bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Seizures in the Flathead Rat: A New Genetic Model of Epilepsy in Early Postnatal Development
Authors: Sarkisian Matthew R. , Rattan Samarjit , D'Mello Santosh R. , LoTurco Joseph J. 
Published: August 2005

Summary: Purpose: Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat. Methods: Animals (n = 76) ages P0–22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mg/kg), valproate (VPA; 400 mg/kg), or ethosuximide (ESM; 600 mg/kg). Results: FHs display episodes of behavior characterized by whole‐body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval. Conclusions: Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single‐locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability.
Hypnotic Recall: A Positive Criterion in the Differential Diagnosis Between Epileptic and Pseudoepileptic Seizures
Authors: Kuyk Jarl , Spinhoven Philip , van Dyck Richard 
Published: August 2005

Summary: Purpose: Because the diagnosis of pseudoepileptic seizures (PESs) is mostly made by excluding epilepsy, availability of a positive criterion for PESs is of great importance. This study was aimed at the validation of a diagnostic technique that intends to provide in such a positive criterion. Methods: In 17 patients with epileptic seizures (ESs) and 20 patients with PESs, a hypnotic procedure was performed by an investigator blind to other data to recover amnesia for the ictus. If recall was obtained, the experimental diagnosis PES was given; if not, ES was diagnosed. The experimental diagnoses were compared with the clinical, EEG‐confirmed diagnoses. Hypnotizability was measured to determine the relation between the outcome of the test and hypnotizability of the patients. Results: Recall for the ictus was obtained in 17 patients. Each of these had a clinical diagnosis of PES. Seventeen patients with “no recall” had a clinical diagnosis of ES, and three patients had PESs. This result yields a specificity of 100% and a sensitivity of 85% for the recall technique. Hypnotizability was significantly higher in patients with PESs than in patients with ESs. In some “low hypnotizables,” recall was obtained, and in some “high hypnotizables,” no recall was obtained. Conclusions: A positive recall test indicates PES. A subgroup of patients with PESs is characterized by a high level of hypnotizability. Hypnotizability is not crucial for outcome of the recall test. High hypnotic abilities are especially found in disorders in which it is supposed that “dissociation” is involved. It can be speculated that PES may be one of the dissociative phenomena.
The Early Prognosis of Epilepsy in Childhood: The Prediction of a Poor Outcome. The Dutch Study of Epilepsy in Childhood
Authors: Arts Willem F. M. , Geerts Ada T. , Brouwer Oebele F. , Peters A. C. Boudewyn , Stroink Hans , van Donselaar Cees A. 
Published: August 2005

Summary:Purpose:To examine which variables available early in the course of childhood epilepsy are associated with a poor short‐term outcome and to develop models to predict such an outcome.Methods:We prospectively followed up 466 children with newly diagnosed epilepsy for 2 years. Variables were collected at intake and after 6 months. Outcome was defined as the duration of the terminal remission (TR): poor (<6 months) and not poor (≥6 months).Results:Of the subjects, 31% had a poor outcome. Multivariate analysis based on the intake variables identified number of seizures, seizure type, and etiology as risk factors for a poor outcome. With the intake and 6‐month variables combined, seizure type, etiology, the number of seizures, and not attaining a 3‐month remission during these 6 months, and the EEG at 6 months were predictive variables. A predictive model based on the multivariate logistic‐regression analysis with the intake variables was correct in 56% of the children in whom it predicted a poor outcome and in 73% of the children in whom it predicted a not‐poor outcome. With the intake and 6‐month variables together, these percentages were 66 and 79%, respectively. The sensitivity of these models was low (29 and 47%, respectively); the specificity was good (90 and 89%).Conclusions:The 2‐year outcome of childhood epilepsy is closely related to its early course. The prognosis is poor in −30% of patients. By using our data, the prediction of a poor outcome is correct in almost two thirds of the patients; however, the models produce many false‐negative predictions.
Estimation of Topiramate in Subdural Cerebrospinal Fluid, Subcutaneous Extracellular Fluid, and Plasma: A Single Case Microdialysis Study
Authors: Lindberger Martin , Tomson Torbjörn , Öhman Inger , Wallstedt Lars , Ståhle Lars 
Published: August 2005

Summary: Purpose: To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments. Methods: In this single case study of a patient with drug‐resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma. Results: The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD ± 0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD ± 0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD ± 0.06), and the correlation coefficient was 0.97. Conclusions: Assuming a protein binding of TPM of −13%, it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.
Time Course of the GABAergic Effects of Vigabatrin: Is the Time Course‐of Brain GABA Related to Platelet GABA‐Transaminase Inhibition?
Authors: Valdizán Elsa M. , García Agueda P. , Armijo Juan A. 
Published: August 2005

