bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Determinants of Epilepsy: The Rotterdam Study
Authors: Li Xinhua , Breteler Monique M. B. , de Bruyne Martine C. , Meinardi Harry , Hauser W. Allen , Hofman Albert 
Published: August 2005

Summary: Purpose: To investigate the relation between vascular determinants and epilepsy in an elderly population. Methods: This is a cross‐sectional, community‐based, case‐control study. The total study population was comprised of 4,944 subjects, 65 of whom had epilepsy which conformed to International League Against Epilepsy (ILAE) criteria. Vascular determinants that were evaluated included a history of stroke or myocardial infarction, peripheral vascular disease, hypertension, serum total cholesterol and left ventricular hypertrophy. Multivariate logistic regression analysis was used to calculate prevalence odds ratios (OR), adjusted for age and gender, as a measure of the strength of the associations. Results: A history of stroke was strongly associated with lifetime epilepsy (OR 3.3; 95% CI [Confidence Interval] 1.3–8.5), as well as with late‐onset epilepsy (OR 3.1; 95% CI 0.9–10.6). All vascular determinants were associated with lifetime epilepsy and late‐onset epilepsy, with odds ratios >1. When stroke patients were excluded, the odds ratios were statistically significant for the relationships between total cholesterol and late‐onset epilepsy (OR 1.3, 95% CI 1.O–1.6) and left ventricular hypertrophy and late‐onset epilepsy (OR 2.9, 95% CI 1.0–8.6). Furthermore, presence of any of these vascular indicators was twice as common among subjects with late–onset epilepsy as compared with subjects without epilepsy (OR 2.0, 95% CI 0.9–4.2), and this was statistically significant when stroke patients were excluded (OR 2.1, 95% CI 1.04.7). Conclusions: These results suggest that there may be a relationship between vascular factors and the risk of late–onset epilepsy, apart from the relationship that exists through clinically overt stroke.
Effects of Valproate, Phenytoin, and MK‐801 in a Novel Model of Epileptogenesis
Authors: Applegate Craig D. , Samoriski Gary M. , Özduman Koray 
Published: August 2005

Summary: Purpose: We have developed and characterized a novel model of epileptogenesis based on the convulsive actions of flurothyl in mice. The hallmark feature of this model is a reliable change in the type of seizure expressed in response to flurothyl from generalized clonic to generalized tonic seizures. The purpose of our study was to evaluate the effects of chronic administration of valproate (VPA), phenytoin (PHT), and MK‐801 on the change in seizure phenotype observed in our model system. Methods: Male C57BL/6J mice received flurothyl seizures on 8 consecutive days. Two hours after the last generalized seizure, chronic drug or vehicle was administered twice daily at 12‐h intervals for 28 days. The drugs evaluated were VPA (250 mg/kg), PHT (30 mg/kg), and MK‐801 (0.5 mg/kg). After a 7‐day drug washout period, mice were retested with flurothyl. Results: Among uninjected or vehicle‐injected control mice, there was a significant increase in the proportion of animals expressing tonic seizures after the 28‐day stimulation‐free interval. Chronic administration of VPA or MK‐801, but not PHT, blocked the characteristic change in seizure type from clonic to tonic. Conclusions: The change in seizure phenotype observed after exposure to our paradigm indicates a fundamental reorganization in the propagation of flurothyl‐initiated seizures. As in electrical kindling, VPA and MK‐801 are effective at blocking or retarding the reorganization, whereas PHT is not. The concordance in pharmacologic profiles between kindling and our model suggests that the processes underlying changes in seizure susceptibility in these two models share mechanisms in common.
Seizure Lateralization During EEG Monitoring in Patients with Bilateral Foci: The Cluster Effect
Authors: Haut Sheryl R. , Legatt Alan D. , O'Dell Christine , Moshé Solomon L. , Shinnar Shlomo 
Published: August 2005

