bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Gabapentin Disposition in Patients with Epilepsy After a High‐Protein Meal
Authors: Benetello P. , Furlanut M. , Fortunato M. , Barldo M. , Pea F. , Togon A. , Testa G.
Published: August 2005

Summary: Purpose: To study the interaction between gaba‐pentin (GBP) and high‐protein meals, 12 patients with epilepsy were administered this drug both while in a fasting state and after a high‐protein meal.

Methods: After having acquired their informed consent, the patients (suffering from partial complex seizures resistant to other anticonvulsants) were randomly assigned to 2 groups of 6 subjects. Each subject was treated in a fasting state with a single 400 (group A) or 800 (group B) mg GBP oral dose. After 24 h, the GBP dose regimen was repeated, but was given after a high‐protein meal. Serum GBP concentrations were measured by LC‐Mass at baseline and 0.5, 1, 2, 3, 5, 7, 9, 12, and 24 h. Saliva GBP concentrations were determined at baseline and 2, 4, 8, and 12 h. GBP urinary excretion was determined at 0–4, 4–8, and 8–12 h intervals. The following kinetic parameters were calculated: area under the concentration time curve from zero time to 24 h after the dose, AUC 0–24 h; maximal serum concentration, Cmax; time to the maximal serum concentration, Tmax; absorption rate constant, ka; elimination rate constant, p; elimination half‐time, t½β. Student's t test for paired data, with significance assigned at P < 0.05, was used.

Results: No statistically significant differences were seen in GBP serum or saliva concentrations or in its urinary excretion (both in A or B group) between fasting and after the high‐protein meal.

Conclusions: High‐protein meals do not seem to interfere with oral disposition of GBP.
Seizure Semiology of Occipital Lobe Epilepsy in Children
Authors: Van den Hout B. M. , Van der Meij W. , Wieneke G. H. , Van Huffelen A. C. , Van Nieuwenhuizen O.
Published: August 2005

Summary: Purpose: Occipital lobe epilepsy in children occurs as an idiopathic form, i.e., Benign Epilepsy with Occipital Paroxysms (BEOP), and a symptomatic form. This study attempted to determine whether seizure semiology could distinguish between the two forms.

Methods: Fifty children (34 boys, 16 girls) with clinical seizures and interictal EEGs presenting occipital spikes were included consecutively in the study. Seizure onset was between the ages of 2 months and 15 years. Epilepsy was considered symptomatic when psychomotor retardation and/or abnormalities at neurological and/or neuroradiological examination were found: 17 children were classified as idiopathic, and the remaining 33 children were classified as symptomatic. Seizure semiology was assessed by means of a structured interview of the children and their parents, using a detailed questionnaire. Seizure semiology was determined to comprise motor (versive or other movements of the eyes, versive movements of the head, (hemiconvulsions), visual, other signs (e.g. vomiting and headache), and impairment of consciousness.

Results: There were no statistically significant differences in seizure semiology between the two groups.

Conclusions: Seizure semiology cannot distinguish between different forms of occipital lobe epilepsy: Further clinical examination, clinical neurophysiological investigations, and neuroimaging studies are needed for a correct classification.
Sensitivity of a Seizure Activity Detection Computer in Childhood Video/Electroencephalographic Monitoring
Authors: Kim Heung Dong , Clancy Robert R.
Published: August 2005

Summary: Purpose: Few data describe the sensitivity of a “Seizure Activity Detection Computer” (SzAC) in childhood video/EEG (VEEG) monitoring, especially for very young children. We examined the accuracy of SzAC in childhood VEEG monitoring in different pediatric age groups.

Methods: We visually analyzed VEEG monitoring samples for randomly designated subsets of 56 patients with childhood epilepsy, reviewing 335 visually detected electrographic seizures to analyze the sensitivity of SzAC for each age group as well as the electrographic characteristics affecting the sensitivity of automated computer‐based seizure detection.

Results: SzAC was positive in 227 of 335 (67.8%) visually identified electrographic seizures in the entire study group. The SzAC sensitivity for infants (age 2 months to 2 years) was 59.7% (43 of 72 seizures); for young children (age 3–10 years), sensitivity 56.5% (91 of 161 seizures). In adolescents (age 11–18 years), SzAC was positive in 93 of 102 (91.2%) seizures‐ i.e., in a significantly greater number of seizures than in younger age groups. SzAC was significantly less sensitive in detecting electrographic seizures characterized as being of short duration or of low voltage.