Summary: Purpose: To analyze the time course of the effects of vigabatrin (VGB) on brain γ‐aminobutyric acid (GABA), and its relation with 4‐aminobutyrate‐2‐ketoglutarate amino‐transferase (GABA‐T) in brain and platelets. Methods: Blood and brain samples were collected at 4, 24, 48, and 72 h after a single dose and after 3 and 8 days of treatment with 200 mg/kg of VGB in rats. Results: Time courses of the GABAergic effects of VGB were different after single and multiple doses: with multiple doses, the inhibition of brain GABA‐T was quicker and longer, the inhibition of platelet GABA‐T was greater and longer, the increase in brain GABA was greater, and recovery began earlier. After pooling the data obtained at 4, 24, 48, and 72 h, we observed a power correlation between the increase in brain GABA in individual rats as percentage of the control and both the inhibition of brain GABA‐T after a single dose of VGB (r=−0.40; p < 0.05), and the inhibition of platelet GABA‐T after 3 days (r=−0.48; p < 0.01) and 8 days of treatment (r=−0.53; p < 0.01). When all data after single and multiple doses were pooled, the increase in brain GABA correlated better with the inhibition of GABA‐T in platelets (r=−0.62; p < 0.001) than in brain (r=−0.38; p < 0.001). Platelet GABA‐T correlated with brain GABA at 4 h (r=−0.64; p < 0.001) and 24 h (r=−0.66; p < 0.001) but not at 48 and 72 h. Conclusions: Platelet GABA‐T reflects the time course of the increase in brain GABA better than does brain GABA‐T after multiple doses of VGB in rats.
Cognitive Functions After Pilocarpine‐Induced Status Epilepticus: Changes During Silent Period Precede Appearance of Spontaneous Recurrent Seizures
Authors: Hort Jakub , Broźek Gustav , Mareš Pavel , Langmeier Miloš , Komárek Vladimír 
Published: August 2005

Summary: Purpose: To study the possible relation between spontaneous recurrent seizures (SRS) and the derangement of cognitive memory. Methods: Status epilepticus (SE) was induced in adult Long‐Evans rats by pilocarpine (320 mg/kg, i.p.) and interrupted after 2 h by clonazepam (CZPs mg/kg, i.p.). In addition to the animals that were given pilocarpine and CZP (group P), two groups received ketamine (100 mg/kg, i.p.): the first group 15 minutes after SE onset (group K15), and the second immediately after the CZP (group K120). Control groups were formed from animals not treated with pilocarpine as well as animals that received pilocarpine but did not develop motor seizures. Spatial cognitive memory was tested in the Morris water maze. Results: Testing was impossible for more than 6 days after SE in group P. Ketamine shortened this period for the two groups that received it. During the silent period, deteriorated cognitive memory progressively improved, but the performance of group P started to worsen before the appearance of SRS. Group K120 only expressed a tendency toward declining performance, whereas group K15 never developed SRS, and the behavior of these animals did not differ from that of the controls after the postseizure period was over. Histologically, massive hippocampal cell loss was seen in group P. Ketamine protected hippocampal cells in a time‐dependent manner; group K15 did not exhibit any obvious necrosis in the hippocampus. Conclusions: There is no close relation between cognitive functions and the appearance of SRS, because ketamine, administered 120 min after the beginning of SE, prevented the derangment of cognitive functions but not the appearance of SRSs.
Mutated Nicotinic Receptors Responsible for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy are More Sensitive to Carbamazepine
Authors: Picard F. , Bertrand S. , Steinlein O. K. , Bertrand D. 
Published: August 2005

Summary:Purpose:The recent linkage between a genetically transmissible form of epilepsy (ADNFLE) and mutations within the α4subunit, one component of the major brain neuronal nicotinic acetylcholine receptor (nAChR), raises the question of the role of this receptor in epileptogenesis. Although acting by different mechanisms, the two genetic alterations so far identified both render the nAChR less efficient. In view of the high sensitivity of ADNFLE to carbamazepine (CBZ), we studied the effects of this drug and of valproate (VPA) on the human α4β2nAChR and its mutations.Methods:The α4β2nAChRs from control and mutant α4subunits were reconstituted inXenopusoocytes and investigated by using a dual‐electrode voltage clamp technique. Acetylcholine (ACh)‐evoked currents recorded in the absence or presence of antiepileptic drugs (AEDs) were studied to analyze the mode of action of these compounds.Results:ACh‐evoked currents at the human α4β2nAChR were readily and reversibly inhibited by ∼100 μMCBZ. This compound was found to be a noncompetitive inhibitor of the nAChR, which probably acts by entering the channel and causing a blockade by steric hindrance. Dose‐response inhibition curves determined on the control receptor and on ADNFLE‐mutant receptors showed a greater sensitivity of the mutants to CBZ, with median inhibitory concentrations (IC50s) in the range of the antiepileptic plasma levels of CBZ. In contrast, VPA had nearly no effect on control and mutant nAChRs.Conclusions:CBZ inhibits the neuronal α4β2nAChRs at pharmacologic concentrations, with ADNFLE mutants displaying about threefold higher sensitivity to this compound. The increased sensitivity of these mutant receptors supports the hypothesis that the antiepileptic activity of CBZ can, at least to some extent, be attributed to the nAChR inhibition.
Electrophysiologic Analysis of a Chronic Seizure Model After Unilateral Hippocampal KA Injection
Authors: Bragin Anatol , Engel Jerome , Wilson Charles L. , Vizentin Elizabeth , Mathern Gary W. 
Published: August 2005

