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...
Adenosine exerts neuromodulatory functions with mostly inhibitory effects, being considered an endogenous anticonvulsant. The hydrolysis of ATP by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the regulation of this nucleoside concentration through its deamination. In this study, we tested the effect of pentylenetetrazole (PTZ)-induced seizures on ectonucleotidase and ADA activities in adult zebrafish brain. Our results have demonstrated that PTZ treatments did not alter ectonucleotidase and ADA activities in membranes and soluble fraction, respectively. However, ecto-ADA activity was significantly decreased in brain membranes of animals exposed to 5mM and 15 mM PTZ treatments (22.4% and 29.5%, respectively) when compared to the control group. Semiquantitative RT-PCR analysis did not show significant changes after the PTZ exposure on ADA gene expression. The decreased adenosine deamination observed in this study suggests a modulation of extracellular adenosine levels during PTZ-induced seizures in zebrafish. PMID:21907764
Siebel, Anna Maria; Piato, Angelo Luis; Capiotti, Katiucia Marques; Seibt, Kelly Juliana; Bogo, Maurício Reis; Bonan, Carla Denise
Teucrium polium (Labiatae) is a plant that widely grows in Iran. Some of species of Teucrium are used for a considerable range of actions in traditional medicine and T. polium has frequently been used as anticonvulsant. In this study, we investigated the protective effects of T. polium ethanolic aqueous extracts and related fractions on seizures induced by pentylenetetrazole (PTZ) and maximal electroshock stimulation (MES). Moreover, presence of alkaloids, terpenoids, tannins and flavonoid contents were evaluated. It was found that aqueous extract (ED50 = 22.4 mg/kg body weight) and related n-butanol fraction (ED50 = 12.6 mg/kg body weight) have antiseizure effects comparing to control groups. There was no difference between preventing of PTZ-induced death and MES-induced hindlimb tonic extension (HLTE) in ethanolic extract comparing to control groups. Our results showed that the amount of flavonoid quantity present in aqueous extract is higher than that of ethanolic extract. These data also showed that the quantity of the flavonoid in n-butanol fraction of aqueous extract is more than other fractions. In conclusion, it was realized that flavonoid rich extracts are more potent than other fractions in showing antiseizure effects.
Khoshnood-Mansoorkhani, Mohammad Javad; Moein, Mahmood Reza; Oveisi, Narjes
Withania somnifera (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of W. somnifera root extract (Ws) alone or in combination with exogenous gamma-amino butyric acid (GABA), a GABA receptor agonist or with diazepam, a GABA receptor modulator against pentylenetetrazol (PTZ, iv) seizure threshold in mice. Minimal dose of PTZ (iv, mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions were recorded as an index of seizure threshold. Ws (100 or 200 mg/kg, po) increased the PTZ seizure threshold for the onset of tonic extension phase whereas a lower dose (50 mg/kg, po) did not show any effect on the seizure threshold. Co-administration of a sub-effective dose of Ws (50 mg/kg, po) with a sub-protective dose of either GABA (25 mg/kg, ip) or diazepam (0.5 mg/kg, ip) increased the seizure threshold. The results suggested that the anticonvulsant effect of W. somnifera against PTZ seizure threshold paradigm involved the GABAAergic modulation. PMID:18697606
Kulkarni, S K; Akula, Kiran Kumar; Dhir, Ashish
High-frequency electrical stimulation of mammillary nuclei (MN) of rat posterior hypothalamus resulted in a significant increase in seizure threshold induced by pentylenetetrazol (PTZ). The anticonvulsant effect was frequency and intensity specific. Stimulation at 100 Hz (1-5 V, 30-200 microA) afforded protection against EEG and behavioral manifestations of PTZ seizures. Stimulation of either low frequency (5 Hz), high intensities (8-20 V, 300-800 microA), or outside the histologically verified MN target region did not increase seizure threshold. In some instances, high-intensity stimulation of MN alone elicited spike-wave epileptiform EEG activity accompanied by either arrest of behavior or myoclonic seizures. In animals with ongoing seizure activity, electrical stimulation of MN disrupted the high-voltage synchronous wave forms on cortical EEG. These data support the concept that electrical perturbation of MN in hypothalamus may functionally inhibit generalization of paroxysmal activity required for expression of the EEG and, in particular, the behavioral component of PTZ seizures. These studies provide additional insight into forebrain-brainstem interactions mediating generalized seizure expression. PMID:7988525
Mirski, M A; Fisher, R S
Recently zebrafish larvae have emerged as a high-throughput model for screening pharmacological activities. The present study was undertaken to investigate the effect of established anticonvulsants, such as valproic acid, carbamazepine, gabapentin, diazepam, lacosamide and pregabalin against pentylenetetrazole (6 mM) seizures in adult zebrafish. Different phases of seizures (increase swim activity, rapid whirlpool-like circling swim behaviour and brief clonus-like seizures leading to loss of posture) were elicited in zebrafish on exposure for 15 min to 6 mM pentylenetetrazole. The exposure of zebrafish to an increasing concentration of the anticonvulsants alongside 6 mM pentylenetetrazole showed concentration-dependent elevation of seizure latency against pentylenetetrazole-induced seizures except for pregabalin, which failed to produce any anticonvulsant activity in zebrafish. Moreover the proconvulsant activity of caffeine was also evaluated using suboptimal concentration (4 mM) of pentylenetetrazole in adult zebrafish. Decrease in seizure latency of different phases of seizures was observed with increasing concentration of caffeine compared with its respective control group. In view of the above findings, the results of the present study suggested that adult zebrafish produce the expected anticonvulsive and proconvulsive effects and could potentially be used as a screen in future epilepsy research.
Gupta, P.; Khobragade, S. B.; Shingatgeri, V. M.
Recently zebrafish larvae have emerged as a high-throughput model for screening pharmacological activities. The present study was undertaken to investigate the effect of established anticonvulsants, such as valproic acid, carbamazepine, gabapentin, diazepam, lacosamide and pregabalin against pentylenetetrazole (6 mM) seizures in adult zebrafish. Different phases of seizures (increase swim activity, rapid whirlpool-like circling swim behaviour and brief clonus-like seizures leading to loss of posture) were elicited in zebrafish on exposure for 15 min to 6 mM pentylenetetrazole. The exposure of zebrafish to an increasing concentration of the anticonvulsants alongside 6 mM pentylenetetrazole showed concentration-dependent elevation of seizure latency against pentylenetetrazole-induced seizures except for pregabalin, which failed to produce any anticonvulsant activity in zebrafish. Moreover the proconvulsant activity of caffeine was also evaluated using suboptimal concentration (4 mM) of pentylenetetrazole in adult zebrafish. Decrease in seizure latency of different phases of seizures was observed with increasing concentration of caffeine compared with its respective control group. In view of the above findings, the results of the present study suggested that adult zebrafish produce the expected anticonvulsive and proconvulsive effects and could potentially be used as a screen in future epilepsy research. PMID:24843189
Gupta, P; Khobragade, S B; Shingatgeri, V M
Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of lithium is mediated via NO-cGMP pathway. Injection of a single effective dose of lithium chloride (25 mg/kg) intraperitoneally (i.p.) increased significantly the seizure threshold (P<0.01). The anticonvulsant properties of the effective dose of lithium were prevented by pre-treatment with the per se non-effective doses of L-ARG [the substrate for nitric oxide synthase; NOS] (30 and 50 mg/kg) or sildenafil [a phosphodiesterase 5 inhibitor] (10 and 20 mg/kg). L-NAME [a non-specific NOS inhibitor] (5, 15 and 30 mg/kg), 7-NI [a specific neural NOS inhibitor] (30 and 60 mg/kg) or MB [a guanylyl cyclase inhibitor] (0.5 and 1 mg/kg) augmented the anticonvulsant effect of a sub-effective dose of lithium (10 mg/kg, i.p.). Whereas several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of lithium. Our findings demonstrated that nitric oxide-cyclic GMP pathway could be involved in the anticonvulsant properties of the lithium chloride. In addition, the role of constitutive NOS versus inducible NOS is prominent in this phenomenon. PMID:20304610
Bahremand, Arash; Nasrabady, Sara Ebrahimi; Ziai, Pouya; Rahimian, Reza; Hedayat, Tina; Payandemehr, Borna; Dehpour, Ahmad Reza
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
Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20-120?mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80?mg/kg) was prevented by 8-phenyltheophylline (0.5?mg/kg, i.p., non-selective adenosine receptor antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (5?mg/kg, i.p., adenosine A1 receptor antagonist) but not by 8-(3-cholorostryl)caffeine (4?mg/kg, i.p., adenosine A2A receptor antagonist). Further, 5'-N-ethylcarboxamidoadenosine (0.005?mg/kg, i.p., non-selective A1 /A2 receptor agonist), or N(6) -cyclohexyladenosine (0.2?mg/kg, i.p., adenosine A1 receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5'-(N-cyclopropyl) carboxamidoadenosine (0.1?mg/kg, i.p., adenosine A2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A1 but not A2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23893477
Akula, Kiran Kumar; Kulkarni, S K
A sensitive method of estimation of generalized seizure thresholds (GSTs) was used to estimate the relative anticonvulsant potencies of four competitive NMDA antagonists against fully amygdala-kindled seizures. All of the antagonists tested showed potent, dose-dependent anticonvulsant activity following focal administration at doses causing no, or only minimal, overt behavioural abnormalities. These doses were similar to those which have previously been
Martin J. Croucher; Katie L. Cotterell; Henry F. Bradford
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...
The epilepsies are a heterogeneous group of neurological diseases defined by the occurrence of unprovoked seizures which, in many cases, are correlated with diurnal rhythms. In order to gain insight into the biological mechanisms controlling this phenomenon, we characterized time-of-day effects on electrical seizure threshold in mice. Male C57BL/6J wild-type mice were maintained on a 14/10 h light/dark cycle, from birth until 6 weeks of age for seizure testing. Seizure thresholds were measured using a step-wise paradigm involving a single daily electrical stimulus. Results showed that the current required to elicit both generalized and maximal seizures was significantly higher in mice tested during the dark phase of the diurnal cycle compared to mice tested during the light phase. This rhythm was absent in BMAL1 knockout (KO) mice. BMAL1 KO also exhibited significantly reduced seizure thresholds at all times tested, compared to C57BL/6J mice. Results document a significant influence of time-of-day on electrical seizure threshold in mice and suggest that this effect is under the control of genes that are known to regulate circadian behaviors. Furthermore, low seizure thresholds in BMAL1 KO mice suggest that BMAL1 itself is directly involved in controlling neuronal excitability.
Gerstner, Jason R.; Smith, George G.; Lenz, Olivia; Perron, Isaac J.; Buono, Russell J.; Ferraro, Thomas N.
Post-traumatic seizures affect 12-35% of children after traumatic brain injury (TBI) and are associated with worse cognitive and functional outcome, even after adjustment for severity of injury. Unfortunately, experimental models of pediatric post-traumatic epilepsy are lacking, and pathogenesis remains poorly understood. We have applied a standard model of TBI in immature rats to determine the effect of TBI on electroconvulsive seizure thresholds later in life. Male rats underwent controlled cortical impact to left parietal cortex on post-natal day (PND) 16-18. Hindbrain, forebrain, and limbic seizure thresholds were assessed, respectively, by tonic hindlimb extension (THE), minimal clonic, and partial psychomotor seizure responses during adolescence (PND 34-40) and at maturity (PND 60-63). Post-traumatic seizure thresholds were compared to those obtained in age- and litter-matched sham craniotomy and naïve controls. TBI during immaturity had no clear effect on THE seizure thresholds. In contrast, TBI lowered minimal clonic seizure thresholds at maturity (p<0.05 vs. sham or naïve rats), but not during adolescence. Consequently, minimal clonic seizure thresholds increased with age for sham and naïve rats but remained similar for TBI rats during adolescence and at maturity. TBI also tended to lower partial psychomotor seizure thresholds, which were determined only during adolescence (p<0.1 vs. naïve). Controlled cortical impact causes both focal cortical injury at the site of impact and ipsilateral hippocampal neuronal death. Since minimal clonic seizures are mediated by the forebrain, partial psychomotor seizures by the limbic system, and THE seizures by the brainstem, the observed pattern of changes in post-traumatic seizure thresholds is not surprising. The apparent age-dependent effects of TBI, however, are unexpected and likely due to a combination of attenuated maturational increases and progressive epileptogenesis. Additional study is needed to delineate the relative contributions of these processes. Given the sustained reduction in post-traumatic minimal clonic seizure thresholds, controlled cortical impact may hold promise as an experimental model of pediatric post-traumatic epilepsy. PMID:18490145
Statler, Kimberly D; Swank, Seth; Abildskov, Tracy; Bigler, Erin D; White, H Steve
The Seizure Severity Questionnaire (SSQ) was developed to evaluate changes in seizure severity and bothersomeness. Determination of a threshold value reflecting meaningful patient benefit on the SSQ would improve clinical interpretation of scale results. The objective of this analysis was to define a minimally important change (MIC) threshold for the SSQ, using data from patients with treatment-resistant partial-onset seizures from two clinical trials (N=776). Minimally important change thresholds were calculated using standard anchor-based methods, with the Patient Global Impression of Change (PGIC) score as the anchor with the categories of 'much improved,' 'minimally improved,' 'much worsened,' and 'minimally worsened' combined. The calculated MIC thresholds (range: 0.34 to 0.50) suggest that a 0.48-point change in the SSQ total score reflects a clinically meaningful change in seizure severity from the patients' perspective. PMID:24139086
Cramer, Joyce A; de la Loge, Christine; Brabant, Yves; Borghs, Simon
This study was designed to evaluate the anticonvulsant effects of imperatorin (a furanocoumarin isolated from fruits of Angelica archangelica) in the mouse maximal electroshock seizure threshold model. The threshold for electroconvulsions in mice was determined at several times: 15, 30, 60 and 120 min after i.p. administration of imperatorin at increasing doses of 10, 20, 30, 40, 50 and 100 mg/kg. The evaluation of time-course relationship for imperatorin in the maximal electroshock seizure threshold test revealed that the agent produced its maximum antielectroshock action at 30 min after its i.p. administration. In this case, imperatorin at doses of 50 and 100 mg/kg significantly raised the threshold for electroconvulsions in mice by 38 and 68% (P<0.05 and P<0.001), respectively. The antiseizure effects produced by imperatorin at 15, 60 and 120 min after its systemic (i.p.) administration were less expressed than those observed for imperatorin injected 30 min before the maximal electroshock seizure threshold test. Based on this study, one can conclude that imperatorin produces the anticonvulsant effect in the maximal electroshock seizure threshold test in a dose-dependent manner. PMID:17602770
Luszczki, Jarogniew J; Glowniak, Kazimierz; Czuczwar, Stanislaw J
The present study was undertaken to compare the anticonvulsant effect of various antiepileptic drugs on the intravenous pentylenetetrazol (PTZ)-induced seizure threshold in mice. Minimal doses of PTZ needed to induce different phases (myoclonic jerks, generalized clonus and tonic extensor) of convulsions were recorded as an index of seizure threshold. Furthermore, TID50 (the dose of an anticonvulsant drug required to increase the PTZ seizure threshold for tonic extensor by 50%) was calculated for all drugs, and from these values the potency ratio was determined. Pentobarbital (10-40 mg/kg i.p.), phenobarbital (5-20 mg/kg i.p.), phenytoin (20-40 mg/kg i.p.), carbamazepine (5-20 mg/kg i.p.), diazepam (0.5-2 mg/kg i.p.), chlordiazepoxide (1-4 mg/kg i.p.), triazolam (0.02-0.08 mg/kg i.p.), clonazepam (0.03125-0.25 mg/kg i.p.), GABA (25-100 mg/kg i.p.), ethanol (1000-4000 mg/kg of 10% v/v p.o.), ashwagandha (50-200 mg/kg p.o.), tiagabine (20 and 40 mg/kg i.p.), gabapentin (50-200 mg/kg i.p.), pregabalin (10-40 mg/kg i.p.), progesterone (20-80 mg/kg s.c.), adenosine (25-200 mg/kg i.p.) and rofecoxib (1-4 mg/kg i.p.) exhibited dose-dependent anticonvulsant effects. The TID50 of triazolam was found to be the lowest among all the drugs tested, indicating higher potency. The relative potency of standard drugs to increase the PTZ seizure threshold for tonic extensor was found to be: triazolam > clonazepam > diazepam > rofecoxib > chlordiazepoxide > phenobarbital > carbamazepine > pentobarbital > pregabalin > phenytoin > progesterone > tiagabine > GABA > adenosine > gabapentin > ashwagandha > ethanol. The results of the present study indicate that the intravenous PTZ seizure threshold may be useful for assessing the anticonvulsant effect of drugs effective against different stages of convulsions. PMID:19907717
Akula, K K; Dhir, A; Kulkarni, S K
This study was designed to investigate the effects of ?-hydroxybutyrate (BHB) on pilocarpine-induced seizures in young mice. Eighty-five male, postnatal day 21, ICR mice were used. All mice were pretreated with scopolamine methylbromide (1 mg/kg) 30 min prior to pilocarpine administration. Experimental mice (n=46) were injected intraperitoneally with BHB (20 mmol/kg), 15 min prior to pilocarpine administration; control animals (n=39) were administered normal saline. Pilocarpine (300 mg/kg) was then administered intraperitoneally to induce seizures. Mice were monitored for 2 h after pilocarpine injection, and seizure behavior grades were evaluated according to Racine's scale. All mice developed typical seizure behaviors of grade 3 or higher. Although the severity in terms of seizure behavior grade was not significantly different between groups, the mean (±SD) latency to the onset of seizure was significantly prolonged in BHB-treated mice (5.15±2.19 min) compared with controls (2.95±1.06 min; p<0.001). This study demonstrates that treatment with BHB significantly prolongs the latency to the onset of seizures induced by pilocarpine in mice and suggests that BHB, one of the ketone bodies, may be direct anticonvulsant. PMID:21723679
Yum, Mi-Sun; Ko, Tae-Sung; Kim, Dong Wook
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 (40 mg/kg, i.p.) had been administered every other day for a period of 12 days, and seizure episodes were noted after each PTZ injection over a period of 30 min. 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 (200 mg/kg) significantly attenuated these behavioral, biochemical, and mitochondrial alterations. Further, treatment with l-arginine (100 mg/kg) or l-NAME (10 mg/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
Perinatal stroke is a common cerebrovascular disorder affecting 1 in every 4000 births; typically associated with epilepsy. We sought to determine seizure susceptibility to pentylentetrazol (PTZ)-induced seizures in developing rats with a history of photothrombotic lesion of sensorimotor cortex induced at postnatal day 7. Lesioned animals were tested at P12 or P25 and compared with sham-operated controls. Three models of epileptic seizures were elicited by PTZ: episodes of spike-and-wave rhythm, minimal clonic seizures and generalized tonic-clonic seizures. PTZ (60 and 100 mg/kg) was administered subcutaneously to assess seizure occurrence, latency and severity. In addition, episodes of rhythmic EEG activity were analyzed at P25 following successive interperitoneal 20 and 40 mg/kg PTZ administration. There was only one significant change in convulsive seizures--decreased latency of generalized seizures in lesioned 12-day-old animals. EEG study demonstrated marked difference between lesioned and control rats. Lesioned rats had longer latencies and longer durations of the first rhythmic episode (following 20 mg/kg PTZ) as compared to controls. After 40 mg/kg of PTZ, 7 in 8 leisioned and 1 in 8 control rats exhibited clonic seizures. Cortical ischemic lesion during early development affected differently the susceptibility of rat's brain to three types of PTZ-induced seizures 5 and 18 days post photothrombotic insults. PMID:23454234
Brima, T; Otáhal, J; Mareš, P
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in Tsc1 or Tsc2 that lead to mammalian target of rapamycin (mTOR) hyperactivity. Patients with TSC suffer from intractable seizures resulting from cortical malformations known as tubers, but research into how these tubers form has been limited because of the lack of an animal model. To address this limitation, we used in utero electroporation to knock out Tsc1 in selected neuronal populations in mice heterozygous for a mutant Tsc1 allele that eliminates the Tsc1 gene product at a precise developmental time point. Knockout of Tsc1 in single cells led to increased mTOR activity and soma size in the affected neurons. The mice exhibited white matter heterotopic nodules and discrete cortical tuber-like lesions containing cytomegalic and multinucleated neurons with abnormal dendritic trees resembling giant cells. Cortical tubers in the mutant mice did not exhibit signs of gliosis. Furthermore, phospho-S6 immunoreactivity was not upregulated in Tsc1-null astrocytes despite a lower seizure threshold. Collectively, these data suggest that a double-hit strategy to eliminate Tsc1 in discrete neuronal populations generates TSC-associated cortical lesions, providing a model to uncover the mechanisms of lesion formation and cortical hyperexcitability. In addition, the absence of glial reactivity argues against a contribution of astrocytes to lesion-associated hyperexcitability.
Feliciano, David M.; Su, Tiffany; Lopez, Jean; Platel, Jean-Claude; Bordey, Angelique
There is evidence that prostaglandin E2 (PGE2) facilitates the seizures induced by pentylenetetrazol (PTZ), but the role of PGE2 receptors (EPs) in the development of seizures has not been evaluated to date. In the current study we investigated whether selective EP ligands alter PTZ-induced seizures in adult male Wistar rats by electrographic methods. Selective antagonists for EP1 (SC-19220, 10 nmol,
M. S. Oliveira; A. F. Furian; L. M. Rambo; L. R. Ribeiro; L. F. F. Royes; J. Ferreira; J. B. Calixto; C. F. Mello
Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of ?1-containing GABAA receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24h after withdrawal from protracted treatment in rats. Withdrawal of 2mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at ?1-containing GABAA receptors, achieved by daily administration of the neutral modulator ?CCt (5mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of ?CCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of ?1-containing GABAA receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at ?1-containing GABAA receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type. PMID:24695241
Kova?evi?, Jovana; Timi?, Tamara; Tiruveedhula, Veera V; Batini?, Bojan; Namjoshi, Ojas A; Mili?, Marija; Joksimovi?, Sr?an; Cook, James M; Savi?, Miroslav M
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
The effects of tianeptine and fluoxetine on pentylenetetrazole (PTZ)-induced seizures in rats were investigated. Female Wistar rats (172–278 g) were used in the study. Tianeptine (1.25, 2.5, 5, 10 and 20 mg\\/kg) and fluoxetine (2.5, 5, 10 and 20 mg\\/kg) or saline were injected to rats intraperitoneally 30 min before PTZ (50 mg\\/kg) injections. Immediately after PTZ administrations, latency and
Mert Ceyhan; Hakan Kayir; I. Tayfun Uzbay
We present a visual sensor network, comprising wide field-of-view (FOV) passive cameras and pan\\/tilt\\/zoom (PTZ) active cameras, which automatically captures high quality surveillance video of selected pedestrians during their prolonged presence in an area of interest. A wide-FOV static camera can track multiple pedestrians, while any PTZ active camera can follow a single pedestrian at a time. The proactive control
Faisal Z. Qureshi; Demetri Terzopoulos
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 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
E. Loyens; A. Schallier; S. Y. Chai; D. De Bundel; P. Vanderheyden; Y. Michotte; I. Smolders
In Ayurveda, Anacyclus pyrethrum has been used as a brain tonic. The present study evaluates the effect of hydroalcoholic extract of A. pyrethrum (HEAP) root against seizures, seizure-induced oxidative stress and cognitive impairment in experimental models of seizures. Male Wistar rats were used in the study. HEAP was administered in doses of 50, 100, 250, 500 in pentylenetetrazole (PTZ) model and 250, 500 and 1000 mg/kg in maximal electroshock (MES) model. Myoclonic jerk latency and generalized tonic clonic seizures (GTCS) were noted in PTZ whereas occurrence of tonic hind limb extension (THLE) was observed in MES seizures. Cognitive deficit was assessed using elevated plus maze and passive avoidance tests. Whole brain reduced glutathione, malondialdehyde levels and cholinesterase activity were measured. HEAP showed 50, 66.7, 83.3 and 100% protection at 50,100, 250 and 500 mg/kg, respectively against GTCS in PTZ induced seizures. In MES induced seizures, HEAP produced 16.7, 33.3 and 50% protection against THLE at 250, 500 and 1000 mg/kg, respectively. HEAP administration significantly prevented seizure induced oxidative stress and cognitive impairment in a dose-dependent manner. HEAP also normalized the decrease in cholinesterase activity caused by seizures. Thus, HEAP showed protective effect against seizures, seizure-induced oxidative stress and cognitive impairment in rats. PMID:21993359
Pahuja, Monika; Mehla, Jogender; Reeta, K H; Joshi, Sujata; Gupta, Yogendra Kumar
Surveillance system is widely applied in various fields in recent years. The demand for monitoring quality is not only to capture the object image, but also to present sharp and recognizable image. Thus, PTZ camera, which has pan and zoom functions, has become the best equipment. How to zoom in object and move camera lens so that the object is
Cheng-Liang Lai; Sung-Ting Tsai
Selective depletion of forebrain noradrenaline has been shown to potentiate various types of experimentally induced seizures. This study was aimed at exploring the role of different types of adrenergic receptors in pentylenetetrazol (PTZ)-induced seizures in rats and the anticonvulsive effect of di-n-propylacetate (DPA). Piperoxane (10 and 20 mg\\/kg, IP) significantly potentiated PTZ-induced tonic seizures and mortality. Similar effects were observed
M. Lazarova; C. Bendotti; R. Samanin
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
Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a
Sheryl R. Haut
This study investigated the anticonvulsant effect of 3-alkynyl selenophene (3-ASP) on pilocarpine (PC)-, pentylenetetrazole (PTZ)- and kainic acid (KA)-induced seizures and mortality in 21-day-old rats. Rats were pretreated by oral route (p.o.) with 3-ASP (10, 25 and 50mg\\/kg) before intraperitoneal (i.p.) administration of PC (400mg\\/kg), PTZ (80mg\\/kg) or KA (45mg\\/kg). 3-ASP increased the latency to the seizure onset on PTZ
Ethel A. Wilhelm; Cristiano R. Jesse; Cristiani F. Bortolatto; Cristina W. Nogueira; Lucielli Savegnago
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...
The author carried out studies on male white rats and examined the effect of imidazol, papaverine and theophyline (drugs affecting the activity of phosphodiesterase), singly or in correlation with GAMA and diazepam on picrotoxic seizure threshold (PSAT). He found that imidazol had various effects on PSAT in accordance with the interval of application and antagonized the effects of GAMA. Papaverine in low doses was ineffective, but in higher doses lowered PSAT; it antagonized the effect of GAMA, elevating the threshold. Papaverine in combination with CAMF antagonized the effect of GAMA, elevating the threshold. Theophyline lowered PSAT; it did not influence the effects of the combined application of GAMA and DIA. He thinks that the obtained changes in PSAT could partly be connected with the mediating influence of imidazol, papaverine and phe theophyline on cerebral phosphodiesterase both after their single application and after examination of their correlations with GAMA or DIA, used singly or in comibination, and partly with their own pharmacologic action. PMID:699866
We mapped the quantitative trait loci (QTL) that contribute to the robust difference in maximal electroshock seizure threshold (MEST) between C57BLKS/J (BKS) and C57BL10S/J (B10S) mice. BKS, B10S, BKS × B10S F1 and BKS × B10S F2 intercross mice were tested for MEST at 8-9 weeks of age. Results of F2 testing showed that, in this cross, MEST is a continuously distributed trait determined by polygenic inheritance. Mice from the extremes of the trait distribution were genotyped using microarray technology. MEST correlated significantly with body weight and sex; however, because of the high correlation between these factors, the QTL mapping was conditioned on sex alone. A sequential series of statistical analyses was used to map QTLs including single-point, multipoint and multilocus methods. Two QTLs reached genome-wide levels of significance based upon an empirically determined permutation threshold: chromosome 6 (LOD = 6.0 at ?69 cM) and chromosome 8 (LOD = 5.7 at ?27 cM). Two additional QTLs were retained in a multilocus regression model: chromosome 3 (LOD = 2.1 at ?68 cM) and chromosome 5 (LOD = 2.7 at ?73 cM). Together the four QTLs explain one third of the total phenotypic variance in the mapping population. Lack of overlap between the major MEST QTLs mapped here in BKS and B10S mice and those mapped previously in C57BL/6J and DBA/2J mice (strains that are closely related to BKS and B10S) suggest that BKS and B10S represent a new polygenic mouse model for investigating susceptibility to seizures. PMID:21129161
Ferraro, T N; Smith, G G; Ballard, D; Zhao, H; Schwebel, C L; Gupta, A; Rappaport, E F; Ruiz, S E; Lohoff, F W; Doyle, G A; Berrettini, W H; Buono, R J
An important role for oxidative stress both as a consequence and as a cause of epileptic seizures has been suggested. Since Achillea wilhelmsii (A. wilhelmsii) has been considered to have the antioxidant effects as well as central nervous system depressant properties, the anti-seizure effects of the plant extract in addition to its effects on brain tissues oxidative damage were investigated in pentylenetetrazole (PTZ)-induced seizures model. Male Wistar rats were divided into 5 groups: (1) Control, (2) PTZ, (3-5) A. wilhelmsii extract groups (AWE). The animals in groups 2-5 were treated with saline or AWE (100, 200 or 400 mg/kg) before single injection of PTZ (90 mg/kg). Latency to first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The brain tissues were then removed for biochemical measurements. MCS latencies in extract treated groups were not different from PTZ group. The animals treated by 200 mg/kg of AWE had a significant higher GTCS latency in comparison with PTZ group (P < 0.001). The MDA levels in PTZ group were significantly higher and the total thiol concentrations were lower than control animals. Pretreatment with all 3 doses of the extract resulted in a significant reduction in the MDA levels (P < 0.05, P < 0.01 and P < 0.001) and a significant elevation in total thiol concentration, as compared with PTZ group (P < 0.05 and P < 0.01). The present study showed that the hydroalcoholic extract of A. wilhelmsii possesses an antioxidant effect in the brain in PTZ induced seizure model. PMID:24968581
Hosseini, Mahmoud; Harandizadeh, Fatemeh; Niazamand, Saeed; Soukhtanloo, Mohammad; Mahmoudabady, Maryam
Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.
Li, Bingjin; Wang, Liang; Sun, Zhihui; Zhou, Yang; Shao, Dongyuan; Zhao, Jing; Song, Yunong; Lv, Jiayin; Dong, Xue; Liu, Changhong; Wang, Pu; Zhang, Xingyi; Cui, Ranji
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.
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.