Conclusions: The overall sensitivity of SzAC in detecting childhood electrographic seizures was 67.8%. The sensitivity was significantly less in younger age groups as compared with that in children aged >11 years. Electrographic seizures of relatively short duration or low voltage were often missed by SzAC.
Identification of Frontal Lobe Epileptic Foci in Children Using Positron Emission Tomography
Authors: da Silva Ednéa A. , Chugani Diane C. , Muzik Otto , Chugani Harry T.
Published: August 2005

Summary: Purpose: Presurgical evaluation for intractable frontal lobe epilepsy (FLE) is difficult and invasive, partly because anatomic neuroimaging studies with computed tomography (CT) and magnetic resonance imaging (MRI) typically do not show a discrete lesion. In adult patients with FLE, functional neuroimaging of glucose metabolism with positron emission tomography (PET) is less sensitive in detecting focal metabolic abnormalities than in temporal lobe epilepsy (TLE). Comparable data on children with FLE are not available.

Methods: We used high‐resolution PET scanning of glucose metabolism to evaluate 13 children (age 17 months to 17 years; mean age 9.5 years) with intractable FLE being considered for surgical treatment. Only children with normal CT and MRI scans were included.

Results: Hypometabolism including the frontal lobe was evident in 12 of the 13 children, was unilateral in 11 of 13, and was restricted to the frontal lobe in 8 of 13. One child showed bilateral frontal cortex hypometabolism and another had anictal PET scan demonstrating unilateral frontal cortex hyper‐metabolism surrounded by hypometabolism. Additional hypo–metabolic areas outside the frontal cortex were observed in 5 children in parietal and/or temporal cortex. Localization of seizure onset on scalp EEG was available in 10 children and corresponded to the location of frontal lobe PET abnormality in 8. However, in 4 of the 10 children, the extent of hypometabolism exceeded the epileptogenic region indicated by ictal EEG. In 2 of the 13 children, the abnormality evident on EEG was more extensive than that evident on PET. In the remaining 3 children for whom only interictal EEG data were available, the PET foci did not correspond in location to the interictal EEG abnormalities. In 11 of the 13 children, the presumed region of seizure onset in the frontal lobe, as based on analysis of seizure semiology, corresponded to the locations of frontal lobe glucose metabolism abnormalities.

Conclusions: Although high‐resolution PET appears to be very sensitive in localizing frontal lobe glucose metabolic abnormalities in children with intractable FLE and normal CT/ MRI scans, the significance of extrafrontal metabolic disturbances requires further study; these may represent additional epileptogenic areas, effects of diaschisis, seizure propagation sites, or secondary epileptogenic foci.
Disclose or Conceal? Strategies of Information Management in Persons with Epilepsy
Authors: Tröster Heinrich
Published: August 2005

Summary: Purpose: When handling information about their disease in their social contacts, persons with epilepsy try to avoid or limit stigmatization. We report two basic strategies of information management: general concealment and preventive disclosure. To test whether persons with epilepsy apply a strategy of preventive disclosure, we hypothesized that they would disclose their epilepsy when anticipating that their disease would make them conspicuous in social contacts and when believing that they would be able to forestall stigmatizing attribution processes through disclosure.

Methods: One hundred nineteen outpatients at the Bethel Epilepsy Center, Bielefeld, Germany, aged 16–74 years responded to a questionnaire assessing willingness to disclose their epilepsy in various fictitious daily scenarios, the perceived risk that the interaction partner might find out about their epilepsy (risk of detection), as well as the anticipated positive and negative social consequences of disclosure in these social situations.

Results: Willingness to disclose varied across the different scenarios, and only a few respondents rejected disclosure categorically. Willingness to disclose depended on the subjectively perceived risk of detection and the anticipated consequences of disclosure: Respondents were more willing to disclose their epilepsy the more they feared that their interaction partner would detect their disease or find out about it in another way and the more they anticipated that disclosure would enable them to exert a favorable impact on their partner's social judgment formation.

Conclusions: Many persons with epilepsy appear to apply a strategy of preventive disclosure with which they strive to influence social judgment formation in their environment by purposefully disclosing their disease to forestall possible stigmatization processes.
Factors Associated with Work Outcome After Anterior Temporal Lobectomy for Intractable Epilepsy
Authors: Reeves A. L. , So E. L. , Evans R. W. , Cascino G. D. , Sharbrough F. W. , O'Brien P. C. , Trenerry Max R.
Published: August 2005

Summary: Purpose: Whereas the effect of anterior temporal lobectomy on seizure frequency is well recognized, less is known about its impact on work status.

Methods: One hundred thirty‐four of 190 consecutive patients with temporal lobectomy participated in this study. Eligibility criteria were developed to ensure that only patients with the potential of achieving specific outcomes were included in the corresponding analyses.

Results: After surgery, significantly more patients were independent in activities of daily living (p < 0.001) or able to drive (p < 0.001). Income from work also increased (p < 0.01). Nearly one fifth of the patients who were eligible for analysis had either a gain (8%) or a loss (11%) of full‐ or of part‐time work. Univariate analyses revealed the following factors to be associated with full‐time work after surgery: student or full‐time work within a year before surgery, full‐time work experience before surgery, full‐ or part‐time employment experience before surgery, no disability benefits before surgery, low post‐surgical seizure frequency, improved postsurgical seizure control, excellent postsurgical seizure control, driving after surgery, and further education after surgery (p < 0.05). Significant factors on multivariate analysis were being a student or having full‐time work within a year before surgery [odds ratio, 16.2 (95% CI, 4.3–60.5)], driving after surgery [15.2 (3.2–72.0)], and obtaining further education after surgery [9.2 (2.2–53.0)].

