bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabotropic Glutamate Receptors, PLCbeta 1 Signaling and Hippocampal Epileptiform Discharges
Authors: Benardo Larry S. 
Published: December 2022

Group I Metabotropic Glutamate Receptors Elicit Epileptiform Discharges in the Hippocampus Through PLCbeta1 Signaling Chuang SC, Bianchi R, Kim D, Shin HS, Wong RK J Neurosci 2001;21:6387–6394 Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neurons and attempted to determine their role in the generation of the network activities. Group I mGluR stimulation causes depolarization of hippocampal neurons. This depolarization is primarily mediated by two sets of conductance change: the opening of a voltage-dependent cationic conductance (mediating I(mGluR(V))) and the closing of a voltage-independent (background) K(+) conductance. I(mGluR(V)) was no longer elicited by group I mGluR agonists in the presence of U73122, a phospholipase C (PLC) blocker. Also, the current could not be activated in hippocampal CA3 neurons from PLCbeta1 knock-out mice. In contrast, suppression of PLC signaling did not affect the group I mGluR-mediated suppression of background K(+) conductance. Thus, the suppression of the background K(+) conductance occurred upstream to PLC activation, whereas the generation of I(mGluR(V)) occurred downstream to PLC activation. Group I mGluR agonists normally elicited rhythmic single cell and population burst responses in the CA3 neurons. In the absence of an I(mGluR(V)) response, CA3 neurons in slices prepared from PLCbeta1–/– mutant mice could no longer generate these responses. The results suggest that I(mGluR(V)) expression in CA3 hippocampal neuron is PLCbeta1-dependent and that I(mGluR(V)) plays a necessary role in the generation of rhythmic single cell bursts and synchronized epileptiform discharges in the CA3 region of the hippocampus.
Excitatory Afferents to the Entorhinal Cortex Play a Role in Temporal Lobe Epileptogenesis
Authors: Benardo Larry S. 
Published: December 2022

Ibotenate Injections into the Pre- and Parasubiculum Provide Partial Protection Against Kainate-Induced Epileptic Damage in Layer III of Rat Entorhinal Cortex Eid T, Du F, Schwarcz R Epilepsia 2001;42:817–824 Purpose A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum. Methods Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later). Results After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV-VI). Conclusions The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy.
Diuretics as Antiepileptic Drugs
Authors: Kanner Andres M. 
Published: December 2022

Are Certain Diuretics Also Anticonvulsants? Hesdorffer DC, Stables JP, Hauser WA, Annegers JF, Cascino G Ann Neurol 2001;50:458–462 A 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 manner. Chlorthiazide's toxic dose for 50% of animals tested (TD50) could not be achieved even with dosing as high as 1,500 mg/kg for furosemide; TD50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.
In Utero Effects of AEDs
Authors: Meador Kimford J. 
Published: December 2022

Long-term Health and Neurodevelopment in Children Exposed to Antiepileptic Drugs Before Birth Dean JC, Hailey H, Moore SJ, Lloyd DJ, Turnpenny PD, Little J. J Med Genet 2002;39:251–259 Objective To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Design Retrospective population-based study. SETTING: Population of the Grampian region of Scotland. Participants Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records, and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood-onset medical problems, developmental delay, and behaviour disorders. Results Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs (AEDs). Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of nonexposed sibs, and developmental delay in 24% of exposed children, compared with 11% of nonexposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of nonexposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of nonexposed sibs), and 20% had behaviour disorders (5% of nonexposed). Conclusion Prenatal AED exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.
Levetiracetam and Oral Contraceptives
Authors: Penovich Patricia E. 
Published: December 2022

