Showing papers in "Epilepsy Currents in 2002"
TL;DR: On the basis of more than a decade of studies on the cellular effects of ethosuximide, currently, the most prudent view is that together with a block of the low threshold, T-type Ca(2)(+) current, a reduction both of the noninactivating Na(+)Current and the Ca( 2)(+)-activated K(+) current in thalamic and cortical neurones contribute to the overall therapeutic action of this antiabsence medicine.
Abstract: On the basis of more than a decade of studies on the cellular effects of ethosuximide, currently, the most prudent view is that together with a block of the low threshold, T-type Ca2+ current, a reduction both of the noninactivating Na+ current, and the Ca2+-activated K+ current in thalamic and cortical neurones contribute to the overall therapeutic action of this antiabsence medicine.
97 citations
TL;DR: Study of mossy fiber sprouting has provided a strong theoretical and conceptual framework for efforts to understand how seizures and injury may contribute to epileptogenesis and its consequences, and it is likely that investigation of Mossy Fiber sprouting will continure to offer significant opportunities for insights into seizure-induced plasticity of neural circuits at molecular, cellular, and systems levels.
Abstract: Neurons and neural circuits undergo extensive structural and functional remodeling in response to seizures. Sprouting of axons in the mossy fiber pathway of the hippocampus is a prominent example of a seizure-induced structural alteration which has received particular attention because it is easily detected, is induced by intense or repeated brief seizures in focal chronic models of epilepsy, and is also observed in the human epileptic hippocampus. During the last decade the association of mossy fiber sprouting with seizures and epilepsy has been firmly established. Many anatomical features of mossy fiber sprouting have been described in considerable detail, and there is evidence that sprouting occurs in a variety of other pathways in association with seizures and injury. There is uncertainty, however, about how or when mossy fiber sprouting may contribute to hippocampal dysfunction and generation of seizures. Study of mossy fiber sprouting has provided a strong theoretical and conceptual framework for efforts to understand how seizures and injury may contribute to epileptogenesis and its consequences. It is likely that investigation of mossy fiber sprouting will continure to offer significant opportunities for insights into seizure-induced plasticity of neural circuits at molecular, cellular, and systems levels.
74 citations
TL;DR: Evidence obtained from transgenic animals and heterologous expression systems supports a major role of T-type calcium channels in both the generation of absence seizures and the action of ethosuximide in human absence epilepsy.
Abstract: The role of calcium channel blockade in the antiepileptic action of ethosuximide is controversial, especially regarding the potency and efficacy of block. However, recent evidence obtained from transgenic animals and heterologous expression systems supports a major role of T-type calcium channels in both the generation of absence seizures and the action of ethosuximide in human absence epilepsy.
70 citations
TL;DR: A convincing argument now develops that routine folic acid supplementation is important for women and men receiving AEDs, and low serum and red blood cell levels in women of childbearing potential increase the risk of fetal birth defects.
Abstract: Folic acid has been a topic of discussion within the epilepsy community for several decades. Folic acid was initially suspected to be epileptogenic (1), but that concern has been resolved, as research has demonstrated that folic acid in less than supraphysiologic concentrations does not promote seizures. Epileptologists are now concerned that folic acid may be too low in persons with epilepsy taking some antiepileptic drugs (AEDs). Low serum and red blood cell levels of folic acid in women of childbearing potential increase the risk of fetal birth defects. For men and women, low levels of folic acid are associated with elevated homocysteine and an increased risk for cardiovascular disease. A convincing argument now develops that routine folic acid supplementation is important for women and men receiving AEDs.
61 citations
TL;DR: The seizure risk is reduced about 40%-50% for the first week after neurosurgery in those given the older AEDs compared with those given placebo or no treatment, and these results are consistent with the guidelines of professional organizations for subsets of neurosur surgery cases.