Conclusions: Anterior temporal lobectomy for intractable epilepsy improves activities of daily living and the ability to drive. Work outcome of this surgery is influenced by presurgical work experience, successful postsurgical seizure control especially to allow driving, and obtaining further education after surgery.
Safety of Long‐Term Lamotrigine in Epilepsy
Authors: Mackay F. J. , Wilton L. V. , Peace G. L. , Freemantle S. N. , Mann R. D.
Published: August 2005

: Purpose: To examine the safety of lamotrigine (LTG) used in general practice to treat epilepsy.

Methods: Information was collected on 11,316 patients who were included in a noninterventional observational cohort study conducted by means of Prescription‐Event Monitoring (PEM). A follow‐up study provided information on the first 3,994 patients who had taken LTG for 3 6 months. Incidence density (ID) measurements were used to rank the frequency of the reported events.

Results: Rash was the most frequently reported nonepileptiform event (ID, 19.7/1,000 patient‐months) in the first month of treatment and resulted in LTG being stopped in 2% of the 11,316 patients. Rash was reported more frequently among children aged 2–12 years (ID, 29.4/1,000 patient‐months) than adults. Other events associated with the use of LTG included headache, drowsiness, nausea, vomiting, malaise, and lassitude. Rare serious events possibly associated with LTG included 12 cases reported as Stevens‐Johnson syndrome, four cases of neutropenia, three cases of thrombocytopenia, and two cases of disseminated intravascular coagulation. There were also individual cases of leucopenia, a meningitic reaction, acute renal failure, hepatotoxicity, and a ‘lupus‐like’reaction possibly associated with the drug. No foetal abnormalities were specifically associated with the use of the drug in pregnancy. No death was attributed to LTG.

Conclusions: Patients had severe epilepsy, inadequately controlled by other antiepileptic agents. The results of these two studies suggest that LTG is acceptably safe when used for the treatment of refractory epilepsy.
Movement‐Induced Seizures: A Case Report
Authors: Pierelli F. , Gennaro G. Di , Gherardi M. , Spanedda F. , Marciani M. G.
Published: August 2005

: Reflex seizures induced by movement are typically evoked by sudden or unattended motor actions. However, tonic seizures may also be triggered by slow movements as observed in nonketotic hyperglycemia or in “praxis‐induced epilepsy.” We report the case of a young, nondiabetic patient affected by recurrent partial tonic postural seizures precipitated by slow movements which were unrelated to cognitive tasks. Ictal EEG did not permit location of the epileptogenic brain region. However, the clinical features suggest possible involvement of the supplementary motor area.
Zonisamide Monotherapy in Newly Diagnosed Infantile Spasms
Authors: Suzuki Yasuhiro , Nagai Toshisaburo , Ono Jiro , Imai Katsumi , Otani Kazumasa , Tagawa Tetsuzo , Abe Jiro , Shiomi Masashi , Okada Shintaro
Published: August 2005

Summary: Purpose: We determined the short‐term efficacy of zonisamide (ZNS) monotherapy in newly diagnosed patients with infantile spasms (IS).

Methods: Eleven hospitals participated in this open, prospective trial. ZNS 3‐10 mg/kg/day was administered as the second‐choice drug to 11 newly diagnosed patients with IS (cryptogenic 3, symptomatic 8) who failed to respond to high‐dose vitamin B6.

Results: Four infants with symptomatic IS had cessation of spasms and disappearance of the hypsarrhythmia. In these responders, the spasms ceased after a few days (1–5 days) of treatment at a dose of ZNS 4–5 mg/kg/day which produced plasma ZNS concentrations ranging from 5.2 to 16.3 kg/ml (mean 9.8 pg/ml). There were two relapses (50%) 4–6 weeks after cessation of seizures, however. Relapse was predicted by effects of ZNS on EEG; the 2 infants in whom an abnormal EEG persisted had relapses, whereas the 2 whose EEG normalized remained seizure‐free (follow‐up 20 and 26 months). No adverse reactions were noted.

Conclusions: ZNS may be effective in the initial treatment of selected patients with IS.
Lamotrigine in Pregnancy and Lactation: A Case Report
Authors: Tomson Torbjörn , Öhman Inger , Vitols Sigurd
Published: August 2005

Summary: Purpose: We investigated the effect of pregnancy on the kinetics of lamotrigine (LTG), passage of LTG over the placenta and the excretion of the drug in breast milk.

