bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of a Single Seizure on Health Status and Health Care Utilization
Authors: Dworetzky Barbara A. , Hoch Daniel B. , Wagner Anita K. , Salmanson Eileen , Shanahan Christopher W. , Bromfield Edward B.
Published: August 2005

Summary: Purpose: To assess the health status of patients after a single seizure.

Methods: We compared single‐seizure patients (SS) with patients who had well‐controlled epilepsy (WC), and uncomplicated hypertension (HT). Patients were adults screened from emergency and outpatient units of two urban teaching hospitals using predefined criteria. The 83 patients (SS, 30; WC, 29; HT, 24) were interviewed by phone about functional status (SF‐36), comorbid illness, cause of illness, number of visits to health providers, and drug side effects.

Results: No significant differences were found among groups for health status, SF‐36 domain, or occurrence of drug side effects. SS patients had significantly lower scores on vitality (p <0.03) and a trend toward lower role physical function (p <0.07) compared with age‐adjusted population norms. SS reported more visits to health providers than WC or HT, and the number of visits remained high at interview 1 year later. Patient knowledge of the “reason” for the seizure was not associated with health status or number of visits.

Conclusions: Health status of patients within 1 year of a single seizure is similar to that of patients with well‐controlled epilepsy or hypertension, but SS patients have greater health care utilization.
Remote Memory in Epilepsy
Authors: Bergin P. S. , Thompson P. J. , Baxendale S. A. , Fish D. R. , Shorvon S. D.
Published: August 2005

Summary: Purpose: There is now a considerable amount of research relating to memory functioning in epilepsy. The majority of studies have focused on the retention of new information, and few reports have measured memory for past events. This study aims to redress this and measure the efficiency of remote memory in epilepsy.

Methods: A remote memory questionnaire was prepared and administered to three groups of patients with epilepsy and a control group without epilepsy. The questionnaire assessed knowledge of public events that occurred between 1980 and 1991, inclusive. The epilepsy groups comprised 33 patients with temporal lobe epilepsy (TLE), 33 with extratemporal epilepsy (ExTE), and 10 with primary generalized epilepsy (PGE). Thirty control subjects were tested.

Results: Patients with TLE performed significantly less well on the questionnaire than all other groups (p = 0.001), but no effect of laterality was recorded; patients with extratemporal or primary generalised epilepsy did not differ from controls. Performance on the questionnaire was not determined by verbal IQ, educational achievement, social class, or drug treatment, but was related to the number of generalised convulsions that had occurred since 1980. The strongest neuropsychological predictors of performance on this questionnaire were measures of verbal memory.

Conclusions: The study demonstrated weak memory for past events in patients with TLE, thereby providing evidence of a broader memory disturbance in this group than has been previously highlighted. A test of remote memory, such as the one designed for this study, is easy to administer and provides clinically important information not available from conventional neuropsychological tests.
Anticonvulsant Efficacy of Topiramate in Phenytoin‐Resistant Kindled Rats
Authors: Reissmüller Elke , Ebert Ulrich , Löscher Wolfgang
Published: August 2005

Summary: Purpose: We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT).

Methods: Anticonvulsant response was tested by determining the afterdischarge threshold (ADT;i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders.

Results: TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders).

Conclusions: The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.
Relation of Cortical Language Distribution and Cognitive Function in Surgical Epilepsy Patients
Authors: Devinsky Orrin , Perrine Kenneth , Hirsch Joseph , McMullen William , Pacia Steven , Doyle Werner
Published: August 2005

Summary: Purpose: To investigate the relation between the number and spatial distribution of language sites and specific patient‐ and epilepsy‐related variables.

Methods: Patients with stimulation‐induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function.

Results: Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full‐scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory.

Conclusions: Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills.
The Value of the Number‐Needed‐to‐Treat Method in Antiepileptic Drug Trials
Authors: Lesaffre Emmanuel , Boon Paul , Pledger Gordon W.
Published: August 2005

Summary: Purpose: There is controversy between clinicians and statisticians on the appropriateness of the number needed to treat (NNT) as a summary statistic to report the effectiveness of a treatment. We examine the two viewpoints and make proposals concerning the reporting of clinical trial results.

Methods: In the context of antiepileptic treatments, we explain the two different viewpoints and illustrate the use of the odds ratio, relative risk, absolute difference, and NNT on the results of randomized clinical trials with topiramate (TPM). Special attention is paid to the use of these summary statistics in meta‐analyses. Here, the NNT is the expected number of patients one would need to treat to achieve a single occurrence of a specified good outcome (e.g., 50% reduction in seizure rate) in comparison to no (or placebo) treatment.

