bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained Efficacy and Long‐term Safety of Oxcarbazepine: One‐year Open‐label Extension of a Study in Refractory Partial Epilepsy
Authors: Beydoun Ahmad , Sachdeo Rajesh C. , Kutluay Ekrem , McCague Kevin , D'Souza Joseph 
Published: August 2003

Summary:  Purpose: To evaluate the long‐term efficacy, tolerability, and safety of oxcarbazepine (OXC) in medically refractory partial epilepsy. Methods: This study is the open‐label extension phase that followed a multicenter, randomized, double‐blind, dose‐response clinical study of OXC monotherapy in patients with medically refractory partial epilepsy. We analyzed the efficacy, tolerability, and safety of OXC during the first 48 weeks of open‐label therapy. To evaluate efficacy, we compared the change in seizure frequency throughout the 48 weeks of treatment with OXC with the baseline seizure frequency that preceded the double‐blind phase of the core study by an intent‐to‐treat and completer analysis. Safety and tolerability were evaluated by using an intent‐to‐treat analysis. Results: Of the 87 patients enrolled in the double‐blind study, 76 patients participated in the open‐label extension phase. Fifty‐five (72%) patients completed 48 weeks of open‐label treatment on a median OXC dose of 2,400 mg/day. Based on an intent‐to‐treat analysis, the median reduction in seizure frequency was 47%(p = 0.0054); the 50 and 75% responder rates were 46.1 and 25.0%, respectively, with 6.6% of patients remaining seizure free. The completer analysis yielded comparable efficacy results. OXC was well tolerated, with 13% of patients exiting because of adverse events. The six most common adverse events, irrespective of their causal relation to OXC, were dizziness, headache, fatigue, diplopia, nausea, and rash. For the most part, these adverse events tended to be transient. Conclusions: The efficacy of OXC is sustained with good safety and tolerability profiles during long‐term treatment of patients with medically refractory partial epilepsy.
Evidence for Distinct Genetic Influences on Generalized and Localization‐related Epilepsy
Authors: Winawer Melodie Rose , Rabinowitz Daniel , Barker‐Cummings Christie , Scheuer Mark L. , Pedley Timothy A. , Hauser W. Allen , Ottman Ruth 
Published: August 2003

Summary:  Purpose: Determining the existence of syndrome‐specific genetic factors in epilepsy is essential for phenotype definition in genetic linkage studies, and informs research on basic mechanisms. Analysis of concordance of epilepsy syndromes in families has been used to assess shared versus distinct genetic influences on generalized epilepsy (GE) and localization‐related epilepsy (LRE). However, it is unclear how the results should be interpreted in relation to specific genetic hypotheses. Methods: To assess evidence for distinct genetic influences on GE and LRE, we examined concordance of GE and LRE in 63 families containing multiple individuals with idiopathic or cryptogenic epilepsy, drawn from the Epilepsy Family Study of Columbia University. To control for the number of concordant families expected by chance, we used a permutation test to compare the observed number with the number expected from the distribution of individuals with GE and LRE in the study families. Results: Of the families, 62% were concordant for epilepsy type, and 38% were discordant. In all analyses, the proportion of concordant families was significantly greater than expected. Conclusions: This suggests that some genetic influences predispose specifically to either GE or LRE. Because of the ascertainment bias resulting from the selection of families containing multiple individuals with epilepsy, we could not test whether there are also shared genetic influences on these two epilepsy subtypes. Population‐based studies will be needed to explore these results further.
Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI Assessment
Authors: Tenney Jeffrey R. , Duong Timothy Q. , King Jean A. , Ludwig Reinhold , Ferris Craig F. 
Published: August 2003

Summary:  Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood‐oxygenation‐level–dependent (BOLD) fMRI in the brain was measured by using T2*‐weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using γ‐butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike–wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.
Electroclinical Patterns and Evolution of Epilepsy in the 4p– Syndrome
Authors: Battaglia Domenica , Zampino Giuseppe , Zollino Marcella , Mariotti Paolo , Acquafondata Celeste , Lettori Donatella , Pane Marika , Vasta Isabella , Neri Giovanni , Dravet Charlotte , Guzzetta Francesco 
Published: August 2003