Methods: We used high‐performance liquid chromatography to determine concentrations of LTG in plasma and in breast milk in a woman who was treated with LTG monotherapy during pregnancy and lactation.

Results: Plasma levels of LTG decreased as pregancy progressed. The ratio of dose to plasma concentration was 5.8 times higher at delivery and 3.6 times higher in late pregnancy as compared with 5 months postpartum, suggesting enhanced clearance of LTG during pregnancy. The concentration ratio of umbilical cord to mother's plasma was 1.2 indicating extensive passage of LTG over the placenta. The LTG plasma concentration in the newborn was still 48 h after birth similar to the plasma levels of the mother at delivery and in the umbilical cord. The ratio of milk to plasma concentration was 0.6 2 weeks after delivery and the plasma concentration in the breastfed child was 25% of the mother's plasma levels. No adverse effects were observed in the newborn.

Conclusions: The kinetics of LTG may be influenced by pregnancy to such a degree that dose adjustments may be indicated. Due to an extensive passage of LTG into breast milk, and a slow elimination in the newborn, LTG concentrations in the nursed infant may reach levels at which pharmacological effects can be expected.
The Worldwide Impact of New Drugs: Development, Distribution, and Use
Authors: Bergen Donna C.
Published: August 2005

Summary: Access to appropriate drug treatments and preventive agents for neurologic disorders is determined by medical, economic, political, social, and personal choices and policies. The development of new agents is dominated by large, often transnational companies located in economically advanced countries. Adequate breadth and stability of pharmaceutical supplies may be jeopardized by local economic, physical, and organizational constraints. Appropriate medical choices of drugs, their number, routes of administration, and sources, are made by physicians informed by their basic and continuing medical education but also influenced to varying degrees by patient expectation, financial incentives, and marketing information provided by the drug industry. Attempts to increase the availability of necessary drug treatment for all include initiatives by the World Health Organization, attention of national health planners to drug development, supply, and use, and industry‐government cooperation. Although there are significant differences among countries, many national health planners have taken similar approaches: increasing attention to cost‐effectiveness in prescribing and to competitive purchasing; the use of essential drug lists, formularies, and generic drugs; the devising of economic incentives for the development of needed but unprofitable drugs; careful planning of drug procurement and storage; and an emphasis on professional and patient education.
Outcome Assessment in Epilepsy: Comparative Responsiveness of Quality of Life and Psychosocial Instruments
Authors: Wiebe Samuel , Rose Kris , Derry Paul , McLachlan Richard
Published: August 2005

Summary: Purpose: Few data exist on the ability of instruments to detect within‐patient change over time in epilepsy, a property referred to as responsiveness. Our aim was to compare the responsiveness of three instruments [i.e., Epilepsy Surgery Inventory‐55 (ESI‐55) and Washington Psychosocial Inventory (WPSI), both epilepsy specific, and Symptom Checklist‐90–Revised (SCL‐90–R), non‐epilepsy specific].

Methods: Instruments were administered at baseline and at 1 year in a prospective cohort of surgically (43) and medically (14) treated patients with temporal lobe epilepsy. Coefficient of Responsiveness and relative efficiency were computed for each scale and for the dimensions of mental health, physical health, and role function.

Results: The ESI‐55 contained the most responsive scales, whereas SCL‐90–R contained the largest number of scales with moderate responsiveness. The largest number of scales with low responsiveness belonged to the WPSI. Sensitivity to between‐treatment differences in change was highest for ESI‐55 and SCL‐90–R. The most efficient scales in detecting differences between treatment groups in the mental, physical, and role‐function dimensions were ESI‐55 emotional well‐being, ESI‐55 health perceptions, and SCL‐90–R hostility, respectively.

Conclusions: Our results support the responsiveness of ESI‐55 scales and suggest that SCL‐90–R is a responsive tool for the assessment of psychologic function and distress in epilepsy. Comparatively, WPSI is relatively unresponsive to small or medium‐size changes.
Usefulness of Ictal and Interictal 99mTC Ethyl Cysteinate Dimer Single Photon Emission Computed Tomography in Patients with Refractory Partial Epilepsy
Authors: Lancman Marcelo E. , Morris Harold H. , Raja Shanker , Sullivan M. Jo , Saha Gopal , Go Raymundo
Published: August 2005

Summary: Purpose: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in ∼90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for ∼6 h. facilitating the performance of ictal studies.

Methods: In a prospective, open‐label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of 99mTc‐ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal 99mTc‐ECD SPECT.

Results: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases.

Conclusions: 99mTc‐ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc‐ECD are similar to those reported with 99mTc‐HMPA0. Because 99mTc‐ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.
Layer‐Specific Pathways for the Horizontal Propagation of Epileptiform Discharges in Neocortex
Authors: Telfeian Albert E. , Connors Barry W.
Published: August 2005

Summary: Purpose: Epileptiform discharges that resemble interictal spikes can be generated by slices of neocortex treated with antagonists of γ‐aminobutyric acid A (GABAA) receptors. These discharges can propagate horizontally for long distances. We tested the hypothesis that propagation occurs through preferred horizontal pathways that lie in a particular cortical layer.

