bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooling Abolishes Neuronal Network Synchronization in Rat Hippocampal Slices
Authors: Javedan Sam P. , Fisher Robert S. , Eder Hans G. , Smith Kris , Wu Jie 
Published: March 2003

Summary:  Purpose: We sought to determine whether cooling brain tissue from 34 to 21°C could abolish tetany‐induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission.Methods: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450–500 μm) from Sprague–Dawley male rats, maintained in an air–fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34°C, reduced to 21°C within 20 min.Results: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40‐Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a γ‐aminobutyric acid (GABA)A‐receptor antagonist. Cooling from 34 to 21°C reversibly abolished gamma oscillations in all slices tested. Short, low‐frequency discharges persisted after cooling in six of 14 slices. Single‐pulse–evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner.Conclusions: Tetany‐induced neuronal network synchronization by GABAA‐sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.
Neocortical Potassium Currents Are Enhanced by the Antiepileptic Drug Lamotrigine
Authors: Zona Cristina , Tancredi Virginia , Longone Patrizia , D'Arcangelo Giovanna , D'Antuono Margherita , Manfredi Mario , Avoli Massimo 
Published: March 2003

Summary:  Purpose: We used field‐potential recordings in slices of rat cerebral cortex along with whole‐cell patch recordings from rat neocortical cells in culture to test the hypothesis that the antiepileptic drug (AED) lamotrigine (LTG) modulates K+‐mediated, hyperpolarizing currents.Methods: Extracellular field‐potential recordings were performed in neocortical slices obtained from Wistar rats aged 25–50 days. Rat neocortical neurons in culture were subjected to the whole‐cell mode of voltage clamping under experimental conditions designed to study voltage‐gated K+ currents.Results: In the in vitro slice preparation, LTG (100–400 μM) reduced and/or abolished epileptiform discharges induced by 4‐aminopyridine (4AP, 100 μM; n = 10), at doses that were significantly higher than those required to affect epileptiform activity recorded in Mg2+‐free medium (n = 8). We also discovered that in cultured cortical cells, LTG (100–500 μM; n = 13) increased a transient, 4AP‐sensitive, outward current elicited by depolarizing commands in medium containing voltage‐gated Ca2+ and Na+ channel antagonists. Moreover, we did not observe any change in a late, tetraethylammonium‐sensitive outward current.Conclusions: Our data indicate that LTG, in addition to the well‐known reduction of voltage‐gated Na+ currents, potentiates 4AP‐sensitive, K+‐mediated hyperpolarizing conductances in cortical neurons. This mechanism of action contributes to the anticonvulsant effects exerted by LTG in experimental models of epileptiform discharge, and presumably in clinical practice.
Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women
Authors: Ragueneau‐Majlessi Isabelle , Levy Rene H. , Janik Franz 
Published: March 2003

Summary:  Purpose: This study was designed to evaluate whether levetiracetam, 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 levetiracetam, 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 levetiracetam 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 levetiracetam and placebo administration.Conclusions: Levetiracetam 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.
Effects of Age and Polytherapy, Risk Factors of Valproic Acid (VPA) Hepatotoxicity, on the Excretion of Thiol Conjugates of (E)‐2,4‐diene VPA in People with Epilepsy Taking VPA
Authors: Gopaul Sashi , Farrell Kevin , Abbott Frank 
Published: March 2003

Summary:  Purpose: Valproic acid (VPA) is an antiepileptic drug (AED) used for generalized and absence seizures. It has a rare but potentially fatal hepatotoxicity side effect, and many researchers believe that reactive metabolites of VPA could be involved. We demonstrated here that the thiol conjugates of (E)‐2,4‐diene VPA were significantly elevated in a high‐risk group of patients.Methods: Thirty‐four patients with seizures were divided into three groups. Group A (n = 14) were being treated with VPA; group B (n = 12) received VPA as well as other AEDs that do not induce P450–VPA metabolism; and group C (n = 8) received VPA and AEDs that induce P450–VPA metabolism. The NAC conjugates of (E)‐2,4‐diene VPA (NAC I and NAC II) were identified in the urine of patients by gas chromatography/mass spectrography NICI analysis.Results: VPA monotherapy (group A) or VPA polytherapy with non–P450‐enzyme–inducing drugs (group B), showed that patients younger than 7.5 years excreted significantly higher concentrations of the two conjugates compared with older patients (older than 7.5 years) in the same groups (p < 0.05). Patients receiving VPA polytherapy with P450‐enzyme–inducing drugs were all older than 7. 5 years (group C). They excreted significantly higher concentrations of NAC I and NAC II compared with patients in groups A and B who were older than 7.5 years (p < 0.05).Conclusions: There were no significant differences in the excretion of NAC I and NAC II between patients in group C and those who were 7.5 years or younger in groups A and B. High doses of VPA also were a significant factor associated with elevated NAC I and NAC II among young patients and in polytherapy patients.
MRI Volumetric Analysis in Rasmussen Encephalitis: A Longitudinal Study
Authors: Takeoka Masanori , Kim Francine , Caviness Verne S. , Kennedy David N. , Makris Nikos , Holmes Gregory L. 
Published: March 2003

