bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsant Actions of Lamotrigine on Spontaneous Thalamocortical Rhythms
Authors: Gibbs John W. , Zhang Yun‐Fu , Ahmed Hasan S. , Coulter Douglas A.
Published: March 2003

Summary:  Purpose: This study examined the actions of lamotrigine (LTG) on epileptiform discharges resembling generalized absence (GA) and primary generalized tonic–clonic (GTC) seizures in rat thalamocortical (TC) brain slices and attempted to characterize further the cellular mechanisms of action of LTG on neuronal ionic conductances.

Methods: Rat TC slices generated spontaneous generalized epileptiform discharges after perfusion with a medium containing no added Mg2+. Using multiple channel extracellular field‐potential recordings in thalamus and cortex, the effects of LTG were characterized on two principal variants of activity that are similar to spike–wave discharges (SWDs) of GA epilepsy and GTC seizure discharges. These were termed simple TC burst complexes (sTBCs) and complex TC burst complexes (cTBCs), respectively. With whole‐cell patch‐clamp recording techniques in acutely dissociated TC neurons, the effects of LTG on GABA (γ‐aminobutyric acid)A‐receptor–mediated currents and the low‐threshold calcium current (IT) were examined.

Results: In field‐potential recording studies in TC slices, both sTBCs and cTBCs were blocked by clinically relevant concentrations of LTG. In patch‐clamp recording studies, LTG was found to be ineffective in the modulation of both GABAA receptors (GABARs) and IT in TC neurons.

Conclusions: The efficacy of LTG on both variants of epileptiform discharges in TC slices clearly parallels its broad human clinical spectrum of action. This demonstrates that neurons within the TC system constitute one probable therapeutic target of LTG. However, LTG did not block either GABAR‐mediated responses or IT in TC neurons. Modulation of these conductances represent likely cellular mechanisms of action of other antiepileptic drugs effective in the control of GA epilepsy. This suggests that LTG may have as yet uncharacterized effects that could combine with its previously defined sodium channel–blocking actions to explain its clinical utility in the control GA seizures.
Cardiac Dysrhythmia Associated with the Immediate Postictal State after Maximal Electroshock in Freely Moving Rat
Authors: Darbin Olivier , Casebeer Doris J. , Naritoku Dean K.
Published: March 2003

Summary:  Purpose: Cardiac autonomic changes accompany complex partial seizures and generalized tonic–clonic seizures, and participate, at least partially, in the sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate variability (HRV) is one of the simplest ways of providing insight into autonomic functions. The entropy quantifies the repetition of complex patterns in a signal and refers to systems randomness, regularity, and predictability. Clinical investigations have reported that entropy decreases in patients with a high risk of sudden cardiac death. The goal of this study was to evaluate the effects of the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate postictal stage in the model of the freely moving rat.

Methods: Entropy changes were correlated with the high and low frequencies of spectral analysis, which reflect the participation of the sympathetic and parasympathetic activities.

Results: MES‐induced arrhythmia is characterized by an HRV increase, an imbalance in favor of the parasympathetic activity, and a decrease in the entropy. Entropy decrease was restricted to the duration of the arrhythmia, suggesting that the postictal arrhythmia may be associated with a higher risk of lethal cardiac complications. Nevertheless, entropy changes did not correlate with spectral changes.

Conclusions: The results suggest that the imbalance demonstrated in the spectral domain explains only partially the contribution of each autonomic system in the complexity of the heart rate during the postictal state.
Focal Ictal β Discharge on Scalp EEG Predicts Excellent Outcome of Frontal Lobe Epilepsy Surgery
Authors: Worrell Gregory A. , So Elson L. , Kazemi John , O'Brien Terence J. , Mosewich Russell K. , Cascino Gregory D. , Meyer Frederic B. , Marsh W. Richard
Published: March 2003

Summary:  Purpose: To determine whether a focal β‐frequency discharge at seizure onset on scalp EEG predicts outcome of frontal lobe epilepsy (FLE) surgery.

Methods: We identified 54 consecutive patients with intractable FLE who underwent epilepsy surgery between December 1987 and December 1996. A blind review of EEGs and magnetic resonance images (MRIs) was performed. Lesional epilepsy is defined as presence of an underlying structural abnormality on MRI.

