (PET) revealed hyperperfusion and hyper glucose metabolism at the tumor. Total removal of the tumor resulted in complete disappearance of hemifacial seizures and improved psychomotor development, indicating that the cerebellar tumor caused hemifacial seizures. A histopathological study confirmed that the tumor was a ganglioglioma. This case and the literature on similar cases indicated that this was a new epileptic syndrome originating in the cerebellum. Early diagnosis and early complete removal of the epileptogenic lesion should be recommended for this syndrome. PMID:19628347
Hanai, Sae; Okazaki, Ken-ichi; Fujikawa, Yoshinao; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Otsuki, Taisuke
The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no
P Yogeeswari; D Sriram; V Saraswat; J. Vaigunda Ragavendran; M. Mohan Kumar; S Murugesan; R Thirumurugan; J. P Stables
Measurement of the near-threshold fatigue crack growth rate (FCGR) behavior provides a basis for the design and evaluation of components subjected to high cycle fatigue. Typically, the near-threshold fatigue regime describes crack growth rates below approximately 10(exp -5) mm/cycle (4 x 10(exp -7) inch/cycle). One such evaluation was recently performed for the binary alloy U-6Nb. The procedures developed for this evaluation are described in detail to provide a general test method for near-threshold FCGR testing. In particular, techniques for high-resolution measurements of crack length performed in-situ through a direct current, potential drop (DCPD) apparatus, and a method which eliminates crack closure effects through the use of loading cycles with constant maximum stress intensity are described.
Freeman, D. C.; Strum, M. J.
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.
Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.
Generalized absence seizures are neurophysiologically, pharmacologically, and developmentally unique and comprise the primary seizure type in a number of different absence epilepsy syndromes. Over the last 10 years, the availability of a number of animal models of generalized absence seizures and of sophisticated in vitro electrophysiological techniques that allow investigation of cortical and thalamic networks has begun to shed light on the pathogenesis of this disorder. The basic underlying mechanism appears to involve thalamocortical circuitry and the generation of abnormal oscillatory rhythms from that particular neuronal network. Biochemical mechanisms operative within thalamocortical circuitry during this neuronal oscillation seem to entail phase-locked gamma-aminobutyric acid (GABA)B-mediated inhibition alternating with glutamate-mediated excitation. The basic cellular mechanism operative within this tension between excitation and inhibition appears to involve the T-type calcium current. Local circuitry within the thalamus may influence these oscillatory rhythms by GABAA-mediated inhibition. Pharmacological factors at play external to thalamocortical circuitry include cholinergic, dopaminergic, and noradrenergic mechanisms. Pathways that utilize these various neurotransmitters project onto the thalamus and/or cortex from sites distant to those structures and may modulate the process either up or down. Perturbation of one or more of these neuronal networks may lead to abnormal neuronal oscillatory rhythms within thalamocortical circuitry, with a resultant generation of bilaterally synchronous spike wave discharges that characterize generalized absence seizures. Our increasing understanding of the basic mechanisms that underlie generalized absence seizures promises to allow, for the first time, a rational design of drug treatment for a seizure disorder based on the pathogenesis of that disorder. PMID:7847856
Snead, O C
A 35-year-old, 50-kg female with a history of epilepsy was scheduled for elective breast surgery (fibroadenoma) under general anaesthesia. She was given glycopyrrolate 0.2 mg, ondansetron 4 mg and tramadol 100 mg i.v. as premedication. Within 5 min, she had an acute episode of generalised tonic–clonic seizure that was successfully treated with 75 mg thiopentone i.v. and after 30 min, she was given general anaesthesia with endotracheal intubation. Surgery, intra-operative period, extubation and post-operative period were uneventful. We conclude that tramadol may provoke seizures in patients with epilepsy even within the recommended dose range.
Raiger, Lalit Kumar; Naithani, Udita; Bhatia, Sonali; Chauhan, Sandeep Singh
A 43-year-old man presented to the Prince of Wales Hospital, Sydney, New South Wales, Australia, after experiencing his first tonic-clonic seizure. For the previous 2 years he had undergone gastroenterological investigation of episodes of gagging associated with hypersalivation and lachrymation, occurring three or four times per week. EEG showed epileptiform discharges in the right anterior temporal region; brain MRI revealed a lesion in the right insular cortex. Video-EEG telemetry demonstrated that the episodes of gagging were focal seizures. Antiepileptic drug therapy resulted in no further episodes occurring over the next 10 months.
Dionisio, S; Koenig, A; Murray, J; Somerville, E
We describe a case of idiopathic long-QT syndrome in a 4-year-old Hispanic girl. She had been seen previously at an outside hospital for possible new-onset seizure disorder but was brought to our emergency department after sustaining an unwitnessed fall. Her ECG was significant for changes consistent with long-QT syndrome. Emergency physicians should understand the necessity of electrocardiography in all pediatric patients who present with multiple spontaneous falls, episodes of dizziness, new-onset seizure activity and syncopal episodes. PMID:8909279
Bell, M R; Kozak, R J
Recent progress in neurobiology suggests that astrocytes - through calcium excitability - are active partners to the neurons by integrating their activity and, in turn, regulating synaptic transmission. In a similar fashion neurons and interneurons are the 'Yin and Yang' of the hippocampus. The dichotomy of excitation and inhibition between pyramidal neurons and interneurons plays a crucial role in the function of the neuronal circuit.We consider a model of a pyramidal cell in contact with one synaptic astrocytes. It has been shown that such a circuit - triggered by transient stimulation - can exhibit sustained oscillations ("seizures") for strong coupling. The question we are considering is, under what conditions synaptic inhibition can stop these seizures?
Nadkarni, Suhita; Jung, Peter
Psychogenic non-epileptic seizures (PNES) are common, but have not been well studied in older patients. We retrospectively reviewed patients with PNES who were 60 years of age and above at the time of "seizure" onset. Over a 27-month period, nine (9.6%) of 94 patients diagnosed with PNES had onset at age 60 or above. None had evidence for coexisting epilepsy. Eight were women. Characteristics of the group were comparable to younger patients with PNES. We conclude that PNES should be considered as a diagnostic possibility in older patients. PMID:16531122
Behrouz, Reza; Heriaud, Leanne; Benbadis, Selim R
A 35-year-old, 50-kg female with a history of epilepsy was scheduled for elective breast surgery (fibroadenoma) under general anaesthesia. She was given glycopyrrolate 0.2 mg, ondansetron 4 mg and tramadol 100 mg i.v. as premedication. Within 5 min, she had an acute episode of generalised tonic-clonic seizure that was successfully treated with 75 mg thiopentone i.v. and after 30 min, she was given general anaesthesia with endotracheal intubation. Surgery, intra-operative period, extubation and post-operative period were uneventful. We conclude that tramadol may provoke seizures in patients with epilepsy even within the recommended dose range. PMID:22529421
Raiger, Lalit Kumar; Naithani, Udita; Bhatia, Sonali; Chauhan, Sandeep Singh
Epileptic seizures show a certain degree of rhythmicity, a feature of heuristic and practical interest. In this paper, we introduce a simple model of this type of behavior, and suggest a measure for detecting and quantifying it. To evaluate our method, we develop a set of test segments that incorporate rhythmicity features, and present results from the application of this measure to test segments. We then analyze electrocorticogram segments containing seizures, and present two examples. Finally, we discuss the similarity of our method to techniques for detecting unstable periodic orbits in chaotic time series.