Results: Although the NNT is readily interpretable in some instances, it exhibits undesirable statistical behavior in other cases. In particular, confidence intervals for the NNT may split into two intervals and extend to positive and negative infinity when treatment efficacy is not clearly established by the data. Meta‐analyses cannot be sensibly conducted directly on the NNT scale.

Conclusions: Although other measures, such as the odds ratio, have been more commonly used in the context of meta‐analyses, clinicians prefer the NNT because it gives them a clearer clinical interpretation of the effectiveness of a (new) treatment. On the other hand, statisticians do not recognize the value of the NNT, as it has undesirable statistical properties. Some reconciliation between the two views could be achieved when the clinicians acknowledge the weak aspects of the NNT and when statisticians realize that statistical appropriateness is not the same as clinical relevance. It is suggested that the NNT be used as a secondary reporting tool not on an equal footing with the classic scales.
Interictal EEG and Ictal Scalp EEG Propagation Are Highly Predictive of Surgical Outcome in Mesial Temporal Lobe Epilepsy
Authors: Schulz R. , Lüders H.O. , Hoppe M. , Tuxhorn I. , May T. , Ebner A.
Published: August 2005

Summary: Purpose: Surgical outcome in patients with mesial temporal lobe sclerosis (MTS) is worse than that in patients with temporal lobe activity (TLE) with tumors. Previous studies of the ictal EEG focused on ictal EEG onset in scalp EEG or ictal EEG propagation in invasive recordings. Ictal EEG propagation with scalp electrodes has not been reported.

Methods: Ictal scalp EEG propagation patterns were studied in 347 seizures of 58 patients with MTS or nonlesional TLE. Interictal epileptiform discharges (IEDs) and the presence of unilateral mesial temporal lobe atrophy in magnetic resonance imaging (MRI) also were studied in these 58 patients. Fortynine patients were operated on (minimal follow‐up of 1 year).

Results: Postoperatively, seizure‐free outcome was seen in (a) 82.8% of patients with regionalized EEG seizure without contralateral propagation, but in only 45.5% of patients with contralateral propagation (p = 0.007); (b) 84.6% of patients with 100% IED lateralized to one temporal lobe, but in only 52.2% with <100% unitemporal IED (p = 0.015); (c) 88.9% with 100% unitemporal IED and regionalized ictal EEG combined, 73.7% with one of both variables, and only 33.3% with <100% ipsitemporal IED combined with contralateral ictal EEG propagation (p = 0.007).

Conclusions: Switch of lateralization or bitemporal asynchrony in the ictal scalp EEG and bitemporal IED are most probably an index of bitemporal epileptogenicity in MTS and are associated with a worse outcome.
Concentric Contraction of the Visual Field in Patients with Temporal Lobe Epilepsy and Its Association with the Use of Vigabatrin Medication
Authors: Hardus P. , Verduin W. M. , Postma G. , Stilma J. S. , Berendschot T. T. J. M. , van Veelen C. W. M.
Published: August 2005

Summary: Purpose: To describe concentric visual field loss found in the presurgical evaluation of patients with drug‐resistant temporal lobe epilepsy and relate the findings to potential causative factors.

Methods: A series of 157 consecutive patients with drug‐resistant temporal lobe epilepsy, who had been selected for neurosurgical treatment, was examined in a study set up as a prospective investigation of their visual fields, to document the loss of visual field resulting from surgery. Pre‐ as well as postoperative visual field examinations were performed following a standard protocol using static and kinetic perimetry. As a number of patients appeared to have an unexplained concentric visual field contraction in the presurgical examination, a relation with potentially causative factors was analyzed in a cross‐sectional study of all these patients. Correlations were sought with duration and severity of the seizure disorder, underlying pathology as indicated by magnetic resonance imaging (MRI) and demonstrated by pathology, any type of antiepileptic drug (AED) ever prescribed, and gender.