Results: Overall, 28 (52%) patients were seizure free, with a mean follow‐up of 46.5 months. Presence of a focal β‐frequency discharge at seizure onset on scalp EEG predicted seizure‐free outcome in lesional (p = 0.02) and nonlesional (p = 0.01) epilepsy patients. At least 90% of patients who had either lesional or nonlesional epilepsy were seizure free if scalp EEG revealed a focal β discharge at ictal onset. Moreover, logistic regression analysis showed that focal ictal β pattern and completeness of lesion resection were independently predictive of seizure‐free outcome. Ictal onset with lateralized EEG activity of any kind and postresection electrocorticographic spikes did not predict surgical outcome (p > 0.05).

Conclusions: Only about 25% of FLE surgical patients have a focal β‐frequency discharge at seizure onset on scalp EEG. However, its presence is highly predictive of excellent postsurgical seizure control in either lesional or nonlesional FLE surgical patients.
Direct Medical Costs of Refractory Epilepsy Incurred by Three Different Treatment Modalities: A Prospective Assessment
Authors: Boon P. , D'Havé M. , Van Walleghem P. , Michielsen G. , Vonck K. , Caemaert J. , De Reuck J.
Published: March 2003

Summary:  Purpose: More than 20% of epilepsy patients have refractory seizures. Treatment options for these patients include continued polytherapy with/without novel antiepileptic drugs (AEDs), epilepsy surgery (ES), or vagus nerve stimulation (VNS). The purpose of this study was prospectively to compare epilepsy‐related direct medical costs (ERDMCs) incurred by these different treatment modalities.

Methods: Eighty‐four patients underwent a complete presurgical evaluation protocol at our institution. As a result, 24 (29%) patients were treated with continued AED polytherapy only; 35 (40%) underwent ES; and 25 (30%) had VNS. In each patient, annual costs in the 2 years preceding the therapeutic decision (ERDMC‐pre) and during the follow‐up afterward (ERDMC‐post) were prospectively calculated. Furthermore, frequency of complex partial seizures with/without secondary generalization (CPS±SG), dosage and number of AEDs, number of hospital admission days, clinic visits, and laboratory tests before and after the therapeutic decision also were prospectively assessed. ERDMC‐pre and ERDMC‐post were compared in and among the three treatment groups.

Results: In patients conservatively treated with AEDs, mean frequency of CPSs decreased from 12 per month to nine per month, whereas mean ERDMCs decreased from $2,525 U.S. to $2,421 U.S. In surgical patients, mean seizure frequency decreased from six to fewer than one per month; mean ERDMCs per year decreased from $1,465 U.S. preoperatively to $1,186 U.S. postoperatively. In the VNS group, mean seizure frequency decreased from 21 per month to seven per month. ERDMCs in this subgroup decreased from $4,826 U.S. to $2,496 U.S. Mean seizure frequency changes were significant when conservatively treated patients were compared with surgically treated and VNS patient groups (χ2 test, p<0.001 and p = 0.0019, respectively). ERDMC changes in conservatively treated patients also were statistically significant when compared with surgically treated and VNS patients (χ2 test, p = 0.0007 and p = 0.0036, respectively). No statistically significant differences were found in ERDMC changes between the surgical and VNS groups (χ2 test, p = 0.387).

Conclusions: Ongoing daily treatment of patients who underwent resective surgery costs significantly less than conservative treatment. For patients in whom resective surgery is not an option, ERDMC show a significant decrease in VNS‐treated patients compared with conservatively treated patients.
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.
Epileptic Syndromes in Childhood: Clinical Features, Outcomes, and Treatment
Authors: Camfield Peter , Camfield Carol
Published: March 2003

Summary: We reviewed the clinical features, outcome, and treatment of many of the epileptic syndromes that begin in the childhood from 2 to 12 years of age, using a review of the literature and personal experience, with most references to authoritative texts. The developmental tasks of childhood are centered on refinement of motor skills and development of complex intellectual and social skills. The childhood onset epilepsies can be divided into benign, intermediate, and catastrophic based on their impact on childhood development. The clearest benign epilepsy is benign rolandic epilepsy, which often does not require medication treatment. The definition of benign occipital epilepsy is still often vague. In the intermediate category, childhood absence epilepsy often has associated learning disorders and a poor social outcome. About 50% of children with cryptogenic partial seizures have a very benign course, even though their epilepsy syndrome is not well defined. Generalized epilepsy with febrile seizures plus (GEFS+) has a dominant inheritance with a defined defect in cerebral sodium channels, but varies considerably in severity within affected members of the same kindred. The catastrophic epilepsies in childhood all have an inconsistent response to AED treatment and include continuous spike‐wave in slow sleep (with variable severity), Landau‐Kleffner syndrome (with a confusing overlap with autistic regression), the Lennox Gastaut syndrome (with broad defining features), and myoclonic‐astatic epiplepsy (with important overlaps with Lennox‐Gastaut). Many of the epilepsies that begin in childhood are benign. Others interfere seriously with cognitive and social development.
Infantile Seizures and Epilepsy Syndromes
Authors: Nordli Douglas R.
Published: March 2003