Harrison, Mary Ann F.; Frei, Mark G.; Osorio, Ivan
Thrombin is a serine protease playing an essential role in the blood coagulation cascade. Recent work, however, has identified a novel role for thrombin-mediated signaling pathways in the central nervous system. Binding of thrombin to protease-activated receptors (PARs) in the brain appears to have multiple actions affecting both health and disease. Specifically, thrombin has been shown to lead to the onset of seizures via PAR-1 activation. In this perspective article, we review the putative mechanisms by which thrombin causes seizures and epilepsy. We propose a potential role of PAR-1 antagonists and novel thrombin inhibitors as new, possible antiepileptic drugs.
Maggio, Nicola; Blatt, Ilan; Vlachos, Andreas; Tanne, David; Chapman, Joab; Segal, Menahem
Epileptic seizures in 211 canine and feline patients diagnosed with idiopathic epilepsy were evaluated for temporal significance in relation to the lunar cycle. Seizure counts were compared among each of the eight individual lunar phases, among each of eight exact lunar phase dates, and by percent of lunar illumination using generalized estimating equations. No statistical significance was found in any of these comparisons excluding a relationship between the onset of epileptic seizures and the phases of the moon. Alteration in anticonvulsant treatment or monitoring of canine and feline patients with idiopathic epilepsy at large was not warranted based on the lunar cycle. PMID:21852516
Browand-Stainback, Laura; Levesque, Donald; McBee, Matthew
... without talking to their health care professional, as stopping anti-seizure treatment suddenly can precipitate withdrawal seizures, a serious and life ... More results from www.fda.gov/drugs/drugsafety
... without talking to their health care professional, as stopping anti-seizure treatment suddenly can precipitate withdrawal seizures, a serious and life ... More results from www.fda.gov/drugs/drugsafety/drugsafetypodcasts
Results of the studies indicate that acute administration of Delta tetrahydrocannabinol(THC), in sufficiently high doses, will abolish spontaneous seizures in the sensitive strain of gerbils. The dose required to prevent the seizures gave rise to a marked...
B. Cox M. ten Ham W. J. Loskota P. Lomax
One hundred twenty-nine schizophrenic inpatients who were administered zotepine were studied to see if they had zotepine-induced convulsive seizures. Twenty-two patients had grand mal seizures during the administration periods. The incidence of the seizure was 17.1% and was higher than that in previous reports. The average duration of zotepine administration before the seizure was 48.3 days. The incidence of the seizure was closely related to the daily dosage of zotepine, but there was no significant correlation between the daily dosage of zotepine and the duration of administration before the onset of the seizure. The patients who received a combined administration with the higher dose of zotepine and other phenothiazines were revealed to be more likely to have the seizure. In addition, young patients and patients with a past history of head injuries showed a high incidence of the seizure with the administration of zotepine. PMID:1353125
Hori, M; Suzuki, T; Sasaki, M; Shiraishi, H; Koizumi, J
Many children with Autism Spectrum Diseases (ASD) present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.
Summary Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality\\u000a and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have\\u000a described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital,\\u000a institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam,
Daniel P. Wermeling
Seizures have both local and remote effects on nervous system function. While propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation, however we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multi-modal studies of partial and secondarily-generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast poly-spike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging (fMRI) weighted for blood oxygenation (BOLD) and blood volume (CBV), demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures; and increases in all these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness.
Englot, Dario J.; Mishra, Asht M.; Mansuripur, Peter K.; Herman, Peter; Hyder, Fahmeed; Blumenfeld, Hal
Cerebrovascular blood flow in absence seizures and flow patterns during the ictal period have not been thoroughly investigated.\\u000a We aimed to evaluate cerebral blood flow changes in typical juvenile absence seizures during the ictal and postictal phases.\\u000a Seizures were recorded in three patients (mean age: 21 ± 1 years) with multiple daily typical absence seizures. Simultaneous\\u000a video electroencephalography and bilateral middle cerebral artery
Semai Bek; Tayfun Ka?ikçi; Gençer Genç; ?eref Demirkaya; Zeki Gökçil; Zeki Odaba?i
The association between partial seizures and cardiac asystole has rarely been reported in the literature. This potentially\\u000a life-threatening symptom has been observed principally in left-sided epilepsies, in particular during seizures originating\\u000a in temporal lobe. We describe a case with ictal bradycardia followed by cardiac asystole during right frontal lobe seizures.\\u000a Video-EEG monitoring recorded two partial seizures with electro-clinical findings suggestive
A. Mascia; P. P. Quarato; A. Sparano; V. Esposito; F. Sebastiano; G. Occhiogrosso; G. Di Gennaro
The authors retrospectively reviewed all neurologic records of an emergency unit from 1999 to 2003 to identify a potential association between lunar phases and seizure occurrence. Overall 859 patients admitted for seizure occurrence were divided into the four quarters of the synodic month according to moon phases. A significant clustering of seizures around the full moon period was observed, supporting the ancient belief of periodic increased seizure frequency during full-moon days. PMID:16682684
Polychronopoulos, P; Argyriou, A A; Sirrou, V; Huliara, V; Aplada, M; Gourzis, P; Economou, A; Terzis, E; Chroni, E
Reviews the college completion/graduation rate thresholds developed by several states and discusses advantages and disadvantages of several statistical approaches, including use of the one standard deviation lower bound method, the logit prediction bound method, the linear regression method, and the logistic regression method. (DB)
Underwood, David G.; Rieck, James R.
A general canonical theory is developed for the systematic approximation of optimum, or Bayes, detection procedures in the critical limiting threshold mode of operation. The approximations to Bayes detectors introduced here are called locally optimum Bayes detectors (LOBD's) and are defined by the condition that they produce the same value of average risk and its derivative for vanishingly small input
We present threshold DSS (Digital Signature Standard) signatures where the power to sign is shared by players such that for a given parameter any subset of signers can collaborate to produce a valid DSS signature on any given message, but no subset of corrupted players can forge a signature (in particular, cannot learn the signature key). In addition, we present
Rosario Gennaro; Stanislaw Jarecki; Hugo Krawczyk; Tal Rabin
We present an RSA threshold signature scheme. The scheme enjoys the following properties: 1. it is unforgeable and robust in the random oracle model, assuming the RSA problem is hard; 2. signature share generation and veriflcation is completely non-inter- active; 3. the size of an individual signature share is bounded by a constant times the size of the RSA modulus.