Summary:  Purpose: Rasmussen encephalitis is a progressive inflammatory process with difficult‐to‐control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early‐stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)‐based volumetric analysis over an interval of 1 year, to assess for volumetric changes.Methods: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray‐ and white‐matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI.Results: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1‐year interval.Conclusions: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy.
Abnormal Neuroimaging in Patients with Benign Epilepsy with Centrotemporal Spikes
Authors: Gelisse Philippe , Corda Davide , Raybaud Charles , Dravet Charlotte , Bureau Michelle , Genton Pierre 
Published: March 2003

Summary:  Purpose: Neuroimaging procedures are usually unnecessary in benign epilepsy of childhood with centrotemporal spikes (BECTS) but are often performed before a specific diagnosis has been reached. By definition, BECTS occurs in normal children; however, recent reports have shown that it also can affect children with static brain lesions. We evaluated the prevalence of abnormal neuroimaging in BECTS and assessed whether the lesions had influenced the clinical and EEG expression of this epilepsy.Results: Among 98 consecutive cases first referred between 1984 and 1999, neuroimaging had been performed in 71 (72%) [magnetic resonance imaging (MRI), 20; computed tomography (CT), 59; MRI+CT, eight]. In ten (14.8%), neuroradiologic procedures were abnormal: enlargement of lateral venticles in five cases including a shunted hydrocephalus in two (no etiology in one, neonatal intraventricular hemorrhage in one), a moderate ventricular dilation in one (neonatal distress), a slight ventricular dilation and hypersignal intensities in the white matter in one (premature birth at 27 weeks), and a moderate enlargement of the right temporal horn in one. A right hippocampal atrophy, a biopercular polymicrogyria, a cavum septum pellucidum, a small cystic lesion located in the epiphysis, and an agenesis of the corpus callosum with macrocrania also were observed once each. The outcome was benign in all, in accordance with the overall prognosis of BECTS.Conclusions: This study confirms that neuroimaging may be abnormal in patients with BECTS and shows that the presence of brain lesions has no influence on the prognosis. Conversely, BECTS can be diagnosed in patients with brain lesions with or without significant neurologic history or abnormalities.
Presurgical Evaluation of Epilepsy by Brain Diffusion: MR‐detected Effects of Flumazenil on the Epileptogenic Focus
Authors: Konermann Stefan , Marks Sonja , Ludwig Tanja , Weber Johannes , De Greiff Armin , Dörfler Arnd , Leonhardt Georg , Wiedemayer Helmut , Diener Hans‐Christoph , Hufnagel Andreas 
Published: March 2003

Summary:  Purpose: After focal status epilepticus, focal alterations of the apparent diffusion coefficient (ADC) have been demonstrated in the epileptogenic zone by using diffusion‐weighted magnetic resonance (MR)imaging (DWI). Effects of flumazenil on an epileptogenic focus have been demonstrated by EEG recordings, but not by functional MRI. We hypothesized that dynamic spatiotemporal alterations of brain diffusion of the epileptogenic focus after application of flumazenil will be detectable by DWI and correlate with the epileptogenic zone.Methods: Twelve adult patients considered for epilepsy surgery with medically intractable temporal lobe epilepsy (TLE; n = 7), extratemporal lobe epilepsy (ETE; n = 2), and TLE+ETE (n = 3) were prospectively examined with DWI interictally (serving as baseline) and 10 min after application of 1 mg flumazenil i.v.Results: The baseline interictal ADC was significantly elevated in the hippocampus on the ictogenic side in the patients with TLE (p = 0.002) as compared with healthy volunteers. The following changes of the mean ADC were seen in different regions of interest (ROIs) after injection of flumazenil: decreases in the hippocampus on the seizure‐onset side by 14.8% (p = 0.005); decreases in the parahippocampal gyrus on both sides by 6.8% (epileptogenic side; p = 0.044) or 7.9% (nonepileptogenic side; NS), respectively; decreases in the cortex on the nonictogenic side by 7.9% (p = 0.047); and no significant changes of the ADC in the other ROIs.Conclusions: ADC decreases measured after application of flumazenil were seen in the seizure‐onset zone as revealed by EEG and structural MRI and are an indicator of focus localization in patients with TLE.
Epileptogenesis Induced by Alternate‐site Kindling in Bilateral Hippocampi
Authors: Matsuda Yoshiki , Yano Michiko , Kitayama Masaomi , Kogure Shinichi , Yamauchi Toshio 
Published: March 2003

