bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossed Cerebellar Diaschisis Related to Recurrent Focal Seizures
Authors: Stübgen Joerg‐Patrick
Published: August 2005

Summary: After several days of recurrent focal motor seizures in a 32‐year‐old pregnant woman, a brain magnetic resonance imaging (MRI) scan showed signal abnormalities restricted to cerebral cortex and contralateral cerebellum that did not enhance after gadolinium administration. Maximal EEG dysfunction and seizure onset correlated anatomically with the area of image change. An aggressive medication regimen and termination of the pregnancy resulted in seizure control, reversal of postictal neurologic deficit, and improvement or resolution of the MRI and EEG abnormalities in 6 weeks. We concluded that the sequence of events suggested the reversible MRI lesions to be the result of repetitive seizure activity and that both localization and resolution of the lesions may be explained by reversible excitotoxic cell damage due to seizure‐related excessive synaptic discharge.
Efficacy and Tolerability of Vigabatrin in Children with Refractory Partial Seizures: A Single‐Blind Dose‐Increasing Study
Authors: Bernardina Bernardo Dalla , Fontana E. , Vigevano F. , Fusco L. , Torelli D. , Galeone D. , Buti D. , Cianchetti C. , Gnanasakthy A. , Iudice A.
Published: August 2005

Summary: The efficacy and tolerability of vigabatrin (VGB) in children with refractory partial epilepsy were assessed in a single‐blind, add‐on, fixed‐sequence, placebo‐controlled trial. After 1‐month observation, the patients entered a 7‐month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2‐month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure‐free (n = 3) or improved markedly (n = 8), treatment was completed at a dose <80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21,12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number of patients who had <50% reduction in seizure frequency after 2, 4, and 6 months was 28, 33, and 35, respectively. Eight patients became seizure‐free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no signscant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment. Increased appetite and sedation were observed in 17 and 11% of cases, respectively. VGB is effective in the management of refractory partial epilepsy in children, and in some patients a positive dose‐response relationship appears to occur over the assessed dosing range.
The Medical‐Moral Account on Epilepsy by Pedro de Horta: A Historical Review
Authors: Soria Emilio D. , Fine Edward J.
Published: August 2005

Summary: We bring to reader's attention the book Medical‐Moral Account of the Most Troublesome and Rigorous Illness of Epilepsy, written in 1754 by the Mexican physician Pedro de Horta. This book is the earliest text on epilepsy written in the New World. We examine Pedro de Horta's medical and religious concepts of epilepsy and analyze concepts of epilepsy in Hispanic communities during the eighteenth century.
Decreased Neuronal Burst Discharge Near Site of Seizure Onset in Epileptic Human Temporal Lobes
Authors: Colder Brian W. , Frysinger Robert C. , Wilson Charles L. , Harper Ronald M. , Engel Jerome
Published: August 2005

We examined auto‐correlation and interval distribution characteristics of neuronal discharge from patients with complex partial seizures. The objective was to compare the interictal firing patterns of neurons in mesial temporal structures ipsilateral to the site of seizure onset with firing patterns of neurons in homologous contralateral structures. Spontaneous interictal recordings of 258 single neurons were acquired from 23 patients. A “burst area” measure was derived from the neuronal auto‐correlation to assess the likelihood of grouped action potential discharge (burst discharge). Large burst area measures indicate a tendency for single neuronal burst discharge, but do not disclose information about interspike intervals within bursts. Although several measures based on single neuronal interspike interval distributions showed no overall difference between hemispheres, burst area was significantly reduced in mesial temporal structures ipsilateral to the site of seizure onset. Possible mechanisms of decreased burst discharge in epileptogenic regions include selective loss of burst‐discharging neurons and increased recurrent inhibition.
Anticonvulsant Activity of Phenobarbital and Valproate Against Maximal Electroshock in Mice During Chronic Treatment with Caffeine and Caffeine Discontinuation
Authors: Gasior Maciej , Borowicz Kinga , Buszewicz Grzegorz , Kleinrok Zdzislaw , Czuczwar Stanistaw Jerzy
Published: August 2005