Abstract: Six prospective, controlled trials have examined the effects of antiepileptic drugs (AEDs) given to prevent the occurrence of seizures following neurosurgery. Some studies have concentrated on specific reasons for the neurosurgery (brain tumor) while others have included people with a variety of indications for surgery. Phenytoin (PHT) has been studied most, but carbamazepine (CBZ) and phenobarbital (PB) have also been evaluated to some extent. Studies of people with traumatic brain injury (some of whom were operated on) provide some, but less direct, evidence of the prophylactic effects of AEDs after neurosurgery. Despite considerable variation in reasons for the neurosurgery, AEDs given, and study design, the overall conclusions are remarkably consistent. The seizure risk is reduced about 40%–50% for the first week after neurosurgery in those given the older AEDs compared with those given placebo or no treatment. After the first few weeks, none of the drugs has been proven to reduce the incidence of seizures and in most situations the best estimate is essentially no effect, but effects on the order of a 25%–50% reduction in late (epileptic) seizures cannot be ruled out. The new generation of AEDs have not been tested as prophylactic agents after neurosurgery. Although there are no guidelines for prophylaxis following neurosurgery in general, these results are consistent with the guidelines of professional organizations for subsets of neurosurgery cases. Those guidelines consider prophylaxis, especially using PHT, to be an option for the first week after surgery but that the routine use of prophylactic anticonvulsants after the first week is not warranted.
51 citations
TL;DR: The identification of a genetically transmissible form of epilepsy that is associated with a mutation in CHRNA4, the gene that encodes the alpha4 subunit of the high-affinity nicotinic acetylcholine receptor, was the first demonstration that an alteration in a ligand-gated ion channel can cause seizures.
Abstract: The identification of a genetically transmissible form of epilepsy that is associated with a mutation in CHRNA4, the gene that encodes the α4 subunit of the high-affinity nicotinic acetylcholine receptor, was the first demonstration that an alteration in a ligand-gated ion channel can cause seizures. Since then, nine mutations have been found, and analysis of their physiologic properties has revealed that all of them enhance receptor function.
36 citations
TL;DR: Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented.
Abstract: Poststroke seizures and epilepsy have been described in numerous clinical studies for many years. Most studies are retrospective in design, include relatively small numbers of patients, have limited periods of follow-up, and report a diversity of findings. Well-designed clinical trials and population studies in the recent past addressed several critical clinical issues and generated important findings regarding the occurrence of poststroke seizures and epilepsy. In contrast, the pathophysiologic events of injured brain that establish poststroke epileptogenesis are not well understood, and animal modeling has had limited development. Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented.
34 citations
TL;DR: Potential anticonvulsant mechanisms are discussed in light of the effects of these diuretics on electrolyte balance and synaptic signaling.
Abstract: Recent epidemiological and experimental studies have suggested that certain diuretics may have significant anticonvulsant actions. Potential anticonvulsant mechanisms are discussed in light of the effects of these diuretics on electrolyte balance and synaptic signaling.
23 citations
TL;DR: Intravenously administered lorazepam is somewhat superior to diazepam for the treatment of status epilepticus.
Abstract: Benzodiazepines are an effective and safe treatment of status epilepticus and serial seizures when used in an out-of-hospital setting. Intravenously administered lorazepam is somewhat superior to diazepam for the treatment of status epilepticus. Treatment of status epilepticus should be initiated when seizures have lasted 5-7 minutes.
20 citations
TL;DR: The advent of such a model, in which epileptogenesis can be reliably induced in an in vitro preparation and the process is complete within hours, may facilitate the exploration of cellular mechanisms underlying epilepsyptogenesis.
Abstract: Activation of metabotropic glutamate receptors (mGluRs) often produces long-lasting effects on the excitability of cortical neurons. For example, mGluR stimulation induces long-term potentiation or depression of excitatory synaptic transmission in the hippocampus. Similarly, the effects of mGluRs on cortical epileptiform activities also are enduring. A transient application of group I mGluR agonists to hippocampal slices produces ictal-like discharges that persist for hours after the removal of the applied agonist. This action of group I mGluRs—transforming “normal” hippocampal slice into an “epileptic-like” one—may represent a form of epileptogenesis. The advent of such a model, in which epileptogenesis can be reliably induced in an in vitro preparation and the process is complete within hours, may facilitate the exploration of cellular mechanisms underlying epileptogenesis.
18 citations
TL;DR: Application of BDNF increased the amplitude and frequency of spontaneous excitatory postsynaptic currents and increased the amplitudes of evoked excitatories in the human epilepsy dentate gyrus.