Summary: Background:Wolf–Hirschhorn syndrome (WHS) is a well‐known clinical entity caused by partial deletion of the short arm of one chromosome 4 (4p– syndrome). Seizures occur in almost all the cases, but studies on the electroclinical disorder and its evolution are still scarce. We present a longitudinal study of the electroclinical features in 10 children with WHS.Methods:Ten patients (five boys and five girls) underwent a detailed clinical assessment and a prolonged EEG study. Six of the 10 also had video‐polygraphy.Results:Nine of the 10 patients had seizures; they were generalized or unilateral clonic and tonic–clonic, and atypical absences associated with myoclonic jerks. Age at onset of seizures varied from 1 day to 2.5 years. In all the patients, including the only one without seizures, two stereotyped EEG patterns were observed, consisting of (a) bursts of rhythmic (3–5 Hz), high‐voltage slow waves located in the posterior regions and increased by sleep, or bursts of rapid spike–wave complexes in the centroparietal and parietooccipital regions; and (b) repetitive rapid posterior spikes. Sleep organization was constantly absent or very poor. The evolution of epilepsy was frequently good, with four seizure‐free cases at the end of follow‐up, two of them weaned from antiepileptic drugs (AEDs).Conclusions:Seizure onset in WHS also can occur at neonatal age. At least two electrical stereotyped patterns of the epileptic disorder are associated with a relevant disorganization of the sleep states. Prognosis of epilepsy is generally good both for the seizure control and for its evolution.
Linguistic Processing in Idiopathic Generalized Epilepsy: An Auditory Event‐related Potential Study
Authors: Henkin Yael , Kishon‐Rabin Liat , Pratt Hillel , Kivity Sara , Sadeh Michelle , Gadoth Natan 
Published: August 2003

Summary:  Purpose: Auditory processing of increasing acoustic and linguistic complexity was assessed in children with idiopathic generalized epilepsy (IGE) by using auditory event‐related potentials (AERPs) as well as reaction time and performance accuracy. Methods: Twenty‐four children with IGE [12 with generalized tonic–clonic seizures (GTCSs), and 12 with absence seizures (ASs)] with average intelligence and age‐appropriate scholastic skills, uniformly medicated with valproic acid (VPA), and 20 healthy controls, performed oddball discrimination tasks that consisted of the following stimuli: (a) pure tones; (b) nonmeaningful monosyllables that differed by their phonetic features (i.e., phonetic stimuli); and (c) meaningful monosyllabic words from two semantic categories (i.e., semantic stimuli). Results: AERPs elicited by nonlinguistic stimuli were similar in healthy and epilepsy children, whereas those elicited by linguistic stimuli (i.e., phonetic and semantic) differed significantly in latency, amplitude, and scalp distribution. In children with GTCSs, phonetic and semantic processing were characterized by slower processing time, manifested by prolonged N2 and P3 latencies during phonetic processing, and prolongation of all AERPs latencies during semantic processing. In children with ASs, phonetic and semantic processing were characterized by increased allocation of attentional resources, manifested by enhanced N2 amplitudes. Semantic processing also was characterized by prolonged P3 latency. In both patient groups, processing of linguistic stimuli resulted in different patterns of brain‐activity lateralization compared with that in healthy controls. Reaction time and performance accuracy did not differ among the study groups. Conclusions: AERPs exposed linguistic‐processing deficits related to seizure type in children with IGE. Neurologic follow‐up should therefore include evaluation of linguistic functions, and remedial intervention should be provided, accordingly.
Recurrent Postictal Psychosis after Remission of Interictal Psychosis: Further Evidence of Bimodal Psychosis
Authors: Adachi Naoto , Kato Masaaki , Sekimoto Masanori , Ichikawa Ichiro , Akanuma Nozomi , Uesugi Hideji , Matsuda Hiroshi , Ishida Shiro , Onuma Teiichi 
Published: August 2003