We evaluated the protective activity (expressed as ED50, values in mg/kg) of phenobarbital (PB, 120 min before testing) and valproate (30 min) alone or combined with caffeine in male mice with seizures induced by maximal electroshock (MES). Both antiepilep‐tic drugs (AEDs) were administered by intraperitoneal (i.p.) injection in a single dose to mice receiving intraperitoneal caffeine either in a single dose 30 min before the test or as pretreatment every 12 h for 3 and 14 days. In addition, we determined the ED50, values of the AEDs 24 and 72 h after 14–day treatment with caffeine. Finally, we studied the influence of a challenge dose of caffeine, injected in mice 24 and 72 h after 14 days of treatment with caffeine, on the protective activity of PB or VPA. Caffeine in a single dose of 23.1 mg/kg reduced the anticonvulsant effect of PB. Its protective activity was further impaired after 3 and 14 days of caffeine treatment. The ED50, for VPA was significantly increased both by the single dose of caffeine and by chronic treatment. The anticonvulsant activity of PB and VPA measured 24 and 72 h after 14–day treatment with caffeine did not differ from control values, but a challenge dose of caffeine injected 24 or 72 h after daily injections for 14 days resulted in a significant reduction in the protective activity of both AEDs. Measurement of the total plasma levels of caffeine, VPA, and PB did not suggest pharmacokinetic interactions as an explanation for our results. Our results indicate that chronic caffeine exposure may progressively reduce the antiepileptic potency of VPA and PB.
Patients' Experiences of and Satisfaction with Care for Their Epilepsy
Authors: Buck Deborah , Jacoby Ann , Baker Gus A. , Graham‐Jones Susanna , Chadwick David W.
Published: August 2005

Summary: Purpose: To determine condition‐specific satisfaction with care, we studied patients'experience of general practitioner (primary physician) and hospital clinic care for their epilepsy and their views about the provision of information concerning the management of their condition.

Methods: A postal questionnaire was sent to an unselected, community‐based population of patients with epilepsy. In addition to clinical and demographic details and previously validated scales of psychosocial well‐being, the instrument contained a series of questions about patients'experiences and views of the care they received for epilepsy from both general practice and the hospital services.

Results: Doctors'interpersonal skills were the most influential factors affecting both patient satisfaction overall and the likelihood that doctors might discuss with patients certain clinical and social issues surrounding the management of the patient's condition. A sizable proportion of patients reported that they received insufficient information, about epilepsy, both from hospital doctors and general practitioners.

Conclusions: Patients with epilepsy place great importance on having a doctor who is approachable, communicative, and knowledgeable and on receiving adequate information about their condition. Clinicians may need to be made more aware of the importance of accessibility and sensitivity to the nonclinical needs of their patients. Such easily implemented changes in the delivery of care would improve services in the United Kingdom for people with epilepsy.
Failure of Naloxone to Modify Electroencephalogram Interictal Epileptiform Discharges in Patients with Primary Generalized Epilepsy After Sleep Deprivation
Authors: Marrosu Francesco , Giagheddu Marcello , Fratta Walter
Published: August 2005

Summary: Sleep deprivation (SD) is a method widely used to activate EEG epileptiform activity, but the basis of this effect remains unknown. One possibility is that SD shares a common mechanism with physical and psychological stresses that also precipitate seizures. Because endogenous opioids are released during stress, opioids may play a role in enhancing epileptiform EEG patterns after SD. We report the effects of SD on EEG epileptiform activity in a small but highly homogeneous population of 13 epileptic patients with idiopathic (primary) generalized epilepsy (IGE). SD increased EEG interictal epileptiform discharges (IEDs); this activation was not modified by naloxone (NAL). Our results, in contrast to those of previous investigations of localization‐related epilepsy, which showed an increase in IEDs after NAL administration, suggest a possible difference in the mechanism whereby SD enhances IEDs in IGE and localization‐related epilepsy.
Cerebellar Hypometabolism in Focal Epilepsy Is Related to Age of Onset and Drug Intoxication
Authors: Seitz Rüdiger J. , Piel Sabine , Arnold Stephan , Schlaug Gottfried , Ebner Alois , Holthausen Hans , Tuxhorn Ingrid , Witte Otto W.
Published: August 2005

Summary: Purpose: We wished to investigate the cerebellar depression of regional cerebral glucose metabolism (rCMRGlu) in patients with focal epilepsy.