Adenosine is an endogenous modulator of brain functions, which presents anticonvulsant properties. In addition, its levels can be increased during neural injury. The modulation of extracellular adenosine levels by ectonucleotidase and adenosine deaminase (ADA) activities may represent a key mechanism in the control of epileptogenesis. In the present study, we investigated the effects of acute seizure episodes and antiepileptic drug (AED) treatments on ectonucleotidases and ADA activities in adult zebrafish brain. Our data have demonstrated that pentylenetetrazole (PTZ)-induced seizures did not alter ATP, ADP, and AMP hydrolysis in brain membrane fractions. However, there was a significant increase on ecto-ADA and soluble ADA activities in PTZ-treated animals immediately after a clonus-like convulsion and loss of posture, which are typical behavioral changes observed in Stage 3. Furthermore, our results have demonstrated that AED pretreatments prevented the stimulatory effect promoted by PTZ exposure on ADA activities. The PTZ and AED treatments did not promote alterations on ADA gene expression. Interestingly, when exposed to PTZ, animals pretreated with AEDs showed longer latency to reach the clonus-like seizure status, which is an effect that matches the suppression of the increase of ADA activity promoted by the AEDs. These data suggest that the adenosine deamination could be involved in the control of seizure development in zebrafish and may be modulated by AED treatments. PMID:23287800
Siebel, Anna Maria; Piato, Angelo Luis; Schaefer, Isabel Costa; Nery, Laura Roesler; Bogo, Maurício Reis; Bonan, Carla Denise
The N-methyl-D-aspartate (NMDA)-type glutamate receptor plays a key role in excitatory synaptic transmission. The overactivation of the NMDA receptor has been implicated in the development of epileptic seizures. D-Serine is a coagonist of the NMDA receptor and its biosynthesis is catalyzed by serine racemase (SR). Here, we examined the effect of d-serine deficiency on the seizures induced by a single injection of pentylenetetrazole (PTZ) using SR knockout (KO) mice. We found that, compared with wild-type (WT) mice, SR-KO mice showed the attenuation of seizure expression in terms of a significantly shortened duration of generalized seizures and resistance to generalized clonic-tonic seizures. Consistently, immunohistochemical analysis of c-Fos demonstrated that the numbers of cells expressing c-Fos induced by high-dose PTZ in the cerebral cortex, hippocampal CA1, hippocampal CA3, and the basolateral nucleus of the amygdala in WT mice were significantly higher than those in SR-KO mice. Moreover, PTZ induced an increase in extracellular glutamate level in the dentate gyrus of WT mice at two different time phases. However, such a PTZ-induced increase in glutamate level was completely inhibited in SR-KO mice. The present findings suggest that SR may be a target for the development of new therapeutic strategies for epileptic seizures. PMID:22742962
Harai, Tomomi; Inoue, Ran; Fujita, Yuko; Tanaka, Ayumi; Horio, Mao; Hashimoto, Kenji; Hongou, Kazuhisa; Miyawaki, Toshio; Mori, Hisashi
Focal seizure - discharge; Jacksonian seizure - discharge; Seizure - partial (focal) - discharge; TLE - discharge; Seizure - temporal lobe - discharge; Seizure - tonic-clonic - discharge; Seizure - grand mal - discharge; Grand mal seizure - discharge; Seizure - generalized - discharge
To confirm seizure susceptibility (SZS) quantitative trait loci (QTLs) on chromosome (chr) 15 identified previously using C57BL/6J (B6) and DBA/2J (D2) mice and to refine their genomic map position, we studied a set of three congenic strains in which overlapping segments of chr 15 from D2 were transferred onto the B6 background. We measured thresholds for generalized electroshock seizure (GEST) and maximal electroshock seizure (MEST) in congenic strains and B6-like littermates and also tested their responses to kainic acid (KA) and pentylenetetrazol (PTZ). Results document that MEST is significantly lower in strains 15M and 15D, which harbor medial and distal (telomeric) segments of chr 15 (respectively) from D2, compared with strain 15P, which harbors the proximal (acromeric) segment of chr 15 from D2, and with control littermates. Congenic strains 15P and 15M exhibited greater KA SZS compared with strain 15D and B6-like controls. All congenic strains were similar to controls with regard to PTZ SZS. Taken together, results suggest there are multiple SZS QTLs on chr 15 and that two QTLs harbor gene variants that affect MEST and KA SZS independently. The MEST QTL is refined to a 19 Mb region flanked by rs13482630 and D15Mit159. This interval contains 350 genes, 183 of which reside in areas where the polymorphism rate between B6 and D2 is high. The KA QTL interval spans a 65 Mb region flanked by markers D15Mit13 and rs31271969. It harbors 83 genes in highly polymorphic areas, 310 genes in all. Complete dissection of these loci will lead to identification of genetic variants that influence SZS in mice and provide a better understanding of seizure biology. PMID:20571108
Ferraro, T N; Smith, G G; Schwebel, C L; Doyle, G A; Ruiz, S E; Oleynick, J U; Lohoff, F W; Berrettini, W H; Buono, R J
To confirm seizure susceptibility (SZS) quantitative trait loci (QTLs) on chromosome (chr) 15 identified previously using C57BL/6J (B6) and DBA/2J (D2) mice and to refine their genomic map position, we studied a set of three congenic strains in which overlapping segments of chr 15 from D2 were transferred onto the B6 background. We measured thresholds for generalized electroshock seizure (GEST) and maximal electroshock seizure (MEST) in congenic strains and B6-like littermates and also tested their responses to kainic acid (KA) and pentylenetetrazol (PTZ). Results document that MEST is significantly lower in strains 15M and 15D, which harbor medial and distal (telomeric) segments of chr 15 (respectively) from D2, compared with strain 15P, which harbors the proximal (acromeric) segment of chr 15 from D2, and with control littermates. Congenic strains 15P and 15M exhibited greater KA SZS compared with strain 15D and B6-like controls. All congenic strains were similar to controls with regard to PTZ SZS. Taken together, results suggest there are multiple SZS QTLs on chr 15 and that two QTLs harbor gene variants that affect MEST and KA SZS independently. The MEST QTL is refined to a 19 Mb region flanked by rs13482630 and D15Mit159. This interval contains 350 genes, 183 of which reside in areas where the polymorphism rate between B6 and D2 is high. The KA QTL interval spans a 65 Mb region flanked by markers D15Mit13 and rs31271969. It harbors 83 genes in highly polymorphic areas, 310 genes in all. Complete dissection of these loci will lead to identification of genetic variants that influence SZS in mice and provide a better understanding of seizure biology.
Smith, G. G.; Schwebel, C. L.; Doyle, G. A.; Ruiz, S. E.; Oleynick, J. U.; Lohoff, F. W.; Berrettini, W. H.; Buono, R. J.
The present study investigated whether the expression of the cAMP response element-binding protein (CREB) in the rat brain is altered following an acute self-limited seizure induced by pentylenetetrazol (PTZ). Male rats were injected intraperitoneally with a single convulsive dose (45 mg\\/kg) of PTZ, and the matched controls were given saline. For immunohistochemistry, animals were perfused with 4% parafomaldehyde at 24
Xiujun Pi; Junho Lee; Fei Li; Howard C. Rosenberg
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.)
Tayfun I Uzbay; Hakan Kayir; Mert Ceyhan
There is evidence that prostaglandin E2 (PGE2) facilitates the seizures induced by pentylenetetrazol (PTZ), but the role of PGE2 receptors (EPs) in the development of seizures has not been evaluated to date. In the current study we investigated whether selective EP ligands alter PTZ-induced seizures in adult male Wistar rats by electrographic methods. Selective antagonists for EP1 (SC-19220, 10 nmol, i.c.v.), EP3 (L-826266, 1 nmol, i.c.v.) and EP4 (L-161982, 750 pmol, i.c.v.) receptors, and the selective EP2 agonist butaprost (100 pmol, i.c.v.) increased the latency for clonic and generalized tonic-clonic seizures induced by PTZ. These data constitute pharmacological evidence supporting a role for EPs in the seizures induced by PTZ. Although more studies are necessary to fully evaluate the anticonvulsant role these compounds and their use in the clinics, EP ligands may represent new targets for drug development for convulsive disorders. PMID:18329178
Oliveira, M S; Furian, A F; Rambo, L M; Ribeiro, L R; Royes, L F F; Ferreira, J; Calixto, J B; Mello, C F
Abstract The purpose of this study was to investigate the effects of an induced period of post-traumatic epilepsy (PTE) on the histopathological damage caused by traumatic brain injury (TBI). Male Sprague Dawley rats were given a moderate parasagittal fluid-percussion brain injury (1.9–2.1 atm) or sham surgery. At 2 weeks after surgery, seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30?mg/kg). Seizures were then assessed over a 1-h period using the Racine clinical rating scale. To evaluate whether TBI-induced pathology was exacerbated by the seizures, contusion volume and cortical and hippocampal CA3 neuronal cell loss were measured 3 days after seizures. Nearly all TBI rats showed clinical signs of PTE following the decrease in inhibitory activity. In contrast, clinically evident seizures were not observed in TBI rats given saline or sham-operated rats given PTZ. Contusions in TBI-PTZ-treated rats were significantly increased compared to the TBI-saline-treated group (p?0.001). In addition, the TBI-PTZ rats showed less NeuN-immunoreactive cells within the ipsilateral parietal cerebral cortex (p?0.05) and there was a trend for decreased hippocampal CA3 neurons in TBI-PTZ rats compared with TBI-saline or sham-operated rats. These results demonstrate that an induced period of post-traumatic seizures significantly exacerbates the structural damage caused by TBI. These findings emphasize the need to control seizures after TBI to limit even further damage to the injured brain.
Bao, Ying-hui; Bramlett, Helen M.; Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Alonso, Ofelia F.
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
Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals
Maria G. Genkova-Papazova; Maria B. Lazarova-Bakarova
This work attempted to answer the question whether the central processes engaged in the memory formation and the epilepsy development are governed by the overlapping mechanisms. The effects of the protein synthesis inhibitor cycloheximide (CHX) were examined on the expression and reconsolidation of pentylenetetrazole (PTZ) - induced kindled seizures and for comparative purposes, on the reconsolidation of conditioned fear response (conditioned freezing). It was found that post-test intracerebroventricular administration of CHX (125microg/5microl) significantly attenuated the expression of a conditioned fear response examined 24h later. Thus, inhibition of de novo brain protein synthesis interfered with the reconsolidation of a conditioned response. CHX given at the same dose repeatedly to fully kindled rats immediately after three consecutive sessions of PTZ-induced seizures (35mg/kg ip) did not modify the strength of convulsions. On the other hand, CHX significantly attenuated the strength of convulsions when the drug was administered 1h before the PTZ injection, which occurred every second day for three consecutive sessions. However, when CHX was omitted in a consecutive session, PTZ induced a fully developed expression of tonic-clonic convulsions, thereby indicating that CHX-induced changes in seizure intensity were transitory. Western Blot analysis confirmed that CHX potently inhibited PTZ-induced protein synthesis (c-Fos) in the rat brain, examined 60min after CHX and PTZ administration. The present findings suggest that the mechanisms underlying kindling are resistant to modification, even under the influence of protein synthesis inhibitors, and that there are important differences between the processes of learning and kindling seizures. PMID:20605533
Maciejak, Piotr; Szyndler, Janusz; Lehner, Ma?gorzata; Turzy?ska, Danuta; Sobolewska, Alicja; Bidzi?ski, Andrzej; P?a?nik, Adam
Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available anti-epileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and then were maintained at normothermic or moderate hypothermic temperatures for 4 hr. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole (PTZ), a GABAA receptor antagonist. PTZ elicited a significant increase in seizure frequency in TBI normothermic animals as compared to sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss, nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizure. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy.
Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Sanchez-Molano, Juliana; Kang, Yuan; Alonso, Ofelia F.; Sick, Thomas J.; Dietrich, W. Dalton; Bramlett, Helen M.
We report pilomotor seizures in two patients who had piloerection or gooseflesh spreading in a pattern like the 'Jacksonian march', confined ipsilaterally to the lesion side. The first patient presented this in conjunction with complex partial seizures. Left anterior temporal lobectomy abolished pilomotor and other seizures. Pathological study demonstrated hippocampal sclerosis. A meningioma near the left sphenoid region, incompletely removed, is the likely cause of pilomotor seizures in the second patient. Carbamazepine reduced these attacks. To our knowledge, hippocampal sclerosis and meningioma have never been linked to pilomotor seizures. PMID:9693227
Yu, H; Yen, D; Yiu, C; Chung, W; Lirng, J; Su, M
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.
Due to increasing security concerns, a complete security system should consist of two major components, a computer-based face-recognition system and a real-time automated video surveillance system. A computerbased face-recognition system can be used in gate access control for identity authentication. In recent studies, multispectral imaging and fusion of multispectral narrow-band images in the visible spectrum have been employed and proven to enhance the recognition performance over conventional broad-band images, especially when the illumination changes. Thus, we present an automated method that specifies the optimal spectral ranges under the given illumination. Experimental results verify the consistent performance of our algorithm via the observation that an identical set of spectral band images is selected under all tested conditions. Our discovery can be practically used for a new customized sensor design associated with given illuminations for an improved face recognition performance over conventional broad-band images. In addition, once a person is authorized to enter a restricted area, we still need to continuously monitor his/her activities for the sake of security. Because pantilt-zoom (PTZ) cameras are capable of covering a panoramic area and maintaining high resolution imagery for real-time behavior understanding, researches in automated surveillance systems with multiple PTZ cameras have become increasingly important. Most existing algorithms require the prior knowledge of intrinsic parameters of the PTZ camera to infer the relative positioning and orientation among multiple PTZ cameras. To overcome this limitation, we propose a novel mapping algorithm that derives the relative positioning and orientation between two PTZ cameras based on a unified polynomial model. This reduces the dependence on the knowledge of intrinsic parameters of PTZ camera and relative positions. Experimental results demonstrate that our proposed algorithm presents substantially reduced computational complexity and improved flexibility at the cost of slightly decreased pixel accuracy as compared to Chen and Wang's method .
Chen, Chung-Hao; Yao, Yi; Chang, Hong; Koschan, Andreas; Abidi, Mongi
Psychogenic seizures are nonepileptic events that are varied in their clinical presentations. These events can be psychiatric or physiologic in their origin and can occur concomitantly in patients with epileptic seizure disorders. The diagnosis often requires laboratory and electrophysiologic investigation; however, historical, clinical, and laboratory findings can aid in making the diagnosis. PMID:7956884
Epilepsy is a neurological disorder with the occurrence of seizures, which are often accompanied by sleep. Prostaglandin (PG) D2 is produced by hematopoietic or lipocalin-type PGD synthase (H- or L-PGDS) and involved in the regulation of physiological sleep. Here, we show that H-PGDS, L/H-PGDS or DP1 receptor (DP1R) KO mice exhibited more intense pentylenetetrazole (PTZ)-induced seizures in terms of latency of seizure onset, duration of generalized tonic-clonic seizures, and number of seizure spikes. Seizures significantly increased the PGD2 content of the brain in wild-type mice. This PTZ-induced increase in PGD2 was attenuated in the brains of L- or H-PGDS KO and abolished in L/H-PGDS KO mice. Postictal non-rapid eye movement sleep was observed in the wild-type and H-PGDS or DP2R KO, but not in the L-, L/H-PGDS or DP1R KO, mice. These findings demonstrate that PGD2 produced by H-PGDS and acting on DP1R is essential for seizure suppression and that the L-PGDS/PGD2/DP1R system regulates sleep that follows seizures. PMID:24333565
Kaushik, Mahesh K; Aritake, Kosuke; Kamauchi, Shinya; Hayaishi, Osamu; Huang, Zhi-Li; Lazarus, Michael; Urade, Yoshihiro
Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.
Haggag, Basma S; Raafat, Mona H; Abdel Kawy, Hala S
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
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
Objective(s): A growing interest has recently been attracted towards the identification of plant-based medications including those with protective effects against cognitive impairment. Sesamol has shown promising antioxidant and neuroprotective effects, therefore, we aimed to evaluate its therapeutic potential in epilepsy which is commonly associated with oxidative stress and cognitive impairment. Materials and Methods: Male Wistar rats received pentylenetetrazole (PTZ) (30 mg/kg, IP) once every other day until the development of kindling, i.e., the occurrence of stage 5 of seizures for three consecutive trials. After the completion of kindling procedure, behavioural tests including elevated plus maze and passive avoidance were performed in order to assess learning and memory. Oxidative stress was assessed by estimation of lipid peroxidation and reduced glutathione. The effects of pretreatment with sesamol (10, 20, and 30 mg/kg, IP) against PTZ-induced seizures, cognitive impairment and oxidative stress were investigated. Results: 32.45 ± 1.86 days after treatment with PTZ, kindling was developed that was associated with myoclonic jerks and generalized tonic-clonic seizures. Moreover, PTZ kindling induced a remarkable cognitive impairment and oxidative stress. Sesamol (30 mg/kg) significantly delayed the development of kindling and prevented seizure-induced cognitive impairment and oxidative stress. Conclusion: Sesamol exerts ameliorative effects in the experimental model of epilepsy. This phytochemical may be considered as a beneficial adjuvant for antiepileptic drugs. PMID:24711892
Hassanzadeh, Parichehr; Arbabi, Elham; Rostami, Fatemeh
Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clin- ically as
Sheryl R. Haut
Angelman syndrome is a neurogenetic condition namely characterized by developmental delay, virtual absence of expressive verbal language, peculiar organization of movement, seizures and happy demeanor. This syndrome has been recognized since 1965, but it seems that Walt Disney presented an original depiction of it in his first full-length animated film, including myoclonic jerks and an apparently generalized tonic-clonic seizure. PMID:10452923
Dan, B; Christiaens, F
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
Synthesis, receptor affinity and effect on pentylenetetrazole-induced seizure threshold of novel benzodiazepine analogues: 3-Substituted 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles and 2-amino-5-(phenoxybenzyl)-1,3,4-oxadiazoles.
The new series of 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles, possessing C-3 thio, alkylthio and ethoxy substituents, and 2-amino-5-(2-phenoxybenzyl)-1,3,4-oxadiazoles were designed and synthesized as novel benzodiazepine analogues. Most of them revealed similar to superior binding affinity to the GABAA/benzodiazepine receptor complex, relative to diazepam as the reference drug. Among them, 5-(4-chloro-2-(2-fluorophenoxy)benzyl)-3-benzylthio-4H-1,2,4-triazole (8l) showed the highest affinity (IC??=0.892 nM) relative to diazepam (IC??=2.857 nM) and also showed the most increase in pentylenetetrazole-induced seizure threshold relative to diazepam as the reference drug. PMID:24530225
Mashayekh, Siavash; Rahmanipour, Narges; Mahmoodi, Behnaz; Ahmadi, Fatemeh; Motaharian, Dina; Shahhosseini, Soraya; Shafaroodi, Hamed; Banafshe, Hamid R; Shafiee, Abbas; Navidpour, Latifeh
This paper proposes a multi-PTZ-camera control mechanism to acquire close-up imagery of human objects in a surveillance system. The control algorithm is based on the output of multi-camera, multi-target tracking. Three main concerns of the algorithm are (1) the imagery of human object's face for biometric purposes, (2) the optimal video quality of the human objects, and (3) minimum hand-off time. Here, we define an objective function based on the expected capture conditions such as the camera-subject distance, pan tile angles of capture, face visibility and others. Such objective function serves to effectively balance the number of captures per subject and quality of captures. In the experiments, we demonstrate the performance of the system which operates in real-time under real world conditions on three PTZ cameras.
Liu, Yu-Che; Huang, Chung-Lin
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
Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF ?), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. PMID:24735834
Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza
Previous seizure models have demonstrated genetic differences in generalized seizure threshold (GST) in inbred mice, but the genetic control of epileptogenesis is relatively unexplored. The present study examined, through analysis of inbred strains of mice, whether the seizure characteristics observed in the flurothyl kindling model are under genetic control. Eight consecutive, daily generalized seizures were induced by flurothyl in mice
Dominick Papandrea; Tara M. Anderson; Bruce J. Herron; Russell J. Ferland
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
Abstract Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35?mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG recordings also revealed that physical exercise prevented PTZ-induced amplitude increase in TBI animals. Neurochemical analysis showed that exercise training increased glutathione/oxidized glutathione ratio and glutathione levels per se. Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na+,K+-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na+/K+-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility.
Silva, Luiz Fernando Almeida; Hoffmann, Mauricio Scopel; Gerbatin, Rogerio da Rosa; Fiorin, Fernando da Silva; Dobrachinski, Fernando; Mota, Bibiana Castagna; Wouters, Angelica Terezinha Barth; Pavarini, Saulo Petinatti; Soares, Felix Alexandre Antunes; Fighera, Michele Rechia
Triheptanoin, the triglyceride of heptanoate, is used to treat certain hereditary metabolic diseases in USA because of its anaplerotic potential. In two chronic mouse seizure models this clear tasteless oil was found to be reproducibly anticonvulsant. Here we investigated the effects of triheptanoin feeding in C3H and CD1 mice using standard acute seizure models. Feeding 30-40% triheptanoin (caloric intake) consistently elevated blood propionyl-carnitines, but inconsistent anticonvulsant effects were observed in the fluorothyl, pentylenetetrazole and 6Hz seizure models. A 2mA consistent increase in the maximal electroshock threshold was found after 3 weeks of 35% triheptanoin feeding (p=0.018). In summary, triheptanoin shows a unique anticonvulsant profile in seizure models, compared to other treatments that are in the clinic. Therefore, despite small and/or inconsistent effects of triheptanoin in acute seizure models, triheptanoin remains of interest as a potential add-on treatment for patients with medically refractory epilepsy. PMID:22260920
Thomas, Nicola K; Willis, Sarah; Sweetman, Lawrence; Borges, Karin
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
SUMMARY The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ?2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities.
Baxendale, Sarah; Holdsworth, Celia J.; Meza Santoscoy, Paola L.; Harrison, Michael R. M.; Fox, James; Parkin, Caroline A.; Ingham, Philip W.; Cunliffe, Vincent T.
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
For the first time, we detected optical changes elicited by seizure activity in pentylenetetrazol (PTZ)-treated rats (n=6) versus saline controls (n=2) over a 30min recording session using a novel time-series analysis of scattering images obtained non-invasively with a real-time multispectral diffuse optical tomography (DOT) system. Spatio-temporal images of absorption and scattering coefficients were recovered from PTZ- and saline-treated rats' brains using a finite element-based DOT image reconstruction algorithm. After pulse artifacts were eliminated, an independent component (IC) analysis was conducted for blind-source separation of the optical signals. The retrieved ICs were compared with concurrently measured EEG signals, and the selected components were further refined using K-means clustering and spectrum analysis tools. The results revealed that changes in absorption and scattering coefficients emerge sooner than changes in the EEG signal and a low frequency peak signal of ?0.3Hz in the spectra of light scattering images after PTZ injection. This low frequency caused by slow volume changes in CNS cells was not detected in control animals. Brain regions that we detected early changes in optical signals and activation maps were confirmed in an additional 3 PTZ-treated rats using the DOT system and concurrent EEG recordings obtained from multiple brain regions. Our results show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure and other CNS disorders with the additional benefit of providing access to physiological parameters that other modalities cannot access. PMID:24530435
Hajihashemi, M Reza; Zhang, Tao; Ormerod, Brandi K; Jiang, Huabei
Exposure of normal adult rats of a variety of species to trains of light flashes leads to acquisition of an enduring high amplitude visual cortical response [Uhlrich DJ, Manning KA, O'Laughlin ML, Lytton WW (2005) Photic-induced sensitization: acquisition of an augmenting spike-wave response in the adult rat through repeated strobe exposure. J Neurophysiol 94:3925-3937]. The photically-induced sensitized response exhibits epileptiform characteristics, including spike-wave morphology, tendency to generalize across the brain, and sensitivity to the anti-epileptic drug ethosuximide. These findings and anecdotal clinical reports raise the possibility that certain sensory stimulation could induce neural plastic changes that affect seizures in some individuals. We hypothesize that photic-induced sensitization can prime seizure-related neural circuitry, resulting in exacerbation of seizures. To test this we compared seizure kindling rates using the pentylenetetrazol (PTZ) model of epileptogenesis in sensitized and unsensitized adult Sprague-Dawley rats. Experimental group rats were sensitized by exposure to repetitive stroboscopic stimulation over 4-6 days until the sensitized photic response fully developed and response magnitude stabilized at its highest plateau. Rats then received a sub-convulsive injection of PTZ (24 mg/kg i.p.) every other day until they attained class 5 seizures. Control rats were not strobed or sensitized, but were otherwise treated identically. Chronic electrodes overlying the dura in occipital cortex recorded the primary visual response. Similar electrodes near the border of somatosensory and motor cortex (SM) were used to record spread of the sensitized response to a patently non-visual region. Rat behavior was monitored by direct observation and digital audio/video recording. All control rats and seven of 14 photically sensitized rats kindled seizures at rates consistent with those reported previously. However, the seven other photically sensitized rats displayed markedly accelerated seizure kindling. Rats with accelerated kindling showed greater spread of the sensitized visual response to somato-motor cortex and, when tested in a post hoc experiment, exhibited a higher likelihood of photo-triggered seizures. These results indicate that photic-induced sensitization in susceptible individuals can prime neural circuitry involved in the generation of PTZ-kindled seizures. PMID:19576967
Manning, K A; Uhlrich, D J
Metabotropic glutamate receptor 5 (mGluR5) regulates the translation of amyloid precursor protein (APP) mRNA. Under resting conditions, mRNA is bound to and translationally repressed by the fragile X mental retardation protein (FMRP). Upon group 1 mGluR activation, FMRP dissociates from the mRNA and translation ensues. APP levels are elevated in the dendrites of primary neuronal cultures as well as in synaptoneurosomes (SN) prepared from embryonic and juvenile fmr-1 knockout (KO) mice, respectively. In order to study the effects of APP and its proteolytic product A? on Fragile X syndrome (FXS) phenotypes, we created a novel mouse model (FRAXAD) that over-expresses human APPSwe/A? in an fmr-1 KO background. Herein, we assess (1) human APPSwe and A? levels as a function of age in FRAXAD mice, and (2) seizure susceptibility to pentylenetetrazol (PTZ) after mGluR5 blockade. PTZ-induced seizure severity is decreased in FRAXAD mice pre-treated with the mGluR5 antagonist MPEP. These data suggest that A? contributes to seizure incidence and may be an appropriate therapeutic target to lessen seizure pathology in FXS, Alzheimer's disease (AD) and Down syndrome (DS) patients.
Westmark, Cara J.; Westmark, Pamela R.; Malter, James S.
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.
Zebrafish have recently emerged as an attractive in vivo model for epilepsy. Seven-day-old zebrafish larvae exposed to the GABAA antagonist pentylenetetrazol (PTZ) exhibit increased locomotor activity, seizure-like behavior, and epileptiform electrographic activity. A previous study showed that 12 out of 13 antiepileptic drugs (AEDs) suppressed PTZ-mediated increases in larval movement, indicating the potential utility of zebrafish as a high-throughput in vivo model for AED discovery. However, a question remained as to whether an AED-induced decrease in locomotion is truly indicative of anticonvulsant activity, as some drugs may impair larval movement through other mechanisms such as general toxicity or sedation. We therefore carried out a study in PTZ-treated zebrafish larvae, to directly compare the ability of AEDs to inhibit seizure-like behavioral manifestations with their capacity to suppress epileptiform electrographic activity. We re-tested the 13 AEDs of which 12 were previously reported to inhibit convulsions in the larval movement tracking assay, administering concentrations that did not, on their own, impair locomotion. In parallel, we carried out open-field recordings on larval brains after treatment with each AED. For the majority of AEDs we obtained the same response in both the behavioral and electrographic assays. Overall our data correlate well with those reported in the literature for acute rodent PTZ tests, indicating that the larval zebrafish brain is more discriminatory than previously thought in its response to AEDs with different modes of action. Our results underscore the validity of using the zebrafish larval locomotor assay as a rapid first-pass screening tool in assessing the anticonvulsant and/or proconvulsant activity of compounds, but also highlight the importance of performing adequate validation when using in vivo models.
Buenafe, Olivia E. M.; Clinckers, Ralph; Smolders, Ilse; de Witte, Peter A. M.; Crawford, Alexander D.; Esguerra, Camila V.
There are many difficulties involved with the treatment of epilepsy, and these problems have driven the search for new agents to control epileptic seizures. Calcitonin is a peptide hormone that has been well studied and shown to have a positive effect on neuropathic and chronic pain. The mechanism by which calcitonin affects these pain syndromes is thought to be similar to the effect of antiepileptic drugs, such as pregabalin, gabapentin and carbamazepine. In this study, we aim to investigate the effects of calcitonin on seizures induced by pentylenetetrazole (PTZ) in rats. The rats were divided into four groups. The first group was the control group, and the rats were given no medications. The second group was given saline+PTZ. The third group was given 50IU/kg calcitonin+PTZ, and the fourth group was given 100IU/kg calcitonin+PTZ. EEG traces, Racine's convulsion stages and the time of onset of the first myoclonic jerk were compared between the groups. Between the groups, there were significant differences in the Racine's convulsion stages, the onset of the 'first myoclonic jerk', and the rate of the spikes in the EEG traces. The differences were more pronounced in the 100IU/kg calcitonin-treated group (p<0.001). It has been stated that calcitonin relieves pain via regulating voltage-gated Ca(2+) and/or Na(+) channels. Calcitonin has a positive effect on convulsions in epileptic rats, possibly using the same mechanisms as is used in the treatment of neuropathic and chronic pain. PMID:24548550
Aksoy, Durdane; Solmaz, Volkan; Erbas, Oytun
Objective(s) Indigofera tinctoria Linn. of Fabaceae family is claimed to be useful to control epileptic seizures in the Indian system of folkore medicine. This study was designed to evaluate tinctoria and to verify the claim. Materials and Methods Seizures were induced in male albino rats with pentylenetetrazole (PTZ). The test group animals were administered ethanolic extract of Indigofera tinctoria (EEIT) orally. The time of onset and duration of clonic convulsions were recorded. Maximal electroshock seizures (MES) were induced in animals. The duration of hind limb tonic extension (HLTE) was recorded. GABA levels and GABA transaminase activity in brain were estimated. Results In PTZ model, EEIT significantly (P< 0.01, P< 0.001) delayed the onset of convulsions and reduced the duration of seizures in a dose dependent manner. A significant (P< 0.05) reduction in the duration of HLTE at higher doses of EEIT was observed in MES model. Increase in brain GABA levels was observed on treatment with EEIT at 500 and 1000 mg/kg doses, suggested that the plant may be acting by facilitating GABAergic transmission. A significant reduction (P< 0.05) in the activity of brain GABA transaminase was observed at higher doses. No neurotoxic signs were observed with rotarod test, pentobarbital induced sleeping time, locomotor activity and haloperidol-induced catalepsy. Conclusion The ethanolic extract of tinctoria was found to be useful to control and treat the variety of seizures.
Garbhapu, Asuntha; Yalavarthi, Prasannaraju; Koganti, Prasad
Epilepsy is a debilitating disease affecting 1-2% of the world's population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit histone deacetylases (HDACs) using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, 2-benzamido-1 4-naphthoquinone (NQN1), significantly decreased swim activity to levels equal to that of valproic acid, 2-n-propylpentanoic acid (VPA). We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogs. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6Hz) and corneal-kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogs for the prevention of seizures and suggest the potential mechanism for this protection may lie in the ability of these compounds to affect energy production. PMID:24291671
Rahn, J J; Bestman, J E; Josey, B J; Inks, E S; Stackley, K D; Rogers, C E; Chou, C J; Chan, S S L
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.
Most medical therapies for epilepsy consist of daily (or multiple-daily) dose, fixed-schedule, pharmacologic oral agents. Despite adherence, many patients continue to experience seizures. Various products have been discovered, designed, and marketed to serve as seizure-abortant therapies. These agents can be administered rapidly, as a "rescue" therapy, once a clinical seizure or cluster of seizures starts. Rescue medications are given as needed in an attempt to disrupt progression of a given seizure, and forestall what would otherwise be a more prolonged or more severe clinical event. Seizure-abortants also serve to aid in the management of seizure emergencies, such as prolonged, repetitive seizures, or status epilepticus. These compounds are not appropriate for all patients. Nevertheless, they do provide therapeutic benefit to several groups of patients: 1) those who perceive the onset of their seizures and have time to perform a self-intervention, 2) patients' caregivers who administer the therapy when they witness the onset of an ictal event, and 3) patients who are in the midst of an out-of-the-hospital seizure emergency (a seizure cluster or status epilepticus). In this article we will review currently available and future rescue therapies for seizures: US Food and Drug Administration (FDA) approved and FDA nonapproved drugs, nonpharmacologic behavioral treatments, the vagus nerve stimulator and the NeuroPace RNS® System (Mountain View, CA). PMID:21509498
Poukas, Valeriya S; Pollard, John R; Anderson, Christopher Todd
Fifteen patients who experienced epileptic seizures while playing video games are described together with a review of 20 cases in the English literature. Nine of the 15 cases and all but two of the reported cases experienced their first seizure while playing video games. Two thirds of patients had idiopathic generalised epilepsy and mainly reported generalised tonic clonic seizures, but
C D Ferrie; P De Marco; R A Grünewald; S Giannakodimos; C P Panayiotopoulos
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
This work investigates the calibration of a stereo vision system based on two PTZ (Pan-Tilt-Zoom) cameras. As the accuracy of the system depends not only on intrinsic parameters, but also on the geometric relationships between rotation axes of the cameras, the major concern is the development of an effective and systematic way to obtain these relationships. We derived a complete geometric model of the dual-PTZ-camera system and proposed a calibration procedure for the intrinsic and external parameters of the model. The calibration method is based on Zhang's approach using an augmented checkerboard composed of eight small checkerboards, and is formulated as an optimization problem to be solved by an improved particle swarm optimization (PSO) method. Two Sony EVI-D70 PTZ cameras were used for the experiments. The root-mean-square errors (RMSE) of corner distances in the horizontal and vertical direction are 0.192 mm and 0.115 mm, respectively. The RMSE of overlapped points between the small checkerboards is 1.3958 mm.
Chang, Yau-Zen; Wang, Huai-Ming; Lee, Shih-Tseng; Wu, Chieh-Tsai; Hsu, Ming-Hsi
Seizures frequently affect the heart rate and rhythm. In most cases, seizure-related cardiac changes are transient and do not appear to cause clinically significant abnormalities for the patient. Great interest in this area of research has been generated because of a possible connection with sudden unexpected death in epilepsy (SUDEP). While there are clear, but rare complications from seizure-related cardiac arrhythmias, such as ictal asystole that causes syncope, the overall risk of seizures on cardiac status and any potential connection between seizures and SUDEP still remain uncertain.
