bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coadministration of Phenytoin and Felbamate: Evidence of Additional Phenytoin Dose‐Reduction Requirements Based on Pharmacokinetics and Tolerability with Increasing Doses of Felbamate
Authors: Sachdeo R. , Wagner M. L. , Sachdeo S. , Shumaker R. C. , Lyness W. H. , Rosenberg A. , Ward D. , Perhach J. L. 
Published: August 2005

Summary: Purpose: This open‐label study investigated the pharmacokinetic interaction of phenytoin (PHT) and felbamate (FBM). Methods: Ten subjects with epilepsy receiving PHT monotherapy were administered increasing doses of FBM (1,200, 1,800, 2,400–3,600 mg/day) at 2‐week intervals. PHT doses were reduced by 20% on an individual basis when evidence of clinically significant intolerance was present. With intolerance, the PHT dose was reduced before the next incremental FBM dose. Blood samples were analyzed for FBM, PHT, and PHT metabolite 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin (HPPH). Results: Total PHT plasma concentrations increased with coadministered FBM. PHT Cmax increased from 15.9 μg/ml at baseline to 20.9 μg/ml after 1,200 mg/day FBM and to 26.8 μg/ml after 1,800 mg/day FBM. Four subjects required a 20% PHT dose reduction after 1,800 mg/day FBM and six after the administration of 2,400 mg/day FBM. All subjects required further 20% PHT reductions before 3,600 mg/day FBM. FBM Cmax and AUCτ were reduced, and apparent clearance increased compared with data from FBM monotherapy. Conclusions: With the initiation of FBM therapy in subjects receiving PHT, the PHT dosage should be reduced by 20%. Further PHT dose reductions are likely to be necessary if the FBM dose is increased. The requirements for reductions in dose might be predicted by clinical signs of PHT intolerance.
GABA Uptake Blocker NNC‐711 Exhibits Marked Anticonvulsant Action in Two Cortical Epileptic Models in Immature Rats
Authors: Bernášková K. , Šlamberová R. , Mareš P. 
Published: August 2005

Summary: Purpose: To study the anticonvulsant action of a γ‐aminobutyric acid (GABA) uptake inhibitor NNC‐711 in two models of cortical epileptogenesis in immature rats. Methods: Twelve‐, 18‐, and 25‐day‐old rat pups with implanted electrodes were used in this study. Epileptogenic foci were elicited by a local application of bicuculline methiodide (BMI) on the sensorimotor cortical region by means of an implanted cannula, and cortical epileptic afterdischarges (ADs) were induced by low‐frequency stimulation (8 Hz) of the same cortical area. Epileptogenic foci were formed after pretreatment with NNC‐711 (1 or 10 mg/kg, i.p.), and epileptic ADs were elicited in the second experimental series. Then NNC‐711 was administered in the same doses, and stimulation was repeated. Results: NNC‐711 did not block the formation of epileptogenic foci, but it significantly suppressed the spontaneous transition of interictal focal into ictal activity in all age groups. The intensity of movements accompanying stimulation of the sensorimotor cortex was less under the influence of NNC‐711 in the 18‐ and 25‐day‐old rats. The duration of cortical ADs was shortened in all age groups, but transient abolition of ADs was observed only after the higher dose in the 25‐day‐old rats. In addition, the intensity of clonic seizures appearing during ADs decreased, and the transition of ADs into another type due to an involvement of limbic structures failed to appear in the 18‐ and 25‐day‐old rats. Conclusions: Primary epileptogenesis in the cerebral cortex was hardly influenced by NNC‐711, but the spread of epileptic activity was markedly suppressed. This effect was better expressed in the 18‐ and 25‐day‐old animals than in the youngest group.
Malformations in Offspring of Women with Epilepsy: A Prospective Study
Authors: Canger R. , Battino D. , Canevini M. P. , Fumarola C. , Guidolin L. , Vignoli A. , Mamoli D. , Palmieri C. , Molteni F. , Granata T. , Hassibi P. , Zamperini P. , Pardi G. , Avanzini G. 
Published: August 2005