Method: In 170 consecutive patients with medically refractory, focal epilepsy the rCMRGlu was measured in cerebellum and brain.

Results: rCMRGlu was markedly decreased in both cerebellar hemispheres and slightly in brain. The cerebellum to brain rCMRGlu ratio was significantly decreased in patients with seizure manifestation in infancy, but was normal due to a progressive decrease in brain rCMRGlu in later age. A subgroup of patients with focal epilepsy involving the frontal lobe had a reduced cerebellum/brain rCMRGlu ratio, whereas in patients with mesiotemporal lobe epilepsy (MTLE), the rCMRGlu was decreased to the same degree in cerebellum and brain. The difference in the cerebellum/brain rCMRGlu ratio between the two groups was accounted for by the younger age of the patients with focal epilepsy involving the frontal lobe, however. In another subgroup of patients with a documented history of critical drug intoxications, the cerebellar rCMRGlu was severely decreased, resulting in a significantly reduced cerebellum/brain rCMRGlu ratio.

Conclusion: Our retrospective study suggests that the cerebellum is particularly vulnerable in infancy to ongoing epileptic activity and high dosage of antiepileptic drugs (AEDs).
Treatment of Epilepsy with Multiple Subpial Transections: An Acute Histologic Analysis in Human Subjects
Authors: Kaufmann Walter E. , Krauss Gregory L. , Uematsu Sumio , Lesser Ronald P.
Published: August 2005

Summary: Multiple subpial transection (MST) is a new surgical technique for treating seizures that arise from functionally critical cortical areas. It has a reported efficacy comparable to that of standard temporal lobe resections. Although the mechanism through which MST works is unknown, the carefully controlled lesions, placed 5 mm apart at the midlevel of the cortical gyri, could produce fiber damage that would prevent horizontal synchronization and spread of epileptic discharges while allowing normal cortical functions such as those related to movement or speech to be preserved. We studied the acute neuropathological features associated with MST in 8 patients with intractable temporal lobe epilepsy. Transections were made along major, temporal gyri just before standard lobectomy was performed. After resection, tissue was processed by conventional histological and immunocytochemical techniques. Macroscopically, subpial transections (STs) were perpendicular to the main gyral axis and had an appropriate spacing. Microscopically, most of the lesions were perpendicular and at midlevel. However, many transections involved the lateral aspects of the small gyri, resulting in oblique or deep STs, some of which reached the gray‐white matter junction due to the complex microscopic neocortical architecture, in which small gyri are superimposed on major lobar gyri, and to the variable cortical thickness. Extensive acute pyknosis and tissue edema were also evident adjacent to the transections. These changes were variable and extended 1–3 mm laterally as irregular columnar blocks. In the deep lesions, myelin pallor and decreased neuro‐filament immunoreactivity were observed in the white matter. Based on the distribution of STs and their adjacent parenchymal injury, we conclude that this technique produces block‐type lesions that probably disrupt propagation of epileptogenic activity. In most instances, midlevel horizontal fibers are damaged; one third of the cases showed additional deep injury that would sever afferent and efferent axons. Therefore, in addition to horizontal desynchronization, a deafferentation mechanism involving different fiber systems may contribute to the antiseizure effects of MST. We hypothesize that preservation of cortical function is mediated by cortex remaining in the sulcus and gyral crown and possibly by reorganization of tissue adjacent to transections.
How Easy are Randomized Controlled Trials in Epilepsy to Find on Medline? The Sensitivity and Precision of Two Medline Searches
Authors: Marson Anthony G. , Chadwick David W.
Published: August 2005