Febrile seizures (FS) require both acute and chronic management. Acute management includes the treatment and differential diagnosis of FS and depend on the presence of seizures and a patient’s level of consciousness upon arrival at hospital: a patient may be discharged after physical examination if there are no seizures and no alteration of consciousness; close observation and laboratory examinations may
Psychogenic seizures are unusual during the first decade of life. To compare the clinical features of psychogenic seizures in young children with those of teenagers, the long-term electroencephalographic and video monitoring studies of all patients younger than 18 years of age with recorded episodes diagnosed as psychogenic seizures were reviewed from a single hospital during the past 7 years. The
Uri Kramer; Lionel Carmant; James J. Riviello; Amy Stauffer; Sandra L. Helmers; Mohamad A. Mikati; Gregory L. Holmes
Epilepsy is a brain disease that requires distributed neuronal networks for its expression. Several characteristics of epilepsy, including its natural history, the latency between an initial insult and the first manifestation of seizures, the complex interaction of seizures with development as a function of developmental stage, the modulating effect of systemic physiological responses, and the fact that seizures are ultimately
Andrew J. Cole; Sookyong Koh; Yi Zheng
Most reports of the ketogenic diet have focused on its efficacy for generalized seizures. Few data are available regarding its effect on focal seizures. We retrospectively studied patients (mean = 7.5 years of age) with medically intractable epilepsy treated by the ketogenic diet. The predominant seizure types in each patient were classified as generalized (100 patients) or focal (34 patients)
Bernhard V Maydell; Elaine Wyllie; Nadia Akhtar; Prakash Kotagal; Kathy Powaski; Karen Cook; Arie Weinstock; A. David Rothner
Rationale: Some types of seizures in children may be difficult to recognize; the diagnosis of seizures arising near the mesial posterior frontal supplementary sensorimotor area (SSMA) may be especially challenging. Such seizures have been well described in adults, but few pediatric cases have been reported even though onset is typically in childhood. Methods: We studied 11 children and adolescents with
Nancy Bass; Elaine Wyllie; Youssef Comair; Prakash Kotagal; Paul Ruggieri; Hans Holthausen
“Taking the history” remains the most important diagnostic tool in the assessment of people who have lost consciousness. The distinction of epileptic and non-epileptic seizures (NES) is particularly difficult and relevant. Whereas epileptic seizures can usually be controlled with antiepileptic drugs, NES are considered an expression of psychosocial distress and may improve with psychotherapy. The recording of typical seizures with
Meike Schwabe; Stephen J. Howell; Markus Reuber
Defining precisely the site of seizure onset has important implications for our understanding of the pathophysiology of temporal lobe epilepsy, as well as for the surgical treatment of the disorder. Removal of the limbic areas of the medial temporal lobe has led to a high rate of seizure control, but the relatively large number of patients for whom seizure control
Edward H. Bertram
It is well documented that prolonged seizures (status epilepticus) can cause neuronal injury and result in synaptic reorganization in certain brain regions. However, the effect of recurrent, relatively short seizures in young animals on subsequent brain development is not known. To study the consequences of recurrent seizures on the developing brain, we subjected immature rats to a total of 50
Z Liu; Y Yang; D. C Silveira; M. R Sarkisian; P Tandon; L.-T Huang; C. E Stafstrom; G. L Holmes
Refractory gelastic seizures are often associated with hypothalamic hamartoma (HH). Presurgical evaluation in such children often points to a distinct cortical region as the source of the seizures. A case of a child with HH and refractory seizures is presented. Video-EEG monitoring revealed a well-defined epileptic focus in the left frontal region. In accordance with the current understanding of the
Uri Kramer; Sergey Spector; Walid Nasser; Vitali Siomin; Itzhak Fried; Shlomi Constantini
Neonatal seizures are markers for time-specific etiologies during antepartum, intrapartum and neonatal time periods. Seizures with or without encephalopathic signs can represent a continuum of maternal, placental, fetal and neonatal risk factors and disease states. A multi-dimensional classification scheme for neonatal seizures is suggested that will help strategize specific therapeutic interventions to optimize neurologic outcome and anticipate later neurological morbidities
Mark S. Scher
...Part 233 Inspection Service Authority; Seizure and Forfeiture AGENCY: Postal Service...Service's rules and regulations regarding the seizure and forfeiture of property into three...sections 233.8 and 233.9, and treats seizures involving personal use quantities of...
Seizures are more common in individuals with intellectual disabilities than in the general population. As a result, differences in functioning for individuals with intellectual disability with and without seizures have been evaluated. Research on differences in psychopathology for individuals with intellectual disability with and without seizures…
Fitzgerald, Mary E.; Matson, Johnny L.; Barker, Alyse
...2011-04-01 2010-04-01 true Seizure or forfeiture. 555.186 Section...of Plastic Explosives Â§ 555.186 Seizure or forfeiture. Any plastic explosive...S.C. 842(l)-(n) is subject to seizure and forfeiture, and all provisions...
...2012-10-01 false Notification of seizure. 12.11 Section 12.11 Wildlife...AND IMPORTATION OF WILDLIFE AND PLANTS SEIZURE AND FORFEITURE PROCEDURES Preliminary Requirements Â§ 12.11 Notification of seizure. Except where the owner or...
...2011-10-01 false Notification of seizure. 12.11 Section 12.11 Wildlife...AND IMPORTATION OF WILDLIFE AND PLANTS SEIZURE AND FORFEITURE PROCEDURES Preliminary Requirements Â§ 12.11 Notification of seizure. Except where the owner or...
A 34 year old woman developed cerebral infarction, following a tonic-clonic seizure. A vertebral artery dissection was demonstrated and may have been caused by arterial trauma during the seizure. This cause of morbidity following convulsive seizures may have been overlooked in the past and needs to be recognised in view of the potential benefits of anticoagulation.
C A Young; D W Chadwick; P R Humphrey
Background:Patients can sustain injuries during seizures and the pattern and type of injury (eg, tongue biting) can be a useful silent witness in the diagnosis of seizures. In addition, the seizure type potentially influences the type of injury.Methods:Patients with dental injury were identified from the Gloucestershire Epilepsy Database (n = 1673). These patients’ notes were reviewed and the following data
R H Thomas; S Higgins; G N Fuller
This presentation will focus on the process of commercializing technology designed to predict/detect seizures. The author will present general design criteria for an implantable device used chronically by an individual with epilepsy to manage their seizur...