Summary: Purpose: The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors. Methods: Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities. Results: The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic‐genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients. Conclusions: The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED‐related factors are the primary risk factors for an increased incidence of congenital malformations.
Antidepressant Drugs and Seizure Susceptibility: From In Vitro Data to Clinical Practice
Authors: Pisani Francesco , Spina Edoardo , Oteri Giancarla 
Published: August 2005

Summary:The use of antidepressant drugs (ADs) in patients with epilepsy still raises uncertainties because of the widespread conviction that this class of drugs facilitates seizures. A detailed knowledge of this issue in its various aspects may help in optimal management of patients suffering concurrently from epilepsy and depression. This article reviews the available data in vitro in animals and humans concerning the known potential of various ADs to induce epileptic seizures. Emphasis has been placed on those variables that may generate confusion in interpreting the results of the various studies. Most ADs at therapeutic dosages exhibit in nonepileptic patients a seizure risk close to that reported for the first spontaneous seizure in the general population (i.e., <0.1%). In patients taking high AD doses, seizure incidence rises markedly and may reach values up to 40%. With a patient history of epilepsy and/or concomitant drugs that act on neuronal excitability, low or therapeutic AD doses may be sufficient to trigger seizures. Experimental data are in partial conflict with human data on the relative potential seizure risk of the various ADs. Therefore, a reliable scale for assigning a relative value to an individual AD or to single AD classes cannot be made. It appears fair to say that maprotiline and amoxapine exhibit the greatest seizure risk, whereas trazodone, fluoxetine, and fluvoxamine exhibit the least. Some ADs may also display antiepileptic effects, especially in low doses, in experimental models of epilepsy and in humans, but the mechanism of this action is largely unknown. The available data suggest that ADs may display both convulsant and anticonvulsant effects and that the most important factor in determining the direction of a given compound in terms of excitation/inhibition is drug dosage. It is probable that drugs that increase serotonergic transmission are less convulsant or, even, more anticonvulsant than others. Because of mutual pharmacokinetic interactions between antiepileptic drugs and ADs, with consequent marked changes in plasma concentrations, it remains to be established whether or not plasma AD levels that are effective against depression also facilitate seizures. Finally, exploring the mechanisms through which ADs modulate neuronal excitability might open new possibilities in antiepileptic drug development.
The Effect of Video‐Game Software in Video‐Game Epilepsy
Authors: Ricci Stefano , Vigevano Federico 
Published: August 2005

Summary:Purpose: The individual role of video‐game (VG) programs in VG activation is still unclear. Strict relations between VG seizures and photo‐ and pattern sensitivity suggest that programs per se may have a role in seizure activation.Methods: We tested a series of 12 commercially available VG programs in 30 subjects aged 7–28 years; test protocol comprised intermittent photic stimulation (IPS), pattern stimulation, and a game session with 12 programs, each played for 5 min, delivered from a 50‐Hz screen.Results: Activation was observed in 17 subjects; marked differences were observed between different games: two programs activated 13 subjects; one program did not provoke activation. High variability between scenes makes it impossible to define mean brightness for the whole program. Activation correlated with “steady maximal brightness” (SMB) within a program; SMB is defined as the brightness in lux of the brightest scene steadily present in a program. SMB varied between 6 and 305 lux in tested programs. Difference in activation between different games was statistically significant (p < 0.001). Pattern sensitivity is strictly correlated with the probability of VG activation (p < 0.001).Conclusions: Our study demonstrates a strong variation in activation between different game programs and a strict relation between VG activation and pattern sensitivity. Programs with SMB >100 lux should be regarded as potentially dangerous; programs with SMB <50 lux may be considered relatively safe.
Video‐Game Epilepsy: A European Study
Authors: Trenité D. G. A. Kasteleijn‐Nolst , da Silva A. Martins , Ricci S. , Binnie C. D. , Rubboli G. , Tassinari C. A. , Segers J. P. 
Published: August 2005