Recognition of the need for more scientifically acceptable review strategies is increasing. Systematic reviews have rarely been performed on randomized controlled trials (RCTs) in the field of epilepsy. We have 355 published RCTs on a database, which will be used as a data source for systematic reviews. We wished to test the sensitivity and precision of two Medline search strategies, and to identify reasons why RCTs were missed. Both a basic and a comprehensive search strategy were used to search Medline from 1966 to 1993. Three journals (Epilepsia, Epilepsy Research, Acta Neurologica Scandinavica) were searched by hand. The sensitivity and precision of these Medline search strategies in these three journals was calculated. We investigated articles missed by our comprehensive search to ascertain why they had been missed. Of the 308 RCTs on the database published between 1966 and 1993, 275 were found by our comprehensive Medline search, whereas 103 were found by our basic search. The overall precision of our comprehensive and basic searches was 35 and 72%, respectively. The overall sensitivity of our comprehensive and basic searches was 86 and 66%, respectively. Our comprehensive search failed to find 16 RCTs published in the three journals searched by hand. Articles were missed because they were inadequately indexed on Medline and/or did not contain adequate methodological information in their titles or abstracts. To find all relevant trials, a search strategy must be as sensitive as possible, but this sensitivity inevitably involves loss of precision. The National Library of Medicine is addressing indexing problems with Medline, but the quality of reports also must be improved to enhance retrieval.
Localization of Temporal Lobe Foci by Ictal EEG Patterns
Authors: Ebersole John S. , Pacia Steven V.
Published: August 2005

Identifying patients whose complex partial seizures originate in temporal neocortex rather than in hippocampus is important because such patients have less favorable outcomes with standard anteromesial temporal resections. We reviewed scalp‐recorded ictal EEGs of 93 epilepsy surgery candidates who either underwent intracranial EEG monitoring (n= 58) or who were referred directly for temporal lobectomy (n= 35). We defined seven patterns of early seizure discharges, grouped patients according to their seizure pattern, and correlated these with the site of seizure onset determined by intracranial EEG. Categorization by seizure pattern was also compared with brain magnetic resonance imaging (MRI) findings and intracarotid amobarbital (Wada) testing. An initial, regular 5‐ to 9‐Hz inferotemporal rhythm (type 1A) was most specific for hippocampal‐onset seizures. Less commonly, a similar vertex/parasagittal positive rhythm (type 1B) or a combination of types 1B and 1A rhythms (type 1C) was recorded. Seizures originating in temporal neocortex were most often associated with irregular, polymorphic, 2‐ to 5‐Hz lateralized activity (type 2A). This pattern was commonly followed by a type 1A theta rhythm (type 2B) or was preceded by repetitive, sometimes periodic, sharp waves (type 2C). Seizures without a clear lateralized EEG discharge (type 3) were most commonly of temporal neocortical origin. These associations between type of seizure pattern and probable site of cerebral origin were statistically significant. MRI and Wada testing did not have as much specificity as ictal patterns in differentiating among seizure origins. We conclude that the initial pattern of ictal discharge on scalp EEG can assist in distinguishing seizures of temporal neocortical onset from those of hippocampal onset. This information can be used to identify patients for invasive monitoring.
Microdialysis Study of the Neuropharmacokinetics of Phenytoin in Rat Hippocampus and Frontal Cortex
Authors: Walker M. C. , Alavijeh M. S. , Shorvon S. D. , Patsalos P. N.
Published: August 2005

Summary: Acute administration of phenytoin (PHT) is used in the treatment of status epilepticus, yet little is known about the neuropharmacokinetics of PHT in brain extracellular fluid (ECF), the pharmacodynamically relevant compartment. To characterize the neuropharmacokinetics of brain ECF PHT we implanted microdialysis probes in rat hippocampus and frontal cortex and placed a catheter in the internal jugular vein. PHT (50 or 100 mag intraperitoneally, i.p.) was then administered, and microdialysate and serum samples were collected. PHT was rapidly absorbed, with a time to maximum concentration (Tmax) of ‐20 min for serum concentrations. PHT rapidly entered the brain ECF compartment, with Tmax values similar to those of serum. In brain ECF, PHT concentrations then plateaued for 40–60 min despite decreasing serum concentrations. The area under the brain ECF concentration‐time curve (AUC) was higher in hippocampus than frontal cortex. The possible mechanisms for these observations include entry of PHT into specific brain areas both across capillaries and through the cerebrospinal fluid (CSF), extensive binding of PHT in brain white matter, and differing blood flow in different brain regions.
Double‐Blind, Placebo‐Controlled Trial of Topiramate as Add‐on Therapy in Patients with Refractory Partial Seizures
Authors: Ben‐Menachem Elinor , Henriksen Olaf , Dam Mogens , Mikkelsen Marianne , Schmidt Dieter , Reid Sybiella , Reife Ross , Kramer Lynn , Pledger Gordon , Karim Rezaul
Published: August 2005