M. T. Rise
The phosphorylated form of histone H2A.X (?-H2AX) is a well-documented early, sensitive and selective marker of DNA double-strand breaks (DSBs). Previously we found that excessive glutamatergic activity increased ?-H2AX in neurons in vitro. Here we evaluated ?-H2AX formation in the adult rat brain following neuronal excitation evoked by seizure activity in vivo. We found that brief, repeated electroconvulsive shock (ECS)-induced seizures (three individual seizures within 60 min) did not trigger an increase ?-H2AX immunostaining. In contrast, a cluster of 5–7 individual seizures evoked by kainic acid (KA) rapidly (within 30 min) induced ?-H2AX in multiple neuronal populations in hippocampus and entorhinal cortex. This duration of seizure activity is well below threshold for induction of neuronal cell death, indicating that the ?-H2AX increase occurs in response to sublethal insults. Moreover, an increase in ?-H2AX was seen in dentate granule cells which are resistant to cell death caused by KA-evoked seizures. With as little as a 5 min duration of status epilepticus (SE), ?-H2AX increased in CA1, CA3 and entorhinal cortex, to a greater extent than observed after the clusters of individual seizures, with still greater increases after 120 min of SE. Our findings provide the first direct demonstration that DNA DSB damage occurs in vivo in the brain following seizures. Furthermore, we found that the ?-H2AX increase caused by 120 min of SE was prevented by neuroprotective preconditioning with ECS-evoked seizures. This demonstrates that DNA DSB damage is an especially sensitive indicator of neuronal endangerment, and that it is responsive to neuroprotective intervention.
Crowe, S.L.; Tsukerman, S.; Gale, K.; Jorgensen, T.J.; Kondratyev, A.
This paper reviews the application of the Fourth Amendment, which protects persons against unreasonable search and seizure, as it applies to the student-college relationship. The topics discussed in terms of federal and state court decisions include warrantless searches, delegation of authority to conduct searches, notice of identity and purpose…
Mondschein, Eric S.; West, Michael A.
|Chapter 5 in a book on school law reviews the law governing search and seizure in the public school setting. Three types of searches illustrate problems encountered by school personnel: the search of a student's person, including the "strip search"; the search of a vehicle; and the search of a school newspaper room. Recent case law indicates that…
Brammer, J. William, Jr.
Chapter 5 in a book on school law reviews the law governing search and seizure in the public school setting. Three types of searches illustrate problems encountered by school personnel: the search of a student's person, including the "strip search"; the search of a vehicle; and the search of a school newspaper room. Recent case law indicates that…
Brammer, J. William, Jr.
|As many as 325,000 school-age children, ages 5-14, have epilepsy in the U.S. Thankfully, with medication, surgery, a special diet or vagus nerve stimulation, most go to school and fully participate in school activities. Children who continue to have seizures, however, may run into problems. Many of these problems can be overcome or prevented…
Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABAA receptors or by hyperpolarizing the GABAA reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABAA receptor-mediated chloride influx shifts EGABA to produce a positive feedback loop that contributes to the initiation of seizure activity.
Lillis, Kyle P; Kramer, Mark A; Mertz, Jerome; Staley, Kevin J
Educators concerned about school safety have resorted to searching students, their lockers, and their possessions. These searches have led to litigation over whether the Fourth Amendment's prohibition of unreasonable searches and seizures applies to public schools. Although courts have upheld reasonable searches, administrators should carefully…
Russo, Charles J.; Stefkovich, Jacqueline A.
The protection afforded a minor student by the fourth amendment is perhaps open to some speculation due to his age and the unique situation presented by the school environment. The search and seizure issue is discussed in terms of the findings in several court cases. For journal availability see HE 508 741. (LBH)
Medlin, Kay Cowden
The pharmacokinetics of levetiracetam were determined prospectively in 18 neonates with seizures. Neonates were found to have lower clearance, higher volume of distribution, and a longer half-life as compared with older children and adults. Mild somnolence was the only adverse effect.
Merhar, Stephanie L.; Schibler, Kurt R.; Sherwin, Catherine M.; Meinzen-Derr, Jareen; Shi, Jing; Balmakund, Tonya; Vinks, Alexander A.
The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis. PMID:23998423
Liimatainen, Suvi; Kai, Lehtimäki; Johanna, Palmio; Tiina, Alapirtti; Jukka, Peltola
This study identifies characteristic features in scalp EEG that simultaneously give the best discrimination between epileptic seizures and background EEG in minimally pre-processed scalp data; and have minimal computational complexity to be suitable for online, real-time analysis. The discriminative performance of 65 previously reported features has been evaluated in terms of sensitivity, specificity, area under the sensitivity-specificity curve (AUC), and relative computational complexity, on 47 seizures (split in 2,698 2 s sections) in over 172 h of scalp EEG from 24 adults. The best performing features are line length and relative power in the 12.5-25 Hz band. Relative power has a better seizure detection performance (AUC = 0.83; line length AUC = 0.77), but is calculated after the discrete wavelet transform and is thus more computationally complex. Hence, relative power achieves the best performance for offline detection, whilst line length would be preferable for online low complexity detection. These results, from the largest systematic study of seizure detection features, aid future researchers in selecting an optimal set of features when designing algorithms for both standard offline detection and new online low computational complexity detectors. PMID:22476713
Logesparan, Lojini; Casson, Alexander J; Rodriguez-Villegas, Esther
A dynamical analogy supported by five scale-free statistics (the Gutenberg-Richter distribution of event sizes, the distribution of interevent intervals, the Omori and inverse Omori laws, and the conditional waiting time until the next event) is shown to exist between two classes of seizures (``focal'' in humans and generalized in animals) and earthquakes. Increments in excitatory interneuronal coupling in animals expose
Ivan Osorio; Mark G. Frei; Didier Sornette; John Milton; Ying-Cheng Lai
Imbalance of the excitatory neurotransmitter glutamate and of the inhibitory neurotransmitter GABA is one of several causes of seizures. ATP has also been implicated in epilepsy. However, little is known about the mechanisms involved in the release of ATP from cells and the consequences of the altered ATP signaling during seizures. Pannexin1 (Panx1) is found in astrocytes and in neurons at high levels in the embryonic and young postnatal brain, declining in adulthood. Panx1 forms large-conductance voltage sensitive plasma membrane channels permeable to ATP that are also activated by elevated extracellular K+ and following P2 receptor stimulation. Based on these properties, we hypothesized that Panx1 channels may contribute to seizures by increasing the levels of extracellular ATP. Using pharmacological tools and two transgenic mice deficient for Panx1 we show here that interference with Panx1 ameliorates the outcome and shortens the duration of kainic acid-induced status epilepticus. These data thus indicate that the activation of Panx1 in juvenile mouse hippocampi contributes to neuronal hyperactivity in seizures.