Summary:With the introduction of Nintendo video‐games on a large scale, reports of children having seizures while playing suggested a possible specific, provocative factor. Although 50% of the photosensitive patients are also sensitive to a 50‐Hz television, nonphotosensitive patients with a history of videogame seizures were described as well. The question arises whether this is a mere coincidence, provoked by fatigue and stress, is related to the reaction to the television screen itself, or depends on the movement and color of the pictures of this specific game.A European study was performed in four countries and five sites. All patients were selected because of a history of television, video‐ or computer‐game seizures, with a history of sunlight‐, discotheque‐, or black and white pattern‐evoked seizures, or were already known to be sensitive to intermittent photic stimulation. A total of 387 patients were investigated; 220 (75%) were female and 214 (55%) of those were <18 years of age.After a routine examination, intermittent photic, pattern, and television stimulation were performed in a standardized way. The patients were investigated with Super Mario World and a standard relatively nonprovocative TV program, both on a 50‐and 100‐Hz television. Regardless of the distance, Super Mario World proved to be more provocative than the standard program (Wilcoxon, p < 0.05). Eighty‐five percent showed epileptiform discharges evoked by intermittent photic stimulation. Forty‐five percent of patients were 50‐Hz television sensitive and 26% were 100‐Hz television sensitive. Pattern sensitivity was found in 28% of patients.The patients, referred because of a television, video‐ or computer‐game seizure, were significantly more sensitive to pattern and to the 50‐Hz television (chi square, p < 0.001). More patients are sensitive when playing Super Mario, compared with the standard program (Wilcoxon, p = 0.001) and more sensitive with playing versus viewing (p = 0.016).Of the patients who were referred because of seizures in front of the television, or evoked by a video‐ or computer game, 14% proved not to be photosensitive. Although no difference in age or use of medication was found, twice as many men were found in this nonphotosensitive group.
Photic Stimulation: Standardization of Screening Methods
Authors: Trenité D. G. A.Kasteleijn‐Nolst , Binnie C. D. , Harding G. F. A. , Wilkins A. 
Published: August 2005

Summary:Purpose: Differences in methodology of intermittent photic stimulation within and between countries in Europe make collaborative research and interpretation of results difficult.Method: Experts in the field of photic stimulation from European countries have given an overview of methods used in routine photic stimulation. A consensus meeting was organized in May 1996 in the Netherlands.Results: Methodology, including specification of a photo stimulator, procedure of photic stimulation, and interpretation of EEG results, has been defined according to available scientific and clinical knowledge.Conclusions: Consensus was reached in setting up a safe, quick, simple and reliable method to determine whether or not patients are photosensitive. A specification of an international standard for intermittent photic stimulation in the routine EEG examination is given with the purpose of improving patient care and facilitating collaborative research.
Monostars: An Aid to Choosing an Antiepileptic Drug as Monotherapy
Authors: Brodie Martin J. 
Published: August 2005

Summary:This article describes a flexible, dynamic system for comparing antiepileptic drugs (AEDs) as monotherapy, taking into account the needs of the patient and the characteristics of the treatment. Because differences in efficacy between AEDs cannot readily be demonstrated in regulatory clinical trials, safety is of paramount importance. Each drug has been judged across 11 criteria. These include knowledge of mechanism of action, suitable pharmacokinetics, drug interactions, delineated range of efficacy, ease of titration, idiosyncratic reactions, sedative burden, neuropsychiatric profile, teratogenic potential, and the likelihood of producing long‐term side effects. The final consideration relates to how “comfortable” the doctor is with prescribing the drug as monotherapy. Scores of ‐1 (drawback), 0 (neutral/unknown), or +1 (advantage) have been allocated under each category, depending on current knowledge and clinical experience. The sum of the individual scores determines the awarding of “stars.” In addition, the positive and negative features of each AED, when used as monotherapy, are highlighted. A range of established and new AEDs has been examined using the “monostars” method, including phenobarbital, phenytoin, carbamazepine, sodium valproate, lamotrigine, gabapentin, oxcarbazepine, and vigabatrin. Scores can be adjusted as new information comes to light. Other agents can be added when suitable monotherapy data become available. This analysis supports the contention that choice of treatment in newly diagnosed epilepsy should take into consideration the patient's age, sex, general health, coexisting disabilities, concomitant medication, and life style. Seizure type, syndrome, and the AED's pharmacology, efficacy, and safety profile should also be considered. Because dosing is often modest, cost should rarely be the overriding factor in choosing a drug for a patient with newly diagnosed epilepsy in the developed world. With these criteria, some of the newer AEDs have potentially more to offer the patient as monotherapy than do the established agents.
Marital Status After Epilepsy Surgery
Authors: Carran Melissa A. , Kohler Christian G. , O'Connor Michael J. , Cloud Blaine , Sperling Michael R. 
Published: August 2005