Summary: Purpose: To determine whether seizures that occur in clusters are more likely to reflect activity of the same focus than are seizures that are widely separated in time. Methods: EEG monitoring data from 14 patients with bilateral independent seizure onsets were analyzed. Twelve of the 14 patients had surface recordings only, and two had implanted electrodes. Interseizure intervals (ISIs) for 151 seizure pairs were measured. Seizure onsets were classified as right hemispheric, left hemispheric, or indeterminate. Seizure pairs were classified as concordant for hemisphere of onset, discordant, or indeterminate. The relation between seizure‐pair concordance and ISI was examined by using univariate analysis and analysis of variance (ANOVA). Results: Both seizures originated from the same hemisphere in 61 (75%) of 81 seizure pairs with ISIs >8 h, compared with 28 (55%) of 51 seizure pairs with ISIs >8 h (p < 0.015). The cluster effect was not more pronounced for ISIs <2 h. ANOVA demonstrated that the relation between IS1 and seizure concordance was not a result of the variability in seizure rates among patients. In three patients, the presence of bilateral foci was not demonstrated until more than five seizures were recorded. Conclusions: Seizures that occur after an IS1 of <8 h are more likely to come from the same side as the previous seizure than are those with longer ISIs. Thus clustered seizures should not be given the same weight as seizures widely separated in time. In addition, more than five seizures may sometimes be needed to adequately assess patients being evaluated for epilepsy surgery.
Antiepileptic Effects of Tiagabine, a Selective GABA Uptake Inhibitor, in the Rat Kindling Model of Temporal Lobe Epilepsy
Authors: Morimoto Kiyoshi , Sato Hitoshi , Yamamoto Yoshitaka , Watanabe Takemi , Suwaki Hiroshi 
Published: August 2005

Summary: Purpose: We determined the antiepileptic profile of tiagabine (TGB), a selective γ‐aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). Methods: The anticonvulsant and adverse effects of TGB were examined in amygdala‐ or hippocampal‐kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC‐7 1 1) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined. Results: TGB (2.5–40 mgkg intraperitoneally, i.p.) had potent and dose‐dependent anticonvulsant effects on both amygdala‐and hippocampal‐kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC‐711 > TGB > SKF‐89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mgkg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus. Conclusions: Our results indicate the clinical usefulness of TGB for treatment of drug‐resistant TLE.
Utility of the Lethargic (lh/lh) Mouse Model of Absence Seizures in Predicting the Effects of Lamotrigine, Vigabatrin, Tiagabine, Gabapentin, and Topiramate Against Human Absence Seizures
Authors: Hosford David A. , Wang Ying 
Published: August 2005

Summary: Purpose: Traditional methods of preclinical screening have predicted the effects of a putative antiepi‐leptic drug (AED) against human absence seizures by testing its efficacy against clonic seizures in the high‐dose pen‐tylenetetrazole (PTZ) model. This high‐dose PTZ model correctly predicted the efficacy of ethosuximide (ESM), benzodiazepines, and valproate (VPA) and the lack of efficacy of phenytoin (PHT) and carbamazepine (CBZ). However, the high‐dose PTZ model erred in predictions for (a) phenobarbital (PB) (PTZ: efficacy; human: noneffi‐cacy); (b) lamotrigine (LTG) (PTZ nonefficacy; human: efficacy); (c) vigabatrin (VGB) (PTZ: nonefficacy; human: proabsence effect); and (d) tiagabine (TGB) (PTZ efficacy; human: possibleproabsence). It also appears to have erred in predictions for gabapentin (GBP) (PTZ efficacy) and topiramate (TPM) (PTZ: efficacy). Because the lh/lh genetic model of absence seizures correctly predicted effects of ESM, clonazepam, VPA, PHT, CBZ, and PB against human absence seizures, we performed this study to test the predictive utility of the lWZh model for LTG, VGB, TGB, GBP, and TPM.Methods: Bipolar recording electrodes were implanted bilaterally into frontal neocortex of 8–week‐old male lWZh mice. With the exception of VGB, vehicle or drugs were administered intraperitoneally (i.p.) on alternating days, and an EEG was used to record effects on seizure frequency. With VGB, vehicle was administered i.p. on day 1, and gradually increasing doses of VGB were administered on successive days. Drug and vehicle effects were compared in corresponding lfi‐min epochs of the 150–min period after administration.Results: LTG (4.8–144 μmol/kg) significantly (p < 0.04) reduced seizure frequency (by 6.5%) compared with vehicle. In contrast, VGB (0.35–11 mmol/kg) and TGB (0.27–27 μmol/kg) significantly increased seizure frequency (300– 700%) and seizure duration (1,700–1,800%; p ≤ 0.001). GBP (18μmol/kg to 1.8 mmol/kg) and TPM (8.9–29.5 pmol/kg) had no significant effect on seizure frequency.Conclusions: In contrast to the high‐dose PTZ model, the lh/lh model correctly predicted the antiabsence effect of LTG, the possible proabsence effects of VGB and TGB, and the lack of effect of GBP and TPM. The lWlh model appears to be superior to the high‐dose PTZ model in predicting efficacy of putative AEDs against human absence seizures.
Hippocampal Volumetry with Magnetic Resonance Imaging: A Cost‐Effective Validated Solution
Authors: Chee Michael W. L. , Low Shoen , Tan Judy S. P. , Lim Winston , Wong Jill 
Published: August 2005