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women Ragueneau-Majlessi I, Levy RH, Janik F Epilepsia 2002;43(7):697–702 Purpose This study was designed to evaluate whether levetiracetam (LEV), a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives. Methods During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either LEV, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase. Results The plasma concentration–time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either LEV or placebo. The ratios of the log-transformed geometric mean areas under the plasma concentration–time curves (AUCs), maximal (Cmax) and minimal (Cmin) plasma concentrations, and trough concentrations on day 21 (C21) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during LEV and placebo administration. Conclusions LEV does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.
Sprouted Mossy Fibers Form Primarily Excitatory Connections
Authors: Coulter Douglas A. 
Published: December 2022

Axon Sprouting in a Model of Temporal Lobe Epilepsy Creates a Predominantly Excitatory Feedback Circuit Buckmaster PS, Zhang GF, Yamawaki R J Neurosci 2002;22:6650–6658 The most common type of epilepsy in adults is temporal lobe epilepsy. After epileptogenic injuries, dentate granule cell axons (mossy fibers) sprout and form new synaptic connections. Whether this synaptic reorganization strengthens recurrent inhibitory circuits or forms a novel recurrent excitatory circuit is unresolved. We labeled individual granule cells in vivo, reconstructed sprouted mossy fibers at the electron-microscopic (EM) level, and identified postsynaptic targets with γ-aminobutyric acid (GABA) immunocytochemistry in the pilocarpine model of temporal lobe epilepsy. Granule cells projected an average of 1.0 and 1.1 mm of axon into the granule cell and molecular layers, respectively. Axons formed an average of one synapse every 7 μm in the granule cell layer and every 3 μm in the molecular layer. Most synapses were with spines (76 and 98% in the granule cell and molecular layers, respectively). Almost all of the synapses were with GABA-negative structures (93 and 96% in the granule cell and molecular layers, respectively). By integrating light microscopic and EM data, we estimate that sprouted mossy fibers form an average of >500 new synapses per granule cell, but <25 of the new synapses are with GABAergic interneurons. These findings suggest that almost all of the synapses formed by mossy fibers in the granule cell and molecular layers are with other granule cells; therefore after epileptogenic treatments that kill hilar mossy cells, mossy fiber sprouting does not simply replace one recurrent excitatory circuit with another. Rather, it replaces a distally distributed and disynaptic excitatory feedback circuit with one that is local and monosynaptic.
Flumazenil Binding and Cortical Malformations
Authors: Theodore William H. 
Published: December 2022

Central Benzodiazepine Receptors in Malformations of Cortical Development: A Quantitative Study Hammers A, Koepp MJ, Richardson MP, Labbe C, Brooks DJ, Cunningham VJ, Duncan J Brain 2001;124:1555–1565 Purpose We calculated [11C]flumazenil volume of distribution ([11C]FMZ-Vd] after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the γ-aminobutyric acid (GABAA)-central benzodiazepine receptor complex. Methods Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomic template for correction for partial volume effect. Results Nine of 10 patients showed single or multiple increases or decreases in [11C]FMZ-Vd in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [11C]FMZ-Vd than the overlying cortex, which was normal. Decreases in [11C]FMZ-Vd were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [11C]FMZ-Vd in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [11C]FMZ-Vd was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Conclusions Flumazenil binding was decreased in some MCDs with increased grey-matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond magnetic resonance imaging (MRI)-detectable structural changes.
Metabotropic Glutamate Receptors and Epileptiform Bursting
Authors: Benardo Larry S. 
Published: December 2022