Results: In this cross‐sectoinal analysis of 157 consecutive patients who were candidates for surgery for temporal lobe epilepsy, absolute concentric contraction of the visual field of 10 to 30 degrees was found in the presurgical examination in 20 (17%) of 118 patients who had ever used vigabatrin (VGB) and in none of 39 who had not had this medication. This difference was significant (p = 0.004). In addition, men [15 (21%) of 72] were significantly more often affected (p = 0.007) than women [five (6%) of 85]. The degree of visual field loss, as indicated by the Esterman grid, showed a positive correlation with the duration of VGB medication. There was no correlation of visual field contraction with a history of meningitis as potential cause of the epilepsy, duration of the epilepsy, status epilepticus in the medical history, or histologic abnormality of the brain tissue removed. Ophthalmologic examination of the patients with concentric contraction revealed no abnormalities. None of the patients with concentric contraction complained spontaneously of their visual field loss.

Conclusions: VGB medication is a causative factor in concentric visual field loss. Visual field examination of patients using VGB should be seriously considered.
Comparison of Intrinsic Optical Signals Associated with Low Mg2+– and 4‐Aminopyridine–Induced Seizure‐Like Events Reveals Characteristic Features in Adult Rat Limbic System
Authors: Buchheim Katharina , Schuchmann Sebastian , Siegmund Herbert , Weissinger Florian , Heinemann Uwe , Meierkord Hartmut
Published: August 2005

Summary: Purpose: To analyze the intrinsic optical signal change associated with seizure‐like events in two frequently used in vitro models—the low‐Mg2+ and the 4‐aminopyridine (4‐AP) models—and to monitor regions of onset and spread patterns of these discharges by using imaging of intrinsic optical signals (IOS).

Methods: Combined hippocampal–entorhinal–cortex slices of adult rats were exposed to two different treatments: lowering extracellular Mg2+ concentrations or application of 100 μM 4‐AP. The electrographic features of the discharges were monitored using extracellular microelectrodes. Optical imaging was achieved by infrared transillumination of the slice and analysis of changes in light transmission using a subtraction approach. The electrographic features were compared with the optical changes. Regions of onset and spread patterns were analyzed in relevant anatomic regions of the slice.

Results: Both lowering extracellular Mg2+ concentrations and application of 4‐AP induced seizure‐like events. The relative duration of the intrinsic optical signal change associated with seizure‐like events in the low‐Mg2+ model was significantly longer compared with that seen with those occurring in the 4‐AP model, although duration of field potentials did not differ significantly in the two models. Seizure‐like events of the low‐Mg2+ model originated predominantly in the entorhinal cortex, with subsequent propagation toward the subiculum and neocortical structures. In contrast, no consistent region of onset or spread patterns were seen in the 4‐AP model, indicating that the seizure initiation is not confined to a particular region in this model.

Conclusions: We conclude that different forms of spontaneous epileptiform activity are associated with characteristic optical signal changes and that optical imaging represents an excellent method to assess regions of seizure onset and spread patterns.
Magnetic Resonance Imaging Follow‐up of Progressive Hippocampal Changes in a Mouse Model of Mesial Temporal Lobe Epilepsy
Authors: Bouilleret Viviane , Nehlig Astrid , Marescaux Christian , Namer Izzie J.
Published: August 2005

Summary: Purpose: Hippocampal sclerosis (HS) is the most frequent lesion found in mesial temporal lobe epilepsy (mTLE). MR imaging is considered to be the most sensitive and specific method to detect HS. Despite extensive studies performed on humans and except in a recent study, the morphologic pattern of HS is usually analyzed when the disease has already fully developed, thus not allowing any insight into the mapping of the progressive morphologic changes inducing the development of mTLE. We have recently characterized a model of mTLE that reproduces the unilateral pattern of HS, induced by intrahippocampal injection of low doses of kainate (KA) in mice.

Methods: In this study, we monitored the temporal evolution of the development of HS in this model of mTLE by using T2‐weighted sequence, T2‐relaxation time measurements, and T1‐weighted spin‐echo technique after injection of gadolinium, from 1 h to 120 days after KA injection.

Results: HS induced by intrahippocampal KA injection occurred in two phases. First, we observed a transient hyperintense T2‐weighted signal in the cortex above the injected hippocampus, most likely indicative of vasogenic edema partly due to the neurotoxic effect of KA. The concomitant increase in the T2 signal in the injected hippocampus and ipsilateral amygdala likely reflects the phase of cytotoxic edema occurring probably in relation to the excitotoxic consequences of both KA and seizure activity. Second, from 15 days on, a persistent unilateral increased T2 signal was detected in the hippocampus, which most probably reflects gliosis.