Methods: Slices were prepared from the primary somatosensory cortex of rats, maintained in vitro, and bathed with the GABAA receptor antagonist picrotoxin. Electrical stimuli were used to evoke single all‐or‐none paroxysmal field potentials (PFP) that were recorded with pairs or arrays of field potential electrodes.

Results: To test which laminae are necessary for propagation, vertical cuts were made to force the PFP to spread horizontally through particular layers. If slices were bathed in a high dose of picrotoxin (35 μM, a bridge of cortex 350 μm thick placed at any lamina was sufficient to support PFP propagation. However, in low picrotoxin doses (2.5 μM), similarly sized bridges had to include tissue from layers 415 or 516 to support propagation. When slices were cut horizontally (i.e., parallel to the pia) in strips, either upper‐, middle‐, or lower‐layer strips were sufficient to support PFP propagation if the picrotoxin concentration was high; however, in low picrotoxin doses, only horizontal strips that included layer 5 could support propagation. Finally, in intact picrotoxin‐treated slices, focal applications of GABA were systematically applied to different laminae as the PFP propagated past; GABA was most effective at blocking or delaying propagation when it was applied to layer 5b.

Conclusions: We conclude that epileptiform propagation can occur through a variety of horizontal pathways when cortical inhibition is strongly impaired. However, when inhibition is reduced only moderately, axonal pathways in layer 5 are critical for seizure spread.
Replication Analysis of a Putative Susceptibility Locus (EGI) for Idiopathic Generalized Epilepsy on Chromosome 8q24
Authors: Sander Thomas , Kretz Rebekka , Schulz Herbert , Sailer Ulrike , Bauer Gerhard , Scaramelli Alejandro , Epplen Jörg T. , Rieß Olaf , Janz Dieter
Published: August 2005

Summary: Purpose: The present replication study was designed to test the validity of a previously mapped susceptibility locus (EGI) for common subtypes of idiopathic generalized epilepsy (IGE) in chromosomal region 8q24.

Methods: Thirty‐eight multiplex families of probands with common IGE syndromes were included in the present study. Parametric and nonparametric multipoint linkage analyses were conducted between the IGE trait (either “idiopathic” generalized seizure or generalized spike‐wave EEG discharges) and three microsatellite polymorphisms (D8S256, D8S284, 0881128) encompassing the putative EGI locus.

Results: Parametric and nonparametric multipoint linkage analysis provided no evidence for linkage between the IGE trait and the markers encompassing the putative EGI locus. Moreover, we noted no indication favoring linkage to this chromosomal region in two distinct subsets of families subdivided by the absence (n = 18) or presence (n = 20) of family members with juvenile myoclonic epilepsy (JME).

Conclusions: We failed to replicate evidence of a major locus (EGI) for common familial IGE in chromosome region 8q24. On the contrary, our present parametric linkage results provide evidence against linkage across the region under a broad range of genetic models. If there is a susceptibility locus for IGE in this region, the effect size or the proportion of linked families is too small to detect linkage in these families. Taking into account the problems in replicating initial linkage claims in oligogenic traits, further linkage studies in additional family sets are necessary to evaluate the validity of the previous linkage finding.
Morphometric Analysis of the Temporal Lobe in Temporal Lobe Epilepsy
Authors: Lee J. W. , Andermann F. , Dubeau F. , Bernasconi A. , MacDonald D. , Evans A. , Reutens D. C.
Published: August 2005

Summary: Purpose: Using high‐resolution magnetic resonance imaging (MRI), we examined the temporal neocortex and the underlying white matter in patients with unilateral temporal lobe epilepsy (TLE) and in control subjects.

Methods: The images of 27 patients and 42 control subjects were registered into stereotaxic space, corrected for image intensity inhomogeneity, and automatically segmented into gray matter, white matter, and cerebrospinal fluid (CSF) over a predetermined extent of the temporal lobe. The surface between the gray matter and CSF was extracted, indices of curvature (IOC) of the surface were calculated, and a frequency histogram of the IOC was obtained.

Results: There was significant bilateral reduction in the total volume of the temporal lobe and in the volume of gray matter. White matter volume was significantly reduced only in the temporal lobe ipsilateral to the seizure focus. There were significant changes in the position and amplitude of peaks in the frequency histogram of the IOC.