Summary: Despite difficulties in precisely identifying and classifying infantile seizures, most infantile epilepsy syndromes can be classified, at least in broad categories. Infants with intractable epilepsy, however, may be difficult to accurately classify. These patients have complex presentations that do not easily allow labeling into “focal” or “generalized” categories. Within each category of infantile epilepsy, there appear to be benign and severe forms. Classifications based on semiology may be easier to use for all infants with epilepsy. At least three broad categories of epilepsy can be identified: infants with myoclonic seizures, infants with spasms, and infants with focal seizures. Within each category benign and severe presentations exist, with clearly defined, unique features. Whether the various presentations of epilepsy in infants can be cleanly separated into these categories, or need to be considered as points along a biologic spectrum, will require further research.
Ictogenesis and Epileptogenesis in EL Mice
Authors: Murashima Yoshiya L. , Yoshii Mitsunobu , Suzuki Jiro
Published: March 2003

Summary:  Purpose: In EL mice, ictogenesis is established at age ∼10 weeks, whereas epileptogenesis is induced through an experience of repetitive seizures during development. An “abnormal neural plasticity” has been suggested to be involved in these pathologic processes. It also is known that two isoforms of nitric oxide (NO) synthetase (nNOS and eNOS) are essential for the long‐term potentiation (LTP), a plastic response of neurons. It appears, therefore, that these NO synthetases might play a major role in the establishment of abnormal neural plasticity. The purpose of the present study was to investigate ictogenesis and epileptogenesis by observing alterations of NO synthetases as well as immediate early gene (IEG) expressions and γ‐aminobutyric acid (GABA) distributions in the brain during development and with respect to seizure history.

Methods: IEG (c‐fos and zif) expression in EL mice were analyzed by in situ hybridization with 35S. Distribution of GABA concentrations and glutamic acid decarboxylase (GAD) activities in the parietal cortex of EL mice was quantitatively determined using ultramicroenzymatic chemistry (Lowry, 1978). Three isoforms of NOS were assayed by immunoblotting analysis for hippocampal tissues of EL mice and their control animals, DDY mice. DNA fragmentation was detected with the TUNEL method.

Results: In EL mouse brains, IEG expression was related to the seizure history, seizure threshold, and age. Even in the interictal period, the animals expressed IEG continuously when their seizure thresholds were very low. Among various IEG expression sites in the brain, hippocampal CA1 was the most remarkable. These IEG expression sites were almost identical to the brain regions of EL mice where GABA concentrations and GAD activities were altered. Unexpectedly, the eNOS content of EL was very small, although eNOS appears to be responsible for NO that mediates an increase in local cerebral blood flow during focal seizures. nNOS, iNOS, and to a lesser extent, eNOS were essential to establish both ictogenicity and epileptogenicity. DNA fragmentation was observed in the hippocampus of EL mice in the interictal period.

Conclusions: Continuous IEG expression and abnormal GABAergic function are involved in the epileptogenesis of EL mice. Transiently expressed IEG, on the other hand, is associated with the ictogenesis. It is conceivable that an excess amount of iNOS (and subsequent increase in harmful antimicrobial NO) and a lesser amount of eNOS (and subsequent decrease in NO or endothelium‐derived relaxing factor, EDRF) may work together to contribute to a focus complex and ictogenesis. Drugs that suppress iNOS and/or potentiate eNOS may be promising candidates for a new type of antiepileptic agent.
Focus Diagnosis of Epilepsy Using Near‐Infrared Spectroscopy
Authors: Watanabe Eiju , Nagahori Yukihiro , Mayanagi Yoshiaki
Published: March 2003

Summary:  Purpose: We sought to establish a noninvasive method for focus diagnosis of epilepsy.

Methods: We examined the use of multichannel near‐infrared spectroscopy (NIRS). It is known as a noninvasive method of functional brain mapping. We monitored cerebral blood volume change with NIRS during long‐term EEG monitoring of epilepsy in 32 cases with intractable epilepsies to diagnose the epileptogenic focus.

Results: In 96% of cases, NIRS showed significant hyperperfusion in the side of seizure foci, whereas ictal SPECT showed hyperperfusion in 69% of cases.