Conclusions: Our findings indicate that longitudinal follow‐up would permit a better understanding of the mechanisms underlying the constitution of HS in humans and eventually development of prevention strategies.
Characterization of Neuronal Migration Disorders in Neocortical Structures: Loss or Preservation of Inhibitory Interneurons?
Authors: Schwarz Petra , Stichel Christine C. , Luhmann Heiko J.
Published: August 2005

Summary: Purpose: Neuronal migration disorders (NMD) are often associated with therapy‐resistant epilepsy. In human cerebral cortex, this hyperexcitability has been correlated with a loss of inhibitory interneurons. We used a rat model of focal cortical NMD (microgyria) to determine whether the expression of epileptiform activity in this model coincides with a decrease in inhibitory interneurons.

Methods: In 2‐ to 4‐month‐old rats, the density of interneurons immunoreactive for γ‐aminobutyric acid (GABA), cal‐bindin, and parvalbumin was determined in fronto‐parietal cortex in nine 200‐μm‐wide sectors located up to 2.5 mm lateral and 2.0 mm medial from the lesion center in primary parietal cortex (Par 1). Quantitative measurements in homotopic areas of age‐matched sham‐operated rats served as controls.

Results: The freeze lesion performed in newborn rat cortex resulted in adult rats with a microgyrus extending in a rostro‐caudal direction from frontal to occipital cortex. The density of GABA‐ and parvalbumin‐positive neurons in fronto‐parietal cortex was not significantly different between lesioned and control animals. Only the density of calbindin‐immunoreactive neurons located 1.0 mm lateral and 0.5 mm medial from the lesion was significantly (Student t test, p > 0.05) larger in freeze‐lesioned rats (5.817 ± 562 and 6,400 ± 795 cells per mm3, respectively; n = 12) compared with measurements in homotopic regions in Parl cortex of controls (4,507 ± 281 and 4,061 ± 319 cells per mm3, respectively; n = 5).

Conclusions: The previously reported widespread functional changes in this model of cortical NMD are not related to a general loss of inhibitory interneurons. Other factors, such as a decrease in GABA receptor density, modifications in GABAA receptor subunit composition, or alterations in the excitatory network, e.g., an increase in the density of calbindin‐immunoreactive pyramidal cells, more likely contribute to the global disinhibition and widespread expression of pathophysiological activity in this model of cortical NMD.
Spatial Distribution of Neuronal Complexity Loss in Neocortical Lesional Epilepsies
Authors: Widman G. , Lehnertz K. , Urbach H. , Elger C. E.
Published: August 2005

Summary: Purpose: Nonlinear EEG analysis is valuable in characterizing the spatiotemporal dynamics of the epilepto‐genic process in mesial temporal lobe epilepsy. We examined the ability of the measure neuronal complexity loss (L*) to characterize the primary epileptogenic area of neocortical lesional epilepsies during the interictal state.

Methods: Spatial distribution of L* (L* map) was extracted from electrocorticograms (n = 52) recorded during presurgical assessment via subdural 64‐contact grid electrodes covering lesions in either frontal, parietal, or temporal neocortex in 15 patients. The exact location of recording contacts on the brain surface was identified by matching a postimplant lateral x‐ray of the skull with a postoperatively obtained sagittal MRI scan. Reprojecting L* maps onto the subject's brain surface allowed us to compare the spatial distribution of L* with the resection range of the extended lesionectomy.

Results: In each of the six patients who became seizure‐free, maximum values of L* were restricted to recording sites coinciding with the area of resection. In contrast, L* maps of most patients who had no benefit from the resection indicated a more widespread extent or the existence of additional, probably autonomous, foci. The mean of L* values obtained from recording sites outside the area of resection correctly distinguished 13 patients (86.7 %) with respect to seizure outcome.

Conclusions: Relevant information obtained from long‐lasting interictal electrocorticographic recordings can be compressed to a single L* map that contributes to a spatial characterization of the primary epileptogenic area. In neocortical lesional epilepsies, L* allows for identification and characterization of epileptogenic activity and thus provides an additional diagnostic tool for presurgical assessment.
Lamotrigine‐Induced Tic Disorder: Report of Five Pediatric Cases
Authors: de Menezes Márcio Affonseca Sotero , Rho Jong M. , Murphy Patti , Cheyette Sarah
Published: August 2005

Summary: Purpose: To describe the clinical spectrum of lamotrigine (LTG)‐induced tics (an uncommon side effect) in children.

Methods: Retrospective analysis of patients from our hospital‐based practice who developed tics while on LTG. Data obtained from medical records, interviews with parents, video‐EEGs, and homemade videotapes.

