bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Chronic Electrical Stimulation of the Centromedian Thalamic Nuclei on Various Intractable Seizure Patterns: I. Clinical Seizures and Paroxysmal EEG Activity
Authors: Velasco Francisco , Velasco Marcos , Velasco Ana Luisa , Jimenez Fiacro 
Published: August 2005

Summary:Twenty‐three patients with various intractable seizure patterns were divided into four groups based on their most frequent seizure type and their clinical and EEG response to chronic electrical stimulation of the centromedian thalamic nuclei (ESCM): group A, generalized tonic‐clonic (GTC, n = 9); group B, partial motor (Rasmussen type) (n = 3); group C, complex partial seizures (CPS, n = 5); and group D, generalized tonic seizures (Lennox‐Gastaut type) (n = 6). CM were radiologically and electrophysiologically localized by means of stereotaxic landmarks and by thalamically induced scalp recruitinglike responses and desynchronization. ESCM consisted of daily 2‐h stimulation sessions for 3 months. Each stimulus consisted of a 1‐min train of square pulses with a 4‐min interstimulus interval, alternating right and left CM. Each pulse was 1.0 ms in duration at 60/s frequency and 8–15 V (400–1,250 μ‐A) amplitude. Voltage (V), current flow (μA) and impedance (kΩ) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10‐s epochs occurred in group A patients between the baseline period (BL) and the ESCM period. These changes persisted for >3 months after discontinuation of ESCM (poststimulation period, Post). Post was accompanied by a significant decrease in the number of paroxysmal EEG discharges. A substantial decrease in seizures and paroxysmal discharges was also observed in patients of group B. In contrast, patients of groups C and D showed no significant changes from BL to ESCM and Post periods, except for a significant decrease in the number of seizures in group D patients from BL to Post periods.
Effects of Monotherapy and Polytherapy on the Blink Reflex in Epileptic Patients
Authors: Lancman Marcelo Elias , Cristiano Edgardo , Golimstok Angel , Granillo Rubens Jorge 
Published: August 2005

Summary:We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences in R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.
Seizures with Clonazepam: Discontinuation and Suggestions for Safe Discontinuation Rates in Children
Authors: Sugai Kenji 
Published: August 2005

Summary:Clinical characteristics of clonazepam (CZP) discontinuation seizures were clarified from 17 patients who developed seizure exacerbation after rapid discontinuation, including abrupt discontinuation, reduction, or replacement with nitrazepam (NZP). Safe discontinuation rates of CZP were estimated by comparing these patients with 23 patients without CZP discontinuation seizures. The seizures consisted of status epilepticus or frequent attacks of generalized tonic‐clonic seizures (GTC) or non‐GTC, and the first attack of GTC. Incidence did not differ significantly between CZP‐effective cases and CZP‐ineffective cases at discontinuation. The reasons for abrupt discontinuation included adverse effects, insufficient efficacy, difficulty in taking CZP owing to pneumonia, or carelessness of the doctors or the families. Seizure exacerbation occurred 1–6 days after CZP discontinuation. Most of the problems improved with readministration of the original or smaller dosages of CZP or of NZP in an amount threefold or more greater than the original CZP dose. Safe discontinuation rates were estimated to be ≤0.04 mg/kg for abrupt discontinuation, ≤0.04 mg/kg/ week for reduction, and replacement with NZP of 2.5 or more times the original amount of CZP. These safe discontinuation rates were prospectively confirmed by 84 cases of CZP discontinuation in 54 other patients, and no seizure exacerbation occurred with these discontinuation rates.
Hematologic Manifestations of Long‐Term Valproate Therapy
Authors: May Ronald B. , Sunder Theodore R. 
Published: August 2005

Summary:Sixty patients receiving long‐term valproate (VPA) monotherapy were studied for hematologic side effects. All were patients in a long‐term care facility and ranged in age from 2 to 29 years (mean 14.6 years). Twenty developed at least one prominent hematologic abnormality. Thrombocytopenia and macrocytosis were the most common findings. In patients with macrocytosis, platelet counts were inversely related to VPA levels. Serum B12 levels were increased in 51 of the patients. In 12 patients with macrocytosis who were extensively studied, no etiology for the increased MCV could be identified. An increased number of Pelger‐Huet‐like cells was noted in these 12 patients. None of the patients demonstrated hepatic dysfunction. Hematologic toxicity was never severe enough to discontinue therapy and always responded to small decrements in VPA therapy. VPA was discontinued in only 1 patient, owing to poor seizure control.
Comparative Study of the Anticonvulsant Effect of γ‐Aminobutyric Acid Agonists in the Feline Kindling Model of Epilepsy
Authors: Morimoto Kiyoshi , Sanei Toshifumi , Sato Keiko 
Published: August 2005