Conclusions: Ictal NIRS is a reliable method to evaluate the focus side in epilepsy, especially when it is coupled with ictal SPECT.
Missed Diagnosis of Unruptured, Huge Left Ventricular Pseudoaneurysm
Authors: Akgun Serdar , Keser Nurgül , Yildirim Tekin , Arsan Sinan
Published: March 2003

We report a case of a huge left ventricular pseudoaneurysm following myocardial infarction. Early after myocardial infarction, the pseudoaneurysm was missed during the cardiac examination. The patient underwent coronary bypass surgery with endoaneurysmorraphy of the pseudoaneurysm, and made a satisfactory recovery. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Role of Contrast Echocardiography in the Assessment of Myocardial Rupture
Authors: Mittle Sumit , Makaryus Amgad N. , Mangion Judy
Published: March 2003

Left ventricular free wall rupture is known to complicate acute myocardial infarction and is the second most common cause of inhospital mortality in this patient population. Contrary to widely held medical belief, this does not always result in immediate fatal pericardial tamponade with hemodynamic collapse. Up to 40% of such occurrences are subacute and may evolve over hours or even days. A high index of suspicion and accurate diagnostic tests are required to identify and treat these patients with emergent surgery. Echocardiography has emerged as an important diagnostic modality to identify this catastrophic condition. Although the literature has scattered reports on the role of transesophageal and transthoracic echocardiography in diagnosing free wall rupture, to date, only one report in the literature used ultrasound contrast agents to better delineate echocardiographic findings. We will present two cases in which echocardiography with use of intravenous ultrasound contrast agents was instrumental in helping to exclude rupture in one case and help identify rupture in another. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Severe Pancytopenia after Leflunomide in Rheumatoid Arthritis
Authors: Auer J. , Hinterreiter M. , Allinger S. , Kirchgatterer A. , Knoflach P.
Published: March 2003

Leflunomide ist eine neue Substanz für die antirheumatische Basistherapie (disease‐modifying antirheumatic drug; DMARD). Bislang wurde unter Leflunomidetherapie keine Knochenmarkstoxizität und Panzytopenie mitgeteilt. Wir berichten über eine 62jährige Frau mit einer 14 Jahre bestehenden rheumatoiden Arthritis, die unter einer Behandlung mit Leflunomide eine schwere Knochenmarkstoxizität und Panzytopenie entwickelte.
Tumormarker
Authors: Fiebiger W. , Wiltschke Ch.
Published: March 2003

Zusammenfassung: Tumormarker sind Substanzen, welche in Tumorzellen produziert bzw. deren Synthesen durch maligne Zellen induziert werden und im Blut oder in anderen Körperflüssigkeiten durch nichtinvasive Methoden nachgewiesen werden können. Die Ursache für die gesteigerte Tumormarkersynthese ist in der Transformation von physiologischen zu malignen Zellen zu sehen. Da jedoch auch andere proliferative Prozesse, wie entzündliche Veränderungen oder benigne Tumoren zu einer Tumormarkersynthese führen können, ist der Aussagewert erhöhter Markerkonzentrationen erheblich eingeschränkt. Bis heute sind Tumormarker, mit Ausnahme des PSA, nicht zum Screening geeignet, auch können diese nur in wenigen Fällen zur Tumorlokalisation (Calcitonin, TG und β‐HCG) herangezogen werden. Wenngleich die Höhe der Markerkonzentrationen bei metastasierten Tumoren zumeist deutlich höher liegt als bei organbegrenzten Malignomen, ist ein Rückschluss auf Tumorgröße/Stadium nicht zulässig. Hilfreich sind Tumormarker hingegen in der Verlaufskontrolle zur Rezidivfrüherkennung und zum Monitoring palliativer Therapiekonzepte.
Plasminogen Activators in Inflammation and Sepsis
Authors: Pechlaner Ch.
Published: March 2003

Summary: Mortality of severe sepsis remains at 40 % to 50 %. Intensive efforts over the past two decades have only marginally improved outcome. Improving outcome in sepsis depends on understanding its pathophysiology, which involves triggers, responses of the organism, and dysfunction. Stress, injury, or infection trigger host responses, including local and systemic orchestrated mechanisms. Dysfunction and outcome depend on both trigger and response. Blood coagulation, inflammation, immunity, and fibrinolysis are critical components of the organism's responses. Understanding their role in sepsis pathophysiology is the key to effective treatment. Relevant studies were identified by a systematic literature search, complemented by manual search of individual citations. Using PubMed, ‘sepsis’ yields more than 62,000 references, ‘plasminogen activators’ more than 21,000. The selection of citations was guided by preference for reviews that expand important threads of argumentation. Single original studies were included when relevant to critical points. This analytical review describes the essential elements of pathophysiology and the current status of sepsis treatment. Based on this context, an emerging therapeutic option will be discussed: plasminogen activators.
Diagnostik und Therapie der endokrinen Orbitopathie – Konsensusrichtlinien*
Authors: Ramschak‐Schwarzer Sigrid , Langmann Andrea , Lindner Susanne , Prettenhofer Ulrike , Moncayo R. , Baldissera I. , Lind P. , Ettl A. , Maschek Wilhelmine , Pichler R. , Weissel M. , Leb G.
Published: March 2003