Summary:  Purpose: To ascertain whether bimodal psychosis (i.e., independent postictal and interictal psychosis) in patients with epilepsy can be characterized by postictal psychosis that develops after interictal psychosis remits. Methods: We reviewed the records of 14 patients with bimodal psychosis treated at a national center hospital.Clinical and psychopathological characteristics of the patients were examined. Results: Among the 14 patients with bimodal psychosis, four initially had interictal psychosis, and 10 initially had postictal psychosis. That is, interictal‐antecedent bimodal psychosis characterized four cases, and postictal‐antecedent bimodal psychosis characterized 10 cases. Patients with interictal‐antecedent bimodal psychosis composed 2.2% of the total patients with epilepsy and psychosis (n = 180) and 28.5% of total patients with bimodal psychosis. All four patients with interictal‐antecedent bimodal psychosis had partial epilepsy with complex partial seizures, bilateral EEG abnormalities, and borderline (or decreased) intellectual functioning. Most of these clinical features are common to both types of bimodal psychosis. Among patients with interictal‐antecedent bimodal psychosis, the mean age at the onset of the initial symptoms was 10.8 years (SD, 4.3 years) for epilepsy, 24.4 (6.1) years for interictal psychosis, and 33.8 (4.5) years for postictal psychosis. Conclusions: In a few patients, postictal psychosis develops after the remission of interictal psychosis. Interictal‐antecedent bimodal psychosis is not likely a discrete entity because of several characteristics common to both types of bimodal psychosis. Patients may have greater vulnerability to psychosis and develop psychotic episodes easily, regardless of the presence of preceding seizures.
Different Electroclinical Manifestations of the Epilepsy Associated with Hamartomas Connecting to the Middle or Posterior Hypothalamus
Authors: Leal Alberto J. R. , Moreira Ana , Robalo Conceição , Ribeiro Constança 
Published: August 2003

Summary:  Purpose: The epilepsy associated with hypothalamic hamartomas (HHs) has typical clinical, electrophysiologic, and behavioral manifestations refractory to drug therapy and with unfavorable evolution. It is well known that only sessile lesions produce epilepsy, but no correlation has been established between the different types of sessile hamartomas and the diverse manifestations of the epilepsy. We correlate anatomic details of the hamartoma and the clinical and neurophysiologic manifestations of the associated epilepsy. Methods: HHs of seven patients with epilepsy (ages 2– 25 years) were classified as to lateralization and connection to the anteroposterior axis of the hypothalamus by using high‐resolution brain magnetic resonance imaging. We correlated the anatomic classification with the clinical and neurophysiologic manifestations of the epilepsy as evaluated in long‐term (24 h) video‐EEG recordings. Results: HHs ranged in size from 0.4 to 2.6 cc, with complete lateralization in six of seven patients. Ictal manifestations showed good correlation with the lobar involvement of ictal/interictal EEGs. These manifestations suggest the existence of two types of cortical involvement, one associated with the temporal lobe, produced by hamartomas connected to the posterior hypothalamus (mamillary bodies), and the other associated with the frontal lobe, seen in lesions connecting to the middle hypothalamus. Conclusions: A consistent clinical and neurophysiologic pattern of either temporal or frontal lobe cortical secondary involvement was found in the patients of our series. It depends on whether the hamartoma connects to the mamillary bodies (temporal lobe cases) or whether it connects to the medial hypothalamus (frontal lobe cases).
Evaluating Devices for Treating Epilepsy
Authors: Litt Brian 
Published: August 2003

