Susceptibility To Convulsions Research Articles

Altered excitatory and inhibitory neocortical circuitry leads to increased convulsive severity after pentylenetetrazol injection in an animal model of schizencephaly, but not of microgyria.

ObjectiveMalformations of the polymicrogyria spectrum can be mimicked in rodents through neonatal transcranial focal cortical freeze lesions. The animals presenting the malformations present both altered synaptic events and epileptiform activity in the vicinity of the microgyrus, but the comprehension of their contribution to increased predisposition or severity of seizures require further studies.MethodsIn order to investigate these issues, we induced both microgyria and schizencephaly in 57 mice and evaluated: their convulsive susceptibility and severity after pentyleneterazol (PTZ) treatment, the quantification of their symmetric and asymmetric synapses, the morphology of their dendritic arbors, and the content of modulators of synaptogenesis, such as SPARC, gephyrin and GAP‐43 within the adjacent visual cortex.ResultsOur results have shown that only schizencephalic animals present increased convulsive severity. Nevertheless, both microgyric and schizencephalic cortices present increased synapse number and dendritic complexity of layer IV and layer V‐located neurons. Specifically, the microgyric cortex presented reduced inhibitory synapses, while the schizencephalic cortex presented increased excitatory synapses. This altered synapse number is correlated with decreased content of both the anti‐synaptogenic factor SPARC and the inhibitory postsynaptic organizer gephyrin in both malformed groups. Besides, GAP‐43 content and dendritic spines number are enhanced exclusively in schizencephalic cortices.SignificanceIn conclusion, our study supports the hypothesis that the sum of synaptic alterations drives to convulsive aggravation in animals with schizencephaly, but not microgyria after PTZ treatment. These findings reveal that different malformations of cortical development should trigger epilepsy via different mechanisms, requiring further studies for development of specific therapeutic interventions.

Knockdown of Lingo-1 by short hairpin RNA promotes cognitive function recovery in a status convulsion model

The purpose of this study was to determine the dynamic changes of the Nogo-66 receptor 1 (NgR1) pathway during epileptogenesis and the potential beneficial of leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (Lingo-1) inhibition on epilepsy rats. The hippocampal changes of the NgR1 pathway during epileptogenesis were determined by western blot analysis of multiple proteins, including neurite outgrowth inhibitor protein A (NogoA), myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), Lingo-1, ras homolog family member A (RhoA) and phosphorylated RhoA (p-RhoA). Lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown the hippocampal expression of Lingo-1. Novel object recognition (NOR) test and Morris Water Maze (MWM) test were employed to determine the cognitive functions of rats. Hematoxylin and eosin (H&E) staining, protein expressions of RhoA, p-RhoA, and myelin basic protein (MBP), as well as convulsion susceptibility test were additionally performed. Our results showed that the NgR1 pathway was activated during epileptogenesis, characterized by up-regulation of NogoA, MAG, OMgp, and Lingo-1, which was especially significant at the chronic phase of epilepsy. The cognitive function, convulsion susceptibility and hippocampal neuronal survival of rats were impaired at the chronic phase of epileptogenesis but all improved by Lingo-1 inhibition; besides, the hippocampal protein expressions of p-RhoA and MBP were significantly decreased at the chronic phase of SC rats but increased after Lingo-1 inhibition. Our results demonstrated that Lingo-1 shRNA can improve epilepsy-induced cognitive impairment, which may be related with the pro-myelination and neuroprotection effects of Lingo-1 inhibition.

Специфические особенности крыс линии Крушинского–Молодкиной как генетической модели генерализованных судорожных припадков

The review summarizes current literature data on the study of epileptiform paroxysmal manifestations in various genetic strains of rats with an inherited predisposition to audiogenic seizures. The mechanisms of audiogenic generalized clonic-tonic reactions development, as well as the physiological and biochemical features of the formation of a state of increased convulsive susceptibility in Krushinsky—Molodkina strain rats are considered. The results of the author's studies of audiogenic seizures and their effects on sleep organization in Krushinsky — Molodkina rats are presented. EEG correlates of generalized clonic-tonic seizures are presented.

Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice.

BackgroundNeurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration.MethodsDHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes.ResultsDHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice.ConclusionAlthough our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status, which may underline observed sex differences in the relationship between DHEAS and various health outcomes.

An enhanced home cage modulates hypothalamic CRH-ir labeling in juvenile rats, with and without sub-threshold febrile convulsions.