Results: Three males and two females (range, 2.5–12 years; mean, 6.9 years) developed a movement disorder within the first 10 months of therapy (maintenance doses, 4–17 mg/kg/day). Four patients exhibited simple motor tics; one patient experienced mostly vocal (i.e., gasping sounds) tics. Laryngo‐scopic evaluation of one 2.5‐year‐old with repetitive gasping sounds was normal. In three cases, tics resolved completely within 1 month of drug cessation; tics recurred in two of these patients after reintroduction of LTG. A fourth patient experienced gradual improvement after stopping LTG over 4 months; the fifth patient's simple motor tics improved spontaneously with a reduction in medication. None of the patients had clinical features of a neurodegenerative disorder, and none met diagnostic criteria for Tourette syndrome. Two patients, however, had a diagnosis of acquired epileptic aphasia syndrome, and one patient had nonprogressive expressive and receptive language dysfunction. A fourth patient had global static encephalopathy, and the fifth patient had only attentional problems. In all patients, tics were not associated with ictal EEG changes.

Conclusions: LTG may infrequently induce simple motor tics, vocal tics, or both. Patients with severe language dysfunction may be particularly susceptible to this uncommon side effect. Further studies are necessary to clarify the population at risk.
Should Patients with Psychogenic Nonepileptic Seizures be Allowed to Drive?
Authors: Benbadis Selim R. , Blustein Joseph N. , Sunstad Linda
Published: August 2005

Summary: Purpose: To investigate the risk of driving accidents in patients with psychogenic nonepileptic seizures.

Methods: First, a survey was conducted in 82 physician‐members of the American Epilepsy Society to determine what they recommend in patients with psychogenic seizures in regard to driving privileges. Second, we studied a population of 20 patients with proven psychogenic nonepileptic seizures diagnosed by prolonged EEG‐video monitoring. We obtained the patients' driving records from the Wisconsin Department of Transportation. We used 1991 Wisconsin crash data as the reference year. We compared the expected number of motor vehicle crashes with the observed number of crashes. χ2 with Yates' correction for continuity was used to test for statistical significance.

Results: Of the 82 physicians questioned, 37 (45%) responded. Among respondents, the distribution was as follows: 49% applied the same restrictions as for patients with epilepsy; 32% did not place patients under any restrictions; and 19% decided on a case‐by‐case basis. The total number of reported crashes in the sample was eight, with no fatal crashes. This was not statistically significant (corrected χ2, 0.53) compared with the expected number of motor vehicle crashes for the sample.

Conclusions: This small series does not support the use of driving restrictions for patients with psychogenic nonepileptic seizures.
Epileptogenicity Correlated with Increased N‐Methyl‐d‐Aspartate Receptor Subunit NR2A/B in Human Focal Cortical Dysplasia
Authors: Najm Imad M. , Ying Zhong , Babb Thomas , Mohamed Armin , Hadam Jennifer , LaPresto Eric , Wyllie Elaine , Kotagal Prakash , Bingaman William , Foldvary Nancy , Morris Harold , Lüders Hans O.
Published: August 2005

Summary: Purpose: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N‐methyl‐d‐aspartate (NMDA) receptor (NR) 2A/B coassembled with NRI subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes.

Methods: The histopathological, morphological, and immu‐nocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from sub‐dural grids. The NMDA antibodies identified subunits NRI (splicing variants la, lb, 2a, and 2b) and NR2A/B.

Results: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity.

Conclusion: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD‐induced epileptogenicity.
A Comparison of Two Methods for Estimating the Health Care Costs of Epilepsy
Authors: Frost Floyd J. , Hurley Judith S. , Petersen Hans V. , Gunter Margaret J. , Gause Douglas
Published: August 2005

Summary: Purpose: Previous studies have estimated medical care costs of epilepsy by applying unit costs to estimated utilization or by summing costs for (a) ambulatory care and hospitalizations coded as epilepsy and (b) procedures and drugs specifically associated with the diagnosis or treatment of epilepsy. These methods may underestimate the cost of medical care for epilepsy. Two methods for estimating the medical care costs of epilepsy (“epilepsy‐attributable cost method” and “case‐control cost method”) were compared.

Methods: The study population was 655 individuals with an epilepsy diagnosis enrolled in a managed care plan in the south‐western United States. The epilepsy‐attributable costs were determined by summing costs for inpatient and outpatient encounters coded as epilepsy, procedures for the diagnosis or treatment of epilepsy, and drugs used to treat epilepsy. The case‐control method determined costs by calculating the difference in total costs between cases and 1,965 age‐ and gender‐matched controls.