Differential Roles for mGluR1 and mGluR5 in the Persistent Prolongation of Epileptiform Bursts Merlin LR J Neurophysiol 2002;87:621–625 Purpose Transient activation of group I metabotropic glutamate receptors (mGluRs) with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces persistent prolongation of epileptiform bursts in guinea-pig hippocampal slices, the maintenance of which can be reversibly suppressed with group I mGluR antagonists. To determine the relative roles of mGluR1 and mGluR5 in these group I mGluR-dependent induction and maintenance processes, subtype-selective antagonists were used. In the presence of picrotoxin, DHPG (50 μ M, 20–45 min) converted interictal bursts into 1- to 3-s discharges that persisted for hours after washout of the mGluR agonist. 2-Methyl-6–(phenylethynyl)-pyridine (MPEP, an mGluR5 antagonist; 25 μ M) and (+)-2-methyl-4-carboxy-phenylglycine (LY367385, an mGluR1 antagonist; 20–25 (μ M) each significantly suppressed the ongoing expression of the mGluR-induced prolonged bursts. However, LY367385 was more effective, reducing the burst prolongation by nearly 90%; MPEP produced only a 64% reduction in burst prolongation. Nevertheless, MPEP was more effective at preventing the induction of the burst prolongation; all 10 slices tested failed to express prolonged bursts both during and after coapplication of DHPG with MPEP. Coapplication of DHPG with LY367385, in contrast, resulted in significant burst prolongation (in 68% of slices tested) that was revealed on washout of the two agents. These results suggest that although both receptor subtypes participate in both the induction and maintenance of mGluR-mediated burst prolongation, mGluR1 activation plays a greater role in sustaining the expression of prolonged bursts, whereas mGluR5 activation may be a more critical contributor to the induction process underlying this type of epileptogenesis.
Responsiveness of Status Epilepticus to Treatment with Diazepam Decreases Rapidly as Seizure Duration Increases
Authors: Goodkin Howard P. , Kapur Jaideep 
Published: December 2022

Characterization of Pharmacoresistance to Benzodiazepines in the Rat Li-pilocarpine Model of Status Epilepticus Jones D, Esmaeil N, Maren S, Macdonald R Epilepsy Res 2002;50(3):301 Status epilepticus is usually initially treated with a benzodiazepine (BZD) such as diazepam (DZP). During prolonged seizures, however, patients often lose their sensitivity to BZDs, thus developing pharmacoresistant seizures. In rats, administration of LiCl followed 20 to 24 hours later by pilocarpine induces a continuous, self-sustained, and reproducible form of status epilepticus that can be terminated with DZP when it is administered soon after the pilocarpine injection. However, when administered after a 45-minute delay, DZP is less effective. Previous findings suggested that the development of pharmacoresistance is related to the stage of status epilepticus. In this study, we characterized the seizure stage dependence of DZP pharmacoresistance. After administration of different doses of DZP at varying time intervals after specific behaviorally and electrographically defined seizure stages, stage-, time-, and dose-dependent pharmacoresistance to DZP developed. We also studied two other antiepileptic drugs (AEDs) commonly used in the treatment of status epilepticus, phenobarbital (PB) and phenytoin (PHT). Consistent with previous studies, our results indicated a similar relation between stage, time, and dose for PB, but not for PHT. Our data are consistent with rapid modulation of γ-aminobutyric acid subtype A (GABAA) receptors during status epilepticus that may result in pharmacoresistance to AEDs that enhance GABAA receptor-mediated inhibition.
Illnesses and Accidents in Epilepsy Patients
Authors: Berg Anne T. 
Published: December 2022

Morbidity and Accidents in Patients with Epilepsy: Results of a European Cohort Study Beghi E, Cornaggia C; The RESt-1 Group Epilepsia 2002;43(9):1076–1083 Purpose To assess the risk of illnesses and accidents in patients with epilepsy and to evaluate the proportion of those risks attributable to epilepsy. Methods Nine hundred fifty-one referral patients with idiopathic, cryptogenic, or remote symptomatic epilepsy and 909 matched controls (relatives or friends) were followed up prospectively for 1 to 2 years in eight European countries (Italy, Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient and control received a diary to keep notes regarding any illness or accident. Patients with epilepsy specifically recorded relations with seizures. Results Six hundred forty-four patients recorded 2,491 illnesses compared with 1,665 illnesses in 508 controls. The cumulative probability of illness in patients was 49% by 12 months and 86% by 24 months (controls, 39% and 75%; P < 0.0001). One hundred ninety-nine patients and 124 controls had 270 and 140 accidents, respectively. The cumulative probability of accident in the cases was 17% and 27% by 12 and 24 months (controls, 12% and 17%; P < 0.0001). The chance of two or more illnesses or accidents was modestly but significantly greater in the patients. Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24% of accidents were seizure related. When illnesses and accidents related to seizures were excluded, the chance of illnesses and accidents was fairly similar in the two groups. Conclusions Patients with idiopathic, cryptogenic, or remote symptomatic epilepsy have a moderately higher risk of illnesses and accidents than do the general population. With few exceptions, the events are trivial. When seizure-related events are excluded, patients with epilepsy are not at any significantly higher risk of illnesses and accidents.
Brain Stimulation for Temporal Lobe Epilepsy
Authors: Marks William J. 
Published: December 2022