Pre and postnatal environments can have a profound impact on offspring development. This is especially true when considering the origin of neurological diseases, including epilepsy, a relatively common and chronic neurological condition, affecting 1-2% of the population. Previously, we have used maternal stress and an enhanced home cage (EHC) in an effort to identify potential factors in the early environment that may increase the risk for experiencing seizures. First, pregnant Long-Evans rats were exposed to a predator stress (PS). Then, at birth, litters were divided into standard cage (SC) and EHC groups until postnatal Day 14 (PD14) when a model of febrile convulsions was used to determine convulsion susceptibility of the various groups. Twenty-four hours later, pup brains were processed for immunohistochemical detection of corticotrophic releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus. Analysis of CRH immunoreactive (-ir) patterns revealed a buffering of CRH-ir in EHC reared offspring. Further, experiencing convulsions led to decreased CRH-ir. Our results support the concept that postnatal environmental influences affect neonatal programming and neurodevelopment of processes that could underlie seizure susceptibility, and that these effects can be modulated by EHC conditions.

3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital

There is accumulating evidence that reactive oxygen species are involved in the development of seizures under pathological conditions, and antioxidant treatments are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of induced seizures has been widely used to study temporal lobe epilepsy. However, research on the use of free radical scavengers following KA-induced status epilepticus (SE) is limited. We examined whether antioxidants already used in humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the acquisition of hyperexcitability when administered as a single dose after SE. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N-acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined the threshold for seizures induced by inhalation of flurothyl ether 12 weeks after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We found that edaravone or NAC prevented neuronal cell loss and mossy fiber sprouting, and increased the threshold for seizures induced by flurothyl ether, even when administered after KA-induced SE. These results demonstrate that a single dose of edaravone or NAC can protect against neuronal cell loss and epileptogenesis when administered after SE ceased by pentobarbital.

Sildenafil influences the anticonvulsant activity of vigabatrin and gabapentin in the timed pentylenetetrazole infusion test in mice

Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has recently been reported to affect convulsant activity in some animal models of seizures and epilepsy. Moreover, its influence on the protective activity of some antiepileptic drugs (AEDs) was also noted. The aim of the present study was to investigate the effect of sildenafil on the anticonvulsant potential of gabapentin (GBP) and vigabatrin (VGB) in the timed intravenous (i.v.) pentylenetetrazole (PTZ) test in mice. The chimney test, the passive avoidance task and the grip strength test were used to estimate some possible side effects caused by the studied AEDs and their combinations with sildenafil. Total brain and free plasma concentrations of GBP and VGB were determined to evaluate the characteristics of interactions. Our studies revealed that GBP (25-100 mg/kg) increases the threshold for the forelimb tonic extension, whereas VGB raises thresholds both, for myoclonic (200-600 mg/kg) and generalized clonic (400-600 mg/kg) seizures in the used model of seizures. GBP at sub-effective dose of 12.5 mg/kg co-administered with sildenafil at doses of 10 and 20 mg/kg significantly increases the threshold for tonic seizures in the i.v. PTZ test in mice. Combination of sub-effective dose of VGB (200 mg/kg) with sildenafil at a dose of 5mg/kg also showed significant anticonvulsant activity against clonic seizures. The studied AEDs and their combinations with sildenafil did not produce any changes in the motor coordination, long-term memory and muscular strength in mice. Sildenafil did not influence total brain and free plasma concentrations of GBP and VGB. Interactions between the studied AEDs and sildenafil were pharmacodynamic in nature and for that reason they are worthy of consideration in the clinical practice.

Influence of sildenafil on the anticonvulsant action of selected antiepileptic drugs against pentylenetetrazole-induced clonic seizures in mice

The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on convulsive susceptibility and the anticonvulsant activity of the studied AEDs in mice, while the acute side effects of sildenafil and its combinations with the studied AEDs were evaluated in the chimney test, step-through passive-avoidance task and grip-strength test in mice. Total brain concentrations of AEDs were also determined. Sildenafil (5–40 mg/kg) did not influence the threshold for PTZ-induced clonic seizures in mice, but increased the anticonvulsant activity of ETS in this test without any significant changes in the total brain concentration. The activity of the remaining AEDs was not significantly changed by sildenafil. Neither sildenafil alone nor its combinations with the studied AEDs produced any changes in the motor coordination, long-term memory and muscular strength in mice. Co-administration of sildenafil with ETS in male epileptic patients with co-existing erectile dysfunctions might lead to the pharmacodynamic interactions that may be beneficial for the patients. Combinations of sildenafil with CZP, VPA, PB and TGB appear to be neutral in terms of their influence on seizures.