Conclusions: The volume of gray matter was negatively correlated with duration of epilepsy, suggesting that neocortical changes may be a consequence of seizures. Changes in the frequency histogram of the IOC suggested an additional alteration in the surface morphology of the temporal lobe in TLE, possibly related to sulcal widening.
Uptake and Costs of Care for Epilepsy: Findings from a U.K. Regional Study
Authors: Jacoby Ann , Buck Debbie , Baker Gus , McNamee Paul , Graham‐Jones Susannah , Chadwick David
Published: August 2005

Summary: Purpose: Epilepsy is a common neurological condition, with significant resource implications for the health services, but few studies to date have examined the uptake and costs of care for this condition. As part of a large prevalence study of epilepsy conducted in one U.K. Health Region, we investigated both direct and indirect costs of epilepsy care and measured and valued the direct costs.

Methods: Data about service use were obtained from primary physician records and patient questionnaires. Unit costs for each item of resource use were generated from several sources.

Results: The greatest direct health care cost is that of hospital‐based care. Pharmaceutical services also represent a significant element of the cost of epilepsy, the financial costs of prescribing newly developed antiepileptic drugs (AEDs) being large relative to those of the older drugs; therefore, the benefits derived from their use must be carefully assessed. The importance of good seizure control is amply illustrated by the findings about the differential costs associated with epilepsy of varying severity. The direct costs of caring for people with poorly controlled epilepsy are significant, with more than half the total cost of epilepsy care accounted for by patients with frequent seizures even though this group represented only a quarter of all patients in the present study.

Conclusions: Our data emphasize the importance of optimizing seizure control as a means of reducing the costs of epilepsy, not only to the person with the condition, but also to society.
Correlation Between Interictal Regional Cerebral Blood Flow and Depth‐Recorded Interictal Spiking in Temporal Lobe Epilepsy
Authors: Guillon Benoit , Duncan Roderick , Biraben Arnaud , Bernard Anne‐Marie , Vignal Jean‐Pierre , Chauvel Patrick
Published: August 2005

Summary: Purpose: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60–70% of cases. Correlation with ictal EEG changes is observed in ∼50–60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship.

Methods: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [99mTc]hexamethyl‐propylene amine oxime (HMPAO)‐SPECT stereo‐EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data.

Results: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes.

Conclusions: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.
NER Rat Strain: A New Type of Genetic Model in Epilepsy Research
Authors: Noda Atsushi , Hashizume Ryoichi , Maihara Toshiro , Tomizawa Yasuhiro , Ito Yoshihiko , Inoue Maki , Kobayashi Kinji , Asano Yuzo , Sasa Masashi , Serikawa Tadao
Published: August 2005

Summary: Purpose: We characterized and evaluated as an animal model of epilepsy NER, a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic‐clonic seizures in a stock of Crj:Wistar.

Methods: Animals were monitored through the inbreeding course, and video‐EEGs were recorded selectively. External seizure‐provoking stimuli were applied to NER and to a control parental strain. F1, F2, and backcross progenies were produced between NER and a nonepileptic unrelated strain. Pathologic study included hematoxylin‐and‐eosin (HE), Klüver‐Barrera's, modified Bodian silver, and neo‐Timm's staining.

Results: After the F9 generation, 94%‐98% of NER exhibited spontaneous tonic‐clonic convulsions, beginning with neck and forelimb clonus, wild jumping/running, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity. Most seizure onsets occurred between 2–4 months of age, and the incidence was 0.45 ± 0.21 seizures in 12 h. Ictal cortical and hippocampal EEGs were characterized by high‐voltage spikes followed by diffuse spike‐and‐wave or polyspike‐and‐wave complexes. NER revealed seizure susceptibility to pentylenetetrazol, tossing, and transcorneal electroshock, but not to tactile, photic, or acoustic stimuli, or to transauricular electroshock. Mating experiments revealed that 0% (0/46) of the animals in F1, 25.5% (13/51) in F2, and 63.6% (56/88) in backcross progenies exhibited spontaneous tonic‐clonic convulsions without sex difference. For all these epileptic traits, no pathologic changes were demonstrated in the CNS.

Conclusions: NER frequently exhibited spontaneous convulsions, controlled by a major autosomal recessive gene for epilepsy, that are comparable to generalized tonic‐clonic seizures in humans. This can serve as a new genetic model in epilepsy research.
Nonconvulsive Status Epilepticus in the Critically Ill Elderly
Authors: Litt Brian , Wityk Robert J. , Hertz Sharon H. , Mullen Paul D. , Weiss Howard , Ryan Dawn D. , Henry Thomas R.
Published: August 2005

Summary: Purpose: To describe the electrographic and clinical features of nonconvulsive status epilepticus (NCSE) in the critically ill elderly and to identify potential predictors of outcome.

Methods: We prospectively identified 25 episodes of altered mentation and NCSE in 24 critically ill elderly patients associated with generalized, focal, or bihemispheric epileptiform EEG patterns. Patients with anoxic encephalopathy were excluded.