Summary:We made a comparative study of the anticon‐vulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [γ‐ami‐nobutyric acid (GABA) receptor agonist 25–100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose‐dependent manner. SKF89976A (GABA uptake inhibitor 0.5–2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, γ‐vinyl GABA (GABA cata‐bolic enzyme inhibitor, GVG 50–200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.
Anticonvulsant Effects of Bretazenil (Ro 16‐6028) During Ontogenesis
Authors: Kubová H. , Rathouská J. , Mare P. 
Published: August 2005

Summary:Anticonvulsant action of a new benzodiaze‐pine, bretazenil (Ro 16–6028), was studied in 240 rats in five age groups: age 7, 12, 18, 25 and 90 days. Motor seizures induced by metrazol (pentamethylenetetrazol, PTZ, 100 mg/kg subcutaneously (s.c.) except for 18‐day‐old rats which received a dose of 90 mg/kg) served as a model. Animals were pretreated with Ro 16–6028 in doses of 0.001–0.1 mg/kg intraperitoneally (i.p.) 10 min before metrazol. Both types of metrazol‐induced seizures, minimal (mMS, predominantly clonic with preserved righting ability) and major (MMS, generalized tonic‐clonic), were suppressed by Ro 16–6028 in a dose‐dependent manner. Major seizures were always more sensitive to Ro 16–6028 than were minimal seizures. The youngest rats exhibited maximal effects of Ro 16–6028 against major seizures. On the other hand, this drug increased the incidence of minimal seizures in 7‐ and 12‐day‐old rats, i.e., in age groups in which this type of seizure is rare under control conditions.
Effects of a Benzodiazepine, Bretazenil (Ro 16‐6028), on Rhythmic Metrazol EEG Activity: Comparison with Standard Anticonvulsants
Authors: Brabcová R. , Kubová H. , Velíšek L. , Mareš P. 
Published: August 2005

Summary:A novel anticonvulsant benzodiazepine breta‐zenil (Ro 16–6028) was studied electrophysiologically in a model of human absence seizures: rhythmic metrazol activity (RMA) in rats. The effects of Ro 16–6028 pretreatment (0.01, 0.05, or 0.1 mg/kg intraperitoneally, i.p.) were compared with those of clonazepam (CZP, 0.02 or 0.1 mg/kg i.p.), valproate (VPA, 200, 300, or 400 mg/kg) and ethosuximide (ESM, 31.25, 62.5, or 125 mg/kg i.p.) in 45 rats with implanted electrocorticographic electrodes. RMA was elicited by an injection of pentylenetetrazol (metrazol, PTZ) in a dose of 40 or 35 mg/kg i.p. The effects of Ro 16–6028 were similar to those of CZP and VPA, i.e., suppression of RMA episodes, an increase in latency and a decrease in number, and total as well as mean duration. On the other hand, ESM differed from these antiepileptic drugs (AEDs) in inability to shorten the duration of RMA episodes. Based on these results, Ro 16–6028 might be predicted to be efficient against human absence seizures.
Allergy to Carbamazepine: Parallel In Vivo and In Vitro Detection
Authors: Troost Roger J. J. , Van Parys Johan A. P. , Hooijkaas Herbert , van Joost Theodoor , Benner Robbert , Prens Errol P. 
Published: August 2005

Summary: Purpose: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. Methods: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross‐reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ‐10,11‐epoxide (CBZ‐E), 10‐monohydroxy‐CBZ (MHD), and 10,11‐dihydroxy‐CBZ (DIOL)]. Results: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross‐reactivity to OCBZ was seen in ‐40% of CBZ‐reactive patients in both PTs and LPAs. Conclusion: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.
Prognosis of Epilepsy: A Review and Further Analysis of the First Nine Years of the British National General Practice Study of Epilepsy, a Prospective Population‐Based Study
Authors: Cockerell Oliver C. , Johnson Anthony L. , Sander Josemir W. A. S. , Shorvon Simon D. 
Published: August 2005