Results: The case‐control epilepsy costs were $2,923 per case compared with epilepsy‐attributable costs of $1,335 per case. The case‐control method found statistically significant differences in costs between cases and controls for inpatient care, prescription drugs, and 8 of 11 categories of outpatient care. The largest contributors to the discrepancy between estimates were inpatient care, emergency department care, laboratory tests, and “other specialist” care.

Conclusions: Epilepsy‐attributable costs accounted for only 46% of the total difference in costs between epilepsy cases and controls. Persons with epilepsy use more medical services than controls, but a substantial portion of this care is not coded to epilepsy.
Zonisamide Reduces the Increase in 8‐Hydroxy‐2′‐Deoxyguanosine Levels Formed During Iron‐Induced Epileptogenesis in the Brains of Rats
Authors: Komatsu M. , Hiramatsu M. , Willmore L. J.
Published: August 2005

Summary: Purpose: To examine the change of 8′‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) levels, which are used as a marker for oxidative DNA damage, in iron‐induced epileptogenic foci of the rat cerebrum.

Method: Male Wistar rats were given a cortical injection of ferric chloride, and their 8‐OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8‐OHdG levels were compared with the nonpretreated rats.

Results: Fifteen minutes after ferric chloride solution injection, the level of 8‐OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8‐OHdG levels within the cerebrum 30 minutes after iron solution injection.

Conclusions: These results indicate that the formation of iron‐induced epileptogenic foci in rats is related to DNA‐damage‐induced reactive oxygen species and that the inhibition of 8‐OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts–induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts–induced acute epileptogenesis.
Audiogenic Seizures Susceptibility in Transgenic Mice with Fragile X Syndrome
Authors: Musumeci Sebastiano A. , Bosco Paolo , Calabrese Giuseppe , Bakker Cathy , De Sarro Giovanni B. , Elia Maurizio , Ferri Raffaele , Oostra Ben A.
Published: August 2005

Summary: Purpose: To evaluate their susceptibility to audiogenie seizures, five groups of knockout mice with various forms of fragile X genetic involvement [hemizygous males (n = 46), and homozygous (n = 38) and heterozygous females (n = 45), and their normal male (n = 45) and female (n = 52) littermates] were studied.

Methods: All mouse groups were tested at ages 17, 22, 35, and 45 days. Audiogenic seizure susceptibility was scored, and the analysis of variance was used for the evaluation of the effects of age and genetic condition on seizure severity score (SSS).

Results: All groups of knockout fragile X mice exhibited SSSs significantly higher than those observed in their wild‐type littermates; among knockout mice, hemizygous males and homozygous females showed the highest SSSs. Hemizygous males showed higher SSSs with increasing age, from 17 to 45 days; homozygous females showed a peak at age 22 days, followed by a decrease; finally, heterozygous females had their highest SSSs at age 17 days.

Conclusions: This study demonstrates that an increased susceptibility to audiogenic seizures is present in fragile X knockout mice at all the ages tested. These results support the validity of this animal model also for epilepsy and seizures in the human fragile X syndrome.
Health Status of People with Epilepsy Compared with a General Reference Population
Authors: Stavem Knut , Loge Jon Håvard , Kaasa Stein
Published: August 2005

Summary: Purpose: To study the impact of epilepsy in a representative sample of people with epilepsy and compare with a normal reference population.

Methods: We collected clinical and demographic data and information on health status by using the Short Form 36 (SF‐36) questionnaire in two populations: (a) 397 patients with confirmed epilepsy attending a county hospital during a 7‐year period, and (b) 1,663 patients from a random sample representative of the entire national population.

Results: The respondents with epilepsy had well‐regulated disease and showed the characteristics of a community sample: 70% had had no seizures during the last year, and 80% used antiepileptic drugs (AEDs). On six of eight SF‐36 scales, patients with epilepsy had lower scores than the normal reference population, and they were less likely to be married, employed, or a full‐time student. Scizure‐free patients with epilepsy had scores close to those of the normal reference population, with higher scores on the social functioning and mental health scales and lower on the role—emotional scale. There were no differences in health status scores between seizure‐free patients using and not using AEDs.