Results: Of 25 hospitalizations, 13 (52%) resulted in death, and 12 (48%) patients survived to discharge. Death was associated with the number of acute, life‐threatening medical problems on presentation (survivors, 1.8; fatalities, 2.8; p = 0.013) and with generalized EEG pattern (p = 0.017). Higher doses or greater number of antiepileptic drugs (AEDs) did not improve outcome. Treatment with intravenous benzodiazepines was associated with increased risk of death (p = 0.033). Ten patients with advance directives were managed outside the intensive care unit (ICU). Mean hospitalization was 39 days in the ICU group and 22 for those with advance directives (p = 0.017).

Conclusions: Severity of illness correlates with mortality in critically ill elderly patients with NCSE. Treatment with intravenous benzodiazepines may increase their risk of death. Aggressive ICU management may prolong hospitalization at considerable cost, without improving outcome. It is unclear whether NCSE affects outcome in the critically ill elderly or is merely a marker for severity of disease in predisposed patients. The benefits of aggressive therapy are unclear. Carefully controlled, prospective trials will be necessary to determine the best therapies for NCSE in the critically ill elderly and the appropriate role of the ICU in their management.
Quality of Life and Personality in Adults with Epilepsy
Authors: Zhu Dan‐tong , Jin Li‐juan , Xie Guang‐jie , Xiao Bo
Published: August 2005

Summary: Purpose: This study was undertaken to understand the quality of life, personality, and associated factors in patients with epilepsy.

Methods: 117 patients with epilepsy and 84 healthy people were studied and tested using the Social Support Scale, the General Well‐being Schedule, the Life‐Event Scale, the Behavior Pattern Scale, and the Eysenck Personality Questionnaire WQ).

Results: There were no significant differences between the patients with epilepsy and the control group in the Social Support Scale results. The General Well‐being Schedule scores were lower for the case patients than for the control group (p < 0.01). Scores for patients with frequent seizures (once a month or more) were lower than those without frequent seizures (less than once per month). The case patients had higher negative scores in the family‐related problem section of the Life Events Scale, compared with the control group (p < 0.05). The patients with epilepsy were also more likely to lie (p < 0.05); their emotions were more changeable (p < 0.01), and their character more introverted (p < 0.05), although their behavior patterns were similar to the controls. We also studied associated factors related to personality, general well‐being, and familial‐negative life‐events.

Conclusions: These results provide information about patients with epilepsy that may be useful in their psychological treatment.
Hyposexuality Produced by Temporal Lobe Epilepsy in the Cat
Authors: Feeney Dennis M. , Gullotta Frank P. , Gilmore Wendy
Published: August 2005

Summary: Purpose: The hypothesis tested in this study was that a unilateral irritative focal epileptic lesion in the temporal lobe results in hyposexuality.

Methods: Focal epilepsy was produced in male cats by unilateral injection of aluminum hydroxide into either the basolatera1 amygdala (temporal lobe group) or anterior sigmoid gyrus (motor cortex group). Weekly sex testing trials with estrous females were conducted prior to and after aluminum hydroxide injection, and mating performance scores were compared with those of normal, unoperated cats (normal control group).

Results: All animals receiving aluminum hydroxide developed electroencephalographic and behavioral manifestations of epilepsy; i.e., interictal EEG spiking and partial or generalized seizures. Cats in the temporal lobe group exhibited a dramatic and complete suppression of sexual behavior at periods from 6 to 26 weeks after aluminum hydroxide injection. The duration of the hyposexuality varied between individual animals and returned to normal as suddenly as the onset occurred, despite the use of AEDs to prevent or control generalized seizure activity. Interictal EEG epileptiform spiking in the amygdala preceded the onset of hyposexuality by 1–12 weeks. By contrast, cats in the motor cortex and normal control groups showed no sign of sexual dysfunction throughout the experimental period, independent of seizure activity andor antiepileptic drug (AED) treatment.

Conclusions: These data support the hypothesis that hyposexuality occurs as a result of epileptiform activity in the temporal lobe, but not in the motor cortex. The precise mechanisms by which this occurs are unknown, but are likely to involve abnormally high‐frequency neuronal activity in temporal lobe structures known to connect with and/or to regulate hypothalamic nuclei that organize male sexual behavior toward receptive females.
The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy
Authors: Baxendale S. A. , van Paesschen W. , Thompson P. J. , Connelly A. , Duncan J. S. , Harkness W. F. , Shorvon S. D.
Published: August 2005

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach.

Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients.

Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story‐recall tasks, while right hippocampal measures explained 18% of the variance in a design‐learning task and 32% of the variance in a figure‐recall task.

Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy‐related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.
Melatonin Inhibits Iron‐Induced Epileptic Discharges in Rats by Suppressing Peroxidation
Authors: Kabuto Hideaki , Yokoi Isao , Ogawa Norio
Published: August 2005

Summary: Purpose: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of post‐traumatic epilepsy. The involvement of iron‐mediated oxygen free radical species and neuronal lipid peroxidation in iron‐induced seizure has been suggested. Melatonin exerts free radical scavenging properties. In this study, we examined the protective effect of melatonin against iron‐induced seizures.