Summary: In a double‐blind, randomized, parallel‐group trial, we compared topiramate (TPM) with placebo as addon therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b. i. d.)] or to the maximal tolerated dose if lower. Twenty‐eight (28) patients were randomized to each treatment group. In the intent‐to‐treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo‐treated patients and 43% of the patients treated with TPM experienced 250% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75–100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentation, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM‐treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefithisk ratio of TPM in resistant partial epilepsy.
The Effects of Neonatal Hypoxia on Kindled Seizure Development and Electroconvulsive Shock Profiles
Authors: Applegate Craig D. , Jensen Frances , Burchfiel James L. , Lombroso Cesare
Published: August 2005

Summary: Purpose: Our previous research indicated that the exposure of rat pups to an hypoxic environment during a discrete developmental period (postnatal days 10‐ 15) produces short‐term seizures and confers an enduring increase in susceptibility to pentylenetetrazol‐ and flurothyl‐ induced seizures. In this study, we evaluated the effects of hypoxic insult in this neonatal period on susceptibility to electrical kindling and corneal electroconvulsive shock.

Methods: Ten‐day‐old rat pups were exposed to a 3% O2 environment, as previously described, and were either kindled or exposed to corneal electroshock at adulthood (70 days old).

Results: Neither kindled seizure development from the septal nucleus or amygdala nor electroconvulsive shock profiles were significantly altered by hypoxic pretreatment.

Conclusions: Results indicate that hypoxia produces increases in seizure susceptibility that are observable in only some experimental seizure models but not in others. This outcome serves to target some anatomic systems more than others in the mechanisms involved in hypoxia‐induced neural reorganization.
Delayed Complications Thirty‐Six Years After Hemispherectomy: A Case Report
Authors: Kalkanis Steven N. , Blumenfeld Hal , Sherman Janet C. , Krebs David E. , Irizarry Michael C. , Parker Stephen W. , Cosgrove G. Rees
Published: August 2005

Summary: Purpose: To describe a late complication of hemispherectomy in a patient in whom symptoms of hydrocephalus developed 36 years after her left‐sided hemispherectomy, the longest delay on record.

Methods: Hemispherectomy has been successfully used in the treatment of intractable epilepsy associated with infantile‐type hemiplegia for a half century. Of the patients, however, up to 33% have late increased cerebrospinal fluid pressure complications attributed to superficial cerebral hemosiderosis. Through a retrospective case analysis, we describe such complications in a 52‐year‐old woman with cognitive impairment, gait instability, urinary incontinence, and right hemineglect 36 years after her initial procedure.

Results: Quantitative, objective measures of cognition and gait‐laboratory testing confirmed the patient's favorable clinical response to ventriculoperitoneal shunting, as well as the complete resolution of her symptoms, including the atypical occurrence of right‐sided hemineglect.

Conclusions: This case uniquely demonstrates the clinical features of a late complication of hemispherectomy while documenting the longest reported delay for developing such adverse sequelae. We also emphasize the need for more extensive follow‐up studies to assess the extent of posthemispherectomy complications.
Localized Cerebellar Hypometabolism in Patients with Complex Partial Seizures
Authors: Savic Ivanka , Altshuler Lori , Passaro Erasmo , Baxter Lew , Engel Jerome
Published: August 2005

Summary: Purpose: We sought to determine the cause of cerebellar dysfunction in epilepsy and whether this dysfunction was directly related to seizures.

Methods: Cerebellar metabolism was evaluated in 48 patients with a well‐defined region of seizure onset and with corresponding hypometabolism. Regions of interest (ROI) were drawn according to a standardized template. If the ROI/honepileptogenic cortex count rate ratio was outside the 95% confidence interval (CI) of controls, the ROI was defined as abnormal. The ratios from cerebellar hemispheres (defined as ipsi‐ or contralateral to the seizure onset region), were compared among controls (n = 8); patients who had seizure onsets and corresponding hypometabolism mesially in a temporal lobe (patient group 1, n = 19); patients whose seizures had onset mesially in a temporal lobe but spread rapidly to the ipsilateral frontal lobe and who had hypometabolism both in the affected temporal lobe and frontal lobe (patient group 2, n = 23); and patients who had seizure onsets and corresponding hypometabolism in the frontal lobe (patient group 3, n = 6).