It is unusual for a newborn to have the classic "tonic-clonic" seizure experienced by adults and older children. Signs of seizure in newborns are either subtle or may become clinically silent. Therefore, the electroencephalogram (EEG) is becoming the most reliable tool for detecting neonatal seizure. Being non-stationary and multicomponent, EEG signals are suitably analyzed using time-frequency (TF) based methods. In this paper, we present a seizure detection method using a new measure based on the matching pursuit (MP) decomposition of EEG data. Signals are represented in the TF domain where seizure structural characteristics are extracted to form a new coherent TF dictionary to be used in the MP decomposition. A new approach to set data-dependent thresholds, used in the seizure detection process, is proposed. To enhance the performance of the detector, the concept of areas of incidence is utilized to determine the geometrical correlation between EEG recording channels. PMID:19162804
Khlif, M S; Mesbah, M; Boashash, B; Colditz, P
5,7-Dihydroxytryptamine (5,7-DHT) injections which caused selective depletion of serotonin in the forebrain enhanced the seizures caused by pentylenetetrazol (PTZ 90 mg\\/kg s.c.) in rats. No effect was observed in rats with 5,7-DHT-induced depletion of spinal serotonin or treated with metergoline (1 mg\\/kg i.p.) or methysergide (10 mg\\/kg i.p.).
M. Lazarova; C. Bendotti; R. Samanin
SUMMARY Although often overshadowed by factors influencing seizure initiation, seizure termination is a critical step in the return to the interictal state. Understanding the mechanisms contributing to seizure termination could potentially identify novel targets for anticonvulsant drug development and may also highlight the pathophysiological processes contributing to seizure initiation. In this article, we review known physiological mechanisms contributing to seizure termination and discuss additional mechanisms that are likely to be relevant even though specific data are not yet available. This review is organized according to successively increasing “size scales”—from membranes to synapses to networks to circuits. We first discuss mechanisms of seizure termination acting at the shortest distances and affecting the excitable membranes of neurons in the seizure onset zone. Next we consider the contributions of ensembles of neurons and glia interacting at intermediate distances within the region of the seizure onset zone. Lastly, we consider the contribution of brain nuclei, such as the substantia nigra pars reticulata (SNR), that are capable of modulating seizures and exert their influence over the seizure onset zone (and neighboring areas) from a relatively great—in neuroanatomical terms—distance. It is our hope that the attention to the mechanisms contributing to seizure termination will stimulate novel avenues of epilepsy research and will contribute to improved patient care.
Lado, Fred A.; Moshe, Solomon L.
Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between 'normal' and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical parameters contributing to the five state variables in our model system. We show that these parameters apply to specific experimental conditions and propose that there exists a wide array of possible biophysical mechanisms for seizure genesis, while preserving central invariant properties. Epileptor and the seizure taxonomy will guide future modeling and translational research by identifying universal rules governing the initiation and termination of seizures and predicting the conditions necessary for those transitions. PMID:24919973
Jirsa, Viktor K; Stacey, William C; Quilichini, Pascale P; Ivanov, Anton I; Bernard, Christophe
A 75 years old man is suffering from recurrent seizures since several years. The seizures start with vegetative symptoms including tingling sensations, followed by a deep feeling of eternity and happiness. In one third of the cases he looses consciousness completely. Several workups have failed to reveal a diagnosis. An ECG loop recorder was implanted which finally revealed an asystole of 15 seconds duration. It was thought that this caused cerebral hypoxia which was triggering focal seizures. A pacemaker was inserted. The attacks of unconsciousness disappeared; however, the spells of vegetative sensations persisted. After antiepileptic treatment was initiated the symptoms improved, however it was not possible to achieve complete control. Is this patient primarily suffering from recurrent asystole or from epilepsy which causes complex seizures with disturbance of cardiac rhythm? The latter phenomenon in its most extreme presentation is better known as sudden unexplained death in epilepsy (SUDEP). The diagnostic approach and therapy of both diseases are discussed. PMID:23188781
Stähli, C; Müller, F; Krause, M
Neonatal seizures are a neurological emergency and prompt treatment is required. Seizure burden in neonates can be very high, status epilepticus a frequent occurrence, and the majority of seizures do not have any clinical correlate. Detection of neonatal seizures is only possible with continuous electroencephalogram (EEG) monitoring. EEG interpretation requires special expertise that is not available in most neonatal intensive care units (NICUs). As a result, a simplified method of EEG recording incorporating an easy-to-interpret compressed trend of the EEG output (amplitude integrated EEG) from one of the EEG output from one or two channels has emerged as a popular way to monitor neurological function in the NICU. This is not without limitations; short duration and low amplitude seizures can be missed, artefacts are problematic and may mimic seizure-like activity and only a restricted area of the brain is monitored. Continuous multichannel EEG is the gold standard for detecting seizures and monitoring response to therapy but expert interpretation of the EEG output is generally not available. Some centres have set up remote access for neurophysiologists to the cot-side EEG, but reliable interpretation is wholly dependent on the 24 h availability of experts, an expensive solution. A more practical solution for the NICU without such expertise is an automated seizure detection system. This review outlines the current state of the art regarding cot-side monitoring of neonatal seizures in the NICU. PMID:23707519
Boylan, Geraldine B; Stevenson, Nathan J; Vanhatalo, Sampsa
A provoked seizure may be due to structural damage (resulting from traumatic brain injury, brain tumor, stroke, tuberculosis, or neurocysticercosis) or due to metabolic abnormalities (such as alcohol withdrawal and renal or hepatic failure). This article is a part of the Guidelines for Epilepsy in India. This article reviews the problem of provoked seizure and its management and also provides recommendations based on currently available information. Seizure provoked by metabolic disturbances requires correction of the triggering factors. Benzodiazepines are recommended for treatment of seizure due to alcohol withdrawal; gabapentin for seizure seen in porphyria; and antiepileptic drugs (AED), that are not inducer of hepatic enzymes, in the seizures seen in hepatic dysfunction. In severe traumatic brain injury, with or without seizure, phenytoin (PHT) may be given for 7 days. In ischemic or hemorrhagic stroke one may individualize the AED therapy. In cerebral venous sinus thrombosis (CVST), AED may be prescribed if there is seizure or computed tomographic (CT) abnormalities or focal weakness; the treatment, in these cases, has to be continued for 1 year. Prophylactic AED is not recommended in cases of brain tumor and neurosurgical procedures and if patient is on an AED it can be stopped after 1 week.
Misra, Usha Kant; Kalita, Jayantee
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
The effects of toluene on the sensitivity to seizures induced by aminophylline were investigated. Mice were pretreated with an ip injection of corn oil or toluene (100-500 mg/kg) followed by a timed intravenous infusion of aminophylline at various time intervals to assess the seizure thresholds and lethal doses. Toluene increased seizure susceptibility to aminophylline in a dose- and time-dependent manner. Toluene-induced enhancement of seizure susceptibility to aminophylline occurred as early as 30 min and persisted for at least 3 days after a single administration of toluene (500 mg/kg). Treatment of benzaldehyde, one of toluene's metabolites, also showed an increase in the susceptibility to aminophylline. The enhancing effect was also observed in caffeine-induced seizures 1 h, but not 1 day after toluene treatment. These results suggest that individuals with toluene exposure may increase the risk for convulsive and even lethal complications associated with the therapeutic use of aminophylline. PMID:14644630
Chan, Ming-Huan; Chen, Hwei-Hsien
Chronic electrical stimulation via corneal electrodes can rapidly yield large numbers of kindled mice with a seizure phenotype reflective of secondarily generalized partial seizures. The corneal kindled mouse model has been found to be a highly sensitive and efficient screening model for antiepileptic drug (AED) discovery. The present study further evaluates the utility of the corneal kindled mouse model as a tool for rapid screening of investigational AEDs. Results obtained with nine AEDs (valproic acid, lamotrigine, phenytoin, carbamazepine, levetiracetam, vigabatrin, topiramate, tiagabine, and ezogabine) with varying mechanisms of action and clinical spectrums, as well as six investigational compounds were evaluated in the corneal kindled mouse. ED(50) values are compared to those obtained in the hippocampal kindled rat, the mouse maximal electroshock (MES) model, the 6Hz partial psychomotor seizure model, and the subcutaneous pentylenetetrazol (scPTZ) test. The results obtained in the corneal kindled mouse demonstrate a positive correlation with those attained employing established preclinical models: MES (r² = 0.9511), scPTZ (r² = 0.9697), 6Hz (r² = 0.9519), and hippocampal kindling (r² = 0.9037). The demonstrated predictive ability of the corneal kindled mouse model supports its use in the early evaluation of investigational AEDs. PMID:20951004
Rowley, Nicole M; White, H Steve
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
Raman spectra of the spin-crossover complex [Fe(ptz) 6](BF 4) 2 (ptz = 1- n-propyl-tetrazole) have been recorded at visible and IR exciting wavelengths as a function of temperature down to 5 K. Distinct Raman markers were associated with the spin-state change and the crystallographic phase-transition of the compound. This allows us to demonstrate that the light-induced exited spin-state trapping (LIESST) and the reverse-LIESST effects as well as the thermal relaxation of the photo-induced phase occur without crystallographic phase change in contrast to the thermal spin-crossover.
Moussa, Nawel Ould; Molnár, Gábor; Ducros, Xavier; Zwick, Antoine; Tayagaki, Takeshi; Tanaka, Koichiro; Bousseksou, Azzedine
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.
Various psychic symptoms as ictal manifestation have been found in epileptic patients. They are classified as psychic seizures within simple partial seizures, and subclassified into affective, cognitive, dysmnesic seizures and so on, although the subclassification is not yet satisfactory and almost nothing is known about their relationships with normal brain functions. In this presentation, the speaker picked ictal fear, déjà vu and out-of-body experience (OBE) from them and suggested that studies on these symptoms could uniquely contribute to the progress of cognitive neuroscience, presenting some results from the research and case study that he had been engaged in. Psychic seizures are prone to be missed or misdiagnosed unless psychiatrists with sufficient knowledge and experience on epilepsy care would not treat them, because they are subjective symptoms that are diverse and subtle, while they have some characteristics as ictal symptoms. PMID:16637586
\\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
Background California sea lions have a large body burden of organochlorine pesticides, and over the last decade they have also been subject to domoic acid poisoning. Domoic acid poisoning, previously recognized in adult animals, is now viewed as a major cause of prenatal mortality. The appearance of a chronic juvenile domoic acid disease in the sea lions, characterized by behavioral abnormalities and epilepsy, is consistent with early life poisoning and may be potentiated by organochlorine burden. Objective We investigated the interactive effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility to domoic acid–induced seizures after completion of neurodevelopment. Methods Embryos were exposed (6–30 hr postfertilization) to either o,p?-DDT or p,p?-DDE (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl sulfoxide solution. These larval (7 days postfertilization) fish were then exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic acid; resulting seizure behavior was monitored and analyzed for changes using cameras and behavioral tracking software. Results Embryonic exposure to DDTs enhanced PTZ seizures and caused distinct and increased seizure behaviors to domoic acid, most notably a type of head-shaking behavior. Conclusion These studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals at completion of neurodevelopment with greater sensitivity to domoic acid–induced seizures. The body burden levels of p,p?-DDE are close to the range recently found in fetal California sea lions and suggest a potential interactive effect of p,p?-DDE embryonic poisoning and domoic acid toxicity.
Tiedeken, Jessica A.; Ramsdell, John S.
Objective: All patients who exhibit seizure-like behavior cannot be evaluated by video-electroencephalography if their routine EEGs are negative, as this would be impractical and cost-prohibitive. The present article reviews a decision-making process that can be used for determining if further neurological evaluation is needed, the differential diagnoses and potential comorbidities involved when making this determination, and an approach to conveying the psychogenic nonepileptic seizure diagnosis to the patient that may help reduce symptom frequency. Design: Literature review. Conclusion: Psychogenic seizures are not caused by abnormal brain electrical activity. The symptoms of psychogenic seizures usually reflect a psychological conflict or a psychiatric disorder. However, psychogenic seizures are not "purposely" produced by the patient, and the patient is not aware that the seizures are non-epileptic, so the patient may become very anxious over having these symptoms. The presentation of the differential diagnosis should be done early in the course of treatment for better patient acceptance, and treatment options should be presented early in the evaluation period. PMID:24563816
Marie Gillig, Paulette
Objective: All patients who exhibit seizure-like behavior cannot be evaluated by video-electroencephalography if their routine EEGs are negative, as this would be impractical and cost-prohibitive. The present article reviews a decision-making process that can be used for determining if further neurological evaluation is needed, the differential diagnoses and potential comorbidities involved when making this determination, and an approach to conveying the psychogenic nonepileptic seizure diagnosis to the patient that may help reduce symptom frequency. Design: Literature review. Conclusion: Psychogenic seizures are not caused by abnormal brain electrical activity. The symptoms of psychogenic seizures usually reflect a psychological conflict or a psychiatric disorder. However, psychogenic seizures are not “purposely” produced by the patient, and the patient is not aware that the seizures are non-epileptic, so the patient may become very anxious over having these symptoms. The presentation of the differential diagnosis should be done early in the course of treatment for better patient acceptance, and treatment options should be presented early in the evaluation period.
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.
Dube, Celine M.; Brewster, Amy L.; Richichi, Cristina; Zha, Qinqin; Baram, Tallie Z.
Clinical evidence, in particular the wide use of theophylline as bronchodilator, suggests that methylxanthines can cause seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by antagonizing the brain’s own anticonvulsant adenosine. Recent evidence suggests that adenosine dysfunction is a pathological hallmark of epilepsy contributing to seizure generation and seizure spread. Conversely, adenosine augmentation therapies are effective in seizure suppression and prevention, whereas adenosine receptor antagonists such as methylxanthines generally exacerbate seizures. The impact of the methylxanthines caffeine and theophylline on seizures and excitotoxicity depends on timing, dose, and acute versus chronic use. New findings suggest a role of free radicals in theophylline-induced seizures and adenosine-independent mechanisms for seizure generation have been proposed.
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
Psychogenic nonepileptic seizures (PNES) are clinical events resembling epileptic seizures but lacking abnormal cortical electrical discharges. They are involuntary manifestations of a psychological distress. PNES are less frequent in the pediatric population than in adults, they represent from 3.5 to 9% of patients admitted for prolonged video-EEG (PV-EEG). Diagnosis is rarely made on history only and PV-EEG is mandatory to obtain a definitive diagnosis. Children as young as 5 years can present with PNES. They are more frequent in girls except in school age children where boys are identically or more represented than girls. PNES can either present with subtle signs, even unresponsiveness, or prominent motor activity. Major differential diagnosis is absences, day dreaming, and complex partial seizures including hyperkinetic frontal seizures. PNES are usually rapidly registered during PV-EEG and provocative methods have not been thoroughly studied in children. Major risk factors are psychological stressors, such as school or family problems. Psychiatric conditions are less frequent than in adults though they should be looked for. Prognosis is better than in adults, and most children become PNES-free. There are no guidelines for treatment, however stressors should be addressed. In general, it should be clearly explained that PNES are not epileptic seizures. PMID:23622297
In this paper, we present a fuzzy rule-based system for the automatic detection of seizures in the intracranial EEG (IEEG) recordings. A total of 302.7 hours of the IEEG with 78 seizures, recorded from 21 patients aged between 10 and 47 years were used for the evaluation of the system. After preprocessing, temporal, spectral, and complexity features were extracted from the segmented IEEGs. The results were thresholded using the statistics of a reference window and integrated spatio-temporally using a fuzzy rule-based decision making system. The system yielded a sensitivity of 98.7%, a false detection rate of 0.27/h, and an average detection latency of 11 s. The results from the automatic system correlate well with the visual analysis of the seizures by the expert. This system may serve as a good seizure detection tool for monitoring long-term IEEG with relatively high sensitivity and low false detection rate. PMID:19963525
Aarabi, A; Fazel-Rezai, R; Aghakhani, Y
In this study we investigated the threshold and latency of seizures in a new model of chemically induced partial seizures, with or without secondary generalization. We performed repeated experiments with a maximum of 20 between day seizures on each individual rat over a period up to 6 months, with resting intervals ranging from 3 to 15 days depending on the
Germán Sierra-Paredes; Germán Sierra-Marcuño
Despite the frequency of seizure disorders in the human population, the genetic and physiological basis for these defects has been difficult to resolve. Although many genetic contributions to seizure susceptibility have been identified, these involve disparate biological processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved makes it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful in both understanding how different physiological processes affect seizure susceptibility and identifying novel therapeutic treatments. We review here factors contributing to seizure susceptibility in Drosophila, a genetically tractable system that provides a model for human seizure disorders. Seizure-like neuronal activities and behaviors in the fruit fly are described, as well as a set of mutations that exhibit features resembling some human epilepsies and render the fly sensitive to seizures. Especially interesting are descriptions of a novel class of mutations that are second-site mutations that act as seizure suppressors. These mutations revert epilepsy phenotypes back to the wild-type range of seizure susceptibility. The genes responsible for seizure suppression are cloned with the goal of identifying targets for lead compounds that may be developed into new antiepileptic drugs.
Parker, Louise; Howlett, Iris C.; Rusan, Zeid M.; Tanouye, Mark A.
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…
A monitor has been designed to detect the onset of status epilepticus associated with complex partial seizures in children. A unique sensor technology was developed to detect the minor, barely perceptible tremors characteristic of partial seizures. A micr...
M. A. Johnson G. Kendall P. J. Cote L. V. Meisel
Iopamidol, a water-soluble contrast agent, has been rarely associated with seizures. We describe a case of generalized tonic-clonic seizure after cervical myelography with iopamidol in a previously healthy young man. In patients presenting with seizures, a history of recent myelography should be considered as an etiology. Iopamidol myelography may be associated with a risk of seizures. Clinicians need to be aware of this complication and inform their patients about such risk.
Singh, Sonal; Rajpal, Chitra; Nannapeneni, Srikanth; Venkatesh, Sundar
\\u000a Nonepileptic seizures (NES) are operationally defined as episodes of involuntary movement, altered responsiveness, or subjective\\u000a experience that resemble epileptic seizures (ES), but are not accompanied by the abnormal electrical discharges in the brain\\u000a that is a seizure. (Lesser, 1996; Reuber and Elger, 2003). When these episodes are caused by psychological processes, they\\u000a are termed psychogenic nonepileptic seizures (PNES). Other terms,
Daniel L. Drane; Erica L. Coady; David J. Williamson; John W. Miller; Selim Benbadis
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 (80 mg/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. PMID:23775703
Saboory, Ehsan; Gholami, Morteza; Zare, Samad; Roshan-Milani, Shiva
Background and purpose of the study Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. Methods The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. Results Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. Major conclusion The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.
Sayyah, M.; Khodaparast, A.; Yazdi, A.; Sardari, S.
The important differential diagnosis between epileptogenic versus non-epileptogenic attacks becomes increasingly difficult with elderly patients: 1) Vasovagal syncopes may occur abruptly, not infrequently with injuries caused by the sudden fall ("Blitz-Synkope"). Other generalized non-epileptic seizures include drop-attacks, amnesic episodes, prolonged syncopes, and seizures caused by faulty metabolism. 2) Focal non-epileptic seizures in advanced age are mainly TIA and prolonged TIA (PRIND). Complicated migraine is more typical for the younger age group. In this connection it must be kept in mind that 10% of TIA are caused by brain tumor, 20% can be traced to cardiac origin. 3) In connection with the non-epileptic seizures mentioned above there may appear singular irregular cloni without any rhythmical sequence. We have come to call this type of attacks "incidental convulsions". Especially in these cases differential diagnosis is of great importance with respect to basically different therapeutic measures. 4) First manifestations of epilepsy in advanced age are--regarding etiology--in the first rank symptoms of cerebral vascular disease or of intracranial tumors. 5) In the diagnostic approach it is necessary to keep in mind all the above-mentioned possibilities and to exploit every possible access to anamnestic exploration, with the patient as well as with his family, friends and colleagues. Essential auxiliary diagnostic methods include EEG, computed tomography, Doppler-sonography, occasionally long-time EEG or ECG, in some cases NMR. PMID:1891917
Barolin, G S
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.
A threshold element is a mathematical model of certain types of logic gates and of a biological neuron. Much work has been done on the subject of threshold elements with fixed thresholds; this study concerns itself with elements in which the threshold may...
W. S. Meisel
Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7-year-old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body temperature elevation, looking at visual patterns, or under intermittent photic stimulation. The case we report widens the spectrum of reflex seizures recorded in patients with Dravet syndrome. Cortical hyperexcitability of genetic origin could explain the tendency of these patients to experience reflex seizures. PMID:23517304
Sanchez-Carpintero, Rocio; Patiño-Garcia, Ana; Urrestarazu, Elena
Background Precise control of anesthetic depth during electroconvulsive therapy (ECT) is crucial because most intravenous anesthetics have anticonvulsant effects. In this study, we investigated the association between anesthetic depth measured by the Alaris auditory evoked potential index (AAI) and seizure inducibility and seizure duration during ECT. Methods Sixty-four ECTs were evaluated in 12 consecutive patients. General anesthesia was performed with a thiopental-based method. The relationship between the pre-ictal AAI, seizure activity and seizure duration was analyzed, and a possible threshold pre-ictal AAI to induce a seizure duration of at least 25 seconds was calculated. Results Forty-one of the 64 ECT stimuli successfully induced seizure activity that lasted longer than 25 seconds. Pre-ictal AAI was significantly correlated to seizure duration (r?=?0.54, p?0.001) and the threshold pre-ictal AAi value was calculated to be 26 (area under curve: 0.76, sensitivity: 70.3% and specificity: 73.9%, p?0.001). ECT with a pre-ictal AAI ? 26 had a higher incidence of successful seizure activity ( p?0.001) and a longer seizure duration (55?±?35 v.s. 21?±?27 seconds, p?0.001). Conclusion Maintenance of a pre-ictal AAI value ? 26 was associated with an increased incidence of successful seizure activities and a longer seizure duration. This is the first report to investigate Alaris AEP monitoring during ECT.
Nuclear inelastic scattering (NIS) spectra of [Fe(ptz) 6](BF 4) 2 (ptz = 1- n-propyl-tetrazole) have been measured for five phases differing in spin state and crystallographic structure. Different spectral patterns have been found for the low-spin and high-spin phases and are described in terms of normal coordinate analysis of the complex molecule. For both low-spin and high-spin phases the conversion from ordered to disordered phase results in splitting of the observed NIS bands. Packing becomes visible in the NIS spectra via coupling of the Fe-N stretching vibrations with those of the terminal n-propyl groups. The DFT-based normal coordinate analysis also reveals the character of Raman markers.
Böttger, Lars H.; Chumakov, Aleksandr I.; Matthias Grunert, C.; Gütlich, Philipp; Kusz, Joachim; Paulsen, Hauke; Ponkratz, Ulrich; Rusanov, Ventzislav; Trautwein, Alfred X.; Wolny, Juliusz A.
SMP-601 (also known as PTZ601, PZ-601, or SM-216601) is a novel parenteral carbapenem with potent activity against multidrug-resistant gram-positive pathogens, including vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA). The pharmacodynamics of SMP-601 against VREF and MRSA were investigated in neutropenic murine thigh infection models. The percentage of the dosing interval that the unbound SMP-601 concentration exceeded the MIC
Ken Eguchi; Katsunori Kanazawa; Yoshiro Eriguchi; Yutaka Ueda
The genetically epilepsy-prone rat is an animal model of inherited generalised tonic-clonic epilepsy that shows abnormal susceptibility to audiogenic seizures and a lowered threshold to a variety of seizure-inducing stimuli. Recent studies suggest a crucial role for glutamate and GABA transporters in epileptogenesis and seizure propagation. The present study examines the levels of expression of the messenger RNAS encoding the
M. T. Akbar; M. Rattray; R. J. Williams; N. W. S. Chong; B. S. Meldrum
Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl? cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24–48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl? cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.
Rusan, Zeid M.; Kingsford, Olivia A.; Tanouye, Mark A.
\\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
Seizures are a nonspecific neurological manifestation of cerebral dysfunction and are not indicative of any particular disease\\u000a processes or pathology. Thus, the evaluation and treatment of seizures in transplant patients generally follows the same clinical\\u000a approach used for other patients. A seizure in a transplant patient is commonly unanticipated and entirely unexplained. The\\u000a effects can be substantial, with aspiration, loss
Greg A. Worrell; Eelco F. M. Wijdicks
A 32-year-old man presented to the emergency department (ED) with seizures 6 hours after a lumbar myelogram with iopamidol (Isovue-M 200, Squibb, Princeton, NJ). Seizures are a rare complication after myelography with the current nonionic contrast agents and have not been previously reported in the emergency medicine literature. Emergency physicians should be aware of this potential complication because outpatient myelograms are frequently performed, and these patients may present to the ED after seizures. PMID:8179742
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.
We investigated the effects of a cell-permeable superoxide dismutase mimetic, manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) on blood-brain barrier (BBB) integrity following pentylenetetrazole (PTZ)-induced seizures in experimental preeclampsia symptoms induced by N(omega)-nitro-l-arginine methyl ester (l-NAME) in pregnant rats. To show the functional and morphological alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopic assessment of horseradish peroxidase (HRP) permeability were performed. Varying degrees of proteinuria were seen and arterial blood pressure increased in l-NAME-treated pregnant rats (p<0.01). MnTMPyP pretreatment and convulsive PTZ challenge significantly decreased the immunoreactivity of occludin in hippocampal capillaries in l-NAME-treated pregnant rats (p<0.01). BBB permeability to NaFlu significantly increased in pregnant rats treated with l-NAME plus PTZ (p<0.01), but MnTMPyP pretreatment did not significantly decrease NaFlu penetration into the brain parenchyma in these animals. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in the capillary endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated with l-NAME and l-NAME plus PTZ with the abundance being more in the latter group. MnTMPyP pretreatment caused a marked reduction in the frequency of HRP reaction product containing vesicles in both experimental settings. In conclusion, the results of the present study provide evidence that MnTMPyP plays an important role in limiting the enhanced vesicle-mediated transcellular transport in BBB endothelium in a rat model of preeclampsia and the differences in the way of transports of NaFlu and HRP might be responsible for the different effects of MnTMPyP on the BBB permeability to these two tracers. PMID:24680906
Orhan, Nurcan; Ugur Yilmaz, Canan; Ekizoglu, Oguzhan; Ahishali, Bulent; Arican, Nadir; Kucuk, Mutlu; Elmas, Imdat; Gürses, Candan; Kalayci, Rivaze; Kaya, Mehmet
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
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.
Dickman, Paul S.; Lyons, Valerie
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
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.
Basim M Uthman
EPILEPSY, or the propensity to have recurrent seizures, is the most common chronic neurological disorder in dogs, with an estimated prevalence of between 0·5 and 5·7 per cent. There are numerous primary intracranial diseases and extracranial (eg, metabolic or toxic) conditions that cause recurrent seizures, although idiopathic epilepsy is the most common in dogs. Metabolic and toxic disorders are much
Kate Chandler; Holger Volk
Current epileptic seizure "prediction" algorithms are generally based on the knowledge of seizure occurring time and analyze the electroencephalogram (EEG) recordings retrospectively. 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 procedure to prospectively analyze continuous, long-term EEG recordings when only the occurring time of the first seizure is known. The algorithm is based on the convergence and divergence of short-term maximum Lyapunov exponents (STLmax) among critical electrode sites selected adaptively. A warning of an impending seizure is then issued. Global optimization techniques are applied for selecting the critical groups of electrode sites. The adaptive seizure prediction algorithm (ASPA) was tested in continuous 0.76 to 5.84 days intracranial EEG recordings from a group of five patients with refractory temporal lobe epilepsy. A fixed parameter setting applied to all cases predicted 82% of seizures with a false prediction rate of 0.16/h. Seizure warnings occurred an average of 71.7 min before ictal onset. Similar results were produced by dividing the available EEG recordings into half training and testing portions. Optimizing the parameters for individual patients improved sensitivity (84% overall) and reduced false prediction rate (0.12/h overall). These results indicate that ASPA can be applied to implantable devices for diagnostic and therapeutic purposes. PMID:12769437
Iasemidis, Leon D; Shiau, Deng-Shan; Chaovalitwongse, Wanpracha; Sackellares, J Chris; Pardalos, Panos M; Principe, Jose C; Carney, Paul R; Prasad, Awadhesh; Veeramani, Balaji; Tsakalis, Konstantinos
A case is presented of a patient with a long history of epilepsy who presents with recurrent seizures and develops a period of asystole. The case highlights the need to consider the potential arrhythmic complications of seizures and the clinical characteristics that may be present in those with epilepsy that may warrant evaluation for arrhythmias. PMID:22877730
Stokes, Michael B; Palmer, Sonny; Moneghetti, Kegan J; Mariani, Justin A; Wilson, Andrew M
The topic of alcohol withdrawal syndrome (AWS), including delirium tremens and especially seizures, is reviewed. From mice and rat studies, it is known that both N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are involved in AWS. During alcohol intoxication chronic adaptations of NMDA and GABA receptors occur, and during alcohol withdrawal a hyperexcitable state develops. In studies on humans, during intoxication the NMDA receptors are activated and mediate tonic inhibition. In withdrawal, a rebound activation of these receptors occurs. Both GABA-A and GABA-B receptors, especially the alpha2 subunit of GABA-A receptors, are also likely involved. Homocysteine increases with active drinking, and in withdrawal, excitotoxicity likely is induced by a further increase in homocysteine, viewed as a risk factor for AWS and also as a screening tool. The dopamine transporter gene is also associated with AWS. Characteristics involves changes in the ECG, especially an increase in QT interval, and EEG changes, including abnormal quantified EEG, at times periodic lateralized epileptiform discharges, and especially seizures, usually occurring 6-48h after the cessation of drinking. Therapy has emphasized benzodiazepines, mainly diazepam and lorazepam, but more standard antiepileptic drugs, like carbamazepine and topiramate, are also effective and safe. PMID:19249388
Hughes, John R
Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance.
Moghim, Negin; Corne, David W.
Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and fosphenytoin are the traditional and best evidence-based options, although intravenous levetiracetam, valproate, and lacosamide are emerging options. Availability of several newer AEDs has greatly expanded the therapeutic armamentarium for safe and efficacious treatment of post-transplant seizures, but future prospective clinical trials and pharmacokinetic studies within this specific patient population are needed.
Shepard, Paul W.
Rationale: Convulsions associated with cocaine toxicity are a serious aspect of cocaine-related emergency room incidents. Seizures\\u000a can result from a single high dose of cocaine, and evidence is accumulating that correlates repetitive administration of sub-convulsive\\u000a doses of cocaine with a decreased seizure threshold, a phenomenon known as pharmacological kindling. A murine model of cocaine kindling has not been characterized. Objectives:
Kathleen A. Miller; Jeffrey M. Witkin; Jesse T. Ungard; Maciej Gasior
In summary, NPY is clearly an important peptide in the adult rat dentate gyrus because it has the potential to influence synaptic transmission and neurogenesis. It may even have other functions, as yet undiscovered, mediated by glia or vasculature. The remarkable plasticity of NPY puts it in a position to allow dentate gyrus function to be modified in a changing environment. The importance of this plasticity in the context of epilepsy cannot be emphasized enough. It could help explain a range of observations about epilepsy that currently is poorly understood. For example, rapid increases in NPY could mediate postictal depression, the period of depression that can last for several hours after generalized seizures. It may mediate the "priming effect," which is a reduction in seizure threshold following an initial period of seizures. Finally, it could contribute to the resistance of dentate granule cells to degeneration after seizures. However, despite the focus in this review on seizure-induced changes, the changes described here also appear to occur after other types of manipulations, which considerably broadens the scope of NPY's role in the brain. PMID:16383008
Scharfman, Helen E; Gray, William P
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
Critically ill patients are subjected to numerous medication effects during their stay in the intensive care unit (ICU). Some\\u000a of them have epileptogenic potentials. The most common pathophysiologic mechanism is through blockade of the ?-aminobutyric\\u000a acid (GABA) receptor, and the most commonly used family of ICU drugs, reducing the seizure threshold, is the antibiotics.\\u000a The exact role of these medications
Rebecca E. Schuman; Panayiotis N. Varelas
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.
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
Reports focusing on auras of ecstasy or pleasure have been limited largely to single case descriptions. We examined 11 consecutive patients with such ictal symptoms. Eight had sensory hallucinations, four had erotic sensations, five described "a religious/spiritual experience," and several had symptoms that were felt to have no counterpart in human experience. Ictal EEG recordings were performed in four patients; two had seizure onset in the right temporal lobe and two in the left. In seven the onset could not be definitely localized. The diagnosis of epilepsy was often delayed. Eight patients wished to experience seizures; self-induction was possible in five and four showed treatment noncompliance. In patients with insufficient drug intake, in whom good compliance should be expected, it is relevant to consider seizures with pleasant symptomatology. According to the literature, experiential and ecstatic seizures seem to have had a substantial impact on our cultural and religious history. PMID:14698700
Asheim Hansen, Bjørn; Brodtkorb, Eylert
Several potential pathophysiologic phenomena, including “cerebral shutdown,” are postulated to be responsible for SUDEP. Since the evidence for a seizure-related mechanism is strong, a poor understanding of the physiology of human seizure termination is a major handicap. However, rather than a failure of a single homeostatic mechanism, such as postictal arousal, it may be a “perfect storm” created by the lining up of a several factors that lead to death.