Summary: Purpose: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer‐based method of volumetric data analysis.Methods: Using a 1.0–T scanner, we obtained 2–mmthick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20–38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743–50). Overlays of individual observers’ tracings were used to fine tune the selection of landmarks and boundaries. Filled‐in silhouette pairs generated from these “training tracings” were compared to determine how well observers could visually quantify area differences.Results: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20–38 years, the mean right and left hippocampal volumes were 2,911 mm3 and 2,836 mm3, respectively. The lower limits of normal were 2,217 mm3 for the right and 2,178 mm3 for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10.Conclusions: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.
A North American Registry for Epilepsy and Pregnancy, a Unique Public/Private Partnership of Health Surveillance
Authors:   The North American Pregnancy and Epilepsy Registry
Published: August 2005

Summary: Purpose: A North American Registry of Epilepsy and Pregnancy (NAREP) has been established as a surveillance mechanism to identify adverse pregnancy outcomes that may be associated with fetal exposure to antiepileptic drugs (AEDs). As public attitudes become more receptive, and medical management more effective, women with epilepsy (WWE), are choosing to become pregnant in increasingly larger numbers. In the United States alone, 800,000 to 11 million WWE are of childbearing age. The offspring of these women have rates of congenital malformations of 1.25–11.5%. Although several factors could contribute to this risk, including AEDs, seizures during gestation, and maternal epilepsy, AEDs are an important variable over which we have some control. Unfortunately, no data currently exist that permit physicians to determine the relative safety of specific AEDs. With the introduction of several new AEDs, there is even further uncertainty about the potential safety of AEDs for treatment of pregnant women. Methods: We have organized a prospective registry for pregnant WWE which will systematically monitor pregnancy outcomes. The registry can serve as an early warning system for adverse outcomes associated with specific AEDs, administered alone or in combination. The registry has required a cooperative effort between the scientific and pharmaceutical communities. The genesis of this effort is described.
Pregnancies of Women with Epilepsy: A Population‐Based Study in Iceland
Authors: Olafsson Elias , Hallgrimsson Jon Thorgeir , Hauser W. Allen , Ludvigsson Peter , Gudmundsson Gunnar 
Published: August 2005

Summary: Purpose: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered o have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. Methods: We performed a historical population‐based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19‐year period in Iceland. Results: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7‐ fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. Conclusions: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.
Sleep‐Wakefulness Alterations in Amygdala‐Kindled Rats
Authors: Raol Y.H. , Meti B.L. 
Published: August 2005

Summary: Purpose: Our aim was to study the relation between epilepsy and sleep–wakefulness cycles in the amygdalakindling model of temporal lobe epilepsy. Methods: Adult male Wistar rats were electrically kindled through bipolar electrodes implanted in the anterior amygdala. Polysomnographic recordings were taken before and after kindled seizures for 6 h. For the studies on the effects of a single, full‐blown seizure, recordings were taken immediately after the seizure and daily thereafter until the recordings returned to baseline values. For studies on the effects of five full‐blown seizures, recordings were taken immediately after the fifth seizure and then on day 1, 2, 3, 5, 7, 14, 21, and 28. Results: Polysomnographic recordings taken immediately after the first full‐blown seizure revealed an initial increase in the duration of deep slow‐wave sleep (SII), a decrease in the light slow‐wave sleep (SI) stage of non‐rapid eye movement (NREM) sleep, and a decrease in the quiet wakefulness (W,) stage of wakefulness. All these parameters returned to baseline values after 24 h. The duration of rapid eye movement (REM) sleep increased and returned to the baseline value after 48 h. Five consecutive full‐blown seizures caused an increase in the duration of SII from the day the seizures occurred until day 28, whereas the duration of SI decreased for 72 h. The duration of REM sleep, decreased only on the day of the seizures and day 1, while decreases in the number of REM episodes were observed on the day of the seizure, day 2 and day 14. Conclusions: Our study indicates that even a single, full‐blown seizure can cause alterations in the architecture of sleep–wakefulness cycles for a short duration, and that multiple seizures produce long‐term effects.
Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication
Authors: Stoffel‐Wagner B. , Bauer J. , Flügel D. , Brennemann W. , Klingmüller D. , Elger C. E. 
Published: August 2005