Summary:  Purpose: Research into new implantable devices for treating epilepsy is expanding rapidly. Pilot studies suggest sufficient safety and potential efficacy to justify proceeding with larger scale clinical trials. Understanding the challenges presented by these trials, the testing and approval process for implantable devices, and how these differ from requirements for antiepileptic drugs (AEDs) is vital to evaluating when and where these new technologies will fit into the therapeutic armamentarium. Methods: Important lessons regarding the limitations of uncontrolled pilot studies, patient registries, and how the Food and Drug Administration (FDA) approval process can influence trials are drawn from the implantable device literature. Some discussion of the role of animal experiments is presented, both as justification for investigational device exemptions and their potential role in establishing safety. Clinical trial experience with the vagal nerve stimulator, the first device approved for the treatment of epilepsy, is also discussed. Results: New implantable devices hold great promise for medically refractory epilepsy patients who have no other therapeutic alternative. If effective, they may become a viable alternative to epilepsy surgery or multiple AED therapy in appropriate patients. Conclusions: The proper evaluation, use, and acceptance of antiepileptic devices will ultimately depend on carefully executed clinical trials that take into account unique aspects of these devices, such as the requirement for surgery, electrode placement, and navigation through FDA‐monitored testing and approval.
Assessing the Efficacy of Antiepileptic Treatments: The Ketogenic Diet
Authors: Thiele Elizabeth A. 
Published: August 2003

Summary: Purpose:To evaluate the evidence for determining if the ketogenic diet is an effective treatment for epilepsy.Methods:A literature review of published data over the past 80 years concerning the ketogenic diet was performed, focusing on efficacy, tolerability, age of patient population, as well as study design.Results:There have been several studies involving prospective and retrospective studies showing the ketogenic diet to be a very efficacious treatment in epilepsy, particularly epilepsy in childhood. However, no Class 1 studies have been published concerning the efficacy of the ketogenic diet.Conclusions:The ketogenic diet appears to be a very effective treatment for epilepsy, particularly in childhood. It would be beneficial to have Class 1 studies available to help better define the role of the diet both in children and adults.
Clinical Trials for Treatment of Primary Generalized Epilepsies
Authors: Faught Edward 
Published: August 2003

Summary:  Purpose: To review the current state of knowledge of the treatment of primary (idiopathic) generalized epilepsy syndromes based on the efficacy results of clinical trials, to highlight obstacles in the design of these trials, and to suggest solutions for future research. Methods: Published reports of controlled clinical trials, as well as large or significant uncontrolled trials of treatments for these syndromes, were reviewed. Trials were selected for discussion based on their importance or their illustration of design issues. Results: Only a few randomized, controlled trials of therapy for these syndromes exist. Conclusions based on this Class I data include efficacy in absence epilepsies for ethosuximide, valproate, and lamotrigine, and for eight drugs for primary generalized tonic‐clonic seizures. Many commonly accepted therapeutic strategies are not based on formal data. No controlled data exist for uncommon syndromes. Conclusions: More clinical trials of therapies for primary generalized epilepsies are needed. To overcome design obstacles, better funding, multicenter cooperation, inclusion of children, study designs requiring fewer patients, equivalent‐control designs, use of EEG and video seizure counting, and better syndrome identification will be required.
Randomized Controlled Trials of Epilepsy Surgery
Authors: Wiebe Samuel 
Published: August 2003

Summary:  Purpose: To review the following aspects of surgical randomized controlled trials (RCTs) in epilepsy: rationale, methodological issues, and state of the art. Methods: An overview of the literature and author's experience with methodological issues in surgical RCTs, contrasting them with those encountered in medical trials; a general comparison of RCTs and non‐RCTs (observational studies); and a literature search for and review of existing surgical RCTs in epilepsy. Results: Nonrandomized (observational) studies provide useful but potentially biased information about the effect of interventions. Because of their ability to deal with bias, RCTs are the optimum vehicle to obtain a true estimate of the effect of interventions, including surgery. Only seven surgical RCTs, encompassing 535 patients, have been performed in epilepsy, with variable adhesion to standard methodology for conducting RCTs. The major issues facing researchers undertaking surgical RCTs in epilepsy include timing of the study in relation to adoption of the intervention as standard practice, acceptance of randomization to an invasive procedure, timing of randomization in relation to the actual intervention, standardization of the surgical procedure, blinding, and patient recruitment. Conclusions: RCTs are the gold standard for evaluating surgical treatments. Despite the large number and types of surgical interventions used to treat epilepsy, only a handful has been subjected to the scientific rigour of RCTs. The challenges faced by researchers undertaking surgical RCTs in epilepsy are substantial but not insurmountable. Possible avenues to address these methodological hurdles are suggested.
Three‐Dimensional Catheter Positioning During Radiofrequency Ablation in Patients: First Application of a Real‐Time Position Management System
Authors: DE GROOT NATASJA M.S. , BOOTSMA MARIANNE , VAN DER VELDE ENNO T. , SCHALIJ MARTIN J. 
Published: August 2003