Summary: Purpose: Unilateral intrahippocampal injections of kainic acid (KA) in rats produce spontaneous recurrent limbic seizures and morphologic changes in hippocampus that resemble hippocampal sclerosis in patients with medically refractory mesial temporal lobe epilepsy (MTLE), that form of temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. Interictal in vivo electrophysiologic studies have revealed high‐frequency (250‐500 Hz) oscillations, termed fast ripples (FRs). These oscillations may uniquely occur in or adjacent to the site of hippocampal KA injection, in areas that generate spontaneous seizures. Similar field potentials also have been demonstrated in the epileptogenic region of patients with TLE. We have now characterized ictal electrographic patterns in this rat model for comparison with those in human TLE and begun to evaluate the role of FRs in the transition to ictus in the KA‐treated rat. Methods: Rats received unilateral intrahippocampal injections of KA and, after the development of spontaneous seizures, were implanted with multiple fixed and moveable microelectrodes for single unit, field potential, and EEG recording. They were then monitored by using video‐EEG telemetry for several weeks to capture and evaluate electrographic and behavioral seizure types. Results were correlated with Timm's stain demonstration of mossy fiber sprouting. Results: Low‐voltage fast (LVF) and hypersynchronous electrographic ictal‐onset patterns were seen in the KA‐treated rat that resembled similar ictal‐onset patterns in patients with TLE. Hypersynchronous, but not LVF, ictal discharges were associated with recurrent FRs. As in the human, hypersynchronous ictal onsets originated predominantly in hippocampus, whereas LVF ictal onsets more often involved extrahippocampal structures. LVF ictal onsets occurred during wakefulness or paradoxical sleep and were usually associated with motor behavior, whereas hypersynchronous ictal onsets occurred during slow‐wave sleep or periods of immobility and were not associated with motor behavior unless there was transition to another ictal electrographic pattern. Mossy fiber sprouting did not correlate with the frequency of ictal EEG discharges exhibited by each rat but was greater in those rats that demonstrated frequent behavioral seizures. Conclusions: The electrographic features of spontaneous seizures in the KA‐treated rat resemble those of patients with medically refractory TLE with respect to EEG pattern and localization. Our data suggest that hypersynchronous ictal onsets represent epileptogenic disturbances in hippocampal circuits, whereas LVF ictal onsets may involve extrahippocampal areas having more direct connections to the motor system. Hypersynchronous seizures may involve the same neuronal mechanisms that generate interictal FRs.
Brain Activation During Intermittent Photic Stimulation: A [15O]‐Water PET Study on Photosensitive Epilepsy
Authors: da Silva Ednéa A. , Müller Ralph‐Axel , Chugani Diane C. , Shah Jagdish , Shah Aashit , Watson Craig , Chugani Harry T. 
Published: August 2005