Summary: Purpose: To characterize features influencing marital status in a group of patients with refractory epilepsy before and after epilepsy surgery and to assess the effect of seizure control on marital status after epilepsy surgery. Methods: We analyzed marital status in 430 epilepsy surgery patients and in a subset with temporal lobe epilepsy. Marital status was assessed in relation to gender and age of epilepsy onset and compared with marital rates for the U.S. population. Patients who had 4 years of postsurgical follow‐up were examined for change in marital status after surgery. Those patients who changed marital status were then evaluated for change in employment. Results: Marital rates were lower than expected in men. Men with onset of epilepsy by age 11 years were less likely to be married than men whose seizures began after age 11 or women whose seizures began at any age. Men and women with temporal lobe epilepsy had higher marriage rates than those with extratemporal lobe epilepsy. More than 4 years after epilepsy surgery (n = 190), patients who had no recurrent seizures were more likely to change marital status (28 of 124, 23%), than those who had recurrent seizures (five of 66, 8%). Seizure‐free women were more likely to divorce (n = 9) than were seizurefree men (n = 1). Most men who married were employed (77%), whereas women who divorced were usually unemployed (67%). Conclusions: The age at which seizures begin influences later marital status in men, who have reduced marriage rates. The abolition of seizures by epilepsy surgery creates new opportunities for changing social relationships. Location of the epileptic focus may influence psychosocial function.
Visual and Quantitative Ictal EEG Predictors of Outcome After Temporal Lobectomy
Authors: Assaf Bassam A. , Ebersole John S. 
Published: August 2005

Summary: Purpose: We investigated whether visual and quantitative ictal EEG analysis could predict surgical outcome after anteromesial temporal lobectomy (AMTL) in which mesial structures, basal, and temporal tip cortex were resected. Methods: We retrospectively reviewed 282 presurgical scalp‐recorded ictal EEGs (21‐ to 27‐channel) from 75 patients who underwent AMTL. We examined the pattern of seizure onset (frequency, distribution, and evolution) and estimated the principal underlying cerebral generators by using a multiple fixed dipole model that decomposes temporal lobe activity into four sublobar sources (Focus 1.1). We correlated findings with a 2‐year postoperative outcome. Results: Sixteen patients had seizures with a well‐lateralized, regular 5 to 9‐Hz rhythm at onset, that most often had a temporal or subtemporal distribution. All patients became seizure free after surgery. In 51 patients, seizure onset was remarkable for lateralized slow rhythms (>5 Hz), which sometimes appeared as periodic discharges, were often irregular and stable only for short periods (>5 s), and had a widespread lateral temporal distribution. Among these a favorable surgical outcome was encountered in patients with seizures having prominent anterior‐tip sources (16 of 17 seizure free), whereas those with dominant lateral or oblique sources had a less favorable outcome (three of 14 and 13 of 18, respectively). Irregular, nonlateralized slowing characterized seizure onsets in eight patients. Three patients became seizure free after surgery. Conclusions: Both visual and quantitative sublobar source analysis of scalp ictal EEG can predict surgical outcome in most cases after AMTL and complement non‐invasive presurgical evaluation.
Cross‐Cultural Adaptation and Use of the Epilepsy Psychosocial Effects Scale: Comparison Between the Psychosocial Effects of Chronic Epilepsy in Sweden and the United Kingdom
Authors: Chaplin John E. , Malmgren Kristina 
Published: August 2005