Results: Significant hypometabolism was noted in the contralateral cerebellum of patients in groups 2 and 3 [p = 0.007 and p = 0.008, respectively; two‐way analysis of variance (ANOVA)]. In contrast, patients in group 1 tended to have lower values in the ipsilateral cerebellum (p = 0.057).

Conclusions: The observed cerebellar changes are consistent with animal data showing that cerebellar connections to frontal lobes are numerous and crossed, whereas the connections to mesial temporal lobes are less abundant, bilateral, with an ipsilateral predominance. The difference between the two groups of patients with mesial temporal seizures suggests that cerebellar dysfunction in partial epilepsy, at least to a certain extent, is related to mechanisms involved in seizure generation and spread.
Local Perfusion of Diazepam Attenuates Interictal and Ictal Events in the Bicuculline Model of Epilepsy in Rats
Authors: Eder Hans G. , Jones David B. , Fisher Robert S.
Published: August 2005

Summary: Purpose: We evaluated the efficacy of local perfusion of diazepam (DZP) in suppression of EEG spikes and behavioral seizures produced by bicuculline methiodide (BMI) applied to rat sensory motor cortex and hippocampus.

Methods: Data were obtained from 37 rats implanted with EEG head plugs and perfusion cannulas. BMI 4 mM, 5 μl was infused on neocortex through the epidural space in 23 rats. BMI 0.1 mM, 2 μl was infused into the left hippocampus in 14 rats.

Results: DZP 0.75–1.0 mg markedly reduced the spiking to a level of 9.9 ± 15.8% of baseline for DZP as compared with 90.2 ± 57.9% of baseline for vehicle‐treated rats. DZP reduced spiking in a hippocampal BMI focus to 1.9 ± 2.4% of baseline spiking, as compared with 98.0 ± 95.6% of that in vehicle‐treated animals. The amount of spread of solution was estimated with methylene blue (MB) injections. Ictal events also were attenuated. In most of the animals, systemic levels of DZP were unmeasurable and injection on the contralateral side did not reduce spiking.

Conclusions: These findings suggest that focal application of antiepileptic drugs (AEDs) in brain may be a useful new avenue for therapy of intractable partial seizures.
Three Patterns of Catamenial Epilepsy
Authors: Herzog Andrew G. , Klein Pavel , Rand Bernard J.
Published: August 2005

Summary: Purpose: On the basis of the neuroactive properties of estradiol and progesterone and the menstrually related cyclic variations of their serum concentrations, we propose the existence of three hormonally based patterns of seizure exacerbation. Because previous reports both support and refute the concept of catamenial epilepsy, we test the hypothesis by charting seizures and menses and measuring midluteal serum progesterone levels to estimate the frequency of epileptic women with catamenial seizure exacerbation.

Methods: One hundred eighty‐four women with intractable complex partial seizures (CPS) charted their seizure occurrence and onset of menstruation on a calendar for one cycle during which they had a midluteal blood sample taken for serum progesterone determination on day 22. Levels >5 ng/ml were considered ovulatory. The cycle was divided into four phases with onset of menstruation being day 1: menstrual (M) = ‐3 to +3, follicular (F) = 4 to 9, ovulatory (O) = 10 to ‐13, and luteal (L) =−12 to −4. Average daily seizure frequency for each phase was calculated and compared among phases by repeated‐measures analysis of variance (ANOVA) and the Student‐Newman‐Keul's test, separately for ovulatory and anovulatory cycles.