Bozorgi, Alireza; Lhatoo, Samden D.
Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures. PMID:24802403
Zhao, Ran-Ran; Xu, Xiao-Chen; Xu, Fei; Zhang, Wei-Li; Zhang, Wen-Lin; Liu, Liang-Min; Wang, Wei-Ping
Tobacco smoking is considered the greatest risk factor for death caused by noncommunicable diseases. In contrast to extensive research on the association between tobacco smoking and diseases such as heart attack, stroke, and cancers, studies on the association between tobacco smoking and seizures or epilepsy are insufficient. The exact roles tobacco smoking and nicotine use play in seizures or epilepsy have not been well reviewed. We reviewed available literature and found that 1) there are vast differences between tobacco smoke and nicotine based on their components and their effects on seizures or epilepsy; 2) the seizure risk in acute active tobacco smokers, women who smoke during pregnancy, electronic cigarette smokers, and the role of smoking in sudden unexplained/unexpected death in epilepsy remain unclear; 3) seizure risks are higher in acute secondhand smokers, chronic active smokers, and babies whose mothers smoke; 4) tobacco smoke protects against seizures in animal models whereas nicotine exerts mixed effects in animals; and 5) tobacco smoking agents can be noneffective, proconvulsant, or anticonvulsant. Finally, the opportunities for future research on this topic is discussed. PMID:24441294
Rong, Lingling; Frontera, Alfred T; Benbadis, Selim R
In the current study the link among the ?-hydroxybutyrate (GHB)/pentylenetetrazole (PTZ)-induced absence-like seizures and concomitant decreases in the core temperature, as well as electroencephalographic (EEG) activity during rewarming from deep hypothermia produced by a drug-free protocol were investigated. During the rewarming period after deep cooling, most Wistar rats suffered from bilaterally synchronous spike and waves with no or mild behavioral correlates. Spike and wave seizures were temperature-dependent and were initially registered when body temperature (Tb) reached 25-27°C, but mostly during the mild hypothermia of 0.3-1.3°C (Tb of 36.3-37.3°C). In chemical absence models, spike and wave discharges were also closely accompanied by mild systemic hypothermia, as both PTZ- and GHB-induced temperature decreases ranged from about 1-1.4°C respectively, together with EEG markers of absence activity. Thus, throughout the different experimental designs, the occurrence of spike and wave discharges was always related to a mild (0.3-1.4°C) decrease of Tb. Benzodiazepine diazepam as the GABAA-positive allosteric modulator and CGP 62349 as the selective antagonist of GABAB receptors were used to determine if their well-known anticonvulsant properties also affect hypothermia elicited by these drugs. Finally, during the course of spontaneous rewarming from deep hypothermia, another selective GABAB-blocking agent, CGP 35348, was used to elucidate if GABAB inhibitory system could be critically implicated in the generation of hypothermia-dependent spike and waves. Diazepam prevented both the PTZ-induced hypothermia and electrographic absence seizures, but these two beneficial effects did not occur in the GHB model. Even though diazepam delayed GHB-induced maximal temperature decrease, the GHB effects remained highly significant. The GABAB antagonist CGP 62349 completely prevented hypothermia as well as absence seizures in both chemical models. Likewise, spike and wave discharges, registered during the spontaneous rewarming from deep hypothermia, were completely prevented by CGP 35348. These findings show that systemic hypothermia should definitely be regarded as a marker of GABAB receptor activation. Moreover, the results of this study clearly show that initial mild temperature decrease should be considered as strong absence-provoking factor. Hypothermia-induced nonconvulsive seizures also highlight the importance of continuous EEG monitoring in children undergoing therapeutic hypothermia after cardiac arrest. Since every change in peripheral or systemic temperature ultimately must be perceived by preoptic region of the anterior hypothalamus as the primary thermoregulatory and sleep-inducing center, the preoptic thermosensitive neurons in general and warm-sensitive neurons in particular, simply have to be regarded as the most probable candidate for connected thermoregulatory and absence generating mechanisms. Therefore, additional studies are needed to confirm their potential role in the generation and propagation of absence seizures. PMID:23415784
Ostoji?, Z S; Ili?, T V; Veskovi?, S M; Andjus, P R
Summary Seizure prediction has proven to be difficult in clinically realistic environments. Is it possible that fluctuations in cortical firing could influence the onset of seizures in an ictal zone? To test this, we have now used neural network simulations in a computational model of cortex having a total of 65,536 neurons with intercellular wiring patterned after histological data. A spatially distributed Poisson driven background input representing the activity of neighboring cortex affected 1% of the neurons. Gamma distributions were fit to the interbursting phase intervals, a non-parametric test for randomness was applied, and a dynamical systems analysis was performed to search for period-1 orbits in the intervals. The non-parametric analysis suggests that intervals are being drawn at random from their underlying joint distribution and the dynamical systems analysis is consistent with a nondeterministic dynamical interpretation of the generation of bursting phases. These results imply that in a region of cortex with abnormal connectivity analogous to a seizure focus, it is possible to initiate seizure activity with fluctuations of input from the surrounding cortical regions. These findings suggest one possibility for ictal generation from abnormal focal epileptic networks. This mechanism additionally could help explain the difficulty in predicting partial seizures in some patients.
Azhar, Feraz; Kudela, Pawel; Bergey, Gregory K.; Franaszczuk, Piotr J.
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
Epilepsy and depression are comorbid disorders, but the mechanisms underlying their relationship have not been identified. Traditionally, many antidepressants have been thought to increase seizure incidence, although this remains controversial, and it is unclear which medications should be used to treat individuals suffering from both epilepsy and depression. Since the neurotransmitter norepinephrine (NE) has both antidepressant and anticonvulsant properties, we speculated that NE transporter (NET) inhibitor antidepressants might be therapeutic candidates for comorbid individuals. To test this idea, we assessed the effects of chronic administration (via osmotic minipump) of the selective NET inhibitor reboxetine on flurothyl-induced seizures in mice. We found that reboxetine had both proconvulsant and anticonvulsant properties; it lowered both seizure threshold and maximal seizure severity. NET knockout (NET KO) mice essentially phenocopied the effects of reboxetine on flurothyl-induced seizures, and the trends were extended to pentylenetetrazole and maximal electroshock seizures (MES). Furthermore, reboxetine had no further effect in NET KO mice, demonstrating the specificity of reboxetine for the NET. We next tested the chronic and acute effects of other classes of antidepressants (desipramine, imipramine, sertraline, bupropion, and venlafaxine) on seizure susceptibility. Only venlafaxine was devoid of proconvulsant activity, and retained some anticonvulsant activity. These results suggest that chronic antidepressant drug treatment has both proconvulsant and anticonvulsant effects, and that venlafaxine is a good candidate for the treatment of epilepsy and depression comorbidity. PMID:16052243
Ahern, Todd H; Javors, Martin A; Eagles, Douglas A; Martillotti, Jared; Mitchell, Heather A; Liles, Larry Cameron; Weinshenker, David
In this retrospective study, we collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of seizure after ischemic stroke for the period of January 1996 to July 2006. Thirty-nine out of 94 children with ischemic stroke had poststroke seizures. Thirty-three out of 39 children with poststroke seizures had new onset seizures but only data of 28 were available. Infection was the most common etiology in the early poststroke seizure group (52.4%) but not in the late poststroke seizure group (0%). Infarction involving arterial ischemic stroke of anterior circulation were the most common in both the early poststroke seizure (61.9%) and the late poststroke seizure group (57.1%). Epilepsy was the most common sequelae in both the early poststroke seizure (38.1%) and late poststroke seizure group (100%). Children who had initial focal neurological sign (100% vs. 38.1%; P=0.007) or the focal cortical dysfunction on EEG (85.7% vs. 33.3%; P=0.029) were prone to develop late poststroke seizures. Late poststroke seizures had a high risk of developing poststroke epilepsy (100% vs. 38.1%; P=0.007). We conclude that seizures commonly occur in childhood ischemic stroke. Most poststroke seizures developed at an early stage. Infection was the most common etiology that caused early poststroke seizures in childhood ischemic stroke. Initial focal neurological signs and focal cortical dysfunction on EEG are risk factors for developing epilepsy. Poststroke seizures did not affect mortality, but there was a significant difference in normal outcome and epilepsy between those with or without poststroke seizures. PMID:18650041
Lee, Jiun-Chang; Lin, Kuang-Lin; Wang, Huei-Shyong; Chou, Min-Liang; Hung, Po-Cheng; Hsieh, Meng-Ying; Lee, Ying-Ying; Lin, Jainn-Jim; Wong, Alex Mun-Ching
The clinical manifestations of seizures change in a predictable fashion with advancing age. For focal seizures these changes can be summarized into domains similar to those used in developmental models. These include fine motor, communication, and gross motor manifestations. Instead of socialization the fourth domain for seizure semiology concerns synchronization. Focal seizures in the very young tend to be simpler with fewer fine motor manifestations. Auras are uncommon, even in young children with some linguistic skill and it is often difficult to discern alteration of consciousness. Infantile focal seizures can present with spasms or even diffuse tonic seizures. In terms of synchronization, orderly secondary generalization is rarely seen so that primary generalized clonic seizures are rarely recorded in infants. Amongst so-called "generalized" seizures spasms are most often seen in the first year of life. Absence seizures, myoclonic-astatic and generalized tonic-clonic seizures are all usually not seen until after age 2 years. A full description of the clinical details of seizures is probably the most important part of the epilepsy history. A detailed knowledge of seizure semiology can make the history more effective and also in the identification of the correct seizure classification. PMID:23622194
Nordli, Douglas R
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.
Summary There is a growing appreciation that patients with seizures are also affected by a number of co-morbid conditions, including an increase in prevalence of depression (Kanner, 2009), sleep apnea (Chihorek et al, 2007), and sudden death (Ryvlin et al, 2006; Tomson et al, 2008). The mechanisms responsible for these associations are unclear. Here we discuss the possibility that underlying pathology in the serotonin (5-HT) system of epilepsy patients lowers the threshold for seizures, while also increasing the risk of depression and sudden death. We propose that post-ictal dysfunction of 5-HT neurons causes depression of breathing and arousal in some epilepsy patients, and this can lead to sudden unexpected death in epilepsy (SUDEP). We further draw parallels between SUDEP and sudden infant death syndrome (SIDS), which may share pathophysiological mechanisms, and which have both been linked to defects in the 5-HT system.
Richerson, George B.; Buchanan, Gordon F.
Transexamic acid (TXA) is an antifibrinolytic that has been used successfully to prevent blood loss during major surgery. However, as its usage has increased, there have been growing reports of postsurgical seizure events in cardiac surgery patients. In this issue of the JCI, Lecker et al. explore this connection and suggest that TXA-mediated inhibition of glycine receptors may underlie the effect. This finding prompted the authors to explore the preclinical efficacy of common anesthetics that function by reducing the TXA-mediated inhibition to prevent or modify postsurgical seizures.
Schwinn, Debra A.; Mackensen, G. Burkhard; Brown, Emery N.
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 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
Psychogenic non epileptic seizure (PNES) can be induced by several induction tests but their relative usefulness has not been evaluated. In this study, we report the sensitivity and specificity of various induction tests in the diagnosis of PNES and assess their discomfort level. The induction tests were: (a) compression of temple region (CTR), (b) verbal suggestion (VS), (c) tuning fork application (TFA), (d) moist swab application (MSA), (e) torch light stimulation (TLS) and (f) saline injection (SI). Up to 3 trials were done for each test except for normal saline injection which was given once. For comparison of these tests, patients with epileptic seizures were included as controls. The time to precipitate PNES was recorded and patients' discomfort levels were noted on a 0-10 scale. Video EEG was recorded in the PNES patients. 140 patients with PNES and 50 controls with epileptic seizures were included. The diagnostic yield of CTR was 65.7%, TFA 61.4%, MSA 60.7%, SI 55.6%, VS 54.3% and TLS 40.7%. These tests did not induce seizures in the controls. All these tests had 100% specificity and 100% positive predictive value in the diagnosis of PNES. The maximum discomfort was reported with SI and minimum with MSA. The similarity of efficacy and discomfort with CTR and TFA appear to be the most optimal induction techniques when compared with VS, AMS, TLS, and SI. PMID:24802296
Goyal, Gourav; Kalita, Jayantee; Misra, Usha K
With a goal of automating visual analysis of electroencephalogram (EEG) data and assessing the performance of various features in seizure recognition, we introduce a mathematical model capable of recognizing patient-specific epileptic seizures with high accuracy. We represent multi-channel scalp EEG using a set of features. These features expected to have distinct trends during seizure and non-seizure periods include features from
Evrim Acar; Canan Aykut Bingol; Haluk Bingol; Rasmus Bro; B. Yener
In this case series we report on eight neonates with refractory seizures who received intravenous levetiracetam when seizures did not respond to two or more conventional anticonvulsants. Six of the eight neonates had an excellent response with either cessation, or reduction in seizures by at least 80%. One neonate showed a partial response while one did not have any reduction in seizure frequency. We did not encounter any adverse effects that could be attributable to levetiracetam. PMID:23664133
Rakshasbhuvankar, Abhijeet; Rao, Shripada; Kohan, Rolland; Simmer, Karen; Nagarajan, Lakshmi
neralpopulation. These disturbances (seizures) result in a variety of intermittent clinical phenomena including motor, sensory, affective,cognitive, autonomic and psychic symptomology. In human epilepsy of mesial temporal lobe origin, seizures begin in the hippocampusand are often propagated throughout the brain. A central feature of the epileptogenic hippocampus is the tendency to make abrupttransitions to well organized oscillations, characteristic of a seizure.
Leonidas D. Iasemidis; Konstantinos E. Pappas; Jose C. Principe; J. Chris Sackellares
We assessed the effect of an opener of ATP-sensitive K+ channel, levcromakalim (BRL 38227, (?)6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H\\/it-1-benzopyran-3-ol) on seizure threshold and severity of the hippocampus-generating partial seizures in rats. For comparison, an ATP-sensitive K+ channel blocker, glibenclamide; K+ channel blocker, tetraethylammonium; Ca2+ channel antagonist, nimodipine and Ca2+ channel agonist, (±)-BAY K 8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridinecarboxylic acid methyl ester) were also examined. Seizure threshold was
Hiroshi Katsumori; Yuji Ito; Haruhiro Higashida; Minako Hashii; Yoshio Minabe
Available from: Journal of Pediatric Psychology, Child Study Center, 1100 N.E. 13th Street, Oklahoma City, Oklahoma 73117. Compared in intelligence, perceptual motor performance, and academic achievement were 30 children (mean age=8.6 years) with seizure disorders and 30 children (mean age=9 years) with learning problems. (IM)
Black, F. William
Occult vascular malformations are frequently associated with intractable seizures and are a common cause of lesional epilepsy. MR imaging can identify and characterize these lesions with accuracy. The presurgical evaluation must be tailored to the individual patient's presentation and circumstances. Surgical results following lesionectomy plus corticectomy may be slightly superior to lesionectomy alone, but the overall prognosis is excellent. PMID:10419577
Cosgrove, G R
Medically-refractory seizures cause inflammation and neurodegeneration. Seizure initiation thresholds have been linked in mice to the serine protease tissue plasminogen activator (tPA); mice lacking tPA exhibit resistance to seizure induction, and the ensuing inflammation and neurodegeneration are similarly suppressed. Seizure foci in humans can be examined using PET employing 2-deoxy-2[18F]fluoro-D-glucose (18FDG) as a tracer to visualize metabolic dysfunction. However, there currently exist no such methods in mice to correlate measures of brain activation with behaviour. Using a novel method for small animal PET data analysis, we examine patterns of 18FDG uptake in wild type and tPA-/- mice and find that they correlate with the severity of drug-induced seizure initiation. Furthermore, we report unexpected activations that may underlie the tPA modulation of seizure susceptibility. The methods described here should be applicable to other mouse models of human neurological disease.
Mirrione, Martine M.; Schiffer, Wynne K.; Fowler, Joanna S.; Alexoff, Dave L.; Dewey, Stephen L.; Tsirka, Stella E.
Summary Purpose To study the development of epilepsy following hypoxia-induced neonatal seizures in Long Evans rats and to establish the presence of spontaneous seizures in this model of early life seizures. Methods Long-Evans rat pups were subjected to hypoxia-induced neonatal seizures at postnatal day 10 (P10). Epidural cortical electroencephalography (EEG) and hippocampal depth electrodes were used to detect the presence of seizures in later adulthood (>P60). In addition, subdermal wire electrode recordings were used to monitor age at onset and progression of seizures in the juvenile period, at intervals between P10–P60. Timm staining was performed to evaluate mossy fiber sprouting in the hippocampi of P100 adult rats that had experienced neonatal seizures. Key Findings In recordings made from adult rats (P60–P180), the prevalence of epilepsy in cortical and hippocampal EEG recordings was 94.4% following early life hypoxic seizures. These spontaneous seizures were identified by characteristic spike and wave activity on EEG accompanied by behavioral arrest and facial automatisms (electroclinical seizures). Phenobarbital injection transiently abolished spontaneous seizures. EEG in the juvenile period (P10–60) showed that spontaneous seizures first occurred approximately 2 weeks after the initial episode of hypoxic seizures. Following this period, spontaneous seizure frequency and duration progressively increased with time. Furthermore, significantly increased sprouting of mossy fibers was observed in the CA3 pyramidal cell layer of the hippocampus in adult animals following hypoxia-induced neonatal seizures. Notably, Fluoro-Jade B staining confirmed that hypoxic seizures at P10 did not induce acute neuronal death. Significance The rodent model of hypoxia-induced neonatal seizures leads to the development of epilepsy in later life, accompanied by increased mossy fiber sprouting. In addition, this model appears to exhibit a seizure-free latent period, following which there is a progressive increase in the frequency of electroclinical seizures.
Rakhade, Sanjay N; Klein, Peter; Huynh, Thanthao; Hilario-Gomez, Cristina; Kosaras, Bela; Rotenberg, Alexander; Jensen, Frances E.
Objectives: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. Methods: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. Results: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. Conclusions: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.
Arndt, Daniel H.; Carpenter, Jessica L.; Chapman, Kevin E.; Cornett, Karen M.; Gallentine, William B.; Giza, Christopher C.; Goldstein, Joshua L.; Hahn, Cecil D.; Lerner, Jason T.; Loddenkemper, Tobias; Matsumoto, Joyce H.; McBain, Kristin; Nash, Kendall B.; Payne, Eric; Sanchez, Sarah M.; Fernandez, Ivan Sanchez; Shults, Justine; Williams, Korwyn; Yang, Amy; Dlugos, Dennis J.
Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG.
Westover, M. Brandon; Bianchi, Matt T.; Shafi, Mouhsin; Hoch, Daniel B.; Cole, Andrew J.; Chiappa, Keith; Cash, Sydney S.
Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG. PMID:23545768
Westover, M Brandon; Bianchi, Matt T; Shafi, Mouhsin; Hoch, Daniel B; Cole, Andrew J; Chiappa, Keith; Cash, Sydney S
SCN1A mutations are the main cause of the epilepsy disorders Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Mutations that reduce the activity of the mouse Scn8a gene, in contrast, are found to confer seizure resistance and extend the lifespan of mouse models of DS and GEFS+. To investigate the mechanism by which reduced Scn8a expression confers seizure resistance, we induced interictal-like burst discharges in hippocampal slices of heterozygous Scn8a null mice (Scn8a(med/+)) with elevated extracellular potassium. Scn8a(med/+) mutants exhibited reduced epileptiform burst discharge activity after P20, indicating an age-dependent increased threshold for induction of epileptiform discharges. Scn8a deficiency also reduced the occurrence of burst discharges in a GEFS+ mouse model (Scn1a(R1648H/+)). There was no detectable change in the expression levels of Scn1a (Nav1.1) or Scn2a (Nav1.2) in the hippocampus of adult Scn8a(med/+) mutants. To determine whether the increased seizure resistance associated with reduced Scn8a expression was due to alterations that occurred during development, we examined the effect of deleting Scn8a in adult mice. Global Cre-mediated deletion of a heterozygous floxed Scn8a allele in adult mice was found to increase thresholds to chemically and electrically induced seizures. Finally, knockdown of Scn8a gene expression in the adult hippocampus via lentiviral Cre injection resulted in a reduction in the number of EEG-confirmed seizures following the administration of picrotoxin. Our results identify the hippocampus as an important structure in the mediation of Scn8a-dependent seizure protection and suggest that selective targeting of Scn8a activity might be efficacious in patients with epilepsy. PMID:24704313
Makinson, Christopher D; Tanaka, Brian S; Lamar, Tyra; Goldin, Alan L; Escayg, Andrew
Epilepsy in neuroepithelial tumors is highly prevalent. Neurogliomas (dysembryoplastic neuroepitheliomas [DNETs] and gangliogliomas) have a seizure incidence of 80-100%, low-grade gliomas of 60-85%, and glioblastoma of 30-60%. With each type, the appearance of seizures is usually the presenting clinical symptom, and with neuroglial tumors often the only clinical sign. Tumor locations in the temporal and insular cortex are associated with a higher risk of developing epilepsy in both neuroglial tumors and low-grade gliomas. Focal seizures with or without alteration of consciousness and/or secondary generalization are common. Focal seizures with altered consciousness are present in 50-70% of neuroglial tumors, and secondarily generalized seizures in 70% of low-grade gliomas. Surgical treatment, particularly gross tumor resection, contributes strongly to seizure freedom, especially in neuroglial tumors. Refractory epilepsy is more common in low-grade gliomas, occurring in 30-35%. Recurrence or worsening of seizures is often associated with tumor recurrence in glioblastomas. Translational studies have revealed a strong prevalence of IDH1 enzyme mutation together with the presence of seizures and long-term survival in low-grade gliomas. Disturbances of glutamate metabolism occur both in low-grade tumors and glioblastomas, and provide insight into mutual cellular pathway abnormalities contributing to both seizure development and tumor growth. Likewise, the recent clinical observations on antitumor activity of the anticonvulsant valproic acid in glioblastoma now provide promising outlooks on single therapies that target both seizures and gliomas. PMID:24328866
Kerkhof, Melissa; Vecht, Charles J
Refractory status epilepticus (RSE) poses significant challenge, with a variety of novel therapeutics employed. Our goal was to evaluate the effectiveness of N-methyl D-aspartate (NMDA) receptor antagonists in the control of RSE. We performed a systematic review of all the literature, with all articles pulled from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to September 2013), reference lists of relevant articles, and gray literature. Two reviewers independently identified all manuscripts pertaining to the administration of NMDA receptor antagonists in humans for the purpose of controlling refractory seizures. Secondary outcome of adverse NMDA antagonist effects and patient outcome was assessed. Two reviewers independently extracted data including population characteristics, treatment characteristics, and outcomes. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total of 759 citations. Twenty-three articles, 16 manuscripts, and seven meeting proceedings, were considered for the review with all utilizing ketamine for seizure control. Only three studies were prospective studies. Fifteen and nine studies pertained to adults and pediatrics, respectively. Across all studies, of the 110 adult patients described, ketamine was attributed to electroencephalogram seizure response in 56.5 %, with a 63.5 % response in the 52 pediatric patients described. Adverse events related to ketamine were rare. Outcomes were poorly documented in the majority of the studies. There currently exists Oxford level 4, GRADE C evidence to support the use of ketamine for refractory seizures in the adult and pediatric populations. Further prospective study of early ketamine administration is warranted. PMID:24519081
Zeiler, F A; Teitelbaum, J; Gillman, L M; West, M
Background: In this study, we tried to identify predictors of acute poststroke seizures (aPSS) in stroke patients. Methods:We analyzed a large prospective hospital-based stroke registry in Germany. 58,874 patients with the diagnosis of transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH) were admitted within 24 h after symptom onset. Predictors for aPSS were identified using multivariate regression
Karsten Krakow; Matthias Sitzer; Felix Rosenow; Helmuth Steinmetz; Christian Foerch
Mutations in the neuronal voltage-gated sodium channel genes SCN1A and SCN2A are associated with inherited epilepsies, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (severe myoclonic epilepsy of infancy). The clinical presentation and severity of these epilepsies vary widely, even in people with the same mutation, suggesting the action of environmental or genetic modifiers. To gain support for the hypothesis that genetic modifiers can influence clinical presentation in patients with SCN1A-derived GEFS+, we used mouse models to study the effect of combining the human GEFS+ mutation SCN1A-R1648H with SCN2A, KCNQ2, and SCN8A mutations. Knock-in mice heterozygous for the R1648H mutation (Scn1aRH/+) have decreased thresholds to induced seizures and infrequent spontaneous seizures, whereas homozygotes display spontaneous seizures and premature lethality. Scn2aQ54 transgenic mice have a mutation in Scn2a that results in spontaneous, adult-onset partial motor seizures, and mice carrying the Kcnq2-V182M mutation exhibit increased susceptibility to induced seizures, and rare spontaneous seizures as adults. Combining the Scn1a-R1648H allele with either Scn2aQ54 or Kcnq2V182M/+ results in early-onset, generalized tonic-clonic seizures and juvenile lethality in double heterozygous mice. In contrast, Scn8a mutants exhibit increased resistance to induced seizures. Combining the Scn1a-R1648H and Scn8a-med-jo alleles restores normal thresholds to flurothyl-induced seizures in Scn1aRH/+ heterozygotes and improved survival of Scn1aRH/RH homozygotes. Our results demonstrate that variants in Scn2a, Kcnq2, and Scn8a can dramatically influence the phenotype of mice carrying the Scn1a-R1648H mutation and suggest that ion channel variants may contribute to the clinical variation seen in patients with monogenic epilepsy.
Hawkins, Nicole A.; Martin, Melinda S.; Frankel, Wayne N.; Kearney, Jennifer A.; Escayg, Andrew
Mice deficient for the gene encoding the RNA-binding protein CELF4 (CUGBP, ELAV-like family member 4) have a complex seizure phenotype that includes both convulsive and non-convulsive seizures, depending upon gene dosage and strain background, modeling genetically complex epilepsy. Invertebrate CELF is associated with translational control in fruit fly ovary epithelium and with neurogenesis and neuronal function in the nematode. Mammalian CELF4 is expressed widely during early development, but is restricted to the central nervous system in adult. To better understand the etiology of the seizure disorder of Celf4 deficient mice, we studied seizure incidence with spatial and temporal conditional knockout Celf4 alleles. For convulsive seizure phenotypes, it is sufficient to delete Celf4 in adulthood at seven weeks of age. This timing is in contrast to absence-like non-convulsive seizures, which require deletion before the end of the first postnatal week. Interestingly, selective deletion of Celf4 from cerebral cortex and hippocampus excitatory neurons, but not from inhibitory neurons, is sufficient to lower seizure threshold and to promote spontaneous convulsions. Correspondingly, Celf4 deficient mice have altered excitatory, but not inhibitory, neurotransmission as measured by patch-clamp recordings of cortical layer V pyramidal neurons. Finally, immunostaining in conjunction with an inhibitory neuron-specific reporter shows that CELF4 is expressed predominantly in excitatory neurons. Our results suggest that CELF4 plays a specific role in regulating excitatory neurotransmission. We posit that altered excitatory neurotransmission resulting from Celf4 deficiency underlies the complex seizure disorder in Celf4 mutant mice.
Wagnon, Jacy L.; Mahaffey, Connie L.; Sun, Wenzhi; Yang, Yan; Chao, Hsiao-Tuan; Frankel, Wayne N.
The present study tested the therapeutic potential for prototype anti-epilepsy drugs using an animal model of infantile febrile seizures. The model consisted of immersion of weanling rats (21 days old) in a 45 degrees C water bath for a maximum of 4 min (four exposures over a 2 week period) and observing for the progression to stage-5 seizures. All compounds were administered orally at the respective ED50 for prevention of seizures in the maximal electroshock (MES) test. Clonazepam effectively lowered the score for seizure grade, shortened the duration of seizures, as well as reduced the number of animals experiencing seizures during three of the four testing periods. MK801 reduced both the maximum seizure grade, and the number of animals experiencing seizures during sessions two and three. However, the dose of MK801 caused behavioral side effects. Valproate actively decreased seizure grade, while it modestly acted to attenuate seizure duration, extended the time to seizure onset, and reduced the number of animals experiencing seizures on testing day 1. Remacemide hydrochloride and phenobarbital were not effective. The method appears useful for evaluating the potential of agents to prevent acute febrile seizures. PMID:9657648
Palmer, G C; Borrelli, A R; Hudzik, T J; Sparber, S
We report the case of a 43-year-old man with history of nonsurgical partial epilepsy who previously failed multiple trials of antiepileptic drugs. Medium-chain triglycerides (MCT) were added to his regular diet in the form of pure oil. Subsequently, his seizure frequency was markedly reduced from multiple daily seizures to one seizure every four days. His seizures recurred after transient discontinuation of MCT over a period of ten days. His seizure improvement was achieved at a dose of four tablespoons of MCT twice daily with no reported side effects. He developed significant diarrhea and flatulence at higher doses. We conclude that MCT oil supplementation to regular diet may provide better seizure control in some patients. MCT oil supplementation may be a more tolerable alternative to the standard ketogenic diet.
Azar, Nabil J.
Gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, although the most commonly encountered form is related to the presence of an hypothalamic hamartoma. We report a patient with gelastic seizures involving the left parietal lobe. Our patient, a 8-year-old girl, underwent video-EEG monitoring, interictal and MRI. The seizures consisted of brief staring followed
René Andrade Machado; Adriana Goicoechea Astencio
Gelastic seizures are often associated with hypothalamic hamartomas. However, focal cortical dysplasias can also cause "laughing seizures", and such cases can be difficult to localize with EEG. This case report presents a 29-year-old woman who was successfully rendered free of gelastic seizures after resection of a frontal cortical dysplasia, localized through MRI and SPECT imaging.[Published with video sequences]. PMID:18077234
Cheung, Christina S; Parrent, Andrew G; Burneo, Jorge G
Seizure after laminectomy for spinal procedure is very rare and has not been reported after lipomyelomeningocele surgery beforehand. Here, two cases of seizure following laminectomy for lipomyelomeningocele are reported. The exact etiology of the event is unknown but anesthetic material, pneumocephalus, intracranial hypotension subsequent to cerebrospinal fluid leakage after spinal procedures, spinal-induced seizure and the potential toxic effect of fat molecules could be considered.
Habibi, Zohreh; Nejat, Farideh; El Khashab, Mostafa
\\u000a The association between seizures and blood pressure elevation remains a common medical emergency encountered in an ICU setting.\\u000a Syndromes such as pre-eclampsia or eclampsia, hypertensive encephalopathy, and posterior leukoencephalopathy commonly present\\u000a with seizures. The primary treatment goal is to reduce the arterial blood pressure. In most cases seizure control is thus\\u000a achieved, but unique medications, such as magnesium sulfate, may
Errol Gordon; Michel T. Torbey
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
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
Asphyxial seizures occurred in 89 of 101,829 infants born alive at term (0.87\\/1000) in three large maternity hospitals from January 1980 to December 1984. These seizures were significantly associated with antenatal complications, primiparity, and prolonged pregnancy. Meconium staining of the amniotic fluid was also associated with asphyxial seizures, but there were high false positive (11%) and false negative (50%) rates.
P D Curtis; T G Matthews; T A Clarke; M Darling; P Crowley; E Griffin; P OConnell; W Gorman; N OBrien; C OHerlihy
Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR?=?2.6, 95% CI?=?1.3–5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR?=?2.2, 95% CI?=?1.1–4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR?=?4.8, 95% CI?=?1.0–23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm the association.
Westmark, Cara J.
Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR?=?2.6, 95% CI?=?1.3-5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR?=?2.2, 95% CI?=?1.1-4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR?=?4.8, 95% CI?=?1.0-23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm the association. PMID:24622158
Westmark, Cara J
The aim of the study was to assess whether post-ictal symptoms can help distinguish patients who have epileptic seizures from those with non-epileptic seizures (NES). We reviewed the spontaneous responses to the question ‘What symptoms do you have after a seizure?’ in 16 patients with epileptic seizures (predominantly focal with secondary generalization or generalized tonic–clonic) and 23 NES patients. Six
Most patients with epilepsy report that seizures are sometimes, or exclusively, provoked by general internal precipitants (such as stress, fatigue, fever, sleep, and menstrual cycle) and by external precipitants (such as excess alcohol, heat, bathing, eating, reading, and flashing lights). Some patients describe very exotic and precise triggers, like tooth brushing or listening to a particular melody. Nevertheless, the most commonly noticed seizure increasers by far are stress, lack of sleep, and fatigue. Recognized reflex seizure triggers are usually sensory and visual, such as television, discotheques, and video games. Visually evoked seizures comprise 5% of the total of 6% reflex seizures. The distinction between provocative and reflex factors and seizures seems artificial, and in many patients, maybe all, there is a combination of these. It seems plausible that all of the above-mentioned factors can misbalance the actual brain network; at times, accumulation of factors leads then to primary generalized, partial, or secondarily generalized seizures. If the provoking factors are too exotic, patients may be sent to the psychiatrist. Conversely, if the seizure-provoking fluctuating mechanisms include common habits and environmental factors, these may hardly be considered as provocative factors. Awareness of precipitating factors and its possible interactions might help us to unravel the pathophysiology of epilepsy and to change the notion that seizure occurrence is unpredictable. This article provides an overview of the epidemiology, classification, diagnosis, treatment, and especially similarities in the variety of provocative and reflex factors with resulting general hypotheses. PMID:22946728
Kasteleijn-Nolst Trenité, Dorothée G A
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-1?, 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.