Paradoxical facilitation of pentylenetetrazole-induced convulsion susceptibility in mice lacking neuronal nitric oxide synthase

The major aim of this study was to elucidate the relationship between nitric oxide (NO) and generalized epilepsy. Mice lacking the neuronal nitric oxide synthase (nNOS) gene (nNOS −/−) were used in this study to determine the relationship between nNOS α and NO in pentylentetrazole (PTZ)-induced convulsions. nNOS −/− mice exhibited severe convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg i.p.) and convulsive doses were lethal in all of the mice (60 mg/kg i.p.) following tonic convulsions. The results were confirmed by using selective nNOS inhibitors in wild-type (nNOS +/+) mice. The higher doses of the nNOS inhibitors 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) and 3-bromo-7-nitroindazole (3Br7NI) inhibited clonic–tonic convulsions induced by a convulsive dose of PTZ (60 mg/kg) in nNOS +/+ mice. In contrast, either TRIM or 3Br7NI at lower doses enhanced convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg) in nNOS +/+ mice similar to nNOS −/− mice treated with PTZ. Such a proconvulsant effect was observed in nNOS +/+ mice pretreated with nNOS inhibitors but not other NOS inhibitors. These results indicate that NO may be regarded as an anticonvulsant or a proconvulsant substance in relation to convulsions induced by PTZ in mice. Pretreatment with N-methyl- d-aspartate (NMDA) receptor antagonists (5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), (E)-(±)-2-amino-4-methyl-5-phospho no-3-pentenoic acid ethyl ester, CGP39551) and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) inhibited a subconvulsive dose of PTZ-induced convulsions in nNOS −/− mice, demonstrating that convulsions induced by PTZ are modulated by endogenous NO production and ionotropic glutamate receptor–mediated stimulation. These results suggest a negative or positive modulation of neuronal interactions by basal or enhanced NO production, respectively.

Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. elegans

Epilepsy is estimated to affect 1–2% of the world population, yet remains poorly understood at a molecular level. We have previously established the roundworm Caenorhabditis elegans as a model for investigating genetic susceptibilities to seizure-like convulsions in vivo. Here we investigate the behavioral consequences of decreasing the activity of nematode gene homologs within the LIS1 pathway that are associated with a human cortical malformation termed lissencephaly. Bioinformatic analysis revealed the nud-2 gene, encoding the worm homolog of mammalian effectors of LIS1, termed NDE1 and NDEL1. Phenotypic analysis of animals targeted by RNA interference (RNAi) was performed using a pentylenetetrazole (PTZ) exposure paradigm to induce convulsions. Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited significant convulsions following PTZ and RNAi treatment. Strains harboring fluorescent markers for GABAergic neuronal architecture and synaptic vesicle trafficking were employed to discern putative mechanisms accounting for observed convulsion behaviors. We found that depletion of LIS1 pathway components resulted in defective GABA synaptic vesicle trafficking. We also utilized combinations of specific genetic backgrounds to create a sensitized state for convulsion susceptibility and discovered that convulsion effects were significantly enhanced when LIS-1 and other pathway components were compromised within the same animals. Thus, interactions among gene products with LIS-1 may mediate intrinsic thresholds of neuronal synchrony.

The influences of extremely low frequency magnetic fields on drug-induced convulsion in mouse.

This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose (LD50) and convulsant dose (CD50) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher CD50, LD50 and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.

The epileptogenic effect of seizures induced by hypoxia: The role of NMDA and AMPA/KA antagonists

Hypoxia of the brain may alter further seizure susceptibility in a different way. In this study, we tried to answer the question how episode of convulsion induced by hypoxia (HS) changes further seizure susceptibility, and how N-methyl- d-aspartic acid (NMDA) and AMPA/KA receptor antagonists influence this process. Adult Albino Swiss mice exposed to hypoxia (5% O 2) developed clonic/tonic convulsions after about 340 s. Mice which underwent 10 s but not 5 s seizures episode subsequently exhibited significantly increased seizure susceptibility to low doses (equal ED 16) of bicuculline (BCC) and NMDA during a 3-week observation period. No morphological signs of brain tissue damage were seen in light microscope on the third day after a hypoxia-induced seizure (HS). Learning abilities assessed in passive avoidance test as well as spontaneous alternation were not disturbed after an HS episode. Pretreatment with AMPA/KA receptor antagonist NBQX effectively prolonged latency to HS and given immediately after seizure episode also attenuated subsequent convulsive susceptibility rise, however, NMDA receptor antagonist, MK-801, appeared to be ineffective. These results suggest that a seizure episode induced by hypoxia, depending on its duration, may play an epileptogenic role. The AMPA/KA receptor antagonist prolongs the latency to HS, and given after this episode, prevents the long-term epileptogenic effect.