Conclusions: Our results confirm that patients with well‐regulated epilepsy have a health status at the level of a general reference population.
A Metabolic and Neuropathological Approach to the Understanding of Plastic Changes That Occur in the Immature and Adult Rat Brain During Lithium‐Pilocarpine–Induced Epileptogenesis
Authors: Dubé Céline , Marescaux Christian , Nehlig Astrid
Published: August 2005

Summary: Purpose: The age‐related functional changes that underlie epileptogenesis remain to be clarified. In the present study, we explored the correlation between metabolic changes, neuronal damage, and epileptogenesis during the silent and chronic phases after status epilepticus (SE) induced by lithium‐pilocarpine in 10‐day‐old (P10), 21‐day‐old (P21), and adult rats.

Methods: Local cerebral metabolic rates for glucose (LCMRglcs) were measured by the [14C]2‐deoxyglucose method during the silent period (14 and 60 days after SE in P10 and P21 rats and only at 14 days after SE in adult rats because the silent phase lasts for about 14 days in adults and 60 days in P21 rats) and the interictal phase of the chronic period (2 months after spontaneous seizures or 6 to 7 months after SE in P10 and P21 rats that do not become epileptic). Neurodegeneration was assessed by the silver staining and cresyl violet techniques.

Results: In P10 rats, there was no damage and no metabolic consequences at any time after SE. During the silent phase in P21 rats, metabolic decreases were recorded at 14 days after SE, mainly in damaged forebrain regions. At 60 days after SE, P21 rats exhibited metabolic increases in both damaged forebrain and intact brainstem areas. In adult rats studied at 14 days after SE, LCMRglcs decreased in damaged forebrain areas involved in the genesis and propagation of seizures and increased in brainstem areas involved in the remote control of epilepsy. During the interictal phase of the chronic period, LCMRglcs decreased in damaged forebrain areas of adult epileptic rats and P21 rats that were not spontaneously epileptic, whereas it was similar to control levels in epileptic P21 rats.

Conclusions: The process of epileptogenesis and its effects differ in duration and functional consequences in P21 and adult rats. The factors that underlie these age‐related differences remain to be explored.
Alterations of Neuronal Connectivity in Area CA1 of Hippocampal Slices from Temporal Lobe Epilepsy Patients and from Pilocarpine‐Treated Epileptic Rats
Authors: Lehmann T.‐N. , Gabriel S. , Kovacs R. , Eilers A. , Kivi A. , Schulze K. , Lanksch W. R. , Meencke H. J. , Heinemann U.
Published: August 2005

Summary: Purpose: Neuronal network reorganization might be involved in epileptogenesis in human and rat limbic epilepsy. Apart from aberrant mossy fiber sprouting, a more wide‐spread fiber rearrangement in the hippocampal formation might occur. Therefore, we studied sprouting in area CA1 because this region is most affected in human temporal lobe epilepsy.

Methods: In slices from hippocampi of patients operated on for temporal lobe epilepsy (n = 134), from pilocarpine‐treated rats (n = 74), and from control rats (n = 15), viable neurons were labeled with fluorescent dextran amines.

Results: In human hippocampi as well as in pilocarpine‐treated rats, the degree of nerve cell loss varied. In 67 of 134 slices from human specimens with distinct Ammon's horn sclerosis and in 23 of 74 slices from pilocarpine‐treated rats, a severe shrunken area CA1 presented with a similar picture: few damaged neurons were labeled, and aberrant fiber connections were not visible. This was in contrast to human resected hippocampi and hippocampi from pilocarpine‐treated rats with no or moderate loss of neurons. In these cases, pyramidal cells remote from the injection site were labeled (human tissue, n = 59 of 134; pilocarpine‐treated rats, n = 39 of 74). In human resected hippocampi without obvious pathology and in control animals, no pyramidal neurons were labeled apart from the injection site.

Conclusions: Axon collaterals of CA1 pyramidal cells are increased in human temporal lobe epilepsy and in pilocarpine‐treated rats. Adjacent CA1 pyramidal cells project via aberrant collaterals to the stratum pyramidale and the stratum radiatum of area CA1. This network reorganization can contribute to hyperexcitability via increased backward excitation.
Topiramate in Lennox–Gastaut Syndrome: Open‐Label Treatment of Patients Completing a Randomized Controlled Trial
Authors: Glauser Tracy A. , Levisohn Paul M. , Ritter Frank , Sachdeo Rǎjesh C. ,   Topiramate YL Study Group
Published: August 2005

Purpose: The response to topiramate (TPM) as long‐term adjunctive therapy was evaluated in patients with Lennox‐Gastaut syndrome (LGS) in a long‐term, open‐label extension to a double‐blind, placebo‐controlled trial.