Dube, Celine M.; Brewster, Amy L.; Baram, Tallie Z.
We have previously reported that dogs can be trained to recognize specific changes preceding an epileptic seizure in humans. Such dogs can provide an overt signal that acts as a useful warning to the human. Early observations suggested that seizure frequency might also be reduced. We report a prospective study of 10 consecutive referrals to our Seizure Alert Dogs ®service
Margaret Huyton; Helen Coyle
The causal relationship between early seizures and subsequent temporal lobe epilepsy has not yet been established. Prospective clinical studies reported that seizures occurring early in life rarely result in hippocampal sclerosis. Likewise, in most experimental models, early seizures occurring before the end of the second postnatal week do not lead to neuronal damage and subsequent epilepsy. In some models, this early event decreases latency sensitivity and threshold to seizures. In the present study, we induced lithium and pilocarpine status epilepticus (SE) in 10-day-old (P10) rats. The goal of this study was to determine whether this early life SE altered the sensitivity to convulsants such as pentylenetetrazol (20 and 25 mg/kg), picrotoxin (2.5 and 4.0 mg/kg) and kainate (5 and 8 mg/kg) during adulthood. The occurrence of electrographic seizures (spike-and-wave discharges, SWD) and/or of behavioral seizures was monitored. There was no difference in latency to and duration of SWDs and seizures between lithium-saline and lithium-pilocarpine exposed rats. Thus, SE induced by lithium and pilocarpine early in life does not change the sensitivity to limbic seizures or seizures induced by GABA(A) antagonists during adulthood. PMID:12350394
Nehlig, Astrid; Dubé, Céline; Koning, Estelle
...SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Controlled Substances, Narcotics, and Marihuana Â§ 162.63 Arrests and seizures. Arrests and seizures under the Controlled Substances Act (84 Stat. 1242, 21...
... disorder catalog Conditions > Malignant migrating partial seizures of infancy On this page: Description Genetic changes Inheritance Diagnosis ... 2014 What is malignant migrating partial seizures of infancy? Malignant migrating partial seizures of infancy (MMPSI) is ...
Incontinentia pigmenti (IP) is a rare affection inherited as X-linked dominant disease. It is usually lethal in male infants. IP can affect ectodermal tissues such as the skin, teeth, eyes, bones, and the central nervous system. Skin lesions occur mostly during the neonatal period and are characterized by a classic progression in 4 stages leading to hyperpigmentation. We report on the case of a female neonate presenting on the 3rd day of life with seizures without obvious cause, in which the diagnosis of IP was made 1 week later when skin lesions appeared. PMID:21795026
Nouri-Merchaoui, S; Mahdhaoui, N; Methlouthi, J; Zakhama, R; Seboui, H
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
We analyzed the frequency and morphological characteristics of the initial EEG manifestations of spontaneous seizures recorded from depth and subdural electrodes in 26 patients for whom pathological analysis of the area of seizure onset was available after resective surgery. Pathological features considered to be positive findings included well-defined structural lesions (hamartoma, neoplasm) or strictly defined mesial temporal sclerosis. Seizure onset was characterized by the frequency of the rhythmic discharge greater than 2 Hz in the first second and by the presence or absence of periodic low-frequency spikes (less than 2 Hz) preceding this stable change in background frequency. These features were correlated with the presence or absence of pathologic abnormalities in temporal and extratemporal locations. Although all patterns and frequencies of seizure onset were recorded in both medial temporal and extratemporal locations, medial temporal seizure onset was significantly more likely to have high frequency (greater than 13 Hz, p less than 0.00001) and tended to show periodic spikes prior to the seizure when it was associated with medial temporal sclerosis compared to when it was not. Extratemporal seizure onset associated with abnormal pathological substrate was significantly more likely to have a lower frequency (less than 13 Hz, p less than 0.05) and no periodic spikes before seizure onset (p less than 0.00001) than extratemporal seizure onset recorded from areas without pathological findings. Variability of seizure onset frequency was a characteristic of temporal, but not extratemporal, seizures (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1592034
Spencer, S S; Guimaraes, P; Katz, A; Kim, J; Spencer, D
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
Anecdotal evidence suggests that some dogs may be able to sense the onset of seizures and other medical conditions in humans, although this has never been explored scientifically. There is, however, evidence that dogs can be specially trained to recognize specific changes preceding a seizure and give an overt signal enabling the dog to warn his\\/her owner. The introduction of
V. Strong; S. W. Brown; R. Walker
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.
Alterations in electrolyte homeostasis associated with major surgery and critical illness are common but usually non-specific. We report an unusual case of hypomagnesaemia induced seizures in a 73-year-old woman who was recovering from ileal resection and limited right hemicolectomy for small bowel volvulus. Hypomagnesaemia as a de novo cause of seizures is rarely reported.
Pande, Shrikant D; Wee, Chee Keong; Maw, Nyein Nyein
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
Electrophysiological recordings show intense neuronal firing during epileptic seizures leading to enhanced energy consumption. However, the relationship between oxygen metabolism and seizure patterns has not been well studied. Recent studies have developed fast and quantitative techniques to measure oxygen microdomain concentration during seizure events. In this article, we develop a biophysical model that accounts for these experimental observations. The model is an extension of the Hodgkin-Huxley formalism and includes the neuronal microenvironment dynamics of sodium, potassium, and oxygen concentrations. Our model accounts for metabolic energy consumption during and following seizure events. We can further account for the experimental observation that hypoxia can induce seizures, with seizures occurring only within a narrow range of tissue oxygen pressure. We also reproduce the interplay between excitatory and inhibitory neurons seen in experiments, accounting for the different oxygen levels observed during seizures in excitatory vs. inhibitory cell layers. Our findings offer a more comprehensive understanding of the complex interrelationship among seizures, ion dynamics, and energy metabolism. PMID:24671540
Wei, Yina; Ullah, Ghanim; Ingram, Justin; Schiff, Steven J
Abstract Objective: To assess the incidence of seizures induced by cycloplegic ophthalmic drops. Materials and methods: A survey among members of the American Association for Pediatric Ophthalmology and Strabismus yielded five patients who received cycloplegic eye drops between 1998 and 2010 and who consequently developed a seizure. Results: The median age of the patients was 5 years (range 3 months to 12 years). Cyclopentolate hydrochloride 1% was the only causative agent. The seizure happened on average 12?min after the instillation of dilating eye drops. Three were generalized convulsions, and two patients had a focal seizure. Past medical history was unremarkable in four cases. In total, 16 previous cases of seizures induced by cycloplegic drugs were identified in reports published between 1890 and 2004, implicating atropine in nine reports, tropicamide and phenylephrine eye drops in one and cyclopentolate in six. Discussion: A small amount of cyclopentolate drops could induce convulsions in young children after only minutes to less than an hour, while a larger dosage of atropine over the span of several hours could cause this rare and unpredictable complication. Predisposing factors were rare and those developing the seizures were healthy subjects. Generalized seizures were much more frequent than focal convulsions. Conclusions: Seizures after instillation of cycloplegic drops are extremely rare. PMID:23815170
Wygnanski-Jaffe, Tamara; Nucci, Paolo; Goldchmit, Mauro; Mezer, Eedy
A number of seizure events, typical of everyday clinical practice, were tested for possible chaos. After a careful elimination of spurious effects, evidence of chaos was found in two seizure events. This was confirmed by direct examination of exponential separation of initially nearby states in low-dimensional trajectory recoveries. The resulting Lyapunov exponent calculation provides a clear indication of chaos in
G. W. Frank; T. Lookman; M. A. H. Nerenberg; C. Essex; J. Lemieux; W. Blume
Febrile seizures (FSs) occur in children older than 1 month and without prior afebrile seizures in the absence of a central nervous system infection or acute electrolyte imbalance. Their pathogenesis is multifactorial. The most relevant familial studies evidence an occurrence rate ranging from 10% to 46% and median recurrence rate of 36% in children with positive familial history for FS. The main twin studies demonstrated a higher concordance rate in monozygotic twins with FS than in dizygotic ones. Linkage studies have proposed 11 chromosomal locations responsible to FS attributed to FEB1 to FEB11. Population-based association studies have shown at least one positive association for 14 of 41 investigated genes with FS. The proinflammatory cytokine interleukin 1? (IL-1?) was the most investigated and also gene associated with susceptibility to FS. A possible role in the overlapping of epilepsy and FS was found for 16 of 36 investigated genes. SCN1A, IL-1?, CHRNA4, and GABRG2 were the most commonly involved genes in this context. The genetic background of FS involves the regulation of different processes, including individual and familial susceptibility, modulation of immune response, and neuronal excitability and interactions with exogenous agents such as viruses. PMID:24399675
Saghazadeh, Amene; Mastrangelo, Mario; Rezaei, Nima
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
Ethylenediamine (EDA) activates GABA(A) receptors via both direct and indirect mechanisms. EDA has been shown to reduce seizures caused by systemic injection of proconvulsants in an animal model of generalized tonic-clonic seizures. However, there does not appear to have been any report on the effects of EDA in other seizure models. Hence, we used male Sprague-Dawley rats to test the effects of EDA on topically applied bicuculline (a model of simple partial seizures) and on maximal electroshock (MES, a model of generalized tonic-clonic seizures). We also examined the effects of EDA on motor coordination using a rotarod treadmill, and its potential anxiolytic properties using an elevated plus maze (EPM). EDA at concentrations of 50 ?M and above reduced the frequency of epileptiform spikes on an electrocorticogram in a concentration-dependent manner. EDA at 100 and 1000 mg/kg i.p. increased the threshold for inducing limb extension on the MES. EDA did not affect the time spent by rats on the rotarod at 10 or 100mg/kg, but significantly reduced the time spent at doses of 1000 mg/kg. In the EPM, EDA at 10 or 100mg/kg significantly increased the frequency of entries and time spent in the open arms. We conclude that EDA has antiepileptic and anxiolytic activity at doses that do not affect motor coordination. PMID:22820302
Addae, Jonas I; Walkins, Kheston; Cruickshank, Rene; Stone, Trevor W
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 since the seizure and a neurological examination was performed which revealed signs consistent with a cervical myelopathy. A cervical MRI scan revealed a disc prolapse with cord compression at C5/6. This was successfully operated and the patient made a good recovery. Given that many of our medical assessment units and emergency department frequently assess patient with seizures, there was an important lesson for us to be more aware of the consequences as well as the cause of seizures. PMID:22691593
Satia, Imran; Goodwin, Lynsey; Madi, Salem; Hamdalla, Hisham
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 case report is presented of a 36-year-old U.S. Coast Guard aviator who had a single seizure while operating a helicopter on the ground. His seizure activity produced a loss of consciousness during which he pushed the cyclic to the left anterior quadrant that resulted in a ground mishap. No risk factors were identified in an extensive neurological workup. The current guidance for handling seizures in military aviation personnel is reviewed, along with considerations for treatment. Although the military aviation selection process carefully screens applicants for seizure history and potential, occasional seizures in the aviation population remain possible. Such events may result in military aircraft mishaps despite careful risk factor surveillance, as demonstrated by this case. PMID:18419038
Simon, Esan; Watts, Darron; Bohnker, Bruce K
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.
The time-varying dynamics of epileptic seizures and the high interindividual variability make their detection difficult. Osorio et al. (1998, Epilepsia, 39, 6) developed an algorithm that has had success in detecting seizures. We present a new strategy for adapting this algorithm or other algorithms to an individual's seizure fingerprint using both seizure and non-seizure training segments and a novel performance criterion that directly incorporates the non-linearity and lack of differentiability of the algorithm. The joint optimization of a linear filter chosen from a bank of candidate filters and of a percentile used in order statistic filtering provides an empirical solution that is both practical and useful, which should translate into improved sensitivity, specificity and detection speed. This premise is strongly supported by the results obtained in a large validation study and the examples illustrated in this article. This strategy is generalizable to other detection algorithms with modular architecture and spectral filters.
Haas, Shane M.; Frei, Mark G.; Osorio, Ivan
Great effort has been made toward defining and characterizing the pre-ictal state. Many studies have pursued the idea that there are recognizable electrographic (EEG-based) features that occur before overt clinical seizure activity. However, development of reliable EEG-based seizure detection and prediction algorithms has been difficult. In this review, we discuss the concepts of seizure detection vs. prediction and the pre-ictal “clinical milieu” and “EEG milieu”. We proceed to discuss novel concepts of seizure detection based on the pre-ictal “physiological milieu”; in particular, we indicate some early evidence for the hypothesis that pre-ictal cell swelling/extracellular space constriction can be detected with novel optical methods. Development and validation of optical seizure detection technology could provide an entirely new translational approach for the many patients with intractable epilepsy.
Binder, Devin K.; Haut, Sheryl R.
Low grade oligodendrogliomas (LGO) are diffusely infiltrating World Health Organization (WHO) grade II gliomas, 20 - 30% of which show contrast enhancement. Seizures are a common presenting feature. It has been suggested that 1p19q co-deletion is associated with occurrence of seizures in adults, however, to date, the relationship of tumor genetics and seizure activity has not been extensively investigated. We sought to assess the influence of 1p19q co-deletion, IDH1-R132H positivity, and radiological variables on seizure activity in LGO patients. Specifically, we examined whether these characteristics were associated with seizure at initial presentation, or if they could predict outcome in terms of seizure free survival. In 62 LGOs, neither tumor location nor tumor enhancement were associated with seizures. 1p19q co-deletion status did not predict seizures when controlled for mutant IDH1-R132H expression, tumor location, or enhancement status (odds ratio (OR) 0.9, 95% confidence interval (CI) 0.1 - 4.3). This study, although of limited statistical power, did not demonstrate an association between 1p19q status and seizure occurrence in LGO's. Replication in a larger cohort would further support our hypothesis that 1p19q status alone cannot be used as a reliable predictor of seizure occurrence in LGO's. PMID:24986208
Mulligan, Linda; Ryan, Elizabeth; O'Brien, Margaret; Looby, Seamus; Heffernan, Josephine; O'Sullivan, Joanne; Clarke, Mary; Buckley, Patrick; O'Brien, David; Farrell, Michael; Brett, Francesca Mary
Occasionally, but more often than has been reported, true epileptic seizures are triggered by non-epileptic syncopes. This combination of syncope and epileptic seizure has been called an anoxic-epileptic seizure. A few examples of such anoxic-epileptic seizures, including the induction of status epilepticus, have been reported in books and medical journals, but no video-recordings have been published. We show here home video recordings of the first three known examples of the transition from the triggering syncope and anoxic seizure, to the subsequent epileptic seizure. In the first two children, a neurally-mediated syncope, probably mediated by prolonged expiratory apnoea (so-called breath-holding spells), induces a long, clonic epileptic seizure with some features of myoclonic absence. In the third example, a compulsive Valsalva in an older autistic child provokes a vibratory tonic epileptic seizure. In addition, we show two further video clips of the most usual type of epileptic seizure induced by syncopes in very young children. In one, the video recording begins after the end of the triggering syncope and shows a rhythmic clonic seizure that includes repetitive vocalizations. The final recoding is of a spontaneous epileptic seizure with features of myoclonic absence: this child had both epilepsy and identical episodes induced by syncopes, that is, anoxic- epileptic seizures. Not only paediatricians and paediatric neurologists, but also adult neurologists and epileptologists in general, should be aware of the important clinical scenario of true epileptic seizures induced by syncopes. This phenomenon is not considered in any international classification. (Published with videosequences) PMID:15075063
Stephenson, John; Breningstall, Galen; Steer, Chris; Kirkpatrick, Martin; Horrocks, Iain; Nechay, Alla; Zuberi, Sameer
Using a measure of nonlinear dynamical changes we term marginal predictability, we report evidence of robust changes in this parameter on scalp EEG in a cohort of patients with medically refractory mesiobasal temporal lobe epilepsy (MBTLE). In the baseline (interictal) state there are distinct differences in this nonlinear measure between epileptic and neurologically normal subjects. At baseline, in patients with MBTLE there are differences in these measures between electrodes adjacent to the ictal onset zone and more remotely placed electrodes. The character of these differences evolves over a period of approximately 30 min before a seizure. We discuss and integrate our findings with two emerging concepts in epileptology, first, the concept of a preictal or transition phase rather than an abrupt movement from interictal to ictal activity, and second, the notion of an epileptic neural network with changes in areas of brain remote from what has traditionally been considered the ictal onset zone influencing "ictogenesis." PMID:14597320
Drury, Ivo; Smith, Brien; Li, Dingzhou; Savit, Robert
A dissociation between clinical and electroencephalographic phenomena is often observable in neonatal seizures. This finding raises important questions, including those related to the management of these patients. Another characteristic of neonatal convulsions is represented by their increased tendency towards status epilepticus. In order to examine the electroclinical correlation and its possible relationship to the occurrence of status epilepticus, recorded video-electroencephalograms of 17 newborns were submitted to detailed analysis. Time of onset, duration and other characteristics of all clinical and electrical events were noted. Five degrees of correlation were observed, from constant concurrence to complete dissociation. Examining the role of different parameters, it was observed that the incidence of electric discharges related significantly to the occurrence of electroclinical dissociation. PMID:10726833
Biagioni, E; Ferrari, F; Boldrini, A; Roversi, M F; Cioni, G
Introduction A laugh-induced seizure is an unrecognized condition and to the best of our knowledge no case has been reported in the medical literature until now. We present an interesting and extremely rare case in which laughing generated the seizure activity that was recorded and confirmed by video electroencephalography. Case presentation A 43-year-old obese Caucasian man with history of bipolar disorder and chronic headache presented with multiple episodes of seizures, all induced by laughter while watching comedy shows. Each episode lasted approximately five seconds. In each instance, he started laughing, then his arms started shaking and he felt like ‘his consciousness was being vacuumed away’. A physical examination revealed normal findings. He had been maintained on valproic acid for bipolar disorder and topiramate for his chronic headache, but this did not control his symptoms. His sleep-deprived electroencephalography and brain magnetic resonance imaging were normal except for an arachnoid cyst measuring 4.2 × 2.1cm in the anterior right middle cranial fossa. His video electroencephalography demonstrated laugh-induced seizure activities. He was then placed on carbamazepine. Following treatment, he had two episodes of mild staring but no frank seizures, and his seizures have remained well controlled on this regimen for more than a year. Conclusions Laugh-induced seizure is a most unusual clinical entity without any previous case report. Confirmatory diagnosis can be made by video electroencephalography recording of seizure activities provoked by laughing. As in gelastic seizure without hypothalamic hamartoma, our case responded well to polytherapy with topiramate and carbamazepine on top of laugh-provocation avoidance. Further study is required to establish the standard treatment of this condition.
Seizures are more common in the neonatal period than any other time in the human lifespan. A high index of suspicion for seizures should be maintained for infants who present with encephalopathy soon after birth, have had a stroke, central nervous system (CNS) infection or intracranial hemorrhage or have a genetic or metabolic condition associated with CNS malformations. Complicating the matter, most neonatal seizures lack a clinical correlate with only subtle autonomic changes and often no clinical indication at all. Over the last three decades, several tools have been developed to enhance the detection and treatment of neonatal seizures. The use of electroencephalography (EEG) and the later development of amplitude-integrated EEG (aEEG), allows for Neurologists and non-Neurologists alike, to significantly increase the sensitivity of seizure detection. When applied to the appropriate clinical setting, time to diagnosis and start of therapy is greatly reduced. Phenobarbital maintains the status of first-line therapy in worldwide use. However, newer anti-epileptic agents such as, levetiracetam, bumetanide, and topiramate are increasingly being applied to the neonatal population, offering the potential for seizure treatment with a significantly better side-effect profile. Seizures in premature infants, continue to confound clinicians and researchers alike. Though the apparent seizure burden is significant and there is an association between seizures and adverse outcomes, the two are not cleanly correlated. Compounding the issue, GABA-ergic anti-epileptic drugs are not only less effective in this age group due to reversed neuronal ion gradients but may cause harm. Selecting an appropriate treatment group remains a challenge. PMID:24796413
Vesoulis, Zachary A; Mathur, Amit M
We studied head turning in 239 complex partial seizures with or without generalization, in 32 patients with unilateral temporal lobe epilepsy. Head turns occurred in 73% of seizures that did not evolve to focal jerking or secondary generalization, and in all 41 seizures that secondarily generalized. In seizures without focal jerking or secondary generalization the most common pattern was that
Bassel Abou-Khalil; Toufic Fakhoury
Summary: Purpose: Noninvasive magnetic resonance imaging was used to assess the evolution of seizure-induced pathology in epileptic, carrier, and normal chickens. Our objective was to determine whether repetitively evoked seizures in an epilep- tic fowl model of generalized seizures resulted in altered brain development. Methods: Data were obtained from seizure and control groups at 45, 90, and 180 days after
Zhao Gong; Andre Obenaus; Nan Li; Gordon E. Sarty; Edward J. Kendall
We report 3 cases presenting ictal vomiting during partial seizures of temporal lobe origin. Two patients had complex partial seizures accompanying vomiting characteristics. Ictal vomiting occurred early in the course of the seizure when rhythmic discharges involved predominantly the left hemispere, the language dominance hemispere. The other patient had ictal vomiting in simple partial seizures which originated from the right
Chien Chen; Der-Jen Yen; Chun-Hing Yiu; Yang-Hsin Shih; Hsiang-Yu Yu; Ming-Shung Su
This study investigated treatment patterns at discharge in infants with neonatal seizures and evaluated the impact of outpatient phenobarbital prophylaxis on the frequency of seizure recurrence and the long-term neurodevelopmental outcome at 1 to 11 years. Infants with neonatal seizures during a 12-year period were identified retrospectively (n = 146), and data were obtained by medical chart review. Outcomes were ascertained by standardized telephone survey. Thirty-three infants (23%) were taking phenobarbital, and 99 infants (68%) were taking no anticonvulsants at discharge. Comparisons were made between these 2 groups. Phenobarbital prophylaxis did not improve neurologic outcomes, either with respect to seizure recurrence or neurologic development. These data have important implications at a time when many are questioning the practice of prophylaxis after neonatal seizures and when newer anticonvulsants are being recommended for treatment of acute neonatal seizures. PMID:17621516
Guillet, Ronnie; Kwon, Jennifer
OBJECTIVE—Despite a high incidence of nocturnal hypoglycemia documented by the use of continuous glucose monitoring (CGM), there are no reports in the literature of nocturnal hypoglycemic seizures while a patient is wearing a CGM device. RESEARCH DESIGN AND METHODS—In this article, we describe four such cases and assess the duration of nocturnal hypoglycemia before the seizure. RESULTS—In the cases where patients had a nocturnal hypoglycemic seizure while wearing a CGM device, sensor hypoglycemia (<60 mg/dl) was documented on the CGM record for 2.25–4 h before seizure activity. CONCLUSIONS—Even with a subcutaneous glucose lag of 18 min when compared with blood glucose measurements, glucose sensors have time to provide clinically meaningful alarms. Current nocturnal hypoglycemic alarms need to be improved, however, since patients can sleep through the current alarm systems.
Buckingham, Bruce; Wilson, Darrell M.; Lecher, Todd; Hanas, Ragnar; Kaiserman, Kevin; Cameron, Fergus
In front of any clinical paroxysmal event in childhood, the first step is to make a positive diagnostic of an epileptic seizure; for this it is necessary to eliminate non epileptic seizures which are different according to age. Then the type of seizures has to be precised, being focal or generalized. EEG will contribute to determine the epileptic syndrome according to interictal and/or ictal findings. The epilepsy syndrome is the main entity to go further in etiology and treatment. According to the type of epilepsy syndrome it will be possible to look for a structural or metabolic cause, or to perform a genetic study. The present classification of seizures and syndromes as proposed by the International League Against Epilepsy (ILAE) allows a common language in the world community as in clinical and therapeutic research. PMID:23424915
Plouin, Perrine; Kaminska, Anna; Eisermann, Monika; Soufflet, Christine
... information: Long QT syndrome (The Basics) Patient information: Myoclonus (The Basics) Patient information: Seizures (The Basics) Patient ... High blood pressure emergencies (The Basics) Patient information: Myoclonus (The Basics) Patient information: Time to stop driving? ( ...
There are an estimated two million people with epilepsy in the United States. Many of these people do not respond to anti-epileptic drug therapy. Two devices can be developed to assist in the treatment of epilepsy. The first is a microcomputer-based system designed to process massive amounts of electroencephalogram (EEG) data collected during long-term monitoring of patients for the purpose of diagnosing seizures, assessing the effectiveness of medical therapy, or selecting patients for epilepsy surgery. Such a device would select and display important EEG events. Currently many such events are missed. A second device could be implanted and would detect seizures and initiate therapy. Both of these devices require a reliable seizure detection algorithm. A new algorithm is described. It is believed to represent an improvement over existing seizure detection algorithms because better signal features were selected and better standardization methods were used.
Olsen, Dale E.; Harris, John C.; Cutchis, Protagoras N.; Cristion, John A.; Lesser, Ronald P.; Webber, W. Robert S.
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)
In the mammalian CNS, glutamate and GABA are the principal neurotransmitters mediating excitatory and inhibitory synaptic events, respectively, and have been implicated in the neurobiology of seizures. Guanine-based purines, including the nucleoside guanosine and the nucleotide GMP, have been shown to antagonize glutamatergic activity at the receptor level and the other purine nucleoside adenosine is a well-known modulator of seizure threshold. In the present study we investigated the anticonvulsant effect of i. p. guanosine and GMP against seizures induced by the glutamate agonist quinolinic acid (QA) or the GABA(A) antagonist picrotoxin in mice. Animals were pretreated with an i.p. injection of saline, guanosine or GMP 30 min before either an i.c.v. injection of 4 microliter QA (36.8 nmol) or a subcutaneous injection of picrotoxin (3.2 mg/kg). All animals pretreated with vehicle followed by QA or picrotoxin presented seizures, which were completely prevented by the NMDA antagonist MK-801 and the GABA agonist phenobarbital, respectively. Guanosine and GMP dose-dependently protected against QA-induced seizures, up to 70 and 80% at 7.5 mg/kg, with ED(50)=2. 6+/-0.4 and 1.7+/-0.6 mg/kg, respectively. Conversely, neither guanosine, GMP nor MK-801 affected picrotoxin-induced seizures, indicating some degree of specificity towards the glutamatergic system. This study suggests anticonvulsant properties of i.p. guanosine and GMP, which may be related with antagonism of glutamate receptors. PMID:10793184
Schmidt, A P; Lara, D R; de Faria Maraschin, J; da Silveira Perla, A; Onofre Souza, D
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 (INap) and a reduced Ca2+ current in first instar larvae, which appeared normal in older third instar larvae. That increased INap may contribute to seizure-like activity is indicated by the observation that feeding sda larvae the antiepileptic drug phenytoin, which was sufficient to reduce INap, rescued both seizure-like episode duration and synaptic excitation of motoneurons. In contrast, feeding of either anemone toxin, a drug that preferentially increases INap, 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 INap 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.
Ketogenic diets (KD) have shown beneficial effects in terms of anticonvulsant and anti-epileptogenic properties in several experimental models. However, few studies have investigated the consequences of KD with regards to the anti-epileptogenic and neuroprotective effects in kindling-induced seizures. Here, postnatal day 28 male Sprague-Dawley rats received one of two experimental diets for 4 weeks: (a) a 'classic' 4:1 KD; and (b) a normal regular rodent chow diet (ND). Fully-kindled seizures were achieved by daily electrical stimulation in the amygdala. Seizure stage and after-discharge duration (ADD) were assessed daily. The after-discharge threshold (ADT) was measured every 5 days. The effects of the two diets on neuronal loss were observed before kindling and 20 days after stimulation by Nissl staining. We found that the progression of seizure stage and ADD was delayed by KD. KD prevented the ADT decrease on day 5. The incidence of generalized seizures was lower in the KD group compared to the ND group. The neuronal density was decreased in the ipsilateral hilus of the dentate gyrus (DG) and CA1 area, as well as the contralateral CA1 area before kindling in the KD group. However, KD prevented neuronal loss in the ipsilateral CA1 area 20 days after stimulation. Our data suggest that KD can protect against epileptogenesis by preventing both after-discharge generation and propagation in kindling seizures. In addition, KD also possesses a neuroprotective function during kindling although it changes hippocampal development in early life. PMID:22178860
Jiang, Yan; Yang, Yi; Wang, Shuang; Ding, Yao; Guo, Yi; Zhang, Man-Man; Wen, Shu-Qun; Ding, Mei-Ping
Hypoglycaemia can lead to acute disorders of cognition, consciousness, epilepsy, transient ischemia, psychosis and chronic disorders of dementia and neuropathy. Misdiagnosis and delay in treatment are common and prolonged hypoglycemia can lead to permanent neurological deficit or fatal coma. Hypoglycemia caused by an insulinoma is a readily treatable condition that should be considered in the differential diagnosis of intractable seizures. The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.
Background: To evaluate seizure characteristic among multiple sclerosis patients with coexistent seizure activity compared to control group. Materials and Methods: This study is a cross-sectional study which was conducted by reviewing the clinical records of patients with definite diagnosis of MS according to McDonald's criteria from March 2007 to June 2011, who referred to the MS clinic of the university. Results: A total of 920 patients with a diagnosis of MS were identified, among whom 29 patients (3.15%) with seizure activity (case) due to MS with the mean age of 32.6 ± 6.23 years were analyzed. Also, fifty MS patients without any seizure occurrence with the mean age of 33.7 ± 7.4 years were used as our control group. In case group, seizure was general tonic clonic in 23 patients (79.3%), complex partial in four (13.8%), and simple partial in two (5.9%). The 26 available interictal EEGs in MS patients showed abnormal EEG pattern in 22 (84.6%) of them, including focal epileptic form discharge or focal slowing in 10 (38.5%), generalized discharge (spike-wave, polyspike, or general paroxysmal fast activity) in 10 (38.5%), and general slowing activity in 10 record (38.5%). MRI reviews of the 26 available brain MRIs showed subcortical white mater lesions in 22 (84.6%) of patients with seizure. All MRIs were performed within one month after the first seizure episode. Amongst 48 available MRIs in our control group, 91.7% (44 cases) showed periventricular lesions and in 8.3% (4 cases) subcortical white matter lesions were reported. Conclusion: The result of this study demonstrated the higher rate of subcortical whit matter lesion in MS patients with seizure occurrence compared to control group.