Abstract: Brain-Derived Neurotrophic Factor Enhances Fast Excitatory Synaptic Transmission in Human Epileptic Dentate GyrusZhu WJ, Roper SNAnn Neurol 2001;50:188–194PurposeBrain-derived neurotrophic factor (BDNF) has trophic effects and modulates synaptic transmission in the hippocampal formation in animal studies. It also is upregulated in acute and chronic epilepsy models and in human temporal lobe epilepsy. This study was undertaken to examine the effects of BDNF on fast synaptic transmission in the human epileptic dentate gyrus.MethodsHippocampal specimens were acquired from patients with temporal lobe epilepsy during surgical removal of the anterior temporal lobe, intended to treat the epileptic condition. Whole-cell patch-clamp recordings were obtained from dentate granule cells in transverse hippocampal slices in vitro.ResultsApplication of BDNF increased the amplitude and frequency of spontaneous excitatory postsynaptic currents and increased the amplitude of evoked excitatory postsynaptic currents. BDNF ha...
TL;DR: The prognosis of patients when they first present with epilepsy is a difficult task and potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome.
Abstract: Determining the prognosis of patients when they first present with epilepsy is a difficult task. Several clinical studies have shed light on this very important topic. Potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome. One predictor of the refractory state appears to be early response to AED therapy. Inadequate seizure control after initial treatment is a poor prognostic sign. Recent research into genetic causes of the refractory state has included investigation of the multiple drug resistance gene, and polymorphisms at drug targets. More work is needed to determine the causes and predictors of drug resistance.
TL;DR: The answer is that the terminals of many neurons are homes to even more than two neurotransmitters, and brain-derived neurotrophic factor acting at the low-affinity neurotrophin receptor p75(NTR) can convert the phenotype of the sympathetic neuron from noradrenergic to cholinergic.
Abstract: The clear challenge for understanding granule cell function in health and epilepsy is to resolve the release of the transmitter at the synaptic endings, the big mossy boutons that synapse onto CA3 pyramidal cells and their filopodial extensions that form the presynaptic part of synapses onto interneurons. Granule cells in young, but not adult 11, rats and in adult guinea pigs seem to release GABA that apparently finds its way to GABAA receptors of CA3 pyramidal cells 12. The inhibitory postsynaptic current (IPSC) has a slow rise time, indicating that the receptors might be somewhat removed from the release site, but there is little doubt about the inhibitory nature of the responses in CA3 pyramidal cells 12. To complicate things further, seizures or repetitive stimulation of the perforant path seems to increase the GABAergic phenotype of granule cells both in biochemical studies 13, 14, 15, 16 and in physiological experiments 11, 17, 18. All the necessary enzymes for GABA synthesis seem to be in place 13, 14, 16, and the vesicular GABA transporter required for packaging GABA into synaptic vesicles also is present 19. The following, with all the possible permutations, are potential consequences of GABA synthesis or release from the granule cell terminals.
To produce fast GABAA receptor–mediated inhibitory events in target cells. These cells include interneurons, CA3 pyramidal cells, mossy cells, and, subsequent to the epilepsy-related mossy fiber sprouting, other granule cells.
To induce slow GABAB receptor–mediated inhibitory events in the target neurons mentioned earlier.
To cause presynaptic inhibition through GABAB receptors of glutamate or GABA release from other neighboring terminals, or from the same terminal that just released the GABA 20.
To elevate ambient levels of GABA producing tonic GABA conductances in hippocampal neurons equipped with nondesensitizing high-affinity GABAA receptors 21, 22.
To buffer pH changes inside the granule cells, akin to the role of GABA in plants 23.
It would be foolish to attempt to speculate on the outcome of all of these possibilities and their interactions. Much of what we want to make of the role of GABA in dentate gyrus granule cells depends on what we believe to be the function of these neurons. They have been described as being the guardians of the hippocampus against an overpowering entorhinal input 24 or as merciless excitotoxic killers of various other cell types 25. Furthermore, the outcome of inhibiting interneurons by the GABA released from phenotypically altered granule cells must be considered. Preliminary findings, after kindling-like repetitive stimulations in slices, point to the existence of granule cell–mediated synaptic GABA responses not only in CA3 pyramidal cells but also in interneurons 11. This disinhibitory alternative must be seriously considered, particularly if we accept that the role of a dentate granule cell is to communicate with a handful of CA3 pyramidal cells while silencing most others. Neuroanatomists tell us that a single granule cell makes synaptic contacts with at least an order of magnitude more interneurons than do the 15 or so CA3 pyramidal cells it innervates 26.