Summary:  Purpose: Alternate‐site kindling (AK), which has been known to induce so‐called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling.Methods: Ten adult rabbits were used. Daily kindling stimulation consisted of a 1‐ s train of 50 pulses (pulse duration, 1 ms) of 80 to 200 μA (base‐to‐peak), which was higher than the afterdischarge (AD) threshold. The concurrent alternating stimulations were delivered to the right and left hippocampus once every 24 h.Results: All animals developed a stage 5 convulsion with a mean of 28.1 ± 3.3 (mean ± SEM) stimulations. The right and left hippocampus received 14.8 ± 1.7 and 14.6 ± 1.6 stimulations, respectively. Behavioral stages induced by stimulation of the right or left hippocampus evolved to generalized seizures along a similar course. Kindling antagonism was not observed. The two sides showed similar increases in AD duration, and similar chronologic changes in interictal discharge (IID) frequency. Simple A‐type IID and complex types of IID appeared at higher rates, whereas simple B‐type IID remained at a relatively low level.Conclusions: The present AK procedure did not induce kindling antagonism, but it induced progression of kindling manifestations. The origin of simple B‐type IID is known to be in the contralateral side, and its intracellular counterpart corresponds to a sequence of small depolarization followed by large hyperpolarization, suggesting that plastic changes in the feed‐forward inhibitory system play an important role in hippocampal kindling.
The Effects of Adjunctive Topiramate on Cognitive Function in Patients with Epilepsy
Authors: Lee Suzee , Sziklas Viviane , Andermann Frederick , Farnham Sara , Risse Gail , Gustafson Mary , Gates John , Penovich Patricia , Al‐Asmi Abdullah , Dubeau Francois , Jones‐Gotman Marilyn 
Published: March 2003

Summary:  Purpose: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy.Methods: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed.Results: In Study 1, significant (p ≤ 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p ≤ 0.05) for tests of fluency, sustained concentration, and visual motor processing speed.Conclusions: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.
The Diagnostic Significance of Video‐EEG Monitoring Findings on Pseudoseizure Patients Differs Between Neurologists and Psychiatrists
Authors: Harden Cynthia L. , Burgut F. Tuna , Kanner Andres M. 
Published: March 2003

Summary:  Purpose: The diagnosis of psychogenic pseudoseizures has improved with the availability of video‐electroencephalography (EEG) monitoring; however, the outcome of this difficult disorder has remained poor. In an attempt to elucidate factors contributing to this poor outcome, we hypothesized that neurologists and psychiatrists differ in their views of the diagnosis and management of psychogenic pseudoseizure patients.Methods: The hypothesis was tested by using a brief anonymous questionnaire administered to neurologists and psychiatrists at continuing medical education (CME) conferences.Results: We found that neurologists and psychiatrists differ significantly in their opinion as to the accuracy of the video‐EEG procedure; psychiatrists view video‐EEG as often inaccurate in the diagnosis of psychogenic pseudoseizures compared with neurologists (p < 0.001). Neurologists, more frequently than psychiatrists, thought that patients' own psychopathology rather than “doctors dropping the ball” was a predominant factor in contributing to therapeutic failure, but this difference between specialties did not reach statistical significance.Conclusions: Resolving the differences between neurologists and psychiatrists would be helpful in caring for psychogenic pseudoseizure patients. These results support the need to encourage psychiatrists to have an integral involvement in epilepsy centers and to improve the understanding of psychogenic pseudoseizures in both disciplines.
The Effect of Electrical Stimulation of the Subthalamic Nucleus on Seizures Is Frequency Dependent
Authors: Lado Fred A. , Velíšek Libor , Moshé Solomon L. 
Published: March 2003