Shaygannejad, Vahid; Ashtari, Fereshteh; Zare, Mohammad; Ghasemi, Majid; Norouzi, Rasul; Maghzi, Helia
Effective treatment of seizures associated with central nervous system (CNS) infection and inflammation depends on rapid diagnosis\\u000a and early attainment of bactericidal activity in the cerebrospinal fluid with appropriate antimicrobial agents, or appropriate\\u000a management of vasculitis-induced cerebral complications. Despite the rarity of these disorders, there is nothing specific\\u000a regarding the management in the intensive care unit of seizures in these
Wendy C. Ziai
A 9 year old girl presented with seizures, weight gain and early morning behavioural changes. She had been commenced on anticonvulsants and was subsequently diagnosed with hyperinsulinaemic hypoglycaemia. This case demonstrates the importance of blood glucose monitoring in children presenting with new-onset seizures and/or with early morning or fasting behavioural changes, the challenges in localizing the lesion, as well as the difficulties in achieving normoglycaemia prior to, and immediately following, surgery. PMID:24698060
Kao, Kung-Ting; Simm, Peter J; Brown, Justin
This hospital based cross sectional analytic study was carried out in department of Pediatrics Dhaka Medical College Hospital and Combined Military Hospital from July 2009 to June 2010 to find out the relationship of iron status with febrile seizure in children. Sixty children aged 6 months to 5 years having febrile seizure were enrolled as cases after taking proper consent by purposive sampling. Sixty age matched children with fever but no seizures were taken as control after taking proper consent. Children having a febrile seizure, developmental delay, hemorrhagic disorder, severe malnutrition or micronutrient deficiency and abnormal CSF findings were excluded from the study. In cases after control of seizure 2 ml of CSF was taken for cytology, biochemistry, Gram & AFB staining. Two milliliter of blood from cases as well as control was collected, released to EDTA bottle for Hb, MCV and MCHC. Again 2 ml of blood was taken in plain test tube for testing serum iron, TIBC and for serum ferritin. Serum iron, TIBC, serum ferritin was estimated by automated analyzer (PENTRA for serum iron, DADE BEHRING for TIBC, IMMULITE 1000 for serum ferritin). There was no significant difference between two groups regarding age (p>0.05), sex (p>0.05). High fever (p<0.001) and continuous fever (p<0.001) was significantly associated with febrile seizure. Seizure was generalized in all with positive family history in 83.3% cases. The Mean±SD of blood Hb (Case 9.8±1.6; Control 10.7±0.9), MCH (Case 22.1±2.3; Control 24.3±3.6) & serum ferritin (Case 55.1±29.3; Control 99.6±81.9) level were significantly low associated with febrile seizure (p<0.05). No significant difference was found between cases and control regarding MCV, serum iron and serum TIBC. PMID:23715348
Choudhury, M A; Zaman, M; Mollah, A H; Hoque, M A; Fatmi, L E; Islam, M N; Bhuiyan, K J; Hossain, M A
Thinking epilepsy is a rare form of reflex epilepsy that can be induced by specific cognitive tasks, and occurs mainly in idiopathic generalized epilepsies. We report a case of complex partial seizures triggered by thinking in a young man with acute bacterial meningitis and a remote head injury. This case illustrates that thinking-induced reflex seizures can be partial and can be provoked by an acute brain insult. PMID:23114680
Nevler, Naomi; Gandelman-Marton, Revital
Background: There is a broad variation in reported frequencies of seizure in multiple sclerosis (MS). In this study, the seizure and its characteristics analyzed among a large group of patients with MS. Patients and Methods: We reviewed the medical records of all definite MS patients referred to the MS Clinic of Kashani hospital, Isfahan, Iran, between 2007 and 2011. Results: Altogether, 34 cases with seizure activity identified among the 920 definite MS subjects (3.69%). Five excluded due to the other probable etiologies rather than MS. In the remained 29 patients (3.15%), the type of seizure was mostly generalized (79.3%); interictal electroencephalography showed an abnormal pattern in 84.6%, brain magnetic resonance imaging revealed subcortical white mater lesions in 84.6% of patients. The mean duration of MS onsets was 8.17 years and the mean interval between MS onset and the first seizure occurrence was 3.7 years. In general, response to antiepileptic treatment was excellent. Conclusion: Seizures can occur at any stage during the course of MS, but it is more common during the early stages.
Zare, Mohammad; Norouzi, Rasul; Shayegannejad, Vahid; Ashtari, Fereshteh; Ghasemi, Majid; Tavahen, Hemaseh; Masaeli, Ali
A 25-year-old woman with recurrent syncopal episodes presented with a first time generalized tonic clonic (GTC) seizure. She had experienced two prior fainting spells lasting seconds and associated with diet pills and dehydration. She had another similar spell prior to falling, sustaining a laceration to the right posterior occiput, and having a witnessed GTC seizure. Her scalp electroencephalography (EEG) showed left temporal slowing with sharp features. T1-weighted and T2-weighted MRI revealed two moderately enhancing focal lesions within the left frontal and temporal regions. These findings raised the possibility of an underlying seizure focus. Repeat imaging studies of this patient 1 month later, however, demonstrated resolution of these findings and an area of encephalomalacia, consistent with a traumatic coup contrecoup injury. A repeat EEG was normal. Therefore, the cause of the loss of consciousness was due to syncope with the consequent head injury giving rise to an isolated seizure. Understanding the underlying cause of a seizure is important in dictating treatment. In this setting the patient was not initiated on seizure medication and has done well. PMID:22245277
Sheen, Volney L
This review focuses on anoxic seizures induced by self terminating syncopes in the young. Anoxic seizures are nonepileptic events consequent upon abrupt interruption of the energy supply to metabolically active cerebral neurones. Anoxic seizures are the most common paroxysmal events misdiagnosed as epilepsy. Neurally mediated syncopes have numerous appellations, especially in the young. This proliferation of terminology likely results from uncertainty regarding pathophysiology. The most important type of self-limiting syncope from the point of view of diagnostic difficulty has been called neurocardiogenic or vasovagal syncope and reflex anoxic seizure, amongst other names: this review includes a video clip of such a child with prolonged asystole. It also includes a detailed case history emphasising the feelings of a patient with this type of syncope who was misdiagnosed as having epilepsy for many years. The second class of self-terminating syncope discussed and illustrated on video is the so-called breath-holding spell of young children. The third example illustrated is the compulsive Valsalva manoeuvre of individuals with autistic spectrum disorder, in which anoxic seizures - as shown on the video clips - are easily misdiagnosed as epileptic seizures, with unfortunate consequences. PMID:11313215
Stephenson, J B
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
This paper describes the sensor technology and associated electronics of a monitor designed to detect the onset of a seizure disorder called status epilepticus. It is a condition that affects approximately 3-5 percent of those individuals suffering from epilepsy. This form of epilepsy does not follow the typical cycle of start-peak-end. The convulsions continue until medically interrupted and are life threatening. The mortality rate is high without prompt medical treatment at a suitable facility. The paper describes the details of a monitor design that provides an inexpensive solution to the needs of those responsible for the care of individuals afflicted with this disorder. The monitor has been designed as a cooperative research and development effort involving the United States Army Armament Research, Development, and Engineering Center's Benet Laboratories (Benet) and the Cerebral Palsy Center for the Disabled (Center), in association with the Department of Neurology at Albany Medical College (AMC). Benet has delivered a working prototype of the device for field testing, in collaboration with Albany Medical College. The Center has identified several children in need of special monitoring and has agreed to pursue commercialization of the device.
Johnson, Mark; Simkins, Thomas
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…
This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on each HRS detector. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB.
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
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
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
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. PMID:23561888
Szabó, C Ákos; Knape, Koyle D; Leland, M Michelle; Cwikla, Daniel J; Williams-Blangero, Sarah; Williams, Jeff T
It is generally accepted that sleep deprivation contributes to seizures. However, it is unclear whether a seizure occurring in the setting of sleep deprivation should be considered as provoked or not and whether this is influenced by seizure type and etiology. This information may have an important impact on epilepsy diagnosis and management. We prospectively analyzed the influence of sleep deprivation on the risk of seizure recurrence in patients with first-ever unprovoked seizures and compared the findings with patients with first-ever provoked seizures. Of 1026 patients with first-ever unprovoked seizures, 204 (20%) were associated with sleep deprivation. While the overall likelihood of seizure recurrence was slightly lower in sleep-deprived patients with first-ever seizures (log-rank p=0.03), sleep deprivation was not an independent predictor of seizure recurrence on multivariate analysis. Seizure recurrence following a first-ever unprovoked seizure associated with sleep deprivation was far more likely than for 174 patients with a provoked first-ever seizure (log-rank p<0.0001). Our findings support the International League Against Epilepsy recommendation that seizures occurring in the setting of sleep deprivation should not be regarded as provoked. PMID:24657503
Lawn, Nicholas; Lieblich, Sam; Lee, Judy; Dunne, John
Objectives Partial seizures are often believed to be associated with EEG signals of low complexity because seizures are associated with increased neural network synchrony. The investigations reported here provide an assessment of the signal complexity of epileptic seizure onsets using newly developed quantitative measures. Methods Using the Gabor atom density (GAD) measure of signal complexity, 339 partial seizures in 45 patients with intracranial electrode arrays were analyzed. Segmentation procedures were applied to determine the timing and amplitude of GAD changes relative to the electrographic onset of the seizure. Results 330 out of 339 seizures have significant complexity level changes, with 319 (97%) having an increase in complexity. GAD increases occur within seconds of the onset of the partial seizure but are not observed in channels remote from the focus. The complexity increase is similar for seizures from mesial temporal origin, neocortical temporal and extra-temporal origin. Conclusions Partial onset seizures are associated with early increases in signal complexity as measured by GAD. This increase is independent of the location of the seizure focus. Significance Despite the often predominant rhythmic activity that characterizes onset and early evolution of epileptic seizures, partial seizure onset is associated with an early increase in complexity. These changes are common to partial seizures originating from different brain regions, indicating a similar seizure dynamic.
Jouny, Christophe C; Bergey, Gregory K; Franaszczuk, Piotr J
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
Ten patients who presented with dorsolateral or frontocentral seizures were studied with chronic subdural grid electrodes. Cortical mapping, sensory-evoked potentials and chronic electrocorticography were obtained for each patient. Seizures were classified as focal, regional or dipolar. At the time of explanation, a selective functional corticectomy was performed. Surgical outcome is presented at a mean follow-up of 36 months. Two patients are seizure-free and 7 patients had a significant reduction in seizure frequency. One patient had no change in seizure pattern. Dorsolateral frontal lobe seizures have a focal functional anatomy and can be surgically treated by selective cortectomy. PMID:1439335
Levesque, M F; Sutherling, W W; Crandall, P H
Five patients who developed seizures following a general anesthetic are described. It is not possible to determine retrospectively whether or not the initial attacks were definitely epileptic, but these patients all subsequently received a diagnosis of psychological nonepileptic convulsions/seizures (also known as pseudoseizures, psychogenic nonepileptic seizures, and nonepileptic attack disorder) established by video/EEG telemetry or ictal EEG recordings. In two cases there was evidence of concurrent epilepsy. We suggest that nonepileptic seizures may develop following postanesthetic seizures and that a psychogenic basis for seizures occurring after general anesthetics needs to be considered. PMID:15582852
Lichter, Ida; Goldstein, Laura H; Toone, Brian K; Mellers, John D C
The authors used /sup 18/F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to study nine patients with clinical absence or generalized seizures. One patient had only absence seizures, two had only generalized tonic-clonic seizures, and six had both seizure types. Interictal scans in eight failed to reveal focal or lateralized hypometabolism. No apparent abnormalities were noted. Two patients had PET scans after isotope injection during hyperventilation-induced generalized spike-wave discharges. Diffusely increased metabolic rates were found in one compared with an interictal scan, and in another compared with control values. Another patient had FDG injected during absence status: EEG showed generalized spike-wave discharges (during which she was unresponsive) intermixed with slow activity accompanied by confusion. Metabolic rates were decreased, compared with the interictal scan, throughout both cortical and subcortical structures. Interictal PET did not detect specific anatomic regions responsible for absence seizure onset in any patient, but the results of the ictal scans did suggest that pathophysiologic differences exist between absence status and single absence attacks.
Theodore, W.H.; Brooks, R.; Margolin, R.; Patronas, N.; Sato, S.; Porter, R.J.; Mansi, L.; Bairamian, D.; DiChiro, G.
We studied 10 patients with intractable epilepsy being evaluated for epilepsy surgery for preictal changes in spiking. All patients were implanted with intracranial electrodes and underwent continuous EEG/audiovisual monitoring. Interictal spikes were detected and recorded continuously by a dedicated computerized system. Edited spikes were counted during 0-5, 5-10, and 0-60 min epochs before each seizure, during epochs of unvarying state of arousal (awake or sleep stage II). When comparing by repeated measures, 1-way ANOVA, total spiking (in all recording channels) did not differ among the different preictal epochs (0-5, 5-10, 0-60 min) in 45 seizures (F = 0.88, P = 0.40, using the Geisser-Greenhouse adjustment--GGA). Likewise, no significant differences were obtained during those same epochs when comparing spiking originating from the channel of seizure onset in 5 patients with 28 seizures of localized onset (F = 1.19, P = 0.38 using the GGA). Our findings indicate that in patients with intractable epilepsy, no changes in spiking occur in the 5 min prior to seizures, when compared to more distant preictal epochs. PMID:1713830
Katz, A; Marks, D A; McCarthy, G; Spencer, S S
The relation between interhippocampal seizure propagation time (IHSPT) and anatomic alterations in the human epileptic hippocampus may provide insight into the pathophysiology of temporal lobe epilepsy (TLE). Using depth electrode recordings, we measured the time required for spontaneous seizures with onset in one hippocampus to become manifest in the contralateral hippocampus in 50 patients who underwent resection of the temporal lobe of seizure origin. Cell densities in individual hippocampal subfields were determined and correlated with mean IHSPT for each patient. Mean IHSPT was significantly and inversely correlated with cell counts in CA4 only (r = -0.38, p less than 0.01, Pearson's product correlation; r = -0.52, p less than 0.001, Spearman's rank order correlation). In 5 patients with bilateral independent hippocampal seizure onset who had temporal lobectomy and a diagnosis of mesial temporal sclerosis, mean IHSPT was consistently longer from the sclerotic temporal lobe than to it. These observations suggest that anatomic changes associated with chronic epilepsy alter propagation patterns. Because CA4 is believed to modulate the output of dentate granule cells and also has commissural connections to the contralateral homotopic area, the association of decreased CA4 cells with prolongation of IHSPT suggests that the observed anatomic alterations may actively (through increased inhibition) or passively (through decreased recruitment) interfere with various routes of seizure propagation. PMID:1396429
Spencer, S S; Marks, D; Katz, A; Kim, J; Spencer, D D
Seizures are a frequent complication associated with several neurogenetic disorders. Antiepileptic medications remain the mainstay of treatment in these patients. We summarized the available data associated with various antiepileptic therapies used to treat patients with neurogenetic disorders who experienced recurrent seizures. A MEDLINE search was conducted to identify articles and abstracts describing the use of antiepileptic therapy for the treatment of various neurogenetic syndromes. Of all the neurogenetic syndromes, only autism spectrum disorders, Angelman syndrome, Rett syndrome, Dravet syndrome, and tuberous sclerosis complex were identified as having sufficient published information to evaluate therapy. Some efficacy trends were identified, including frequent successes with valproic acid with clonazepam for epilepsy with Angelman syndrome; valproic acid, stiripentol, and clobazam (triple combination therapy) for epilepsy with Dravet syndrome; and vigabatrin for infantile spasms associated with tuberous sclerosis complex. Due to a paucity of information regarding the mechanisms by which seizures are generated in the various disorders, approach to seizure control is primarily based on clinical experience and a limited amount of study data exploring patient outcomes. Although exposure of the developing brain to antiepileptic medications is of some concern, the control of epileptic activity is an important undertaking in these individuals, as the severity of eventual developmental delay often appears to correlate with the severity of seizures. As such, early aggressive therapy is warranted. PMID:23400943
Faulkner, Michele A; Singh, Sanjay P
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
Seizures are a frequent sequela of impaired brain development and can be expected to affect more children with radiation-related brain damage than children without such damage. This report deals with the incidence and type of seizures among survivors prenatally exposed to the atomic bombing of Hiroshima and Nagasaki, and their association with specific stages of prenatal development at the time of irradiation. Fetal radiation dose was assumed to be equal to the dose to the maternal uterus. Seizures here include all references in the clinical record to seizure, epilepsy, or convulsion. Histories of seizures were obtained at biennial routine clinical examinations starting at about the age of 2 years. These clinical records were used to classify seizures as febrile or unprovoked (without precipitating cause). No seizures were ascertained among subjects exposed 0-7 weeks after fertilization at doses higher than 0.10 Gy. The incidence of seizures was highest with irradiation at the eighth through the 15th week after fertilization among subjects with doses exceeding 0.10 Gy and was linearly related to the level of fetal exposure. This obtains for all seizures without regard to the presence of fever or precipitating causes, and for unprovoked seizures. When the 22 cases of severe mental retardation were excluded, the increase in seizures was only suggestively significant and only for unprovoked seizures. After exposure at later stages of development, there was no increase in recorded seizures.
Dunn, K.; Yoshimaru, H.; Otake, M.; Annegers, J.F.; Schull, W.J. (Radiation Effects Research Foundation, Hiroshima (Japan))
Psychogenic non-epileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) at Veterans Affairs Medical Centers (VAMCs) and cause significant long-term disability. An understanding of psychiatric factors associated with PNES could aid in earlier diagnosis and treatment. We studied 50 consecutive veterans diagnosed with PNES and 37 veterans diagnosed with epileptic seizures (ES), evaluated at a VAMC EMU. We reviewed all available mental health evaluations prior to EMU evaluation. Univariate comparisons included axis I diagnoses, axis II diagnoses, and psychiatric hospitalizations. Predictive models of seizure classification were evaluated by logistic regression. A diagnosis of post-traumatic stress disorder (PTSD) preceded the diagnosis of PNES in 58% of patients and the diagnosis of ES in 13.5% (p<0.001). On logistic regression, PTSD was the only significant psychiatric diagnosis (odds ratio 9.2). Major depression and alcohol abuse were common diagnoses but did not differentiate PNES and ES groups. PMID:23103308
Salinsky, Martin; Evrard, Collette; Storzbach, Daniel; Pugh, Mary Jo
The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children. Citation: Izzo A; McSweeney J; Kulik T; Khatwa U; Kothare SV. “Nocturnal seizures” in idiopathic pulmonary arterial hypertension. J Clin Sleep Med 2013;9(10):1091-1092.
Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V.
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
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.
Thresholds in transmission are responsible for critical changes in infectious disease epidemiology. The epidemic threshold indicates whether infection invades a totally susceptible population. The reinfection threshold indicates whether self-sustained transmission occurs in a population that has developed a degree of partial immunity to the pathogen (by previous infection or vaccination). In models that combine susceptible and partially immune individuals, the reinfection threshold is technically not a bifurcation of equilibria as correctly pointed out by Breban and Blower. However, we show that a branch of equilibria to a reinfection submodel bifurcates from the disease-free equilibrium as transmission crosses this threshold. Consequently, the full model indicates that levels of infection increase by two orders of magnitude and the effect of mass vaccination becomes negligible as transmission increases across the reinfection threshold. PMID:15967188
Gomes, M Gabriela M; White, Lisa J; Medley, Graham F
The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and in total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy, to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy, and to determine whether seizure worsening is associated with a low ratio to nonpregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observational study. Concomitant medications and seizure frequency were recorded. Serum total and free CBZ and CBZ-EPO were collected at each visit. Changes in the clearance of all four compounds and free fractions of CBZ and CBZ-EPO were compared with nonpregnant baseline. During pregnancy, the ratios to baseline concentrations of total and free CBZ and CBZ-EPO were compared for months with and without increased seizure frequency. Total and free CBZ and CBZ-EPO clearances were calculated in 15 pregnancies in 12 women. Clearances did not change for any of these compounds during pregnancy. The free fraction of CBZ increased from 0.23 at baseline to a maximum of 0.32 in the third trimester (p=0.008). In the six women on CBZ monotherapy with adequate seizure diaries and blood sampling, seizure worsening did not correspond to a ratio to baseline concentration of less than 0.65 for total or free CBZ or CBZ-EPO. In conclusion, total and free CBZ and CBZ-EPO clearances did not change substantially during pregnancy, and seizure frequency worsening was not associated with decreased concentrations of total or free CBZ; therefore, therapeutic drug monitoring may not be necessary for all women on CBZ during pregnancy. Further studies with larger sample sizes are needed before definitive recommendations can be made. Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy. PMID:24632353
Johnson, Emily L; Stowe, Zachary N; Ritchie, James C; Newport, D Jeffrey; Newman, Melanee L; Knight, Bettina; Pennell, Page B
Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurological dysfunction, including seizures. Dietary fatty acids are known as an important energy source and reduce seizure activity in selected acute animal models. This study investigated whether chronic treatment with fish oil or with oleic acid attenuates MMA-induced seizures and whether maintenance of Na(+),K(+)-ATPase activity was involved in such an effect. Adult male Wistar rats were given fish oil (85 mg/kg), oleic acid (85 mg/kg) or vehicle (0.42% aqueous Cremophor EL™, 4 mL/kg/body weight/day), p.o., for 75 days. On the 73th day a cannula was implanted in the right lateral ventricle with electrodes over the parietal cortex for EEG recording. On the 76th day the animals were injected with NaCl (2.5 ?mol/2.5 ?L, i.c.v.), or with MMA (2.5 ?mol/2.5 ?L, i.c.v.), and seizure activity was measured by electroencephagraphic (EEG) recording with concomitant behavior monitoring. The effect of prostaglandin E2 (PGE2) on Na(+),K(+)-ATPase activity of slices of cerebral cortex from NaCl-injected animals was determined. Fish oil increased the latency to MMA-induced tonic-clonic seizures, reduced the mean amplitude of ictal EEG recordings, and prevented PGE2-induced decrease of Na(+),K(+)-ATPase activity in cortical slices in vitro. Oleic acid decreased mean amplitude of ictal EEG recordings. The results support that fish oil decreases MMA-induced seizures. The decreased sensitivity of Na(+),K(+)-ATPase to the inhibitory effect of PGE2 in fish oil-treated animals may be related to the currently reported anticonvulsant activity. PMID:23375884
Banderó, Cristina Ruedell Reschke; Salvadori, Mirian G S S; Gomes, Anajara Teixeira; Dal Ri, Nadja M K; Furian, Ana Flávia; Oliveira, Mauro Schneider; Rambo, Leonardo Magno; Scorza, Fulvio A; Cysneiros, Roberta M; Emanuelli, Tatiana; Mello, Carlos Fernando
The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.
Perucca, Piero; Dubeau, Francois; Gotman, Jean
Poisoning with many xenobiotics may result in seizures, which are usually generalized. Seizures leading to unexplained disturbances of consciousness are usually generalized tonic-clonic, absence seizures and complex partial seizures Prolonged seizures without recovery of consciousness during interictal period are called status epilepticus. This paper presents the etiology, patomechanism, clinical characteristics, as well as diagnostic and therapeutic principles of toxic seizures. Additionally, the clinical description of nonepileptic psychogenic seizures is given, which often need to be differentiated with true seizures. PMID:24466702
Ciszowski, Krzysztof; Mietka-Ciszowska, Aneta
When dealing with seizure detection/prediction problems, there are three main performance metrics that must be optimized: false positive rate, false negative rate, detection delay or, if the problem is seizure prediction, it is desirable to obtain the gre...
R. Esteller J. Echauz M. D. Alessandro G. Vachtsevanos B. Litt
Amantadine has demonstrated efficacy in small series for absence and myoclonic type seizures. We examined the efficacy of amantadine for treating refractory absence seizures in a cohort of pediatric patients. We retrospectively reviewed medical records for patients with absence seizures treated with amantadine at Cook Children's Medical Center after January 2007. Abstracted data included sex, age at initiation, concomitant antiepileptic drugs, amantadine dosing, and seizure frequency. Outcomes at 3, 6, and 12 months after initiation were categorized as >90%, ?50%, or <50% reduction in seizure frequency. Of 13 patients included in the study, many were exposed to multiple antiepileptic drugs (median, 3; range, 1-6). Three were implanted with a vagus nerve stimulator. A response of at least 50% seizure reduction was reported in more than 50% of patients reviewed at 3, 6, and 12 months after initiating treatment. Among responders, a majority had >90% reduction in seizure frequency. Amantadine may constitute an efficacious alternative treatment for refractory absence seizures. PMID:22490771
Perry, M Scott; Bailey, Laurie J; Kotecha, Amy C; Malik, Saleem I; Hernandez, Angel W
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
This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on each HRS detector. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB. Edited 4/30/91 to add comments to disable/re-enable cross-talk tables.
Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful. PMID:1622519
Lahat, E; Aladjem, M; Eshel, G; Bistritzer, T; Katz, Y
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
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.
Albino Sprague-Dawley rats were exposed in a previously O2 flushed, CO2 free chamber. The exposure began with attainment of 60 psi (gauge) and the end point was the first generalized oxygen toxicity seizure. Animals were exposed to reversal diurnal conditions since weanlings until their sleep-wake cycles had completely reversed, and then divided into four groups of 20 based on the time of day exposed. The time of exposure to oxygen at high pressure prior to seizure was now significantly longer in the group exposed from 1900 to 2000 hr and a reversal of the circadian rhythm of oxygen toxicity seizure susceptibility was noted. Animals maintained on normal diurnal conditions were deprived of sleep on the day of exposure for the 12 hours prior to exposure at 1900 hr, while controls were allowed to sleep. There was no significant differences in the time prior to seizure between the deprived animals and the controls with an n = 40. Thus the inherent threshold in susceptibility to high-pressure oxygen seizures seems not to be a function of sleep itself, but of some biochemical/physiologic event which manifests a circadian rhythm.
Dexter, J. D.; Hof, D. G.; Mengel, C. E.
Multiple quantitative trait locus (QTL) mapping studies designed to localize seizure susceptibility genes in C57BL/6 (B6, seizure resistant) and DBA/2 (D2, seizure susceptible) mice have detected a significant effect originating from midchromosome 5. To confirm the presence and refine the position of the chromosome 5 QTL for maximal electroshock seizure threshold (MEST), reciprocal congenic strains between B6 and D2 mice were created by a DNA marker-assisted backcross breeding strategy and studied with respect to changes in MEST. A genomic interval delimited by marker D5Mit75 (proximal to the acromere) and D5Mit403 (distal to the acromere) was introgressed for 10 generations. A set of chromosome 5 congenic strains produced by an independent laboratory was also studied. Comparison of MEST between congenic and control (parental genetic background) mice indicates that genes influencing this trait were captured in all strains. Thus, mice from strains having D2 alleles from chromosome 5 on a B6 genetic background exhibit significantly lower MEST compared with control littermates, whereas congenic mice harboring B6 chromosome 5 alleles on a D2 genetic background exhibit significantly higher MEST compared with control littermates. Combining data from all congenic strains, we conclude that the gene(s) underlying the chromosome 5 QTL for MEST resides in the interval between D5Mit108 (26 cM) and D5Mit278 (61 cM). Generation of interval-specific congenic strains from the primary congenic strains described here may be used to achieve high-resolution mapping of the chromosome 5 gene(s) that contributes to the large difference in seizure susceptibility between B6 and D2 mice. PMID:17698926
Ferraro, Thomas N; Smith, George G; Schwebel, Candice L; Lohoff, Falk W; Furlong, Patrick; Berrettini, Wade H; Buono, Russell J
Granule cells in the dentate gyrus are born throughout life, and various stimuli can affect their development in the adult brain. Following seizures, for instance, neurogenesis increases greatly, and some new cells migrate to abnormal (ectopic) locations, such as the hilus. Previous electrophysiological studies of this population have shown that they have intrinsic properties that are similar to normal granule cells, but differ in other characteristics, consistent with abnormal integration into host circuitry. To characterize the response of ectopic hilar granule cells to perforant path stimulation, intracellular recordings were made in hippocampal slices from rats that had pilocarpine-induced status epilepticus and subsequent spontaneous recurrent seizures. Comparisons were made with granule cells located in the granule cell layer of both pilocarpine- and saline-treated animals. In addition, a few ectopic hilar granule cells were sampled from saline-treated rats. Remarkably, hilar granule cells displayed robust responses, even when their dendrites were not present within the molecular layer, where perforant path axons normally terminate. The evoked responses of hilar granule cells were similar in several ways to those of normally positioned granule cells, but there were some differences. For example, there was an unusually long latency to onset of responses evoked in many hilar granule cells, especially those without molecular layer dendrites. Presumably this is due to polysynaptic activation by the perforant path. These results indicate that synaptic reorganization after seizures can lead to robust activation of newly born hilar granule cells by the perforant path, even when their dendrites are not in the terminal field of the perforant path. Additionally, the fact that these cells can be found in normal tissue and develop similar synaptic responses, suggests that seizures, while not necessary for their formation, strongly promote their generation and the development of associated circuits, potentially contributing to a lowered seizure threshold. PMID:14580952
Scharfman, H E; Sollas, A E; Berger, R E; Goodman, J H; Pierce, J P
Understanding how seizures spread throughout the brain is an important problem in the treatment of epilepsy, especially for implantable devices that aim to avert focal seizures before they spread to, and overwhelm, the rest of the brain. This paper presents an analysis of the speed of propagation in a computational model of seizure-like activity in a 2-dimensional recurrent network of integrate-and-fire neurons containing both excitatory and inhibitory populations and having a difference of Gaussians connectivity structure, an approximation to that observed in cerebral cortex. In the same computational model network, alternative mechanisms are explored in order to simulate the range of seizure-like activity propagation speeds (0.1–100 mm/s) observed in two animal-slice-based models of epilepsy: (1) low extracellular , which creates excess excitation and (2) introduction of gamma-aminobutyric acid (GABA) antagonists, which reduce inhibition. Moreover, two alternative connection topologies are considered: excitation broader than inhibition, and inhibition broader than excitation. It was found that the empirically observed range of propagation velocities can be obtained for both connection topologies. For the case of the GABA antagonist model simulation, consistent with other studies, it was found that there is an effective threshold in the degree of inhibition below which waves begin to propagate. For the case of the low extracellular model simulation, it was found that activity-dependent reductions in inhibition provide a potential explanation for the emergence of slowly propagating waves. This was simulated as a depression of inhibitory synapses, but it may also be achieved by other mechanisms. This work provides a localised network understanding of the propagation of seizures in 2-dimensional centre-surround networks that can be tested empirically.
Hall, David; Kuhlmann, Levin
We report a case of a 42-year-old male who developed generalized tonic-clonic seizure with sudden, brief decrease in bispectral index (BIS) value while undergoing emergency kidney transplantation. Few reports have been made on intraoperative pitfall of BIS value associated with seizure. This case report suggests seizure should be taken into account as a reason for such brief fall of BIS, especially while under general anesthesia or in other specific cases in which clinical signs of seizure are unseen.
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
\\u000a Fulminant hepatic failure and other causes of multiorgan dysfunction can be associated with seizures. These seizures can be\\u000a convulsive or nonconvulsive, and may significantly affect the pathobiology of the patient’s critical condition. The use of\\u000a continuous electroencephalography has become very important in the identification and treatment of seizures in critically\\u000a ill patients with hepatic or other metabolic disorders. Seizures arise
Andrew Beaumont; Paul M. Vespa
Agomelatine is a potent MT1 and MT2 melatonin receptor agonist as well as a 5-HT2C serotonin receptor antagonist. It was approved by the European Medicines Agency as an antidepressant drug in year 2009. On the other hand, the involvement of melatonin and serotonin receptors in the modulation of seizure threshold has been demonstrated previously. The purpose of this study was to investigate the effect of agomelatine on penthylenetetrazol-induced seizure threshold in male mice. Therefore, we evaluated the effect of acute (12.5, 25, 50, 75 and 100mg/kg, p.o. and chronic (25, 50 and 75mg/kg, p.o., once a day, for 7 days) agomelatine administration on mouse model of intravenous penthylenetetrazol-induced seizure. For evaluation of nitrergic system involvement in the anticonvulsant effect of agomelatine, co-administration of multiple nitric oxide synthase (NOS) inhibitors [L-NAME, a non-selective NOS inhibitor, (5mg/kg, p.o.), aminoguanidine, a selective iNOS inhibitor, (100mg/kg, p.o.) or 7-nitroindazol, a selective nNOS inhibitor, (60mg/kg, p.o.)] and agomelatine (50 and 75mg/kg) were examined. In acute study, agomelatine (50 and 75mg/kg) increased clonic seizure threshold compared to control group (P<0.05 and 0.01, respectively). In chronic study, agomelatine had no effect on clonic seizure threshold compared with control mice. Co-administration of L-NAME, aminoguanidine or 7-nitroindazol with agomelatine (50 and 75mg/kg) prevented a agomelatine-induced anti-convulsant effect. Our results suggest that agomelatine has anticonvulsant activity in intravenous penthylenetetrazol-induced seizure in acute therapy and this effect can be at least in part due to iNOS or nNOS induction. PMID:24803306
Dastgheib, Mona; Moezi, Leila
Focal, secondarily generalizing epileptic seizures were released by magnetic stimulation in a patient with focal epilepsy. The stimulation induced seizures had a similar clinical appearance to the patient's spontaneous seizures. They were released exclusively by an angulated “figure-of-8” coil which stimulates the brain more focally as compared to the commonly used flat round coil. The epileptic focus could be located
J. Classen; O. W. Witte; G. Schlaug; R. J. Seitz; H. Holthausen; R. Benecke
Alterations of consciousness are critical factors in the diagnosis of epileptic seizures. With these alterations in consciousness, some persons report sensations of separating from the physical body, experiences that may in rare cases resemble spontaneous out-of-body experiences. This study was designed to identify and characterize these out-of-body-like subjective experiences associated with seizure activity. Fifty-five percent of the patients in this study recalled some subjective experience in association with their seizures. Among our sample of 100 patients, 7 reported out-of-body experiences associated with their seizures. We found no differentiating traits that were associated with patients' reports of out-of-body experiences, in terms of either demographics; medical history, including age of onset and duration of seizure disorder, and seizure frequency; seizure characteristics, including localization, lateralization, etiology, and type of seizure, and epilepsy syndrome; or ability to recall any subjective experiences associated with their seizures. Reporting out-of-body experiences in association with seizures did not affect epilepsy-related quality of life. It should be noted that even in those patients who report out-of-body experiences, such sensations are extremely rare events that do not occur routinely with their seizures. Most patients who reported out-of-body experiences described one or two experiences that occurred an indeterminate number of years ago, which precludes the possibility of associating the experience with the particular characteristics of that one seizure or with medications taken or other conditions at the time. PMID:24592228
Greyson, Bruce; Fountain, Nathan B; Derr, Lori L; Broshek, Donna K
Tremor rats (tremor homozygous rats) exhibit spontaneous absence-like seizure, which is characterized by a sudden immobility with staring and the appearance of 5- to 7-Hz spike and wave complexes in cortical and hippocampal electroencephalogram (EEG). In this study, we examined the development of the seizure and the mode of inheritance. All tremor homozygous and heterozygous rats exhibited the seizure by
Takafumi Higashiguchi; Tadoo Serikawa; Takahisa Yamada; Katsumi Kogishi; Akira Kondo; Junzo Yamada
Automated detection of seizures is still a challenging problem. This study presents an approach to detect seizure segments in Laplacian electroencephalography (tEEG) recorded from rats using the tripolar concentric ring electrode (TCRE) configuration. Three features, namely, median absolute deviation, approximate entropy, and maximum singular value were calculated and used as inputs into two different classifiers: support vector machines and adaptive boosting. The relative performance of the extracted features on TCRE tEEG was examined. Results are obtained with an overall accuracy between 84.81 and 96.51%. In addition to using TCRE tEEG data, the seizure detection algorithm was also applied to the recorded EEG signals from Andrzejak et al. database to show the efficiency of the proposed method for seizure detection.