Summary: Purpose: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone‐binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs. Methods: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17a‐hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle‐stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin‐like growth factor–I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid–stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men. Results: In the female patients, TSH, DHEAS, follicularphase LH, and luteal‐phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17α‐hydroxyprogesterone, free testosterone, inhibin B, and the testosterone LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone LH ratio in 50% indicates an impaired Leydig's cell function. Conclusions: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17α‐hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.
Bilateral Temporal Hypometabolism in Epilepsy
Authors: Blum David E. , Ehsan Tajammul , Dungan David , Karis John P. , Fisher Robert S. 
Published: August 2005

Summary: Purpose: Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known. Methods: We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH. Results: BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age‐matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MFU. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH. Conclusions: Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery.
Myoclonic Absence‐Like Seizures and Chromosome Abnormality Syndromes
Authors: Elia Maurizio , Guerrini Renzo , Musumeci Sebastiano A. , Bonanni Paolo , Gambardella Antonio , Aguglia Umberto 
Published: August 2005

Summary: Purpose: We explored the relationship between myoclonic absence seizures (MAS) and underlying chromosome disorders. Methods: Among 14 patients with MAS observed in three centers, 5 had typical cryptogenic myoclonic absence epilepsy (MAE), 2 had MAS associated with other seizure types (1 with signs of a neuronal migration abnormality and 1 with signs of a metabolic disorder), and 7 had MAS, with or without other seizure types, complicating a chromosome abnormality syndrome‐2 with trisomy 12p, 4 with Angelman syndrome, and 1 with inv dup (15). Results: In the 7 patients with chromosomopathy, MAS appeared at a mean age of 2.9 years (range 4 months to 6 years 6 months), had a duration of 4–20 s, and were accompanied by reduced awareness and rhythmic myoclonic jerks involving proximal limb muscles. Ictal EEG showed 2‐ to 3‐Hz generalized spike‐and‐wave discharges. Conclusions: In these patients, MAS differed slightly from those of typical MAE: age of onset was earlier, absences were of shorter duration, and no clear increase in muscular tone was noted. Abnormal expression of genes codifying for the subfamily of K+ channels and for γ‐aminobutyric acid‐3 subunit receptors (GABRBS), both located in the chromosome segments involved in the chromosomopathies presented by our patients, could be responsible for the same generalized seizure type. Chromosome analysis should be performed in patients with mental retardation and MAS, especially when the ictal pattern does not completely overlap that observed in MAE.
Quantifying the Costs of Serious Adverse Drug Reactions to Antiepileptic Drugs
Authors: Schlienger Raymond G. , Oh Paul I. , Knowles Sandra R. , Shear Neil H. 
Published: August 2005

Summary: Purpose: We assessed from an institutional perspective the direct costs of severe adverse cutaneous or hypersensitivity reactions due to antiepileptic drug (AED) therapy that led to hospitalization or prolonged hospital stay. Methods: Patients admitted for or developing severe AED‐induced cutaneous or hypersensitivity reactions while in hospital from January 1990 through June 1996 were identified by ICD‐9 codes E936, E937, E693, E695.1, E995.1, and E995.2. Identified cases were analyzed retrospectively by chart review and were included in the analysis if a causal relationship was determined to be possible, probable, or definite. Clinical outcomes were abstracted and related direct costs of the adverse drug reactions (ADRs) calculated.Results: A total of 384 cases were identified by ICD‐9 codes, of which 13 cases (mean age ± SD 52.9 ± 21.0 years) were included for further analysis. Eight patients (62%) were admitted because of an ADR (median length of stay 9.5 days; range 4–43), five (38%) experienced an ADR during hospitalization (median duration of ADR episodes 8.5 days; range: 7–21 days). The median direct medical costs of the ADRs were Canadian (CDN) $3,128 (range 1,149–21,293) per patient.Conclusions: The management of serious cutaneous and hypersensitivity ADRs due to AEDs is associated with considerable direct medical costs. These figures should be considered along with drug acquisition costs and treatment of clinical successes and failures in the overall assessment of the economic impact of pharmacotherapy. Prospective collection of direct costs associated with ADRs in clinical trials would be of value.