Santiago, Marcelo F.; Veliskova, Jana; Patel, Naman K.; Lutz, Sarah E.; Caille, Dorothee; Charollais, Anne; Meda, Paolo; Scemes, Eliana
This paper develops the fusion of audio and video features by Dempster-Shafer theory for seizure detection. In audio analysis, Mel frequency cepstral coefficient (MFCC) and zero-crossing rate (ZCR) are applied to hidden Markov model (HMM) for audio type classification and probability computation. The results are transferred to belief of evidence and combined with the results from videos. Results have been
Yu-ting Shen; Pau-choo Chung; Monnique Thonnet; Patrick Chauvel
As many as 325,000 school-age children, ages 5-14, have epilepsy in the U.S. Thankfully, with medication, surgery, a special diet or vagus nerve stimulation, most go to school and fully participate in school activities. Children who continue to have seizures, however, may run into problems. Many of these problems can be overcome or prevented…
As parents and caregivers, their job is to help their children become happy, healthy, and productive members of society. They try to balance the desire to protect their children with their need to become independent young adults. This can be a struggle for parents of teens with seizures, since there are so many challenges they may face. Teenagers…
Neonatal seizures are a potentially life-threatening pediatric problem with a variety of causes, such as birth trauma, asphyxia, congenital anomalies, metabolic disturbances, infections, and drug withdrawal or intoxication. Thorough and timely evaluations of such patients are necessary to identify and treat the underlying etiology, therefore reducing potential morbidity and mortality. We review neonatal seizures and hypocalcemia and present the case of a 6-day-old male infant who presented to a tertiary pediatric emergency department with seizure-like episodes. He was found to have markedly low serum calcium, magnesium, and parathyroid hormone concentrations, as well as a significantly elevated serum phosphate concentration. The etiology of these abnormalities was found to be maternal ingestion of extremely high doses of calcium carbonate during the third trimester of her pregnancy, an occurrence that has been reported only once in the literature. Education pertaining to the dangers of excessive calcium carbonate intake during pregnancy may be an important piece of anticipatory guidance for pregnant mothers with symptoms of gastroesophageal reflux, and questioning the mother of a neonate presenting with seizures about such over-the-counter medications may help to elucidate the diagnosis. PMID:24084610
Thornton, Matthew D; Chen, Lei; Langhan, Melissa L
We reviewed the records of 98 consecutive patients, 18 years of age or younger, with pathologically confirmed supratentorial astroglial neoplasms at the Children’s Hospital, Boston, to evaluate the importance of seizures in their presentation and natural history. Tumors were diagnosed using the WHO criteria as pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, glioblastomas, giant cell glioblastomas, oligoastrocytomas and gangliogliomas. Our results were
Joseph A. Shady; Peter Mc L. Black; William J. Kupsky; Nancy J. Tarbell; Michael Scott; Traci Leong; Gregory Holmes
The neurobiological doctrine governing the concept of neurogenesis has undergone a revolution in the past few years. What was once considered dubious is now well accepted: new neurons are born in the adult brain. Science fiction is quickly becoming a reality as scientists discover ways to convert skin, bone, or blood cells into neurons. In the epilepsy arena, widespread interest has developed because of the evidence that neurogenesis increases after seizures, trauma, and other insults or injuries that alter seizure susceptibility. This review discusses some of the initial studies in this field, and their often surprising functional implications. The emphasis will be on the granule cells of hippocampus, because they are perhaps more relevant to epilepsy than other areas in which neurogenesis occurs throughout life, the olfactory bulb and subventricular zone. In particular, the following questions will be addressed: 1. Do granule cells that are born in the adult brain become functional, and what are the limits of their function? Do they behave homogeneously? Results from our own laboratory have focused on cells that become established outside the normal boundaries of the granule cell layer, forming a group of "ectopic" granule cells in the hilar region. 2. Is increased neurogenesis beneficial, or might it actually exacerbate seizures? Evidence is presented that supports the hypothesis that new granule cells may not necessarily act to ameliorate seizures, and might even contribute to them. Furthermore, cognitive deficits following seizures might in part be due to new circuits that develop between new cells and the host brain. 3. How do the new cells interact with the host brain? Several changes occur in the dentate gyrus after seizures, and increased neurogenesis is only one of many. What is the interdependence of this multitude of changes, if any? 4. Is neurogenesis increased after seizures in man? Research suggests that the data from human epileptics are actually inconsistent with the studies in animal models of epilepsy, because there is little evidence of increased neurogenesis in epileptic tissue resected from intractable epileptics. Yet neurogenesis has been shown to occur in humans throughout adult life. What might be the reasons for these seemingly disparate results? PMID:15250595
Scharfman, Helen E
Article abstract—Objective: To evaluate the effects of sleep on partial seizures arising from various brain regions. Methods: The authors prospectively studied 133 patients with localization-related epilepsy undergoing video-EEG moni- toring over a 2-year period. Seizure type, site of onset, sleep\\/wake state at onset, duration, and epilepsy syndrome diagnosis were recorded. Periorbital, chin EMG, and scalp\\/sphenoidal electrodes were used. A subset
S. T. Herman; T. S. Walczak; C. W. Bazil
This study aimed to investigate whether children with recurrent febrile seizures within a 24-hour period need to be worked up differently from children with simple febrile seizures. Inclusion criteria included the following: (i) children with first seizure cluster between 4 months and 3 years of age, (ii) children who had more than one febrile seizure within 24 hours, and (iii) children who returned to baseline between and after each event. Thirty-two patients met the inclusion criteria over a 3-year period. All patients underwent brain CT and/or MRI and EEG. All head CTs were normal. Two children had abnormal MRI findings - both benign: one is thought to represent postictal changes, and the other one is an incidental arachnoid cyst. Of the 4 abnormal EEGs, one showed epileptiform discharges, while the others showed generalized ictal or postictal features. We propose the term "simple febrile seizures plus (SFS+)" to describe children who have more than one seizure within 24 hours but who are otherwise not different in presentation from children with SFS. PMID:23624109
Grill, Marie F; Ng, Yu-Tze
Recent evidence suggests that hippocampal damage can be both the result of seizure activity and the cause of further chronic epilepsy. A review of current models of status epilepticus-induced brain damage reveals that excitotoxic mechanisms probably mediate the lesions in most brain regions. NMDA receptors appear to play a dominant role, although non-NMDA glutamate receptors are important in several specific neuronal populations. In the immature brain, a number of unique metabolic features determine a different set of vulnerabilities, resulting in a brain which is more resistant than the adult's to certain mechanisms of brain damage, but quite vulnerable to others. The inhibition of growth by severe seizure activity has implications for the developing brain that have not yet been fully explored. The mechanisms by which seizure-induced hippocampal lesions cause chronic epilepsy have been explored in several recent animal models. A rearrangement of hippocampal circuits may result from death of selected populations of inhibitory neurons, or from misdirected regeneration by excitatory neurons. It could lead to chronic epilepsy through loss of normal inhibition, through sprouting of new excitatory connections, through conservation of excitatory connections which in a healthy brain would be pruned during development, or through facilitation of kindling by one of these mechanisms. These recent results are beginning to reconcile the pathology seen in human hippocampi ablated for intractable epilepsy with that observed in experimental animals, and offer the promise of even greater advances in the future. They suggest a mechanism for Gower's dictum that "seizures beget seizures" and highlight the importance of the interneurons of the dentate gyrus in epileptogenesis. PMID:7818023
Wasterlain, C G; Shirasaka, Y
Intoxication with nerve agents produces prolonged central nervous system seizures (status epilepticus) that can produce irreversible brain pathology (15). This report summarizes our recent findings regarding the neurotransmitter changes that occur in discrete brain regions as a function of seizure duration and the differential effectiveness of anticholinergic, benzodiazepine and excitatory amino acid (EAA) antagonist drugs in terminating soman-induced seizures when given at different times after seizure onset. These results are discussed in relation to a model we have proposed to explain the sequence of electrophysiological, biochemical and neurochemical events and mechanisms controlling nerve agent-induced seizures.