Methods: We examined the protective effect of melatonin against in vitro iron‐induced oxidative damage in homogenates from rat cerebral cortex, by measuring the concentration of thiobarbituric acid reactive substances (TBARS), as an index of oxidative damage. We also examined the effect of melatonin on the appearance of epileptic discharges in the EEG following injection of FeCl3 into the sensorimotor cortex in anesthetized rats, and by measuring the concentration of TBARS in the brain tissue.

Results: FeCl3 increased the concentration of TBARS in brain homogenates in a concentration‐dependent manner, and melatonin reduced FeCl3‐induced rise in TBARS in a dose‐response fashion. Pretreatment with melatonin suppressed or delayed the development of FeCl3‐induced epileptic discharges and decreased the concentration of TBARS in brain tissues.

Conclusions: Our results suggest that iron ion generates oxygen free radical species that induce neuronal macromolecular peroxidation and seizure, and that melatonin inhibits iron‐induced seizures by scavenging free radicals.
Does Presurgical IQ Predict Seizure Outcome After Temporal Lobectomy ? Evidence from the Bozeman Epilepsy Consortium
Authors: Chelune Gordon J. , Naugle Richard I. , Hermann Bruce P. , Barr William B. , Trenerry Max R. , Loring David W. , Perrine Kenneth , Strauss Esther , Westerveld Michael
Published: August 2005

Summary: Purpose: Considerable debate exists Concerning whether the presence of low preoperative IQ should be a contraindication for focal resective epilepsy surgery.

Methods: We examined the relationship between baseline IQ scores and seizure outcome in 1,034 temporal lobectomy cases from eight epilepsy surgery centers participating in the Bozeman Epilepsy Consortium.

Results: Those patients who continued to have seizures following surgery had statistically lower preoperative IQ scores than those who were seizure‐free (p < 0.009), but only by 2.3 points. This small but statistically significant relationship was fairly robust; it was observed across seven of the eight centers, and indicates that the findings can be generalized. Among patients with IQ scores of ≤75, 32.8% continued to have seizures following surgery, whereas 23.8% and 16.9% were not seizure‐free when IQ scores were between 76 and 109 and ≥110, respectively. Relative risk analyses revealed no significant increase in risk among patients with low IQ scores who had no structural lesions other than mesial temporal sclerosis. However, patients with IQ scores of ≤75 had nearly a fourfold (390%) increase in risk for continued seizures as compared with those with higher IQ scores if structural lesions were present.

Conclusions: While our results suggest that preoperative IQ scores alone are not good predictors of seizure outcome and should not be used to exclude patients as potential surgical candidates. IQ scores can be useful for counseling patients and their families concerning the relative risks of surgery.
Familial Occurrence of Epilepsy in Children with Newly Diagnosed Multiple Seizures: Dutch Study of Epilepsy in Childhood
Authors: Callenbach Petra M. C. , Geerts Ada T. , Arts Willem Frans M. , van Donselaar Cees A. , Boudewyn Peters A. C. , Stroink Hans , Brouwer Oebele F.
Published: August 2005

Summary: Purpose: To study the familial occurrence of epilepsy in children with newly diagnosed multiple unprovoked seizures.

Methods: Between August 1988 and September 1992, 462 children with two or more unprovoked seizures were included in the prospective Dutch Study of Epilepsy in Childhood. Seizures and epilepsy syndromes of probands were classified according to the International Classifications. Probands with at least 1 first‐degree relative with epilepsy were selected. Seizures and syndromes of their relatives were classified using medical files and telephone interviews.

Results: In 42% of the probands, the epilepsy was classified as localization‐related, in 57% as generalized, and in 1% as undetermined whether focal or generalized. The 47 (10.2%) children with at least 1 first‐degree relative with epilepsy less frequently had localization‐related epilepsy (23%) and more often had generalized epilepsy (77%) as compared with the total group of probands. Fifty‐eight first‐degree and 21 other relatives had epilepsy. Thirty‐three of the 40 (83%) first‐degree relatives with idiopathic or cryptogenic epilepsy had the same seizure type as the proband, but detailed information about their seizures was sometimes difficult to obtain. Of the 12 first‐degree relatives with epilepsy syndromes classifiable according to the International League Against Epilepsy (ILAE) 7 (58%) had the same syndrome as the proband.

Conclusions: In 10% of children with newly diagnosed epilepsy, the condition is familial. Relatively more often, these children have generalized epilepsy syndromes as compared with children with a negative family history. Most of the relatives with idiopathic or cryptogenic epilepsy had the same sei‐ zure type as the proband. These findings confirm the role of genetic factors in the pathogenesis of epilepsy.