Zusammenfassung: Am 22. 9. 2001 wurden in Graz im Rahmen des VI. Grazer Hormonsymposions neuere Erkenntnisse zu Diagnose und Therapie der endokrinen Orbitopathie (EO) interdisziplinär behandelt. Im Zuge der abschließenden Roundtable‐Diskussion wurde ein Konsensvorschlag erarbeitet, dessen Ergebnis dargestellt wird.
Technische Grundlagen der 18F‐Fluorodeoxyglukose‐Positronen‐emissionstomographie‐Diagnostik
Authors: Standke R.
Published: March 2003

Zusammenfassung: Die Positronenemissionstomographie liefert regionale Information bezüglich dynamischer, physiologischer und biochemischer Prozesse im lebenden Körper. Der Positronenzerfall wird durch die aus der Annihilation resultierenden Gammaquanten nachgewiesen. Zwei gegenüberliegende Detektoren zählen nur dann ein Ereignis, wenn beide nahezu gleichzeitig (koinzident) 511‐keV‐Gammaquanten registrieren. Der Positronenzerfall wird irgendwo auf der Verbindungslinie zwischen den Detektoren (die sog. Koinzidenzlinie) lokalisiert. Hierbei können infolge von Streuung oder zufälligen Koinzidenzen mögliche Fehlregistrierungen auftreten. Verschiedene Bauformen derzeitiger PET‐Scanner werden vorgestellt und die Eigenschaften der bei der PET gebräuchlichen Szintillationskristalle erörtert. Die Akquisition im 2D‐ und im 3D‐Modus wird beschrieben. Korrekturmethoden für die Schwächung, Streuung und Totzeitverluste werden behandelt. Für die quantitative Analyse wird der relative Parameter Standard Uptake Value definiert. Abschließend werden Hybridsysteme wie kombinierte PET/CT‐Scanner und der Einsatz von CT‐Daten für die Schwächungskorrektur behandelt.
Clinical Applications of FDG‐PET in Oncology
Authors: Czernin J.
Published: March 2003

Summary: Positron emission tomography together with F‐18‐deoxyglucose (FDG) has emerged as a valuable clinical tool in the field of oncology. FDG‐PET diagnoses, stages and restages most cancers with a high diagnostic accuracy. The effects of chemotherapy on tumour metabolism can be monitored with this whole‐body technique. Recent studies have established a high prognostic accuracy of PET for predicting the clinical outcome of cancer patients.  The current review addresses the role of FDG‐PET for diagnosing, staging and restaging of lung cancer, colorectal cancer, lymphoma, melanoma and breast cancer staging and provides a brief outlook for future applications of clinical PET imaging.
Host location by adult and larval codling moth and the potential for its disruption by the application of kairomones
Authors: Hughes William O. H. , Gailey Darren , Knapp Jenny J.
Published: March 2003

Many fruit boring insect pests are difficult to control because of the short time span during which the damaging stage can be targeted before it becomes protected by the host fruit. We investigated the host location behaviour of the codling moth Cydia pomonella (L.) (Lepidoptera: Totricidae) to its apple host (Malus domestica Mill.) in the laboratory, with a view to the potential for extending the susceptible time span by disrupting the host location behaviour of the insects. We found that apple extract arrested neonate larvae. It also both attracted adult female moths and stimulated oviposition. α‐farnesene did not result in these effects to the same degree, suggesting that other components of apple odour are also important in the host location behaviour of this insect. By presenting a source of apple extract alongside an apple host, we examined whether the location of the apple host by larval and adult moths could be disrupted. We found that the application of apple extract could significantly increase the time taken for neonate larvae to locate an apple source. The source of apple extract also competed with the apple host, resulting in fewer eggs being oviposited near the apples. The results suggest that it may be possible to disrupt the host location behaviour of both the neonate larval and adult stage by the application of host kairomones.