McDonough, J.H.; Shih, T.M.; Adams, N.L.; Koviak, T.A.; Cook, L.A.
The seizures which accompany specified situations occur in about 5% of population. They are frequent in patients at developmental age due to a different degree of brain maturity. A single, occasional seizure event which occurs in specified situations is not an epilepsy but it constitutes a significant clinical problem which requires a thorough diagnostics and procedure. We discuss situation-related seizures (also called acute symptomatic seizures) in children, excluding febrile convulsions. We bring attention to situation-related seizures characteristic only of developmental age. PMID:19172835
Szwed-Bia?ozyt, Barbara; Marsza?, Elzbieta
Midazolam meleate, a water soluble 1,4 benzodiazepine, was used intravenously in 20 patients suffering seizures, of whom 12 were in status epilepticus. In all cases, midazolam in a dose of 2.5-15 mg rapidly terminated the seizure. There were no complications from the use of midazolam. The causes of the seizures were varied but alcohol-withdrawal seizures were the single largest cause. Thirteen patients were taking some form of anticonvulsant medication but only three were in the therapeutic range. Midazolam is seen to be an effective agent in the emergency treatment of seizures.
Galvin, G M; Jelinek, G A
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.
Jensen, Frances E.
Time-domain noise analysis techniques such as the Rossi-[alpha], the variance-to-mean, and the interval-distribution methods can be used to measure fundamental reactor parameters in a wise variety of reactor systems, provided the power level of the system is not too high. Simple expressions have been derived that define the maximum power level (i.e., the reactor noise threshold) above which time-domain reactor
The photeneutron thresholds for a number of elements which have 100% ; abundance (or nearly so) in one stable isotope have been measured. The following ; values in Mev were found: Na (12.47 plus or minus 0.05), Al (12.98 plus or ; minus 0.08), P (12.50 plus or minus 0.05), V (11.16 plus or minus 0.05), Mn ; (10.14 plus
B. G. Chidley; L. Katz; S. L. f Kowalski
\\u000a Entrusted undeniable signatures are like undeniable signatures, except that the disavowal protocol can only be run by a court\\u000a in order to resolve a formal dispute. This paper introduces threshold entrusted undeniable signature scheme without trusted\\u000a center. It is shown how the power to run a disavowal protocol of entrusted undeniable signature can be distributed to n agents such that
Seungjoo Kim; Dongho Won
During and just after World War II there was intense interest in the threshold for seeing faint sources against illuminated backgrounds. Knoll, Tousey and Hulburt (1946, 1948) determined the threshold for (effectively) point sources seen against backgrounds ranging in brightness from darkness to subdued daylight. Blackwell (1946) gave contrast ratios for sources of various sizes ranging from point sources up to circular disks of 6 degrees diameter, all seen against the same range of brightnesses, and determined by a very large number of visual observations made by a team of observers. I have combined the two sets of results, and represented them by an improvement on the theoretical formula for threshold illuminance as a function of background brightness which was suggested by Hecht (1934). My formula agrees very well with the observations, and is very suitable for incorporation into computer programs. Applications have been made to problems where the background brightness is caused by light pollution, and the source size is determined by the seeing. These include the optimum magnification and limiting magnitude of telescopes, and the analysis of visual limiting magnitudes determined by Bowen (1947) to determine the night sky brightness at Mount Wilson in 1947.
Garstang, R. H.