Results: The 1,324 seizures recorded during 98 ovulatory cycles occurred with significantly greater (p < 0.001) average daily frequency during the M (0.59) and O (0.50) phases than during the F (0.41) and L (0.40) phases, offering support for perimenstrual (catamenial 1) and preovulatory (catamenial 2) patterns of seizure exacerbation. The 1,523 seizures recorded during 86 anovulatory cycles occurred with significantly lower (p < 0.001) average daily frequency during the F phase (0.49) than during all other phases (M = 0.78, O = 0.74, L = 0.74), offering support for seizure exacerbation throughout the second half of inadequate luteal phase cycles (catamenial pattern 3). Although 71.4% of the women with ovulatory cycles and 77.9% with inadequate luteal phase cycles had seizure exacerbation in relation to one of the three patterns of catamenial epilepsy, approximately one third of the women showed at least a twofold increase in average daily seizure frequency. We propose a twofold or greater increase as a reasonable definition of catamenial epilepsy.

Conclusions: Charting of seizures and menses and determination of day 22 progesterone levels during each cycle may be sufficient to establish the existence of three distinct patterns of catamenial epilepsy. Approximately one third of women with intractable CPS may have catamenial epilepsy.
Anticonvulsant Activity of Felbamate in Amygdala Kindling Model of Temporal Lobe Epilepsy in Rats
Authors: Wlaź Piotr , Löscher Wolfgang
Published: August 2005

Summary: Purpose: Previous studies have demonstrated that felbamate (FBM, 2‐phenyl‐1,3‐propanediol dicarbamate) at nontoxic doses exerts potent anticonvulsant activity in a variety of animal epilepsy or seizure models. We further characterized the anticonvulsant activity of FBM by using the kindling model of temporal lobe epilepsy (TLE).

Methods: The experiments were performed in fully kindled rats. The anticonvulsant effect of FBM was assessed by determining seizure severity, after discharge (AD) duration and seizure duration either at the focal seizure threshold, or after supra threshold stimulation. In addition, the neurological performance of kindled rats after FBM administration was evaluated in the open field and by the rotorod test.

Results: FBM at doses of 12.5–50 mg/kg, given intraperitoneally (i.p.) 60 min before testing, dose‐dependently increased the AD threshold (ADT). The maximal effect was achieved after the highest dose tested and reached almost 600% of the control ADT. This dose of FBM significantly diminished other seizure parameters, e.g., seizure severity, seizure duration, and AD duration. When the rats were stimulated with suprathreshold current (500 μA) seizure severity was moderately but significantly reduced. No behavioral abnormalities were noted in kindled rats after administration of either of the doses.

Conclusions: FBM potently increases the threshold for focal seizures and reduces seizure severity, seizure duration, and AD duration at doses that produce no adverse behavioral effects in amygdala‐kindled rats. These data are thus compatible with clinical experience with FBM in TLE and substantiate that kindling is a good predictor of anticonvulsant activity against TLE.
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

: 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.
Cerebellar Atrophy After Acute Phenytoin Intoxication
Authors: Kuruvilla Thomas , Bharucha N. E.
Published: August 2005

Summary: There is some evidence that long‐term phenytoin (PHT) use may occasionaly give rise to irreversible cerebellar atrophy, but it is unclear whether such changes can occur after acute PHT intoxication. We describe a 38‐year‐old patient with accidental acute PHT overdose who developed severe cerebellar atrophy. This case provides evidence that acute PHT intoxication can, on rare occasions, result in irreversible cerebellar degeneration.
Vagus Nerve Stimulation
Authors: Schachter Steven C. , Saper Clifford B.
Published: August 2005

Summary: Left vagus nerve stimulation (VNS) is a promising new treatment for epilepsy. In 1997, VNS was approved in the United States as an adjunctive treatment for medically refractory partial‐onset seizures in adults and adolescents. For some patients with partial‐onset seizures, the adverse effects of antiepileptic drugs (AEDs) are intolerable; for others, no single AED or combination of anticonvulsant agents is effective. Cerebral resective surgery is an option to pharmacotherapy in some cases, but many patients with partial‐onset seizures are not optimal candidates for intracranial surgery. VNS entails implantation of a programmable signal generator—the Neurocybernetic Prosthesis (NCP)—in the chest cavity. The stimulating electrodes of the NCP carry electrical signals from the generator to the left vagus nerve. Although the mechanism of action of VNS is not known, controlled studies have shown that it is safe and well‐tolerated by patients with long‐standing partial‐onset epilepsy. Side effects, which are generally of mild to moderate severity, almost always disappear after the stimulation settings are adjusted. Encouraging results have also been reported in pediatric patients.
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.