Long-term Amygdalohippocampal Stimulation for Refractory Temporal Lobe Epilepsy Vonck K, Boon P, Achten E, De Reuck J, Caemaert J Ann Neurol 2002;52(5):556–565 Short-term deep brain stimulation (DBS) recently has been shown to be efficacious in refractory temporal lobe epilepsy. We (a) evaluated long-term DBS in medial temporal lobe structures in patients with normal magnetic resonance imaging (MRI) findings and (b) investigated the use of long-term DBS electrodes for the localization of the ictal onset zone before DBS. In three patients with complex partial seizures (CPSs), DBS electrodes were implanted in the amygdalohippocampal region to identify and subsequently stimulate the ictal onset zone. CPSs were compared before and after prolonged DBS. Side effects were carefully monitored. DBS electrodes yielded high-quality electroencephalogram recordings showing unilateral seizure onset in medial temporal lobe structures. For all patients, unilateral amygdalohippocampal stimulation was performed. After a mean follow-up of 5 months (range, 3–6 months), all patients had a greater than 50% reduction in seizure frequency. In two patients, antiepileptic drugs could be tapered. None of the patients reported side effects. This open study demonstrates the feasibility of consecutive electroencephalographic recordings and DBS in medial temporal lobe structures using DBS electrodes. These results prompt further studies in a larger patient population to establish the efficacy and safety of long-term DBS as an alternative treatment for refractory temporal lobe epilepsy.
Contribution of Current and past Traumatic Events to Pseudoseizures and Epilepsy
Authors: Harden Cynthia L. 
Published: December 2022

Comparative Study of Trauma-Related Phenomena in Subjects with Pseudoseizures and Subjects with Epilepsy Fleisher W, Staley D, Krawetz P, Pillay N, Arnett JL, Maher J Am J Psychiatry 2002;159:660–663 Purpose The purpose of this study was to examine potential differences in measures of trauma-related phenomena between subjects with pseudoseizures and subjects with intractable epilepsy. Methods Thirty-one adult subjects with pseudoseizures and 32 subjects with intractable epilepsy (confirmed by video-EEG) were recruited from the epilepsy unit of a tertiary care hospital. Each participant completed the Impact of Event Scale, the Davidson Trauma Scale, the Mississippi Scale for Combat-Related Post-traumatic Stress Disorder (PTSD), the Dissociative Experience Scale, and the Pittsburgh Sleep Quality Index, as well as demographic, seizure history, and family-functioning measures. Results Subjects with pseudoseizures had significantly higher mean scores on the Davidson Trauma Scale, Mississippi Scale for Combat-Related PTSD, Impact of Event Scale, and Pittsburgh Sleep Quality Index than did subjects with epilepsy. In addition, a significantly higher percentage of subjects with pseudoseizures had scores above the clinical cutoff level of 30 on the Dissociative Experience Scale. Conclusions Subjects with pseudoseizures exhibited trauma-related profiles that differed significantly from those of epileptic comparison subjects and closely resembled those of individuals with a history of traumatic experiences. Interventions aimed at trauma-related issues may be beneficial for patients with pseudoseizures.