Sensitivity and density of glutamate receptor subtypes in the hippocampal formation are altered in pentylenetetrazole - kindled rats

Kindling induced by 13 intraperitoneal injections of 40 mg/kg pentylenetetrazole (PTZ) over a period of 4 weeks resulted in a significant long-lasting increase in both the convulsive susceptibility of animals to the convulsant and the density of the specific [3H]-L-glutamate binding sites in the hippocampus. The quisqualate- and kainate-sensitive [3H]-L-glutamate binding sites were increased 24 h after the final PTZ injection, whereas the N-methyl-D-aspartate (NMDA)-sensitive sites had only a tendency to be enhanced. Furthermore, we investigated [3H]-L-glutamate binding on metabotropic receptors and found a significant increase in the hippocampus following PTZ kindling. In addition, in hippocampal tissue of kindled rats (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)-stimulated inositol phosphate formation is increased. It can be concluded that the increase in metabotropic glutamate receptor (mGluR) density may be the expression of a specific enhancement in susceptibility of the glutamatergic systems to this excitatory amino acid developing in the course of PTZ-induced kindling.

Role of the claustrum in convulsive evolution of visual afferent and partial nonconvulsive seizure in primates.

We tested cross-species validity of the role of the claustrum in the convulsive evolution of the visual afferent and amygdaloid seizure and the specificity of the claustral lesioning effect. In 7 Senegalese baboons, we examined the effect of unilateral claustral lesioning on generalized convulsive seizures either kindled from the amygdaloid nucleus (AM) and cingulate cortex (CG) or induced by intermittent photic stimulation (IPS) after systemic administration of D,L-allylglycine (AG). A lesioned area common to all animals was the anterior half of the left claustrum. Postoperative restimulation of the kindled left AM or CG evoked only nonconvulsive seizures. When few convulsive seizures emerged in 1 CG-kindled animal, they were mirror image of the kindled seizure and arose from the nonlesioned right hemisphere. Restimulation of the kindled right AM or CG reactivated kindled seizures. An IPS-induced generalized convulsive seizure was transformed into a secondarily generalized seizure arising from the nonlesioned right hemisphere. The primate claustrum regulates the convulsive evolution of partial seizures originating from nonmotor structures such as the AM and CG and also regulates the convulsive development that follows IPS. Our findings suggest that predisposed susceptibility expressed at the claustrum may be involved in the clinical variation with respect to convulsive evolution of nonmotor partial seizures and convulsive susceptibility to IPS in human primates.

The effects of a single neonatally induced convulsion on spatial navigation, locomotor activity and convulsion susceptibility in the adult rat

The effect of a single neonatal convulsion on subsequent behaviour was investigated in the male rat. Convulsions were induced by heat or pentylenetetrazol on days 1, 10 or 21. As adults, locomotor activity, spatial ability and convulsion susceptibility were measured. Significant differences were seen in some measures and some groups but a single neonatal convulsion did not induce a consistent and significant pattern of behavioural change, despite the persistent change in hippocampal physiology shown in a previous study.

Corticosteroids enhance convulsion susceptibility via central mineralocorticoid receptors.

Recently, interest in the roles of central nervous system mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) has increased. In vitro results have implicated MR in the enhancing effects of corticosteroids and GR in the suppressing effects of corticosteroids on hippocampal excitability. Although indirect evidence exists suggesting that opposing actions of central MR and GR occur in vivo, direct evidence from studies employing receptor agonists and antagonists is only beginning to emerge. Work in our laboratory suggests that increased corticosterone levels are associated with increased severity of ethanol, pentobarbital, and diazepam withdrawal. Further work with chemical convulsants suggests that MR mediate excitatory effects of corticosteroids on convulsion susceptibility. The circadian rhythm in convulsion susceptibility varies with the circadian rhythm of plasma corticosterone levels and MR binding. The types of convulsions affected by manipulations of MR activity are believed to be of limbic origin, suggesting that limbic convulsions may be alleviated by the use of specific MR antagonists. In addition, because MR are substantially bound at rest and maximally occupied during the circadian peak in corticosteroid levels and during stressor exposure, these receptors are implicated in the maintenance of and in changes in the arousal state of animals.