This paper presents a novel model-based patient-specific method for automatic detection of seizures in the intracranial EEG recordings. The proposed method overcomes the complexities in the practical implementation of the patient-specific approach of seizure detection. The method builds a seizure model (set of basis functions) for a priori known seizure (the template seizure pattern), and uses the statistically optimal null filters as a building block for the detection of similar seizures. The process of modeling the template seizure is fully automatic. Overall, the detection method involves the segmentation of the template seizure pattern, rejection of the redundant and noisy segments, extraction of features from the segments to generate a set of models, selection of the best seizure model, and training of the classifier. The trained classifier is used to detect similar seizures in the remaining data. The resulting seizure detection method was evaluated on a total of 304 h of single-channel depth EEG recordings from 14 patients. The system performance is further compared to the Qu-Gotman patient-specific system using the same data. A significant improvement in the proposed system, in terms of specificity, is observed over the compared method. PMID:22361656
Yadav, R; Swamy, M N S; Agarwal, R
The aim of the study was to analyse the semiology of seizures in children with frontal lobe epilepsy (FLE) and to compare them with other paediatric cohorts described in the literature as well as with adult counterparts. We analysed 174 registered seizures of 18 cases under 12 years with lesional epilepsy whose frontal origin was defined by the concordance of neuroimaging and ictal electrographic findings, and confirmed by surgery in the six cases operated on. Seizures were generally short, with a high daily frequency and usually related to sleep. The most characteristic semiological pattern consisted of complex motor seizures, particularly hypermotor. Often seizures corresponded to a mixture of different semiological patterns (tonic, gelastic, automotor, hypermotor, versive) presenting in the same seizure, often as a unique type in the same patient. With regard to several aspects the semiology of FLE in our cohort looks like that reported in adult series, in particular as to the frequency of complex motor seizures. However, our cohort was also characterised by a more protean array of seizure semiology, stressing the occurrence of seizures typically present in adults (versive and complex motor) and of some seizure patterns more characteristic in children such as epileptic spasms; moreover, the rare occurrence of secondarily generalised tonic clonic seizures (SGTCS) was confirmed. PMID:18461504
Battaglia, D; Lettori, D; Contaldo, I; Veredice, C; Sacco, A; Vasco, J; Martinelli, D; Chieffo, D; Tartaglione, T; Colosimo, C; Di Rocco, C; Guzzetta, F
The unpredictable and random occurrence of seizures is of the most distressful issue affecting patients and their families. Unattended seizures can have serious consequences including injury or death. The objective of this study is to develop a small, portable, wearable device capable of detecting seizures and alerting patients and families on recognition of specific seizures' motor activity. Ictal data were prospectively obtained in consecutive patients admitted to two video-EEG units. This study included patients with a history of motor seizures, clonic or tonic, or tonic-clonic seizures or patients with complex partial seizures with frequent secondary generalization. A "Motion Sensor" unit mounted on a bracelet was attached to one wrist. The "Sensor" contains a three-axis accelerometer and a transmitter. The three-axis movements' data were transmitted to a portable computer. Algorithm specially developed for this purpose analyzed the recorded data. Seizures' alerts were compared with the video-EEG data. Ictal data were acquired in 15 of the 31 recruited patients. The algorithm correctly identified 20 of 22 (91%) captured seizures and generated an alarm within a median period of 17 seconds. All events lasting >30 seconds (i.e., 19 events) were identified. The system failed to identify 2 of 22 seizures (9%). There were eight false alarms during 1,692 hours of monitoring. Preliminary data suggest that this motion detection device/alarm system can identify most motor seizures with high sensitivity and with a low false alarm rate. PMID:21221012
Kramer, Uri; Kipervasser, Svetlana; Shlitner, Arie; Kuzniecky, Ruben
The international seizure classification recognizes that partial-onset seizures can become secondarily generalized, but generalized-onset seizures are expected to remain generalized. We report six patients who had recorded seizures with generalized onset, but subsequent evolution into a focal discharge. The clinical seizure onset was generalized absence or myoclonic, and the most common subsequent clinical pattern was prolonged behavioral arrest with mild automatisms, and then postictal confusion. The ictal discharge started with generalized spike-and-wave activity and then acquired a focal predominance. Interictal epileptiform activity was generalized. There were no focal magnetic resonance imaging abnormalities. Four patients were misdiagnosed with complex partial seizures. All patients were initially refractory, but three became seizure-free and three improved after treatment with antiepileptic medications appropriate for absence or myoclonic seizures. Generalized-onset seizures that acquire focal features are easily misdiagnosed as complex partial. These seizures have a more favorable response to medications effective against generalized absence and myoclonic seizures. PMID:19260942
Williamson, Randy; Hanif, Samrina; Mathews, Gregory C; Lagrange, Andre H; Abou-Khalil, Bassel
Background A responsive electrical stimulation pattern based on our recently developed novel seizure prediction method was designed to suppress the penicillin-induced epileptic seizures. Methodology Seizures were induced by Penicillin injection at rat cortex. A responsive electrical stimulation system was triggered prior to seizures predicted with phase synchronisation. Rats with induced seizures were stimulated by the electrical pulses at a responsive or 1 Hz periodic pattern of an open system. The effectiveness of stimulation on seizures suppression was assessed by measuring the average number and duration of seizures per hour. Results The prediction algorithm reliably identified seizures in real time and triggered the responsive stimulation. This type of electrical stimulation dramatically suppressed seizure activity and the performance was better than the open stimulation system with fewer and shorter seizures. Conclusions A responsive electrical stimulation system triggered by the phase synchronisation prediction is able to significantly suppress seizures. Significance Responsive electrical stimulation could achieve superior treatment performance and reduce power consumption and side effects.
Wang, Lei; Wang, Shouyan; Xu, Canhua; Fu, Feng; Jing, Xiaorong; Zhang, Hua; Dong, Xiuzhen
A 12-month-old female neutered crossbreed was referred for investigation of seizure-like episodes occurring only at intense exercise. Thorough medical, neurological and cardiac investigations were performed and excluded the most commonly known causes of seizure-like activity. The dog was fitted with an ambulatory electrocardiography device and underwent another exercise-induced seizure. The electrocardiogram during the episode revealed a sinus tachycardia at approximately 300 beats/minute. A video recording of the episode revealed generalised tonic clonic limb activity with jaw chomping and frothing at the mouth typical of seizure activity. Antiepileptic medications were not prescribed and the owner was advised not to exercise the dog intensely. The dog responded well and did not seizure after 12?months of mild-moderate off-lead exercise. As all the seizures in this case were triggered by intense physical activity, it is suggested that this may be a new form of reflex seizure activity. PMID:23387942
Motta, L; Dutton, E
Although pathophysiologically distinct, syncope and seizures share clinical characteristics which may make diagnosis difficult. Adding to diagnostic complexity are the facts that seizures and syncope may coexist in the same patient, syncope may be associated with seizure-like motor manifestations, and seizures may be complicated by cardiac arrhythmia and syncope. Combined EEG/ECG telemetry is sometimes necessary to establish the correct diagnosis. These techniques also provide an opportunity to study the role of certain cortical regions in the modulation of cardiac function. There is an increasing understanding of the central autonomic pathways involved in the genesis of the cardiovascular changes that occur during epileptic seizures. This article reviews the use of EEG/ECG telemetry in the evaluation of syncope and seizures, and the neuroanatomic circuitry involved in the production of the cardiovascular manifestations of seizures. PMID:16477491
Britton, Jeffrey W; Benarroch, Eduardo
Epilepsy is more common in patients with multiple sclerosis (MS) than in the general population, occurring in 2-3% of patients. Convulsions may be either tonic–clonic in nature or partial complex. In these individuals, seizures most likely result from lesions present in the cerebral cortex and subcortical white matter. A Jacksonian seizure is a type of simple partial seizure characterized by abnormal movements that begin in one group of muscles and progress to adjacent groups of muscles. We describe a case of Jacksonian seizure as the relapse symptom of MS. Focal motor seizures of this patient have been observed before and presumably marking the clinical onset or during acute bouts of MS. In this case, Jacksonian seizures appear to be the sign of a flare of MS, while the majority of seizures had been reported occur unrelated to MS relapses.