Summary: Purpose: To understand the prognosis of newly diagnosed epilepsy to provide rational therapy and advice for patients and their physicians. Methods: The National General Practice Study of Epilepsy (NGPSE) is the first large population‐based study that has assessed the prognosis of patients with newly diagnosed epilepsy prospectively over a prolonged period. We review the previously published data on the prognosis of epilepsy after 9 years of follow‐up. One thousand ninety‐one patients with newly diagnosed or suspected epilepsy who were attending 1 of 275 general practices throughout the United Kingdom between 1984 and 1987 were ascertained. Cases in this study were defined as the occurrence of one or more seizures, including provoked seizures. Prognosis in terms of remission of seizures, and mortality, was analyzed in the patients who were classified 6 months after recruitment as having definite epilepsy (n = 564) or possible/probable epilepsy (n = 228). Results: Only 33 patients were completely lost to follow‐up. After 9 years, 86% [95% confidence interval (CI) 81, 901 of patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI 61, 73, had achieved a remission of 5 years. For the complete cohort, with possible/probable epilepsy included, the rates increased to 87% (CI 83, 91) for 3‐year remission and 71% (CI 65, 77) for 5–year remission. The proportion of patients with definite epilepsy who were still in remission at 9‐year follow‐up (terminal remission) was 68% (CI 62, 74) for 3‐year remission and 54% (CI 48, 60) for 5‐year remission. When stratified by etiology, the proportions achieving 5–year remission by 9 years was 69% (CI 60, 77) for idiopathic seizures, and 61% (CI 46, 75) for remote symptomatic epilepsy. Age and seizure type had small effects on the chances of achieving remission, with children experiencing slightly lower rates than older patients, and partial seizures having lower remission rates than generalized seizures. The overall standardized mortality ratio (SMR) for patients with definite or possible/probable epilepsy was 2.5 (CI 2.1, 2.9), and 3.0 (CI 2.5, 3.7) for patients who were classified as having definite epilepsy. The SMR for patients with idiopathic epilepsy was 1.6 (CI 1.0, 2.4), for those with remote symptomatic epilepsy it was 4.3 (CI 3.3, 5.3, and for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5). Conclusions: Overall, most patients with epilepsy wiil enter remission; however, there is a higher than expected risk of death, especially in those with symptomatic epilepsy.
Effects of Sleep and Sleep Stage on Epileptic and Nonepileptic Seizures
Authors: Bazil Carl W. , Walczak Thaddeus S. 
Published: August 2005

Summary: Purpose: Previous studies of patients with epilepsy and animal models of epilepsy suggest that sleep increases the frequency, duration, and secondary generalization of seizures. This information is, however, incomplete. Methods: We retrospectively examined video‐EEG monitoring reports from our comprehensive epilepsy center. We recorded seizure type, site of onset (for partial seizures), sleep state at onset, and whether partial seizures secondarily generalized. Seizures arising from sleep were then reviewed to determine sleep state. Results: We analyzed 1,116 seizures in 188 patients. Thirty‐five percent of complex partial seizures (CPSs) starting during sleep underwent secondary generalization compared with 18% in wakefulness (p < 0.0001). Frontal lobe CPSs secondarily generalized at equal rates during sleep (22%) and wakefulness (20%), but temporal lobe CPSs generalized much more frequently during sleep (45%) than in wakefulness (19%; p < 0,0001). Frontal lobe seizures were more likely to occur during sleep (37%) than were temporal lobe seizures (26%; p = 0.0068). CPSs were more frequent in stages 1 and 2 and occurred rarely during REM. Seizures starting during slow‐wave sleep were significantly longer than seizures starting during wakefulness or stage 2 sleep. Psychogenic nonepileptic seizures (PNESs) were rare between midnight and 6 a.m. and never occurred during sleep. Conclusions: Sleep has a pronounced effect on secondary generalization of partial seizures, especially those of temporal lobe origin. Frontal lobe seizures occur more often during sleep than do temporal lobe seizures, and occurrence during sleep helps to distinguish PNESs from CPSs.
Colonic Absorption of Antiepileptic Agents
Authors: Stevenson Cheryl Miles , Kim JaeSun , Fleisher David 
Published: August 2005