Summary:  Purpose: Animal studies and anecdotal human case reports have indicated that the subthalamic nucleus (STN) may be a site of anticonvulsant action.Methods: We tested the hypothesis that continuous electrical stimulation of the STN inhibits seizures acutely. We determined the effects of three stimulation frequencies, 130 Hz, 260 Hz, and 800 Hz, on generalized clonic and tonic–clonic flurothyl seizures. Adult male rats were implanted with concentric bipolar stimulating electrodes in the STN bilaterally. After recovery, rats underwent flurothyl seizures to compare the effects of each stimulation frequency on seizure threshold. Rats were tested 4 times, twice in the stimulated condition, and twice in the unstimulated condition. The order of trials was random, except that stimulation trials alternated with control trials. Flurothyl seizure thresholds under each stimulation condition were compared with control values from the same animal.Results: Bilateral stimulation of the STN at 130 Hz produced a significant increase in the seizure threshold for clonic flurothyl seizures, whereas stimulation at 260 Hz did not appear to have any effect on seizures. STN stimulation at 800 Hz significantly lowered seizure threshold for tonic–clonic seizures.Conclusions: We conclude that electrical stimulation of the STN can be anticonvulsant, but the effects appear to depend on the stimulation frequency and the type of seizure.
Seizure Control and Cognitive Outcome after Temporal Lobectomy: A Comparison of Classic Ammon's Horn Sclerosis, Atypical Mesial Temporal Sclerosis, and Tumoral Pathologies
Authors: York Michele K. , Rettig Gayle M. , Grossman Robert G. , Hamilton Winifred J. , Armstrong Dawna D. , Levin Harvey S. , Mizrahi Eli M. 
Published: March 2003

Summary:  Purpose: Neuropathologic examination of resected tissue after anterior temporal lobectomy (ATL) for treatment of complex partial seizures revealed several distinct histologic substrates. Our study examined the relation between neuropathology, seizure control, and cognition in ATL patients and described preliminary profiles to aid in the prediction of outcome.Methods: Of the 149 patients who underwent ATL from 1980 to 1999, long‐term follow‐up was available for 145. Specimens from 124 of the 145 patients had histologic findings consistent with one of three diagnoses: classic Ammon's horn sclerosis (cAHS; n = 75), atypical mesial sclerosis (Atypical; n = 21), or low‐grade tumor (Tumor; n = 28). The other 20 patients had diverse pathologies that were insufficient for analysis. ATL patients underwent a complete preoperative and 68 underwent a postoperative neuropsychological evaluation.Results: Of the 145 patients, 84% of cAHS, 57% of Tumor, and 29% of Atypical patients had a ≥95% reduction in seizure frequency. Neuropsychological testing suggested that cAHS patients demonstrate more generalized preoperative cognitive impairment than do the Atypical or Tumor patients. The Atypical group recalled significantly less nonverbal material after surgery than did the cAHS or Tumor groups. Stratification by both pathology and surgery side revealed that the right Atypical patients declined more on information processing and set shifting.Conclusions: Patients with cAHS or Tumor demonstrated better seizure control and fewer declines in cognitive functioning after ATL than did the Atypical patients, highlighting the need to investigate this group as a distinct entity.
Cross‐cultural Differences in Levels of Knowledge about Epilepsy
Authors: Doughty Julie , Baker Gus A. , Jacoby Ann , Lavaud Virginie 
Published: March 2003

Summary:  Purpose: To study how much people with epilepsy in Europe know and understand about their condition and how this might affect their lives.Methods: Clinical, demographic, psychosocial details and information assessing knowledge were collected by using self‐completion questionnaires mailed to members of epilepsy support groups.Results: Data were collected from 6,156 people with epilepsy from ten European countries. There were significant between‐country differences in all variables considered. Overall levels of knowledge were acceptable when measured by the epilepsy knowledge questionnaire (EKQ, medical items). However, there were some gaps in knowledge, particularly in issues relating to medication and cause of epilepsy.Conclusions: This is the largest study of its kind to date. Results clearly highlighted that levels of knowledge differed significantly between countries. Overall, people with epilepsy are reasonably well informed about epilepsy, although some gaps in knowledge were evident.