Feltane, Amal; Boudreaux-Bartels, G. Faye; Besio, Walter
Of all partial seizures, those of frontal lobe origin (FLPS) are most bizarre and are often mistaken for psychogenic seizures (PS). The reverse can also be true. To clarify the confusing clinical presentation of these different seizure types, we compared the clinical ictal characteristics of 63 FLPS in 11 patients with 29 PS in 12 patients. Patients with PS had significantly later age at onset and longer ictal duration. There was no statistically significant difference between the two groups with respect to history of psychiatric disorder, ictal pelvic thrusting, rocking of body, side-to-side head movements, or rapid postictal recovery, all of which previously have been reported as characteristic features of PS. Turning to a prone position during the seizure occurred only in FLPS. Nocturnal occurrence, short ictal duration, younger age at onset, stereotyped patterns of movements, and MRI and EEG abnormality suggested FLPS. PMID:1620332
Saygi, S; Katz, A; Marks, D A; Spencer, S S
If a picture contains dark objects on a light background, or vice versa, the objects can be separated from the background by thresholding the picture. A good place to choose the threshold is at the average gray level of those picture points where the valu...
J. S. Weszka A. Rosenfeld
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.
... neurons) in the brain, where they transport potassium ions out of cells. These channels transmit a particular type of electrical signal called ... 4 months. It has been suggested that potassium channels formed from the KCNQ2 and KCNQ3 proteins play a ... neuron ; potassium ; seizure ; symptom You may ...
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
Introduction: Occurrence of generalized tonic-clonic seizures (GTCS) is one of the most important risk factors of seizure-related complications and comorbidities in patients with epilepsy. Their prevention is therefore an important aspect of therapeutic management both in idiopathic generalized epilepsies and in focal epilepsies. Areas covered: It has been shown that the efficacy of antiepileptic drugs (AEDs) varies across epilepsy syndromes, with some AEDs efficacious against focal seizures with secondary GTCS (sGTCS) but aggravating primary GTCS (pGTCS). In patients with pGTCS, evidence-based data support the preferential use of valproic acid, lamotrigine, levetiracetam and topiramate. In patients with sGTCS, all AEDs approved in the treatment of focal epilepsies might be used. Expert opinion: Both in pGTCS and sGTCS, additional data are required, specifically to inform about the relative efficacy of AEDs in relation to each other. Although valproic acid might be the most efficacious drug in idiopathic generalized epilepsies, it should be avoided in women of childbearing age due to its safety profile. In patients with sGTCS, AEDs for which the impact on this seizure type has been formally evaluated and which have demonstrated greater efficacy than placebo might preferentially be used, such as lacosamide, perampanel and topiramate. PMID:24798217
Rheims, Sylvain; Ryvlin, Philippe
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…
Fever can precipitate ventricular tachycardia in adults with Brugada syndrome, but such a link has not been reported in children. A 21-month-old white girl presented repeatedly with decreased conscious level and seizures during fever. During a typical episode, rapid ventricular tachycardia was documented. The resting 12-lead electrocardiogram revealed a Brugada electrocardiogram signature. Resting electrocardiograms of the asymptomatic brother and mother
Jonathan Robert Skinner; Seo-Kyung Chung; Carey-Anne Nel; Andrew Neil Shelling; Jackie Robyn Crawford; Neil McKenzie; Ralph Pinnock; John Kerswell French; Mark Ian Rees
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.
Background: Atomoxetine (Strattera™), has recently been approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adolescents and adults. Atomoxetine acts by inhibiting the reuptake of norepinephrine. There are limited reports of the effects of atomoxetine in overdose. We report a case of isolated atomoxetine overdose resulting in seizure and mild cardiac toxicity. Case Report: A 17-year-old female ingested
John Kashani; Anne-Michelle Ruha
We utilized a novel ratiometric nanoquantum dot fluorescence resonance energy transfer (NQD-FRET) optical sensor to quantitatively measure oxygen dynamics from single cell microdomains during hypoxic episodes as well as during 4-aminopyridine (4-AP)-induced spontaneous seizure-like events in rat hippocampal slices. Coupling oxygen sensing with electrical recordings, we found the greatest reduction in the O2 concentration ([O2]) in the densely packed cell body stratum (st.) pyramidale layer of the CA1 and differential layer-specific O2 dynamics between the st. pyramidale and st. oriens layers. These hypoxic decrements occurred up to several seconds before seizure onset could be electrically measured extracellularly. Without 4-AP, we quantified a narrow range of [O2], similar to the endogenous hypoxia found before epileptiform activity, which permits a quiescent network to enter into a seizure-like state. We demonstrated layer-specific patterns of O2 utilization accompanying layer-specific neuronal interplay in seizure. None of the oxygen overshoot artifacts seen with polarographic measurement techniques were observed. We therefore conclude that endogenously generated hypoxia may be more than just a consequence of increased cellular excitability but an influential and critical factor for orchestrating network dynamics associated with epileptiform activity. PMID:24598521
Ingram, Justin; Zhang, Chunfeng; Cressman, John R; Hazra, Anupam; Wei, Yina; Koo, Yong-Eun; Ziburkus, Jok?bas; Kopelman, Raoul; Xu, Jian; Schiff, Steven J
The 15-month study aimed at validating the epileptic seizure warning system designed by McDonnell Douglas Astronautics Corporation found it to be reasonably efficient in a test population of 13. Besides the history and description of the study, technical ...
S. S. Viglione
The treatment of neonatal seizures has not changed significantly over the last 50 years despite advances in antiepileptic drug (AED) development for older children and adults. Recently new drugs have emerged some of which address age-specific challenges or mechanisms and will be discussed in this review. The loop diuretic bumetanide blocks the neuronal NKCC1 co-transporter and is thought specifically to supress seizures in the immature brain. Levetiracetam has been used in children and infants with good efficacy, an excellent safety profile, and near-ideal pharmacokinetic characteristics. Randomised controlled trials are now underway to test the efficacy of some newer AEDs for neonatal seizures. Topiramate has been shown to have neuroprotective properties in addition to its antiepileptic action and trials in babies with hypoxic-ischaemic encephalopathy are now planned. There is an urgent need to develop age-specific AEDs for preterm and term babies. These drugs must be evaluated with multicentre, collaborative trials using innovative methods and high ethical standards to overcome age-specific challenges with the ultimate aim of improving the outcome for neonates with seizures. PMID:23688938
Pressler, Ronit M; Mangum, B
The syndrome of malignant migrating partial seizures in infancy (MMPSI) was first reported in 1995, and is now included among the childhood epileptic syndromes in the revision proposal of the ILAE Commission on classification and terminology. The main clinical features are seizure onset in the first 6 months of life, occurrence of almost continuous migrating polymorphous focal seizures, associated with multifocal ictal EEG discharges, progressive deterioration of psychomotor development combined with frequent evolution of acquired microcephaly, and lack of a significant familial and etiological context. Eventually, children develop major axial hypotonia, pyramidal and extrapyramidal signs with athetotic movements and strabismus. Neuroradiological, biochemical, and genetic investigations thus far have note contributed to our knowledge about this syndrome. Etiology is still unknown, though it appears reasonable to suspect a genetic etiology for MMPSI; a channelopathy may be responsible for the age-dependent cortical neuronal hyperexcitability. Seizures are markedly drug resistant and outcome is generally severe. However, some patients may respond favourably to bromide, stiripentol associated with clonazepam, and, more recently, to levetiracetam. Vagus nerve stimulation and a ketogenic diet have been tried also but with poor or inconclusive results. Based on age at onset, MMPEI may be placed between early epileptic encephalopthies and infantile spasms. PMID:23622207
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
Background: The risk of developing immediate postoperative seizures in patients undergoing supratentorial brain tumor surgery without anti-epileptic drug (AED) prophylaxis is 15-20%. Patients who present with pre-operative seizures and patients with supratentorial meningioma or supratentorial low grade gliomas are at significantly higher risk. There is little data on the efficacy of levetiracetam as a prophylactic AED in the immediate postoperative period (within 7 days of surgery) in these patients. Methods: We conducted a retrospective chart review of 165 adult patients classified as higher risk for postoperative seizures who underwent brain tumor resection at Duke University Hospital between time May 2010 and December 2011. All patients had received levetiracetam monotherapy in doses of 1000-3000 mg/day in the immediate postoperative period. Results: We identified 165 patients with following tumor locations: Frontal 83 (50.3%), Temporal 37 (22.4%), Parietal 30 (18.2%), Occipital 2 (1.2%) and 13 (7.8%) with single lesions involving more than one lobe. Histology revealed: Glioma 98 (59.4%), Meningioma 57 (34.5%) and Brain Metastases 6 (3.6%). Preoperatively, 88/165 (53.3%) patients had presented with seizures. 12/165 patients (7.3%) developed clinical seizures (generalized 10, partial 2) in the immediate post-operative period. Other than somnolence in 7 patients (4.2%), no major side-effects were noted. Conclusions: The incidence of seizures was significantly lower in patients treated with levetiracetam (7.3%) when compared with the expected (15-20%) rate without AED prophylaxis based on the previous literature. Levetiracetam appears effective and safe for seizure prevention in patients undergoing brain tumor resection and who are at significantly higher risk of developing post-operative seizures. These findings warrant confirmation in a prospective randomized trial.
Gokhale, Sankalp; Khan, Shariq Ali; Agrawal, Abhishek; Friedman, Allan H.; McDonagh, David L.
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: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.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.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?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?
Scharfman, Helen E.
Objectives To define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous intracerebral hemorrhage (ICH). Design Prospective cohort study. Setting Three tertiary care pediatric hospitals. Participants Seventy-three pediatric subjects with spontaneous ICH including 20 perinatal (?37 weeks gestation to 28 days) and 53 childhood subjects (>28 days to <18 years at presentation). Main outcome measures Acute symptomatic seizures (clinically evident and electrographic-only within 7 days), remote symptomatic seizures, and epilepsy. Results Acute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 (60%) perinatal and 19 (36%) childhood subjects, P=.07. Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9/32 (28%) with continuous EEG monitoring. One-and two-year remote symptomatic seizure-free survival were 82% (95% CI 68%–90%) and 67% (95% CI 46%–82%), respectively. One- and two-year epilepsy-free survival were 96% (95% CI 83%–99%) and 87% (95% CI 65%–95%), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy (P=.014, P=.025 and P=.0365, respectively log-rank test). Conclusions Presenting seizures are common in perinatal and childhood ICH. Continuous EEG may detect electrographic seizures in some subjects. Single remote symptomatic seizures occur in many, and development of epilepsy is estimated to occur in 13% at two-years. Elevated intracranial pressure requiring acute intervention is a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy.
Beslow, Lauren A; Abend, Nicholas S; Gindville, Melissa C; Bastian, Rachel A; Licht, Daniel J; Smith, Sabrina E; Hillis, Argye E.; Ichord, Rebecca N; Jordan, Lori C
Postictal values of prolactin, LH and FSH have been recorded in patients with both generalised tonic-clonic and partial seizures. Elevations of prolactin and LH were seen immediately and at 20 minutes in males and females with generalised attacks. At sixty minutes values for prolactin had fallen to baseline levels, but LH remained elevated. FSH values were increased in females only, at twenty and sixty minutes. Following partial seizures prolactin was elevated, especially with complex partial seizures, at twenty minutes. These results are discussed in the light of known electrophysiological mechanisms relating to partial seizures, and clinical guidelines for the use of neurohormonal tests in the evaluation of seizures are suggested.
Dana-Haeri, J; Trimble, M r; Oxley, J
Some antiepileptic drugs (AEDs) have been reported to aggravate generalized seizures. We have seen three children whose myoclonic seizures increased on starting treatment with Levetiracetam. In all seizures aggravation was temporally associated to the introduction of the drug. All became seizure-free on withdrawal of levetiracetam with a switch to an alternative antiepileptic drug and this persisted for at least 6 months. This suggests that some children with myoclonic seizures may have an aggravation on starting treatment with levetiracetam but this requires further studies. PMID:22990039
Liu, Yong-Hong; Wang, Xiao-Li; Deng, Yan-Chun; Zhao, Gang
Neonatal seizures are inherently different from seizures in the child and the adult. The phenotype, often exhibiting electroclinical dissociation, is unique: neonatal seizures can be refractory to antiepileptic drugs otherwise effect for older patients. Recent experimental and human-based research reveals that the mechanism of neonatal seizures, as well as their long-term sequelae on later brain development, appears to involve a large number of age-specific factors. These observations help explain the resistance of neonatal seizures to conventional therapy as well as identify potential areas of risk for later neurocognitive development. Emerging targets from this research may suggest new therapies for this unique population of patients.
Jensen, Frances E.
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.
Bithalamic infarctions initially presenting as a convulsive seizure are rarely reported and, to our best knowledge, have never been reported in China. Here, we present a patient with convulsive seizure at the onset of bilateral paramedian thalamic infarction. The diffusion-weighted imaging revealed that the infarct area is supplied by Percheron artery. Associated with the relationship between seizure and centrencephalic system and reticular formation as previously reported, we suggest that seizure could be the onset symptom of paramedian thalamic infarction. Physicians should recognize this condition, because both seizure control and early ischemic stroke management are required. PMID:23762679
Wang, Jianping; Fu, Xiaojie; Jiang, Chao; Liu, Hengfang; Zhao, Yuanzheng; Han, Wei
Bithalamic infarctions initially presenting as a convulsive seizure are rarely reported and, to our best knowledge, have never been reported in China. Here, we present a patient with convulsive seizure at the onset of bilateral paramedian thalamic infarction. The diffusion-weighted imaging revealed that the infarct area is supplied by Percheron artery. Associated with the relationship between seizure and centrencephalic system and reticular formation as previously reported, we suggest that seizure could be the onset symptom of paramedian thalamic infarction. Physicians should recognize this condition, because both seizure control and early ischemic stroke management are required.
Wang, Jianping; Fu, Xiaojie; Jiang, Chao; Liu, Hengfang; Zhao, Yuanzheng; Han, Wei
Stimulation of the vagus nerve has become an effective method for desynchronizing the highly coherent neural activity typically associated with epileptic seizures. This technique has been used in several animal models of seizures as well as in humans suffering from epilepsy. However, application of this technique has been limited to unilateral stimulation of the vagus nerve, typically delivered according to a fixed duty cycle, independently of whether ongoing seizure activity is present. Here, we report that stimulation of another cranial nerve, the trigeminal nerve, can also cause cortical and thalamic desynchronization, resulting in a reduction of seizure activity in awake rats. Furthermore, we demonstrate that providing this stimulation only when seizure activity begins results in more effective and safer seizure reduction per second of stimulation than with previous methods. Seizure activity induced by intraperitoneal injection of pentylenetetrazole was recorded from microwire electrodes in the thalamus and cortex of awake rats while the infraorbital branch of the trigeminal nerve was stimulated via a chronically implanted nerve cuff electrode. Continuous unilateral stimulation of the trigeminal nerve reduced electrographic seizure activity by up to 78%, and bilateral trigeminal stimulation was even more effective. Using a device that automatically detects seizure activity in real time on the basis of multichannel field potential signals, we demonstrated that seizure-triggered stimulation was more effective than the stimulation protocol involving a fixed duty cycle, in terms of the percent seizure reduction per second of stimulation. In contrast to vagus nerve stimulation studies, no substantial cardiovascular side effects were observed by unilateral or bilateral stimulation of the trigeminal nerve. These findings suggest that trigeminal nerve stimulation is safe in awake rats and should be evaluated as a therapy for human seizures. Furthermore, the results demonstrate that seizure-triggered trigeminal nerve stimulation is technically feasible and could be further developed, in conjunction with real-time seizure-predicting paradigms, to prevent seizures and reduce exposure to nerve stimulation. PMID:11050139
Fanselow, E E; Reid, A P; Nicolelis, M A
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
To describe early symptomatic and late seizures in a cohort of patients with acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their determinants, we performed a prospective registry and follow-up study of CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were more frequent in patients with motor and sensory deficits and in those with focal oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%) patients had late seizures, which were multiple in 4 (4.8%). Late seizures were more frequent in patients with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither early symptomatic seizures nor late seizures were related to functional prognosis at the last follow-up (median = 1 year). There is a moderate risk of seizure recurrence early in the course and during the first year after CVDST. Seizures can be a cause of acute death, but might not have an independent influence on functional outcome. Pharmacological prevention of seizures after CVDST should probably be limited to patients with early symptomatic seizures and cerebral lesions on admission CT/MR. PMID:12499715
Ferro, J M; Correia, M; Rosas, M J; Pinto, A N; Neves, G
Background Mesial temporal lobe epilepsy (mTLE) has been suggested to follow a circadian rhythm. Previous research found an afternoon peak in mTLE seizure occurrence. We evaluated the pattern of seizure occurrence in patients with well-localized mTLE and hypothesized that peak seizure frequency would occur in the afternoon, and that this pattern would not be altered by age, gender, or seizure focus. Methods We retrospectively identified consecutive mTLE patients with a seizure-free outcome following anterior temporal lobectomy from 1993-2004 with video-EEG captured seizures. We recorded and plotted the 24-hour clock time for each seizure and performed cosinor analysis. SAS Proc GLIMMIX was used to fit the linearized transform of the cosinor model. Negative binomial regression fitted by the generalized estimating equations (GEE) method was also performed to estimate and compare the mean seizure rates over a 24-hour day. Results Sixty mTLE patients monitored between 2-16 days were analyzed. Mean (standard deviation), median number of seizures per subject were 10.47(7.86), 9.00. Cosinor plots indicated that the function had two modes: 7-8 a.m. and 4-5 p.m. GEE analysis was consistent with peak seizure frequency occurrence at 6-8 a.m. (p<0.0001) and 3-5 p.m. (p<0.01). Conclusions We found a bimodal pattern of seizure occurrence in human mTLE, with peak seizure frequencies occurring between 6-8 a.m. and 3-5 p.m. confirming an afternoon peak, as well as a previously unsuspected morning peak in seizure occurrence that provides rationale for future investigations of antiepileptic drug chronopharmacology and informs patient counseling regarding patterns of seizure occurrence.
Karafin, Matthew; St. Louis, Erik K.; Zimmerman, M. Bridget; Sparks, Jon David; Granner, 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.
Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1? (IL-1?) and high mobility group B1 (HMGB1) in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1? or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1? reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-? or HMGB1 local applications. These findings demonstrate that both IL-1? and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.
Chiavegato, Angela; Zurolo, Emanuele; Losi, Gabriele; Aronica, Eleonora; Carmignoto, Giorgio
This document presents expressions for modeling the detection threshold for narrowband and broadband passive sonars using either power or amplitude detection, cross correlation sonars, CW and FM active sonars with or without replica correlation, as well a...
R. L. Dawe
Mice deficient for CELF4, a neuronal RNA-binding protein, have a complex seizure disorder that includes both convulsive and non-convulsive seizures, and is dependent upon Celf4 gene dosage and mouse strain background. It was previously shown that Celf4 is expressed predominantly in excitatory neurons, and that deficiency results in abnormal excitatory synaptic neurotransmission. To examine the physiological and molecular basis of this, we studied Celf4-deficient neurons in brain slices. Assessment of intrinsic properties of layer V cortical pyramidal neurons showed that neurons from mutant heterozygotes and homozygotes have a lower action potential (AP) initiation threshold and a larger AP gain when compared with wild-type neurons. Celf4 mutant neurons also demonstrate an increase in persistent sodium current (INaP) and a hyperpolarizing shift in the voltage dependence of activation. As part of a related study, we find that CELF4 directly binds Scn8a mRNA, encoding sodium channel Nav1.6, the primary instigator of AP at the axon initial segment (AIS) and the main carrier of INaP. In the present study we find that CELF4 deficiency results in a dramatic elevation in the expression of Nav1.6 protein at the AIS in both null and heterozygous neurons. Together these results suggest that activation of Nav1.6 plays a crucial role in seizure generation in this complex model of neurological disease.
Sun, Wenzhi; Wagnon, Jacy L; Mahaffey, Connie L; Briese, Michael; Ule, Jernej; Frankel, Wayne N
We present a multistage fuzzy rule-based algorithm for epileptic seizure onset detection. Amplitude, frequency, and entropy-based features were extracted from intracranial electroencephalogram (iEEG) recordings and considered as the inputs for a fuzzy system. These features extracted from multichannel iEEG signals were combined using fuzzy algorithms both in feature domain and in spatial domain. Fuzzy rules were derived based on experts' knowledge and reasoning. An adaptive fuzzy subsystem was used for combining characteristics features extracted from iEEG. For the spatial combination, three channels from epileptogenic zone and one from remote zone were considered into another fuzzy subsystem. Finally, a threshold procedure was applied to the fuzzy output derived from the final fuzzy subsystem. The method was evaluated on iEEG datasets selected from Freiburg Seizure Prediction EEG (FSPEEG) database. A total of 112.45 hours of intracranial EEG recordings was selected from 20 patients having 56 seizures was used for the system performance evaluation. The overall sensitivity of 95.8% with false detection rate of 0.26 per hour and average detection latency of 15.8 seconds was achieved.
Rabbi, Ahmed Fazle; Fazel-Rezai, Reza
Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.
Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.
Objective To investigate the feasibility of using noninvasive EEG source imaging approach to image continuous seizure activity in pediatric epilepsy patients. Methods Nine pediatric patients with medically intractable epilepsy were included in this study. Eight of the patients had extratemporal lobe epilepsy and one had temporal lobe epilepsy. All of the patients underwent resective surgery and seven of them underwent intracranial EEG (iEEG) monitoring. The ictal EEG was analyzed using a noninvasive dynamic seizure imaging (DSI) approach. The DSI approach separates scalp EEGs into independent components and extracts the spatio-temporal ictal features to achieve dynamic imaging of seizure sources. Surgical resection and intracranial recordings were used to validate the noninvasive imaging results. Results The DSI determined seizure onset zones (SOZs) in these patients were localized within or in close vicinity to the surgically resected region. In the seven patients with intracranial monitoring, the estimated seizure onset sources were concordant with the seizure onset zones of iEEG. The DSI also localized the multiple foci involved in the later seizure propagation, which were confirmed by the iEEG recordings. Conclusions Dynamic seizure imaging can noninvasively image the seizure activations in pediatric patients with both temporal and extratemporal lobe epilepsy. Significance EEG seizure imaging can potentially be used to noninvasively image the SOZs and aid the pre-surgical planning in pediatric epilepsy patients.
Lu, Yunfeng; Yang, Lin; Worrell, Gregory A.; Brinkmann, Benjamin; Nelson, Cindy; He, Bin
Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769
Holm, Ingrid A; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R; Kinney, Hannah C; Krous, Henry F
Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians.
Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.
Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes. PMID:24374407
Pallud, Johan; Audureau, Etienne; Blonski, Marie; Sanai, Nader; Bauchet, Luc; Fontaine, Denys; Mandonnet, Emmanuel; Dezamis, Edouard; Psimaras, Dimitri; Guyotat, Jacques; Peruzzi, Philippe; Page, Philippe; Gal, Beatriz; Párraga, Eduardo; Baron, Marie-Hélène; Vlaicu, Michaela; Guillevin, Rémy; Devaux, Bertrand; Duffau, Hugues; Taillandier, Luc; Capelle, Laurent; Huberfeld, Gilles
In order to observe the pattern of behaviour, the underlying Stressors and possible association with psychosocial factors\\u000a in Pediatric Non-Epileptic Seizure (NES); 22 children with unusual feature of poor control of their symptoms were studied.\\u000a Detailed historical account, examination including psychiatric evaluation, EEG and CT Scan in all and video recording with\\u000a provocative procedures were done wherever feasible. Ten males
S. K. Tamer
Objective : To characterize non-epileptic seizures (NES) in the elderly and compare their features with NES of a younger control group. Methods : The database of the epilepsy monitoring unit of the Cleveland Clinic Foundation (CCF) was searched for patients aged 60 years and older having undergone long-term video-\\/EEG monitoring between 1994 and 2002,with the subsequent diagnosis of NES. Videotapes
Christoph Kellinghaus; Tobias Loddenkemper; Dudley S. Dinner; Deepak Lachhwani; Hans O. Lüders
A previously unreported epileptic condition characterised by onset before 6 months of age, nearly continuous electroencephalographic seizures involving multiple independent areas originating in both hemispheres, no identifiable cause, and poor outcome has been described by Coppola et al. We report three cases presenting the same clinical and EEG pictures. They show a peculiar epileptic condition unlike the other early epileptogenic encephalopathies, so they may represent a new infantile epileptic syndrome. PMID:11395285
Veneselli, E; Perrone, M V; Di Rocco, M; Gaggero, R; Biancheri, R
The kccDHS1 allele of kazachoc (kcc) was identified as a seizure-enhancer mutation exacerbating the bang-sensitive (BS) paralytic behavioral phenotypes of several seizure-sensitive Drosophila mutants. On their own, young kccDHS1 flies also display seizure-like behavior and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. The product of kcc shows substantial homology to KCC2, the mammalian neuronal K+–Cl? cotransporter. The kccDHS1 allele is a hypomorph, and its seizure-like phenotype reflects reduced expression of the kcc gene. We report here that kcc functions as a K+–Cl? cotransporter when expressed heterologously in Xenopus laevis oocytes: under hypotonic conditions that induce oocyte swelling, oocytes that express Drosophila kcc display robust ion transport activity observed as a Cl?-dependent uptake of the K+ congener 86Rb+. Ectopic, spatially restricted expression of a UAS-kcc+ transgene was used to determine where cotransporter function is required in order to rescue the kccDHS1 BS paralytic phenotype. Interestingly, phenotypic rescue is largely accounted for by targeted, circumscribed expression in the mushroom bodies (MBs) and the ellipsoid body (EB) of the central complex. Intriguingly, we observed that MB induction of kcc+ functioned as a general seizure suppressor in Drosophila. Drosophila MBs have generated considerable interest especially for their role as the neural substrate for olfactory learning and memory; they have not been previously implicated in seizure susceptibility. We show that kccDHS1 seizure sensitivity in MB neurons acts via a weakening of chemical synaptic inhibition by GABAergic transmission and suggest that this is due to disruption of intracellular Cl? gradients in MB neurons.
Hekmat-Scafe, Daria S.; Mercado, Adriana; Fajilan, Adriel A.; Lee, Ann W.; Hsu, Richard; Mount, David B.; Tanouye, Mark A.
Electroconvulsive therapy (ECT) has unparalleled antidepressant efficacy, but its cognitive side effects may be persistent. Research suggests that the side effects may be at least partially dissociable from the therapeutic effects of ECT, suggesting that distinct cortical networks may underlie them and introducing a role for focal seizure induction as a means of minimizing side effects. In magnetic seizure therapy (MST), magnetic fields avoid tissue impedance and induce electrical currents confined to superficial cortex, facilitating focal seizure induction. The translational development strategy for MST has included: (1) device development, (2) feasibility in animals and initial human trials, (3) testing in nonhuman primates on safety and mechanisms of action (with neuroanatomical, neurophysiological and cognitive endpoints), (4) safety testing in patients, (5) initial efficacy testing in patients, (6) dosage optimization, and (7) randomized comparison with ECT. These stages have been iterative, with results of early clinical testing prompting device enhancements that were, in turn, tested in nonhuman primates prior to human trials. Safety testing was aided by development of a nonhuman primate model of human ECT, and the validation of a cognitive battery for the monkey that is sensitive to the range of effects of ECT on human memory. Human testing has been facilitated by the development of an international consortium of centers addressing various aspects of technique and dose/response relationships. Challenges facing MST are common to other device based therapies: characterizing dose/response relationships, optimizing efficacy, and developing efficient and reliable methods to induce lasting therapeutic change in the circuitry underlying depression.
Rowny, Stefan; Benzl, Karla; Lisanby, Sarah H.
Patients with ecstatic epileptic seizures report an altered consciousness, which they describe as a sense of heightened perception of themselves – they “feel very present” – and an increased vividness of sensory perceptions. Recently, the anterior insula has been proposed as the region where these seizures originate, based on the results of ictal nuclear imaging in three patients, the first induction of ecstatic auras by electrical stimulation, and the functional characteristics of the anterior insula in neuroimaging literature. Specifically, the anterior insula is thought to play a key role in integrating information from within the body, the external world, as well as the emotional states. In addition, the anterior insula is thought to convert this integrated information into successive global emotional moments, thus enabling both the construct of a sentient self as well as a mechanism for predictive coding. As part of the salience network, this region is also involved in switching from mind wandering toward attentional and executive processing. In this review, we will summarize previous patient reports and recap how insular functioning may be involved in the phenomenon of ecstatic seizures. Furthermore, we will relate these hypotheses to the results from research on meditation and effects of drug abuse. PMID:24436968
Picard, Fabienne; Kurth, Florian
Flint Hills Scientific, L.L.C. (FHS) has invented what is believed to be the first real-time epileptic seizure detection and short-term prediction method in the world. They have demonstrated an IBM PC prototype with a multi-channel EEG monitoring configuration. This CRADA effort applied AlliedSignal FM and T hardware design, manufacturing miniaturization, and high quality manufacturing expertise in converting the prototype into a small, portable, self-contained, multi-channel EEG epileptic seizure detection and warning device. The purpose of this project was to design and build a proof-of-concept miniaturized prototype of the FHS-developed PC-based prototype. The resultant DSP prototype, measuring 4'' x 6'' x 2'', seizure detection performance compared favorably with the FHS PC prototype, thus validating the DSP design goals. The very successful completion of this project provided valuable engineering information for FHS for future prototype commercialization as well as providing AS/FM and T engineers DSP design experience.
Elarton, J.K.; Koepsel, K.L.
This work presents a new method that combines symbol dynamics methodologies with an Ngram algorithm for the detection and prediction of epileptic seizures. The presented approach specifically applies Ngram-based pattern recognition, after data pre-processing, with similarity metrics, including the Hamming distance and Needlman-Wunsch algorithm, for identifying unique patterns within epochs of time. Pattern counts within each epoch are used as measures to determine seizure detection and prediction markers. Using 623 hours of intracranial electrocorticogram recordings from 21 patients containing a total of 87 seizures, the sensitivity and false prediction/detection rates of this method are quantified. Results are quantified using individual seizures within each case for training of thresholds and prediction time windows. The statistical significance of the predictive power is further investigated. We show that the method presented herein, has significant predictive power in up to 100% of temporal lobe cases, with sensitivities of up to 70–100% and low false predictions (dependant on training procedure). The cases of highest false predictions are found in the frontal origin with 0.31–0.61 false predictions per hour and with significance in 18 out of 21 cases. On average, a prediction sensitivity of 93.81% and false prediction rate of approximately 0.06 false predictions per hour are achieved in the best case scenario. This compares to previous work utilising the same data set that has shown sensitivities of up to 40–50% for a false prediction rate of less than 0.15/hour.