Summary: Purpose: To establish Swedish weightings for the Epilepsy Psycho‐Social Effects Scale (EPSES) and examine differences between Sweden and the U.K. in attitudes toward chronic epilepsy. Methods: After translation and back‐translation of the EPSES into Swedish, weightings were established through a paired comparison study in which 24 epilepsy professionals participated. The EPSES was then given to a hospital‐based sample of 57 patients with chronic epilepsy and the results compared with a British sample matched for age, sex, and frequency of seizures. Results: In the professional judgments of the EPSES statements, there were statistically significant differences in only four of 42 statements. Attitudes to employment, to medication, and to fear of seizures were considered more serious in the U.K., whereas social isolation was considered more a problem in Sweden. Patient attitudes to chronic epilepsy were found to be largely similar in the U.K. and Sweden; however, attitudes to employment, to the future, and to fear of seizures were significantly more a problem for patients in the U.K. Conclusions: The results indicate a great similarity in the interpretation of problems as measured by the EPSES in the U.K. and in Sweden. The differences in attitudes found are discussed in relation to economic and legislative differences between the two countries. Social as well as cultural differences should be taken into account when using standardized questionnaires. It is suggested that culturally specific weightings should be calculated and that these should be reevaluated at regular intervals.
Lack of Association Between Juvenile Myoclonic Epilepsy and HLA‐DR13
Authors: Hellard Stéphanie Le , Neidhart Elisabeth , Thomas Pierre , Feingold Josué , Malafosse Alain , Tafti Mehdi 
Published: August 2005

Summary: Purpose: We sought to replicate and extend a previously reported positive association between juvenile myoclonic epilepsy and HLA‐DR13. Methods: Ninety‐three subjects with juvenile myoclonic epilepsy and 93 normal blood donors, entirely of white origin with their families mostly of French extraction, underwent DNA‐based HLA‐DR13 and DQB6 typing. Results: None of the investigated alleles or combination of alleles (DRB1*1301‐DQB1*0603 or DRB1*1302‐DQB1*0604) showed a significant difference between patients and controls. Conclusions: Unlike previously reported positive association, in this population, there is no evidence that susceptibility to juvenile myoclonic epilepsy is associated with HLA‐DR13.
Sleep Problems and Daytime Behavior in Childhood Idiopathic Epilepsy
Authors: Cortesi Flavia , Giannotti Flavia , Ottaviano Salvatore 
Published: August 2005

Summary: Purpose: To evaluate the presence of sleep problems and their association with behavioral and adjustment problems in children with idiopathic epilepsy. Methods: A parental questionnaire was used to assess sleep problems in 89 children with idiopathic epilepsy for comparisons with 49 siblings and 321 healthy control children, equally distributed for age and sex. Sleep problems were clustered into five factors: parasomnias, parent/child interaction during the night, sleep fragmentation, daytime drowsiness, and bedtime difficulties. Daytime behavior and psychological adjustment were assessed by means of the Child Behavior Checklist. Maternal distress and disturbance was evaluated by the Malaise Inventory. The better to identify factors associated with sleep problems in the children with epilepsy, multiple regression analysis was performed. Results: Children with epilepsy showed significantly more sleep problems than did both siblings and healthy controls. Within the epileptic group, children with current seizures complained more of sleep problems than did the seizure‐free children. Moreover, children with epilepsy showed more behavioral problems and maladjustment. Age, paroxysmal activity density, duration of illness, seizure frequency, and behavioral problems were significantly associated with sleep problems in the epileptic group. Conclusions: The results of this study in a highly selected sample pointed out the presence of sleep problems, and adjustment and behavioral problems in children with idiopathic epilepsy. The presence of epilepsy, although benign, in childhood is associated with adaptive problems of the child. From this point of view, the alteration of some sleep habits may be a sign of emotional maladjustment. Although parents failed to perceive them as a problem, our findings indicate that attention to sleep and behavioral problems is important in clinical management of children with idiopathic epilepsy.