Summary:Purpose: Intermittent photic stimulation (IPS) is an activation procedure used during electroencephalogram (EEG) recording to elicit paroxysmal discharges in individuals with photosensitivity. Specific responses on EEG recording may be provoked by IPS at different frequencies of flickering in normal individuals and in patients with photosensitive epilepsy.Methods: Changes in regional cerebral blood flow (rCBF) were studied during IPS in two groups of subjects by using [15O]‐water positron emission tomography (PET): a control group consisting of eight healthy adults with photic driving response during IPS on EEG recording (mean age, 25 ± 10.5 years) without history of neurologic or psychiatric abnormalities and a patient group consisting of four adults (mean age, 33 ± 7.5 years) with history of photosensitive epilepsy. [15O]‐water PET scanning with concomitant EEG monitoring was performed during baseline and IPS at 4‐, 14‐, and 30‐Hz frequencies.Results: The control group showed photic driving response at 14‐Hz IPS frequency. The patient group showed photoparoxysmal response at 14 and 30 Hz, but not at 4 Hz. Changes in rCBF were determined by means of statistical parametric mapping. Increases in rCBF in occipital cortex (Brodmann's areas 17, 18, and 19) were observed in both groups. In addition, during photic driving responses, the control group showed rCBF increases in the insula and in the thalamus, on the right side. The patient group showed a significant rCBF increase in the hypothalamic region inferior to the left caudate nucleus during photoparoxysmal response. This activation was not found in the control group. Increased rCBF also was observed in the patient group in the head of the left caudate nucleus, in the left hippocampus, and in left insula during IPS without photoparoxysmal response. No activations in these regions were observed during photoparoxysmal response.Conclusions: These data may indicate involvement of the hypothalamus in photosensitive epilepsy and may suggest a modulatory function of the caudate nucleus, which might be associated with an inhibition of epileptic discharges during IPS in patients with photosensitive epilepsy.
Low‐Luminance Visual Stimuli Compared with Stroboscopic IPS in Eliciting PPR in Photosensitive Patients
Authors: Takahashi Takeo , Nakasato Nobukazu , Yokoyama Hiroyuki , Tsukahara Yasuo 
Published: August 2005

Summary:Purpose: Photosensitivity is thought to play the most important role in the genesis of electronic screen games induced seizures (ESGIS). To elicit photoparoxysmal response (PPR) effectively, we performed EEG activation by low‐luminance visual stimuli: 20 cd/m2 deep‐red flicker and flickering 2 c/deg geometric pattern stimuli produced by strobofilters. We investigated efficacy of eliciting PPR by use of Grass PS33‐plus stroboscopic 18‐Hz intermittent photic stimulation (IPS) and low‐luminance 18‐Hz visual stimuli.Methods: We studied 31 photosensitive patients. We gave stroboscopic IPS (eyes closed and eyes open); after deep‐red flicker stimulation (eyes open), we gave flickering geometric‐pattern stimuli by using dot, vertical grating, and horizontal grating patterns.Results: Stroboscopic IPS elicited PPR in 14 patients, whereas absence of PPR provocation was found in 17 patients. Low‐luminance visual stimuli elicited PPR in 30 patients, whereas absence of PPR provocation was found in only one patient. These PPR provocation differences in both stimuli were statistically significant (p < 0.001).Conclusions: The data suggest that low‐luminance visual stimuli as described are useful for EEG diagnosis of ESGIS when seizures are thought to be due to photosensitivity.
Comparative Anticonvulsant and Mechanistic Profile of the Established and Newer Antiepileptic Drugs
Authors: White H. Steve 
Published: August 2005

Summary:Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory‐mediated neurotransmission, or reduction of excitatory‐mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic‐based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. For many of the newer AEDs, several molecular mechanisms of action have been identified. For example, felbamate (FBM), lamotrigine (LTG), zonisamide (ZNS), topiramate (TPM), oxcarbazepine (OCBZ), and possibly gabapentin (GBP) share a similar mechanism with that defined for phenytoin (PHT) and carbamazepine (CBZ), i.e., a voltage‐ and use‐dependent block of voltage‐sensitive sodium (Na+) channels. In addition to their effects on Na+ currents, TPM, ZNS, and FBM also appear to act as allosteric modulators of the GABAA receptor, whereas GBP appears to increase brain GABA levels. GBP, ZNS, FBM, LTG, and OCBZ attenuate voltage‐sensitive calcium (Ca2+) channels, albeit through different mechanisms and with different classes of Ca2+ channels. FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA‐ and AMPA/kainate‐mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.
Tiagabine
Authors: Schachter Steven C. 
Published: August 2005

Summary:Tiagabine (TGB) is a recently approved antiepileptic drug (AED) that inhibits γ‐aminobutyric acid (GABA) reuptake into neurons and glia, a mechanism of action that is specific and unique among the AEDs. TGB is potent and has linear and predictable pharmacokinetics. It has no clinically relevant effects on hepatic metabolism or serum concentrations of other AEDs, effects on laboratory values, or interactions with common non‐AEDs. TGB is effective as add‐on therapy for partial seizures in patients with medically refractory epilepsy in doses ranging from 30 to 56 mg daily. Conversion to TGB monotherapy can be achieved in patients with medically refractory epilepsy, although additional controlled studies are needed to confirm the efficacy of TGB as monotherapy and to establish the effective dosage range. In controlled studies, the most common adverse events of TGB are dizziness, asthenia, somnolence, accidental injury, infection, headache, nausea, and nervousness. These are usually mild to moderate in severity and almost always resolve without medical intervention.