Najafi, Mohammad Reza; Chitsaz, Ahmad; Najafi, Mohammad Amin
Most work on threshold concepts has hitherto related to discipline-specific undergraduate education, however, the idea of generic doctoral-level threshold concepts appeared to us to provide a strong and useful framework to support research learning and teaching at the graduate level. The early work regarding research-level threshold concepts is…
Kiley, Margaret; Wisker, Gina
Seizure-suppressor mutations provide unique insight into the genes and mechanisms involved in regulating nervous system excitability. Drosophila bang-sensitive (BS) mutants present a useful tool for identifying seizure suppressors since they are a well-characterized epilepsy model. Here we describe the isolation and characterization of a new Drosophila seizure-suppressor mutant that results from disruption of the meiotic gene mei-P26, which belongs to the RBCC-NHL family of proteins. The mei-P26 mutation reduces seizures in easily shocked (eas) and slamdance (sda) epileptic flies following mechanical stimulation and electroconvulsive shock. In addition, mutant mei-P26 flies exhibit seizure thresholds at least threefold greater than those of wild type. The mei-P26 phenotypes appear to result from missense mutation of a critical residue in the NHL protein-protein interaction domain of the protein. These results reveal a surprising role for mei-P26 outside of the germline as a regulator of seizure susceptibility, possibly by affecting synaptic development as a ubiquitin ligase.
Glasscock, Edward; Singhania, Ayush; Tanouye, Mark A.
In previous studies we showed that autonomous absence seizure generation and termination can be explained by realistic neuronal models eliciting bi-stable dynamics. In these models epileptic seizures are triggered either by external stimuli (reflex epilepsies) or by internal fluctuations. This scenario predicts exponential distributions of the duration of the seizures and of the inter-ictal intervals. These predictions were validated in rat models of absence epilepsy, as well as in a few human cases. Nonetheless, deviations from the predictions with respect to seizure duration distributions remained unexplained. The objective of the present work is to implement a simple but realistic computational model of a neuronal network including synaptic plasticity and ionic current dynamics and to explore the dynamics of the model with special emphasis on the distributions of seizure and inter-ictal period durations. We use as a basis our lumped model of cortical neuronal circuits. Here we introduce 'activity dependent' parameters, namely post-synaptic voltage-dependent plasticity, as well as a voltage-dependent hyperpolarization-activated current driven by slow and fast activation conductances. We examine the distributions of the durations of the seizure-like model activity and the normal activity, described respectively by the limit cycle and the steady state in the dynamics. We use a parametric ?-distribution fit as a quantifier. Our results show that autonomous, activity-dependent membrane processes can account for experimentally obtained statistical distributions of seizure durations, which were not explainable using the previous model. The activity-dependent membrane processes that display the strongest effect in accounting for these distributions are the hyperpolarization-dependent cationic (Ih) current and the GABAa plastic dynamics. Plastic synapses (NMDA-type) in the interneuron population show only a minor effect. The inter-ictal statistics retain their consistency with the experimental data and the previous model.
Koppert, M. M. J.; Kalitzin, S.; Lopes da Silva, F. H.; Viergever, M. A.
This paper presents the results of our study on finding a lower complexity and yet a robust seizure prediction method using intracranial electroencephalogram (iEEG) recordings. We compare two classifiers: a low-complexity Adaboost and the more complex support vector machine (SVM). Adaboost is a linear classier using decision stumps, and SVM uses a nonlinear Gaussian kernel. Bipolar and/or time-differential spectral power features of different sub-bands are extracted from the iEEG signal. Adaboost is used to simultaneously classify as well as rank the features. Eliminating the low discriminating features reduces computational complexity and power consumption. The top features selected by Adaboost were also used as a feature set for SVM classification. The outputs of classifiers are regularized by applying a moving-average window and a threshold is used to generate alarms. The proposed methods were applied on 8 invasive recordings selected from the EPILEPSIAE database, the European database of EEG seizure recordings. Doublecross validation is used by separating data sets for training and optimization from testing. The key conclusion is that Adaboost performs slightly better than SVM using a reduced feature set on average with significantly less complexity resulting in a sensitivity of 77.1% (27 of 35 seizures in 873h recordings) and a false alarm rate of 0.18 per hour. PMID:24111182
Bandarabadi, Mojtaba; Dourado, Antonio; Teixeira, Cesar A; Netoff, Theoden I; Parhi, Keshab K
Increased levels of intracellular zinc have been implicated in neuronal cell death in ischaemia, epilepsy and traumatic brain damage. However, decreases in zinc levels also lead to increased neuronal death and lowered seizure threshold. In the present study we investigated the physiological role of zinc in neurodegeneration and protection following epileptic seizures. Cells located in the strata oriens and lucidum of the CA3 region accumulated high concentrations of zinc and died. A decrease in zinc level could prevent the death of these neurones after seizures. Most of these cells were GABAergic interneurones. In contrast, neurones in the CA3 pyramidal cell layer accumulated moderate amounts of zinc and survived. Zinc chelation led to an increase in the mortality rate of these cells. Furthermore, in these cells low concentrations of intracellular zinc activated Akt (protein kinase B), thus providing protection against neurodegeneration. These results demonstrate that intracellularly accumulated zinc can be neurotoxic or neuroprotective depending on its concentration. This dual action is cell type specific.
Cote, Amelie; Chiasson, Marilou; Peralta, Modesto R; Lafortune, Kathleen; Pellegrini, Luca; Toth, Katalin
Trimetazidine, a novel anti-ischemic agent, is used in the therapy of angina, vertigo and chorioretinal diseases. It has also been examined for its effect on nociception, inflammation and neuroprotection in various animal models. The present study was designed to investigate the effect of trimetazidine on electrically induced seizures in mice. Trimetazidine was administered orally in doses of 5, 10 and 20mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test in mice. Trimetazidine in 10 and 20mg/kg doses significantly raised the seizure-threshold current in the ICES test. Further, co-administration of per se ineffective dose of trimetazidine (5mg/kg, p.o.) with sub-anticonvulsant dose of nimodipine (10mg/kg, p.o.) and phenytoin (12.5mg/kg, p.o.) offered significant protection in the ICES test. These results indicate that trimetazidine possesses significant anticonvulsant activity against electro-convulsions in the mice. PMID:20444628
Jain, Seema; Bharal, Nidhi; Mediratta, Pramod Kumari; Sharma, Krishna Kishore
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. PMID:15450934
Threshold models have a wide variety of applications in economics. Direct applications include models of separating and multiple equilibria. Other applications include empirical sample splitting when the sample split is based on a continuously-distributed variable such as firm size. In addition, threshold models may be used as a parsimonious strategy for nonparametric function estimation. For example, the threshold autoregressive model
Bruce E. Hansen
The Stochastic Coherent Adaptive Large Eddy Simulation (SCALES) is a novel wavelet-based approach that resolves energy containing turbulent motions using wavelet multiresolution decomposition and self-adaptivity. The extraction of the most energetic structures is achieved using wavelet thresholding filter with a priori prescribed threshold level. This strategy, although successful, has a major drawback: the thresholding criterion is global and does not
Alireza Nejadmalayeri; Oleg V. Vasilyev; Alexei Vezolainen; Giuliano de Stefano