Eftekhar, Amir; Juffali, Walid; El-Imad, Jamil; Constandinou, Timothy G.; Toumazou, Christofer
Absence seizures are characterized by bilateral spike-and-wave discharges (SWDs) in thalamo-cortical circuits. In view of clinical studies indicating a critical involvement of intralaminar thalamic nuclei, we thought it timely to characterize the specific role and activity patterns of the respective neurons. Electrocorticographic (ECoG), intracellular, and unit activity recordings were performed in vivo from intralaminar thalamic neurons of the centrolateral (CL) and the paracentral (PC) thalamic nucleus in an established genetic rat model of absence epilepsy (WAG/Rij). Neurons in PC are depolarized to produce tonic series of action potentials at seizure-free episodes, and are rhythmically silenced concomitant with SWDs in a spike-locked manner. Rebound from spike-locked inhibition is associated with a transient increase in action potential activity. Neurons in CL possess a relatively negative membrane potential with overall low electrogenic activity at seizure-free episodes and generate burst-like discharges during SWDs that are locked to the decaying phase of the spike component on the ECoG. The SWD-locked membrane responses reverse close to the presumed chloride equilibrium potential, indicating GABA(A) receptor-mediated inhibitory postsynaptic potentials (IPSPs), with cell-type specific differences in polarity. In PC neurons, hyperpolarizing IPSPs result in spike-locked silencing of tonic firing and rebound burst discharges, while in CL neurons, IPSPs are depolarizing and trigger low-threshold burst firing likely mediated by a t-type Ca(2+) conductance. These data show a unique pattern of rhythmic SWD-locked IPSPs in PC and CL associated with paroxysms apt to impose a transient dysfunctional state to thalamo-striato-prefrontocortical networks during absence seizures. PMID:21458572
Gorji, Ali; Mittag, Christoph; Shahabi, Parviz; Seidenbecher, Thomas; Pape, Hans-Christian
Reorganization of seizure networks during epileptogenesis involves cortico-subcortical and interhemispheric interactions. In the audiogenic kindling (AK) model of generalized tonic-clonic seizures, upstream seizure propagation along ascending brainstem-to-forebrain pathways determines progressive intensification of repeated sound-induced convulsions. Full-blown audiogenic seizures are bilaterally symmetric and their repetition results in bisynchronous recruiting the cortex in secondary epileptogenesis. The present study describes lateral asymmetry of initial behavioral and EEG manifestations of audiogenic seizures and AK in Wistar and WAG/Rij rats with acoustic hypersensitivity. These rats exhibit consistent individual lateralization of running seizures (run directionality) induced by repeated binaural stimulation. Since this initial preconvulsive running reflects seizure onset in the auditory brainstem, the running asymmetry suggests non-symmetric early epileptic activation of brainstem substrates by sound in these rats. Repetition of the asymmetric brainstem seizures led to asynchronous recruiting the cortex into seizure network and lateralization of running seizures was predictive for asymmetry of early cortical seizure manifestations in Wistar and WAG/Rij rats. Both electrographic markers of AK, spreading depression (SD) and post-running afterdischarge, first appeared in the cortex ipsilateral to run direction, suggesting lateralized brainstem-to-forebrain seizure generalization during AK. At the population level, no bias in lateralization of running and SD was found in Wistar and WAG/Rij rats but incidence of secondary cortical seizures varied, depending on strain and run laterality. Among Wistar rats, cortical seizures developed more rarely in right-runners than in left-runners, suggesting enhanced resistance of the right hemisphere to epileptogenesis in rats of this strain. WAG/Rij rats with mixed (absence and audiogenic) epilepsy showed weak lateralization of early cortical seizures and no left-right difference in their incidence during AK. Present findings suggest (1) lateralized brainstem-to-forebrain seizure propagation and hemispheric difference in its facility in Wistar rats, (2) alterations of intra- and interhemispheric seizure propagation in WAG/Rij rats with genetic absence epilepsy. PMID:22525136
Vinogradova, L V; Shatskova, A B
Wet dog shakes (WDS) and head shakes (HS) are associated with experimentally induced convulsive seizures. We sought to determine whether these behaviors are correlated or not with major (status epilepticus (SE) or fully kindled animals) or minor (non-SE or partially kindled animals) seizure severity. WDS are directly correlated with SE induced by intracerebral star fruit extract (Averrhoa carambola) injection and with kindled animals in the amygdala fast kindling model. On the other hand, WDS are inversely correlated with SE induced by intracerebral bicuculline and pilocarpine injections. Systemic pilocarpine in animals pretreated with methyl-scopolamine barely induced WDS or HS. The role of shaking behaviors may vary from ictal to anticonvulsant depending on the experimental seizure model, circuitries involved, and stimulus intensity. The physical presence of acrylic helmets may per se inhibit the HS response. Also, methyl-scopolamine, a drug incapable of crossing the blood-brain barrier, can induce HS in animals without acrylic helmets. PMID:15820339
Rodrigues, Marcelo Cairrão Araújo; Rossetti, Franco; Foresti, Maira Licia; Arisi, Gabriel Maisonnave; Furtado, Márcio Araújo; Dal-Cól, Maria Luiza Cleto; Bertti, Poliana; Fernandes, Artur; Santos, Francisco Leite; Del Vecchio, Flávio; Garcia-Cairasco, Norberto
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
Aims: To describe a large series of children with anoxic-epileptic seizures (AES)—that is, epileptic seizures induced by syncopes. Methods: Retrospective case-note review in a tertiary paediatric neurology unit. For all 27 children seen with a definite diagnosis of AES between 1972 and 2002, a review of clinical histories, videotapes, and EEG/ECG studies was undertaken. Main outcome measures were: age of onset, frequency and type of syncopes; age of onset and frequency of AES; type and duration of induced epileptic seizures; effect of treatment of syncopal and epileptic components. Results: Median age of onset of syncopes was 8 months (range 0.2–120), frequency 2 in total to 40/day, median total ?200. Syncopes were predominantly reflex asystolic (RAS), prolonged expiratory apnoea (cyanotic breath-holding spells), or of mixed or uncertain origin; there was one each of ear piercing and hair grooming vasovagal syncope and one of compulsive Valsalva. Median age of onset of AES was 17 months (range 7–120), frequency from total 1 to 3/day, median total 3. The epileptic component was almost always bilateral clonic; three had additional epilepsy, one each with complex partial seizures, myoclonic absences, and febrile seizures plus. Median duration of epileptic component was 5 minutes (range 0.5–40, mean 11). Cardiac pacing prevented RAS in two patients: most other anti-syncope therapies were ineffective. Diazepam terminated the epileptic component in 6/8. Valproate or carbamazepine abolished AES in 5/7 without influencing syncope frequency. Conclusions: Although uncommon compared with simple syncopes, syncope triggered epileptic seizures (AES) are an important treatable basis of status epilepticus.
Horrocks, I; Nechay, A; Stephenson, J; Zuberi, S
We recorded occipitotemporal seizures induced by intermittent photic stimulation in three children with brain injuries, aged 10 to 13 years. All had a history of seizures and showed occipital spikes on EEG, but were seizure free and were not being treated at the time of investigation. In all, photic stimulation induced seizures in the right occipital lobe. They were followed by clinical and EEG signs suggesting infrasylvian spreading to ipsilateral mesiotemporal limbic structures and by vomiting, appearing at late stages of the attacks. Seizure spread was very slow in two patients in whom attacks lasted 16 and 25 minutes. Patients with occipital epileptiform abnormalities presenting with ictal vomiting are often diagnosed as having vague migraine-epilepsy syndromes. We conclude that vomiting can be a late ictal phenomenon resulting from temporal lobe spread of seizures originating in the occipital lobe. PMID:8309569
Guerrini, R; Ferrari, A R; Battaglia, A; Salvadori, P; Bonanni, P
Seizures are one of the most common pediatric neurologic disorders. Many complications secondary to seizures have been described in the literature including head trauma, fractures, drowning and burns. However, to the best of our knowledge, rupture of the myotendinous insertion of the temporalis muscle on the mandible secondary to a seizure has never been described in the literature. We report the case of a unilateral temporalis muscle rupture in a 16-year-old boy who developed unilateral facial swelling following new onset tonic-clonic seizures. We emphasize on the computed tomography and magnetic resonance imaging findings in this case report. Two mechanisms have been proposed to explain such an injury. The favored mechanism in our patient is a pull on the temporalis myotendinous insertion on the mandible following vigorous and brisk deviation of the head and neck during seizure. Radiologists should be familiar with this type of injury following seizures in order to prevent misdiagnosis and subsequently mistreatment.
Naffaa, Lena N; Tandon, Yasmeen K; Rubin, Michael
Seizures are one of the most common pediatric neurologic disorders. Many complications secondary to seizures have been described in the literature including head trauma, fractures, drowning and burns. However, to the best of our knowledge, rupture of the myotendinous insertion of the temporalis muscle on the mandible secondary to a seizure has never been described in the literature. We report the case of a unilateral temporalis muscle rupture in a 16-year-old boy who developed unilateral facial swelling following new onset tonic-clonic seizures. We emphasize on the computed tomography and magnetic resonance imaging findings in this case report. Two mechanisms have been proposed to explain such an injury. The favored mechanism in our patient is a pull on the temporalis myotendinous insertion on the mandible following vigorous and brisk deviation of the head and neck during seizure. Radiologists should be familiar with this type of injury following seizures in order to prevent misdiagnosis and subsequently mistreatment. PMID:24976940
Naffaa, Lena N; Tandon, Yasmeen K; Rubin, Michael
The sensitivity of the Seizure Severity Questionnaire (SSQ) was evaluated using pooled data from open-label extensions of two clinical trials in patients with partial-onset seizures. The SSQ includes questions relating to frequency and helpfulness of warning signs as well as frequency, severity, and bothersomeness of ictal and postictal effects. Differences between mean change from baseline for each SSQ item for responders and nonresponders were described and compared between patients solely with complex partial seizures (CPSs: responders, n=166; nonresponders, n=127) and those solely with secondarily generalized partial seizures (SGPSs: responders, n=26; nonresponders, n=24) at baseline. Seizure Severity Questionnaire total score and individual SSQ items related to ictal movement, consciousness, bothersomeness of postictal effects, and frequency of postictal emotional effects showed differentiation between seizure type responders. These data provide further validation of the SSQ by demonstrating its sensitivity in describing treatment effects. PMID:24275520
Borghs, Simon; de la Loge, Christine; Brabant, Yves; Cramer, Joyce
Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Nav1.1 VGSC ?-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Electrophysiological analyses of DS and GEFS+ mouse models have led to the hypothesis that SCN1A mutations reduce the excitability of inhibitory cortical and hippocampal interneurons. To more directly examine the relative contribution of inhibitory interneurons and excitatory pyramidal cells to SCN1A-derived epilepsy, we first compared the expression of Nav1.1 in inhibitory parvalbumin (PV) interneurons and excitatory neurons from P22 mice using fluorescent immunohistochemistry. In the hippocampus and neocortex, 69% of Nav1.1 immunoreactive neurons were also positive for PV. In contrast, 13% and 5% of Nav1.1 positive cells in the hippocampus and neocortex, respectively, were found to co-localize with excitatory cells identified by CaMK2? immunoreactivity. Next, we reduced the expression of Scn1a in either a subset of interneurons (mainly PV interneurons) or excitatory cells by crossing mice heterozygous for a floxed Scn1a allele to either the Ppp1r2-Cre or EMX1-Cre transgenic lines, respectively. The inactivation of one Scn1a allele in interneurons of the neocortex and hippocampus was sufficient to reduce thresholds to flurothyl- and hyperthermia-induced seizures, whereas thresholds were unaltered following inactivation in excitatory cells. Reduced interneuron Scn1a expression also resulted in the generation of spontaneous seizures. These findings provide direct evidence for an important role of PV interneurons in the pathogenesis of Scn1a-derived epilepsies.
Dutton, Stacey B.; Makinson, Christopher D.; Papale, Ligia A.; Shankar, Anupama; Balakrishnan, Bindu; Nakazawa, Kazu; Escayg, Andrew
A system and method for predicting and avoiding a seizure in a patient. The system and method includes use of an implanted surface acoustic wave probe and coupled RF antenna to monitor temperature of the patient's brain, critical changes in the temperature characteristic of a precursor to the seizure. The system can activate an implanted cooling unit which can avoid or minimize a seizure in the patient.
Gopalsami, Nachappa (Naperville, IL); Kulikov, Stanislav (Sarov, RU); Osorio, Ivan (Leawood, KS); Raptis, Apostolos C. (Downers Grove, IL)
Generalized seizures during Interferon-alpha (IFN-?) therapy have been repeatedly described in about 1%–4% of patients. However, the mechanisms underlying IFN-? induced seizures are not known. We describe a patient who developed partial and secondary generalized seizures during IFN-? therapy while displaying a focal disruption of her blood-brain barrier (BBB) corresponding with pathological electroencephalography (EEG). To test our hypothesis that IFN-?
Uwe Heinemann; Akiva Korn; Haim Golan; Alon Friedman
\\u000a Seizures after cardiopulmonary arrest are a common problem in the intensive care unit, occurring in as many as one-third of\\u000a these patients during hospitalization. The etiology, treatment, and prognostic importance of seizures in this setting have\\u000a not been well delineated in the literature. Whether seizures exacerbate global hypoxic–ischemic brain injury in humans remains\\u000a unclear, which raises uncertainty about how aggressively
Matthew A. Koenig; Romergryko Geocadin
Seizures after cardiopulmonary arrest are a common problem in the intensive care unit, occurring in as many as one-third of\\u000a these patients during their hospitalization. The etiology, treatment, and prognostic importance of seizures in this setting\\u000a have not been well-delineated in the literature. Whether seizures exacerbate global hypoxic-ischemic brain injury in humans\\u000a remains unclear, which raises uncertainty about how aggressively
Matthew A. Koenig; Romergryko Geocadin
This research discloses methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming. 76 figs.
Hively, L.M.; Clapp, N.E.; Day, C.S.; Lawkins, W.F.
Seizures caused by ingestion of drugs and toxins require specific treatment aiming to terminate epileptiform activity and\\u000a to eliminate the toxin. Withdrawal from regularly ingested drugs can also be accompanied by seizures requiring admission to\\u000a an intensive care unit. This chapter discusses diagnostic and therapeutic particulars of seizures induced by illicit drugs\\u000a of abuse, environmental toxins, and heavy metals.
Andreas R. Luft
\\u000a Seizures caused by ingestion of drugs and toxins do require specific treatment aiming to terminate epileptiform activity and\\u000a to eliminate the toxin. Withdrawal from regularly ingested drugs can also be accompanied by seizures requiring ICU care. This\\u000a chapter discusses diagnostic and therapeutic particularities of seizures induced by illicit drugs of abuse, environmental\\u000a toxins, and heavy metals.
Andreas R. Luft
\\u000a Working with children with epilepsy is like reading a good mystery. When learning or emotional problems occur, the neuropsychologist\\u000a 's job is to help identify “whodunit.” The list of likely suspects from the epilepsy perspective include whatever is atypical\\u000a about the brain that is the basis of the seizures, seizures themselves, abnormal electrical discharges between seizures (also\\u000a known as sub-clinical
Lynn Bennett Blackburn
Methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming.
Hively, Lee M. (Knoxville, TN); Clapp, Ned E. (Knoxville, TN); Daw, C. Stuart (Knoxville, TN); Lawkins, William F. (Knoxville, TN)
Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients’ quality of life.
Englot, Dario J.; Blumenfeld, Hal
Numerous orthopaedic injuries can follow a seizure and are often diagnosed late. This is the first documented case of a missed bilateral anterior shoulder dislocation following a seizure. The possible reasons for the greater incidence of posterior dislocations are examined and why bilateral anterior dislocations following a seizure are so rare. The article discusses the reasons for the delay and highlights potential pitfalls and learning points for junior emergency department doctors.
O'Connor-Read, Laurence; Bloch, Benjamin; Brownlow, Harry
Studies of human seizure disorders have revealed that susceptibility to seizures is greatly influenced by genetic factors. In addition to causing epilepsy, genetic factors can suppress seizures and epileptogenesis. Examination of seizure-suppressor genes is challenging in humans. However, such genes are readily identified and analyzed in a Drosophila animal model of epilepsy. In this article, the epilepsy phenotype of Drosophila seizure-sensitive mutants is reviewed. A novel class of genes called seizure-suppressors is described. Mutations defining suppressors revert the “epilepsy” phenotype of neurological mutants. We conclude this review with particular discussion of a seizure-suppressor gene encoding DNA topoisomerase I (top1). Mutations of top1 are especially effective at reverting the seizure-sensitive phenotype of Drosophila epilepsy mutants. In addition, an unexpected class of anti-epileptic drugs has been identified. These are DNA topoisomerase I inhibitors such as camptothecin and its derivatives; several candidates are comparable or perhaps better than traditional anti-epileptic drugs such as valproate at reducing seizures in Drosophila drug-feeding experiments.
Song, Juan; Tanouye, Mark A.
Seizures induce excitatory shifts in the reversal potential for GABAA receptor-mediated responses, which may contribute to the intractability of electroencephalographic seizures and preclude the efficacy of widely-used GABAergic anticonvulsants such as phenobarbital. We now report that in intact hippocampi prepared from neonatal rats and transgenic mice expressing Clomeleon, recurrent seizures progressively increase the intracellular chloride concentration ([Cl?]i) assayed by Clomeleon imaging and invert the net effect of GABAA receptor activation from inhibition to excitation assayed by the frequency of action potentials and intracellular Ca2+ transients. These changes correlate with increasing frequency of seizure-like events and reduction in phenobarbital efficacy. The Na+-K+-2Cl? (NKCC1) co-transporter blocker bumetanide inhibited seizure-induced neuronal Cl? accumulation and the consequent facilitation of recurrent seizures. Our results demonstrate a novel mechanism by which seizure activity leads to [Cl?]i accumulation, thereby increasing the probability of subsequent seizures. This provides a potential mechanism for the early crescendo phase of neonatal seizures.
Dzhala, Volodymyr I.; Kuchibhotla, Kishore V.; Glykys, Joseph C.; Kahle, Kristopher T.; Swiercz, Waldemar B.; Feng, Guoping; Kuner, Thomas; Augustine, George J.; Bacskai, Brian J.; Staley, Kevin J.
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 neonates had drug refractory seizures and demonstrated similarities in electro-clinical pattern, clinical course and outcome. Their seizures started with tonic posturing and after 10-20s tonic posturing was superimposed by focal or multifocal cloni or myocloni. Ictal EEG started with voltage attenuation followed by bilateral or alternating focal epileptic discharges. The interictal EEG was abnormal. One child died, while the other three children became seizure free but had severe motor delay and mental retardation. In one of those three children, a de novo missense mutation was detected in the voltage gated potassium channel gene KCNQ2, indicating a genetic relationship between drug refractory neonatal seizures of unknown etiology with tonic clonic or myoclonic sequences and the well-known syndrome of benign familial neonatal convulsions (BFNC). PMID:16039833
Schmitt, Bernhard; Wohlrab, Gabriele; Sander, Thomas; Steinlein, Ortrud K; Hajnal, Beatrice Latal
Neonatal seizures caused by hypoxia can be refractory to conventional anticonvulsants. Currently, there is no effective postnatal intervention for newborn infants with hypoxic encephalopathy to prevent brain injury and long-term neurologic sequelae. We previously developed a rat model of perinatal hypoxia-induced seizures with subsequent long-term increases in seizure susceptibility and showed that these epileptogenic effects are selectively blocked by the alpha-amino-3-hydoxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione. Using this model of perinatal seizures, we evaluated the efficacy of topiramate, a structurally novel anticonvulsant drug recently shown to attenuate AMPA/kainate currents. Topiramate effectively suppressed acute seizures induced by perinatal hypoxia in a dose-related manner with a calculated ED50 of 2.1 mg/kg, i.p. Furthermore, in animals that had seizures suppressed by topiramate during acute hypoxia, there were no long-term increases in susceptibility to kainate-induced seizures and seizure-induced neuronal injury. Our results suggest that topiramate may have clinical potential as a therapeutic agent for refractory seizures in human neonates. PMID:11558793
Koh, S; Jensen, F E
BACKGROUND Long QT is a cardiac electrical disorder. One of the symptoms of long QT caused by fatal ventricular arrhythmia is seizure. In some studies it was indicated that up to 35% of seizures induced by long QT may be misdiagnosed as other causes of seizure. METHODS In a case-control study, patients experiencing primary seizure with unknown etiology and referring for clinical diagnosis were selected as the case group. The control group consisted of patients hospitalized for other reasons except seizure. Corrected QT Interval (QTc) was measured for each patient on an electrocardiogram, and the two groups were compared. Long QT was defined as a QT more than 0.46 seconds. RESULTS Among 508 subjects who were recruited in this study 254 children were in the case group and 254 were in the control group. There were 66 children experiencing seizure and long QT in the case group. In the control group, 48 children with long QT were observed; the difference was statistically significant (P = 0.02). Syncope and sudden death were not significantly different between the two groups. CONCLUSION The present study showed that children with unknown causes of seizure have more frequently long QTc, which implies the possibility of an arrhythmic origin of some seizures. Therefore, it is advised to get an electrocardiography for patients with unknown causes of seizure.
Sadrnia, Saeid; Yousefi, Parsa; Jalali, Leila
Abrupt cessation of alcohol intake after prolonged heavy drinking may trigger alcohol withdrawal seizures. Generalized tonic-clonic seizures are the most characteristic and severe type of seizure that occur in this setting. Generalized seizures also occur in rodent models of alcohol withdrawal. In these models, the withdrawal seizures are triggered by neuronal networks in the brainstem, including the inferior colliculus; similar brainstem mechanisms may contribute to alcohol withdrawal seizures in humans. Alcohol causes intoxication through effects on diverse ion channels and neurotransmitter receptors, including GABA(A) receptors--particularly those containing delta subunits that are localized extrasynaptically and mediate tonic inhibition--and N-methyl-D-aspartate (NMDA) receptors. Alcohol dependence results from compensatory changes during prolonged alcohol exposure, including internalization of GABA(A) receptors, which allows adaptation to these effects. Withdrawal seizures are believed to reflect unmasking of these changes and may also involve specific withdrawal-induced cellular events, such as rapid increases in alpha4 subunit-containing GABA(A) receptors that confer reduced inhibitory function. Optimizing approaches to the prevention of alcohol withdrawal seizures requires an understanding of the distinct neurobiologic mechanisms that underlie these seizures. PMID:16372057
Rogawski, Michael A
The effect of anesthetic and subanesthetic doses of urethane on the development of amygdala kindled seizures and on the expression of previously kindled seizures was studied in hooded rats. An anesthetic dose of urethane almost completely eliminated evoked after discharge and completely eliminated convulsive behavior in both groups. It also eliminated the seizure response to pentylenetetrazol. Subanesthetic doses of urethane strongly attenuated the expression of previously kindled seizures. These results suggest that urethane may not be an appropriate anesthetic for the study of epileptiform phenomena.
Cain, D.P.; Raithby, A.; Corcoran, M.E.
The Gabor atom density (GAD) is a measure of complexity of a signal. It is based on the time-frequency decomposition obtained by the matching pursuit (MP) algorithm. The GAD/MP method was applied to EEG data recorded from intracranial electrodes in patients with intractable complex partial seizures. GAD shows that epileptic seizures, which are reflections of increased neuronal synchrony, are also periods of increased and changing signal complexity. The GAD/MP method is well suited to analyzing these signals from seizures characterized by rapid dynamical changes. The period of organized rhythmic activity exhibits lower complexity than that seen during other phases of the seizure. PMID:17271672
Jouny, C C; Franaszczuk, P J; Adamolekun, B; Bergey, G K
Background: Tramadol poisoning has increased in recent years. Seizure is one of the side-effects of tramadol toxicity. There is a controversy about possible preventive effect of naloxone in tramadol poisoning induced seizure. Therefore, this study was performed to compare seizure incidence in tramadol poisoning patients who received and did not receive naloxone, as an opioid antagonist. Methods: This study involved prospective data collection followed by retrospective analysis on 104 tramadol poisoning patients who were admitted in a referral poisoning center. The incidences of seizure were compared between patients received naloxone and those did not. Outcome was considered as survived without or with complications and death. Logistic Regression analysis was used to determine the effects of different variables on seizure incidence. Results: 70 (67.3%) of the patients were men. The mean age of the patients was 26.3 ± 9 years old. 18.3% of the patients received naloxone in their treatment period. Seizure incidence was significantly higher among tramadol poisoning patients who did not receive naloxone compare with those received naloxone (14.1% vs. 5.1%). Among different variable studied, age had a significant effect on predicting of seizure (odds ratio = 2.09; 95% of confidence interval: 1.82-2.26; P value, 0.004). Conclusions: Although the seizure incidence was lower in patients with tramadol poisoning who received naloxone, the logistic regression did not support the preventive effect of naloxone on seizure in tramadol poisoning cases.
Eizadi-Mood, Nastaran; Ozcan, Dilek; Sabzghabaee, Ali Mohammad; Mirmoghtadaee, Parisa; Hedaiaty, Mahrang
We describe a 30-year-old female with intractable symptomatic epilepsy caused by an insular calcified mass, which was histologically proved as psammomatous meningioma. Seizures were described as consciousness impairment, motionless stare and automatism. After total removal of the tumor with a neuronavigation system and motor evoked potential (MEP) monitoring, seizures completely disappeared without neurological deficit. We emphasize that insular meningioma presents complex partial seizures which mimic medial temporal lobe epilepsy and seizures are controlled by total resection of the tumor. PMID:22915702
Imoto, Hirochika; Fujii, Masami; Maruta, Yuichi; Sadahiro, Hirokazu; Ideguchi, Makoto; Ishihara, Hideyuki; Nomura, Sadahiro; Suzuki, Michiyasu
We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.
Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.
We introduce a natural generalization of the well-studied group testing prob- lem: A test gives a positive (negative) answer if the pool contains at least u (at most l) positive elements, and an arbitrary answer if the number of positive elements is between these fixed thresholds l and u. We show that the p posi- tive elements can be determined
To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases)…
Sillanpaa, Matti; Schmidt, Dieter
Ethnopharmacological relevanceKhat is a plant with psychostimulant properties whose parts, mainly leaves and twigs, are chewed for its euphoriant effects. Khat use and ethanol abuse are increasingly becoming global health concerns especially among many disadvantaged social groups. The present studies were undertaken to investigate seizure susceptibility and responses following chronic co-administration of khat and ethanol.
Paul E. Alele; James B. Rujumba
Electroconvulsive therapy (ECT) has unparalleled antidepressant efficacy, but its cognitive side effects may be persistent. Research suggests that the side effects may be at least partially dissociable from the therapeutic effects of ECT, suggesting that distinct cortical networks may underlie them and introducing a role for focal seizure induction as a means of minimizing side effects. In magnetic seizure therapy (MST), magnetic fields avoid tissue impedance and induce electrical currents confined to superficial cortex, facilitating focal seizure induction. The translational development strategy for MST has included: (1) device development, (2) feasibility in animals and initial human trials, (3) testing in nonhuman primates on safety and mechanisms of action (with neuroanatomical, neurophysiological and cognitive endpoints), (4) safety testing in patients, (5) initial efficacy testing in patients, (6) dosage optimization, and (7) randomized comparison with ECT. These stages have been iterative, with results of early clinical testing prompting device enhancements that were, in turn, tested in nonhuman primates prior to human trials. Safety testing was aided by development of a nonhuman primate model of human ECT, and the validation of a cognitive battery for the monkey that is sensitive to the range of effects of ECT on human memory. Human testing has been facilitated by the development of an international consortium of centers addressing various aspects of technique and dose/response relationships. Challenges facing MST are common to other device-based therapies: characterizing dose/response relationships, optimizing efficacy, and developing efficient and reliable methods to induce lasting therapeutic change in the circuitry underlying depression. PMID:19348798
Rowny, Stefan B; Benzl, Karla; Lisanby, Sarah H
This is a case study presented by the University of Pittsburgh Department of Pathology in which a 26-year-old nurse is experiencing headaches and seizures. Visitors are given both the microscopic and gross descriptions, including neuroimaging results, 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 neuropathology.
Hamilton, Ronald; Martinez, A. Julio (Augusto Julio)
A 70-year-old lady with a resected Dukes B colon cancer, receiving adjuvant capecitabine and bevacizumab chemotherapy was admitted with Hickman line sepsis. During her admission, she developed seizures and periods of unresponsiveness and was suspected to have brain metastases. She was started on high dose steroids and sodium valproate and appeared to respond to this treatment. However an MRI scan revealed that she did not have brain metastases but a rare neurological condition called reversible posterior leukoencephalopathy syndrome, which can be fatal if not treated but has a good prognosis if the cause is identified and treated.
Lewis-Hanna, Demiana Lenzi; Pamma, Gurjeet
Resected epileptic tissues exhibit elements of chronic neuroinflammation that include elevated TNF? and increased TNF? receptor activation, but the seizure related consequences of chronic TNF? expression remain unknown. Twenty four hours after acute limbic seizures the rat hippocampus exhibited a rapid upregulation of TNFR1, but a simultaneous downregulation of TNFR2. These limbic seizures also evoked significant increases in measures of neuroinflammation and caused significant neuronal cell death in both the hilus and CA3 of the hippocampus. In order to mimic a state of chronic TNF? exposure, adeno-associated viral vectors were packaged with a TNF receptor 1 (TNFR1) specific agonist, human TNF?, or a TNF receptor 1/2 agonist, rat TNF?. Subsequently, chronic hippocampal overexpression of either TNFR ligand caused microglial activation and blood-brain barrier compromise, a pattern similar to limbic seizure-induced neuroinflammation. However, no evidence was found for neuronal cell death or spontaneous seizure activity. Thus, chronic, in vivo TNF? expression and the subsequent neuroinflammation alone did not cause cell death or elicit seizure activity. In contrast, chronic hippocampal activation of TNFR1 alone significantly increased limbic seizure sensitivity in both amygdala kainic acid and electrical amygdala kindling models, while chronic activation of both TNFR1 and TNFR2 significantly attenuated the amygdala kindling rate. With regard to endogenous TNF?, chronic hippocampal expression of a TNF? decoy receptor significantly reduced seizure-induced cell death in the hippocampus, but did not alter seizure susceptibility. These findings suggest that blockade of endogenous TNF? could attenuate seizure related neuropathology, while selective activation of TNFR2 could exert beneficial therapeutic effects on in vivo seizure sensitivity. PMID:23333565
Weinberg, Marc S; Blake, Bonita L; McCown, Thomas J
Both clinical and experimental studies suggest that the immature nervous system is unusually susceptible to seizures during critical periods in postnatal life. A late onset of gamma-aminobutyric acid (GABA)-mediated synaptic inhibition could conceivably play a contributing role in this phenomenon. Numerous studies have shown that neural systems that use GABA in the neonatal brain are different than those of adulthood. GABA is an excitatory neurotransmitter that likely plays a neurotrophic role in neuronal differentiation. Other reports suggest that unique, possibly transient, GABAergic interneuron populations exist in the embryonic and neonatal nervous system. At these early times in development, the immature nervous system is remarkably resistant to seizure generation. However, as the hippocampus and neocortex enter the critical period of enhanced seizure susceptibility, inhibitory GABA systems mature rapidly. At this time, blockade of GABA type A (GABAA) receptors produce unusually severe seizure discharges. In hippocampus, concurrent exuberant outgrowth of recurrent excitatory axon collaterals and synapses appear to play a role in the generation of these seizures. As the hippocampus matures, these axons are morphologically remodeled and nearly 50% of branches within arbors are pruned. This pruning of axon branches corresponds in time with the decrease in seizure susceptibility that characterizes adulthood. Developmental remodeling of neuronal connectivity is a common feature of most areas of the central nervous system. Results from an audiogenic seizure model of early onset epilepsy suggest that prevention of axon arbor remodeling by transient sensory deprivation can lead to a permanent overinnervation of target nuclei and chronic seizure susceptibility. Early life seizures may have a similar effect. Recent results in one model have shown that repeated seizures induced by intrahippocampal injections of tetanus toxin during a critical period results in a chronic epilepsy. Future studies should attempt to determine if the synchronized discharging of early-life seizures prevents the remodeling of neuronal connectivity that normally takes place during postnatal development and results in an overinnervated and chronically hyperexcitable hippocampus. PMID:10514815
Swann, J W; Pierson, M G; Smith, K L; Lee, C L
Purpose: To determine whether male and female populations of patients with psychogenic non-epileptic seizures (PNES) are similar, in terms of demographic and social factors, aetiological factors, the clinical characteristics of events and path to diagnosis. Methods: Prospective study by semi-structured interview of 160 consecutive patients (117 female and 43 male) with video EEG confirmed diagnosis of PNES + epileptic seizures
M. Oto; P. Conway; A. McGonigal; A. J. Russell; R. Duncan
The aim of this prospective population-based study was to systematically define a cluster of diagnostic items which can assist in the early identification and classification of epileptic and non-epileptic seizures. A cohort of patients aged ?14 years, suspected with a first epileptic seizure, were included in this study. A team of neurologists evaluated and classified all cases. Diagnostic items for
Irene A. W Kotsopoulos; Marc C. T. F. M de Krom; Fons G. H Kessels; Jan Lodder; Jaap Troost; Mascha Twellaar; Tiny van Merode; André J Knottnerus