Without any detailed experimental evidence, it will take a long time to decide whether the GABAergic phenotype of granule cells is pro- or antiepileptogenic. Nevertheless, by simultaneously releasing fast excitatory and inhibitory transmitters at times of neuronal conflagration, as in epilepsy, granule cells have revealed their ultimate Janus faces. In ancient Rome, of the many temples dedicated to Janus, one was called Ianus Geminus. It was a double-gated temple built in the Forum, serving a symbolic function. When its gates were closed, showing only one face, it signified peace within the Roman Empire. When the gates were open, both faces showing, it meant war. Alternatively, if the second face of Janus really looks into the past, the presence of GABA in granule cells during epilepsy may just be the reactivation of a developmental program reminding us of their GAD-given right to be GABAergic.
TL;DR: An experimentally and clinically testable hypothesis is proposed, concerning the origin of very fast EEG oscillations that sometimes precede the onset of focal seizures, that may play a causal role in the initiation of seizures.
Abstract: A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of and Perhaps Initiating, SeizuresTraub RD, Whittington MA, Buhl EH, LeBeau FE, Bibbig A, Boyd S, Cross H, Baldeweg TEpilepsia 2001;42:153–170We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed...
TL;DR: Measurements obtained during the slow oscillation indicated that glial cells phasically take up part of the extracellular K+ extruded by neurons during the depolarizing phase of the slow sleep oscillations and spike-wave seizures.
Abstract: Spatial Buffering During Slow and Paroxysmal Sleep Oscillations in Cortical Networks of Glial Cells In VivoAmzica F, Massimini M, Manfridi AJ Neurosci 2002;22:1042–1053The ability of neuroglia to buffer local increases of extracellular K+ has been known from in vitro studies. This property may confer on these cells an active role in the modulation and spreading of cortical oscillatory activities. We addressed the question of the spatial buffering in vivo by performing single and double intraglial recordings, together with measures of the extracellular K+ and Ca2+ concentrations ([K+]out and [Ca2+]out) in the cerebral cortex of cats under ketamine and xylazine anesthesia during patterns of slow sleep oscillations and spike-wave seizures. In addition, we estimated the fluctuations of intraglial K+ concentrations ([K+]in). Measurements obtained during the slow oscillation indicated that glial cells phasically take up part of the extracellular K+ extruded by neurons during the depolarizing phase of the slow o...
TL;DR: A brief review summarizes the relationship between imaging and function at baseline and predicting cognitive outcome following temporal lobectomy.
Abstract: Although temporal lobectomy is an effective alternative treatment for many patients with medication-resistant epilepsy, the risk of cognitive morbidity is not inconsequential. The ability to predict cognitive outcome is increasingly dependent on convergent information from multiple sources, including direct (e.g., Wada test) and indirect (e.g., psychometric testing) functional assessments along with magnetic resonance imaging studies that detect structural abnormalities. This brief review summarizes the relationship between imaging and function at baseline and predicting cognitive outcome following temporal lobectomy.
TL;DR: Kim et al. as discussed by the authors found that mice lacking α 1G T-type Ca2+ channels are resistant to Absence Seizures in Mice Lacking α1G T Type Ca2 + channels.
Abstract: Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ ChannelsKim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW, Shin...
TL;DR: The Risk of Seizures After Receipt of Whole-Cell Pertussis or Measles, Mumps, and Rubella Vaccine is high.
Abstract: The Risk of Seizures After Receipt of Whole-Cell Pertussis or Measles, Mumps, and Rubella VaccineBarlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP, Black SB, Shinefield HR, Ward ...
TL;DR: This work evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults and tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy.
Abstract: Are Certain Diuretics Also Anticonvulsants?Hesdorffer DC, Stables JP, Hauser WA, Annegers JF, Cascino GAnn Neurol 2001;50:458–462A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39–0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31–0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1–1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent man...
TL;DR: An incidence study was conducted to identify all cases of first stroke in adult residents of northern Manhattan and found that early seizure and status epilepticus within 7 days of stroke were identified through medical record review.