Influence of nitric oxide synthesis inhibition on convulsive susceptibility in different seizure models in mice

Influence of nitric oxide synthesis inhibition on convulsive susceptibility in different seizure models in mice

Seizure susceptibility in immature rats with micrencephaly induced by prenatal exposure to methylazoxymethanol acetate

The administration of the alkylating neurotoxin methylazoxymethanol acetate (MAM) to pregnant rats on day 15 of gestation induces, in the offspring, a marked micrencephaly, characterized by an impaired formation of intemeurons at cortical, hippocampal and striatal levels. Since in man developmental CNS malformations are often associated with severe epileptogenic encephalopathies with seizures appearing in the first months or years of life, we have studied the development of kainic-acid- and bicuculline-induced seizures in 15- and 30-day-old rats, prenatally exposed to MAM. Compared to controls, a higher susceptibility to seizures has been found in micrencephalic rats aged 15 days, while no significant differences have been observed in those aged 30 days. It is hypothesized that the cerebral global anatomical dysgenesis caused by MAM underlies the higher seizure susceptibility shown by animals during the first periods of life. Successively, the processes of adjustment occurring between the cerebral regions affected by the neurotoxic action of MAM and the afferent and efferent pathways spared by the substance may re-establish adequate intemeuronal relationships and, therefore, a normal convulsive susceptibility.

Sensitivity of the circadian rhythm of kainic acid-induced convulsion susceptibility to manipulations of corticosterone levels and mineralocorticoid receptor binding

Increases in Corticosterone levels have been associated with enhanced susceptibility and decreases in Corticosterone levels have been associated with decreased susceptibility to convulsions in mice. The proconvulsant effects of Corticosterone are believed to be mediated by central mineralocorticoid receptors (MR). Both convulsion susceptibility and plasma corticosteroid levels display circadian rhythmicity. When Corticosterone levels are at their lowest, hippocampal MR binding is submaximal, whereas when corticosterone levels are at their circadian peak, hippocampal MR binding is maximal. In the present experiments the relationship between circadian rhythms of susceptibility to kainic acid-induced convulsions and plasma Corticosterone levels was investigated. In addition, the effects of exogenously administered Corticosterone and the MR antagonist spironolactone were examined at times of different convulsion susceptibility. In general, lower plasma Corticosterone levels were associated with decreased convulsion susceptibility and higher plasma Corticosterone levels were associated with greater convulsion susceptibility. Corticosterone, administered when endogenous levels were low, had a proconvulsant effect. Spironolactone, administered when Corticosterone levels were higher and hippocampal MR were presumably maximally occupied, had an anticonvulsant effect. These results indicate that the circadian rhythm in susceptibility to kainic acid-induced convulsions is sensitive to manipulations of Corticosterone levels and MR binding. Degree of central MR occupancy may, in part, mediate convulsion susceptibility in humans as well as laboratory animals.

Video Game-Related Seizures: A Report on 10 Patients and a Review of the Literature

To further describe the features, postulated pathophysiology, treatment, and outcome of seizures occurring while playing or watching video games (video game-related seizures (VGRS)). We evaluated retrospectively 10 patients with VGRS seen by us and reviewed 25 reported cases. The 35 patients ranged in age from 1 to 36 years (mean: 13.2); and 26 subjects (74%) were male. Eight individuals (29%) had prior infrequent nonfebrile seizures, 4 (11%) had febrile convulsions, and 2 (6%) had a family history of epilepsy. VGRS consisted of generalized tonic-clonic seizures in 22 of 35 individuals (63%); absences in 2 (6%); simple partial seizures in 6 (19%); complex partial seizures in 4 (11%); and other manifestations in 4. Neurologic examination and computed tomographic and magnetic resonance imaging scans were normal. Electroencephalograms demonstrated generalized or focal, interictal or ictal epileptic patterns in 11 of 21 patients (52%) and photoparoxysmal responses in 17 of 32 (53%). Eleven of 15 individuals (73%) treated with video game (VG) abstinence alone, 3 of 6 who received anticonvulsants but played VGs, and 7 of 12 treated with combined VG abstinence and anticonvulsants had no further seizures. We postulate that a special convulsive susceptibility of selected neurons in striate, peristriate, infratemporal, and posterior parietal cortices to particular visual stimuli plays a major role in VGRS. VG abstinence is the treatment of choice of VGRS. Anticonvulsant medication is suggested only for those individuals who continue to play VGs or suffer from seizures triggered by other, unavoidable visual stimuli, or from unprovoked attacks.