Summary: Purpose: To evaluate a canine intestinal access‐port model to study colonic absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen to study absorption of a lipophilic and hydrophilic compound, respectively. Methods: Drug plasma level—time plots were generated subsequent to small intestinal and colonic drug administration of both drugs. The poorly water‐soluble phenytoin was administered in two doses to evaluate the impact of dissolution rate limits on colonic absorption. Maximal plasma concentration (Cmax) and area under the plasma level‐time curve (AUC) were used to assess the relative contribution of colonic absorption to plasma levels. Results: Whereas colonic gabapentin AUC and Cmax were only 0.25 and 0.15 of those seen after small intestinal administration, colonic phenytoin AUC and Cmax were one half and equivalent to, respectively, those observed for small intestinal administration. Furthermore, colonic administration of a higher phenytoin dose showed secondary maxima and continued increases in drug plasma levels with time. Conclusions: Colonic gabapentin absorption is poor compared with upper intestinal absorption, consistent with membrane transport rate limits to the absorption of this hydrophilic AED. Peak phenytoin plasma levels from colonic and small intestinal administration are comparable, indicating membrane transport does not limit absorption of this lipophilic agent. Continued plasma‐level increases from higher phenytoin doses are consistent with dissolution‐rate control of drug absorption in the colon. We suggest that colonic absorption provides a greater potential for toxicity from phenytoin overdose as a function of continued drug dissolution than for gabapentin overdose.
Characterization of Phenytoin‐Resistant Kindled Rats, a New Model of Drug‐Resistant Partial Epilepsy: Comparison of Inbred Strains
Authors: Cramer Sybille , Ebert Ulrich , Löscher Wolfgang 
Published: August 2005

Summary: Purpose: Previous work from our laboratory showed that amygdala‐kindled Wistar outbred rats can be selected according to the increase of afterdischarge threshold (ADT) after phenytoin application. Animals that consistently do not respond to phenytoin (PHT) with an ADT increase (non‐responders) are the first animal model of pharmacoresistant complex partial seizures. In this study, we determined the ability to respond to PHT in male kindled rats of different inbred strains. Methods: The experiments were performed in fully kindled rats of five different inbred strains, Wistar‐Kyoto, Lewis, Fischer 344, ACI, and Brown Norway. The response type of each rat was revealed by four consecutive PHT applications (75 mg/kg, i.p.) in fully kindled rats. Results: PHT application resulted in plasma concentrations ranging from some 16 μg/ml in Lewis rats to 35 μg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer 344 rats. The rats of each strain did not show a homogeneous response to PHT. A significant increase of ADT was found after 86–97% of applications in Lewis, Wistar‐Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in only 34% of experiments. This led to a considerable number of responders (i.e., consistent ADT increase by >20%) in Fischer 344, Wistar‐Kyoto, and Lewis rats. The only strain revealing nonresponders (i.e., consistent lack of ADT increase by >20% with PHT treatment) was Brown Norway. Conclusions: Inbred strains, although genetically more homogenous than outbred strains, differ in their response to PHT. Brown Norway rats can offer advantages for further detailed investigation of the resistance to PHT in the kindling model of complex partial seizures.
Individual Memory Change After Anterior Temporal Lobectomy: A Base Rate Analysis Using Regression‐Based Outcome Methodology
Authors: Martin Roy C. , Sawrie Stephen M. , Roth David L. , Gilliam Frank G. , Faught Edward , Morawetz Richard B. , Kuzniecky Ruben 
Published: August 2005

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression‐based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. Methods: Memory change was operationalized using regression‐based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. Results: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25–50% of left ATL patients on verbal semantic and episodic memory tasks, while one‐third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one‐third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one‐fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. Conclusions: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropscyhological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression‐to‐the‐mean before drawing predictive conclusions.
Clonidine‐ and Methohexital‐Induced Epileptiform Discharges Detected by Magnetoencephalography (MEG) in Patients with Localization‐Related Epilepsies
Authors: Kirchberger K. , Schmitt H. , Hummel C. , Peinemann A. , Pauli E. , Kettenmann B. , Stefan H. 
Published: August 2005

Summary: Purpose: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short‐acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike‐provoking properties of clonidine in comparison to methohexital. Methods: After oral premedication with clonidine, short‐lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. Results: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. Conclusions: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.