Abstract: Prevalence and Predictors of Early Seizure and Status Epilepticus after First StrokeLabovitz DL, Allen Hauser W, Sacco RLNeurology 2001;57:200–206BackgroundEarly seizure (ES) has been reported in 2 to 6% of strokes and is a predictor of recurrent seizures. Acute stroke has been reported to cause 22% of all cases of status epilepticus (SE) in adults. The determinants of ES and SE after stroke, however, are not well understood.MethodsAn incidence study was conducted to identify all cases of first stroke in adult residents of northern Manhattan. Cases of ES and SE within 7 days of stroke were identified through medical record review. Statistical analyses were performed by using univariate and multivariate logistic regression models.ResultsThe cohort consisted of 904 patients; ES occurred in 37 (4.1%). The frequency of ES by stroke subtype and location was deep infarct in two (0.6%) of 356, lobar infarct in 20 (5.9%) of 341, deep intracerebral hemorrhage (ICH) in four (4.0%) of 101, lobar ICH in seven (14.3%)...
TL;DR: In this model, intrinsic bursts evoked by threshold-straddling depolarization, and their underlying spike after depolarizations (ADPs), were resistant to antagonists of N-, P/Q-, or L-type Ca2+ channels but...
Abstract: Upregulation of a T-Type Ca2+ Channel Causes a Long-Lasting Modification of Neuronal Firing Mode after Status EpilepticusSu H, Sochivko D, Becker A, Chen J, Jiang Y, Yaari Y, Beck HJ Neurosci 2002;22:3645–3655A single episode of status epilepticus (SE) causes numerous structural and functional changes in the brain that can lead to the development of a chronic epileptic condition. Most studies of this plasticity have focused on changes in excitatory and inhibitory synaptic properties. However, the intrinsic firing properties that shape the output of the neuron to a given synaptic input also may be persistently affected by SE. Thus 54% of CA1 pyramidal cells, which normally fire in a regular mode, are persistently converted to a bursting mode after an episode of SE induced by the convulsant pilocarpine. In this model, intrinsic bursts evoked by threshold-straddling depolarizations, and their underlying spike after depolarizations (ADPs), were resistant to antagonists of N-, P/Q-, or L-type Ca2+ channels but...
TL;DR: Low-frequency stimulation of the Kindling Focus Delays Basolateral Amygdala Kindling in Immature Rats and indicates a strong antiepileptogenic potential.
Abstract: Low-frequency Stimulation of the Kindling Focus Delays Basolateral Amygdala Kindling in Immature RatsVeliSek L, VeliSkova J, Stanton PKNeurosci Lett 2002;326:61–63.Stimulation of deep brain sites is a new approach for treatment of intractable seizures. In adult rats, low-frequency stimulation (LFS; 1–3 Hz) of the kindling site interferes with the course of kindling epileptogenesis. In this study we determined whether the LFS is effective against the fast kindling in the basolateral amygdala in immature, 15-day-old rats. LFS (15 min of 1-Hz stimulation) was applied after each of the 1-s, 60-Hz kindling stimulus. LFS suppressed afterdischarge duration and seizure stage throughout the course of kindling, which indicates a strong antiepileptogenic potential. As the kindling and LFS stimulation patterns are similar to those used for induction of long-term potentiation and long-term depression (LTD), respectively, LTD or depotentiation may play a role in the mechanism of action.
TL;DR: Sisodiya SM, Lin WR, Harding BN, Squier MV, Thom M. as mentioned in this paper showed that expression of drug-resistance proteins in Common Causes of Refractory Epilepsy.
Abstract: Drug Resistance in Epilepsy: Expression of Drug-resistance Proteins in Common Causes of Refractory EpilepsySisodiya SM, Lin WR, Harding BN, Squier MV, Thom M.Brain 2002;125(Pt 1):22–31Epilepsy is r...
TL;DR: Aggravation of Partial Seizures by Antiepileptic Drugs: Is There Evidence from Clinical Trials?Neurology 2002;59:79–83Somerville ERObjectives to assess clinical trials for evidence that antie pileptic drugs cause seizures.
Abstract: Aggravation of Partial Seizures by Antiepileptic Drugs: Is There Evidence from Clinical Trials?Neurology 2002;59:79–83Somerville ERObjectivesTo assess clinical trials for evidence that antiepilepti...