Three‐Dimensional Reai‐Time Position Management. Introduction: Precise localization of target sites for radiofrequency catheter ablation (RFCA) of arrhythmias is hampered by the relative inaccuracy of X‐ray localization procedures. This study evaluated the efficacy of a three‐dimensional (3D) real‐time position management system in guiding RFCA procedures in patients.Methods and Results: Patients (n = 30, age 59 ± 20 years) referred for ablation of either atrial flutter (n = 10), ventricular tachycardia (n = 15), or accessory pathways (n = 5) were studied. The real‐time position management system uses ultrasound ranging techniques to track the position of an ablation catheter relative to two multitransducer reference catheters, positioned in the right atrium or coronary sinus and the right ventricle. Each catheter contains three or four ultrasound transducers. The distance between the transducer(s) is determined hy calculating the time necessary for an ultrasound pulse to reach other transducers, assuming the speed of sound in blood is 1,550 m/sec. The proximal His bundle was marked at the beginning and the end of the procedure as an electrical landmark to verify reproducibility. After identification of target sites, the position of each lesion created with the ablation catheter was marked. Successful ahlation was achieved in 94% of the patients. The distance between the location of the proximal His hundle as marked at the beginning and at the end of the procedure was 2.0 ± 1.2 mm (range 1.5 to 3.5).Conclusion: The new 3D real‐time position management system facilitated RFCA procedures as it allowed accurate and reproducible 3D tracking of the mapping and ablation catheter.
Diagnosis and Therapy of Atrial Tachyarrhythmias in the Dual Chamber Implantable Cardioverter Defibrillator
Authors: DIJKMAN BARBARA , WELLENS HEIN J.J. 
Published: August 2003

Atrial Arrhythmias in ICD Patients. Introduction: Devices capable of monitoring and treating atrial taihyarrhythmias provide information about the natural history of the arrbythmias and potentially can influence their natural course by electrical therapy early after onset.Methods and results: Types of atrial arrhythmias and efficacy of device therapies were evaluated in 30 patients implanted with the Medtronic model 7250 Jewel AF implantable cardioverter defibrillator (ICD). All patients had structural heart disease and documented sustained ventricular and atrial arrhythmias (27 with atrial fibrillation [AF]) before implant. Twenty patients were taking amiodarone, and three were taking sotalol. During 20 ± 10 months of follow‐up, 600 atrial arrhythmia recurrences were documented in 50% of patients. AF was diagnosed in 19%. fast polymorphic atrial tacbycardia (AT) in 20%, fast monomorpbic AT in 57%. and slow AT in 4% of episodes. The two adaptive pacing therapies, burst and ramp, together with the 50‐Hz burst, were successful in 57% of delected atrial arrhythmias. Burst and ramp were responsible for 49% and 50‐Hz burst for 51% of successfully treated arrbytbmias; 33% of the episodes terminated spontaneously. No ventricular proarrbythmia was observed due to atrial pacing therapies. In 30% of episodes, dual chamber pacing was required due to post termination bradycardia. Atrial arrhythmia recurrences in patients with dilated cardiomyopathy were not amenable to pacing therapies. Several aspects of atrial arrhythmia diagnosis, therapy, and documentation that are specific for functioning of the Jewel AF arc discussed.Conclusion: Atrial arrhythmias in ICD patients with diseased hearts who are taking Class III antiarrbythmics frequently had longer cycle lengths than AF. Half of these arrhythmias could be terminated with pacing therapies; one third terminated spontaneously.