Methods: In 97 patients with LGS (mean age, 11 years), dosages of TPM and concomitant antiepileptic drugs (AEDs) were adjusted to optimal clinical response (mean TPM dosage, 10 mg/kg/day).

Results: For those patients who had completed 6 months of TPM therapy, drop attacks were reduced ges;50% in 55% of patients; 15% of patients had no drop attacks for ges;6 months at the last visit. After treatment up to 3+ years, 71% of patients who started open‐label TPM were continuing therapy at the last visit.

Conclusions: During long‐term therapy, TPM is effective and well tolerated in controlling the treatment‐resistant drop attacks and seizures associated with LGS.
Epilepsy, Pregnancy, and the Child
Authors: Kaneko Sunao
Published: August 2005

Women with epilepsy have many legitimate concerns regarding the effects of their condition and the use of antiepileptic drugs (AEDs) on their unborn children. These concerns fall into 4 areas: increased seizure frequency during pregnancy, risk of birth defects, risks associated with breast‐ feeding, and psychomotor retardation in offspring. Studies have shown that many of these risks can be minimized with appropriate management and counseling. Data also show that psychomotor retardation in offspring of mothers with epilepsy is generally transitory. In this article, associations between maternal use of AEDs, birth defects, intrauterine growth retardation, and the psychomotor development are discussed together with how best to alter AED therapy to minimize them.
Time‐Course of Changes of SPECT, EEG, and Seizures in Temporal Lobe Epilepsy
Authors: Shimizu Teruhiko , Nakano Takashi , Yoshikawa Jun , Ohmori Ken‐ichi
Published: August 2005

Purpose: Rccent reports havc shown that diagnostic imaging by SPECT is uscfiil in the assessment of cpilcptogcnic foci in the brain. We investigated the relationship betwcen the time‐course of SPECT, EEG, and seizure changes over 3‐ to 6‐year periods. Changes wcre correlatcd with therapeutic effect assessments and predicted prognoses. In our study, SPECT and EEG data werc recorded on the same day.

Subjects: Subjects comprised 27 outpaticnts with temporal lobe epiIcpsy, mean age and duration of disease of 39.2 years and 23.2 years, respectively. Seizure frequencies were weekly in 4 subjects, monthly in 7, yearly in 6, no seizure for I to 4 years in 6, and no seizure for 2 3 years in 4.

Methods: The early phase SPECT images were taken 30 minutes after intravcnous administretion of 1231‐IMP. Resting EEG was sub‐scqucntly recorded. SPECT scanning was performed on horizontal and coronary sections. Regional cerebral blood flow findings were coin‐parcd by visual inspection.

Results: In 9 of the 14 subjects whose seizure severity improved over time, focal spikes wcrc tiot observed i n either examination, or disappeared by second examination. I n contrast, only 5 of the 14 subjects had normal basic EEG activity by the second examination. SPECT usually did not improve. Only I ol the 14 subjects whose seizure scvcrity improved over time showed normalized SPECT findings. No subjects with scizure severity rating “unchanged” or “worsened” showed normalized SPECT findings. SPECT normalized i n only I of the 16 subjects i n whoin focal spikes wcrc not observed in either cxamination, or disappeared by second examination.

Conclusions: In our present study, improvement of seizures with treatment or over tiinc wits likely to be correlated with improvement in focal spikes but not with SPECT findings. This agrees with the report of Michihiro et al. in that focal spike disappearance preceded SPECT finding normalization during treatment.
Dipole Tracing Examination for the Electric Source of Photoparoxysmal Response Provoked by Half‐Field Stimulation
Authors: Kobayashi Kazuhiko , Yasuda Kimiko , Takanashi Jun‐ichi , Sugita Katsuo , Kohno Yoichi , Iwasa Hiroto , Nakajima Yoshio
Published: August 2005

Purpose: Dipole tracing (DT) is a computer‐aidcd noninvasive method used to estimate the location of epileptic discharges from the scalp EEG. In DT equivalent current dipoles (ECDs), which rcflcct the electric source in the brain, are rcsponsible for the potential distribution on the scalp EEC. Thercfore, the DT method is useful to estimatc the focal paroxysmal discharges. In this study we examined the location of the clectric source of photoparoxysmal response (PPR) using scalpskull‐brain dipolc tracing (SSB‐DT) after hal[‐field stimulation, which produced focal PPR on the scalp EEG.

Methods: We studied 4 cases of photoscnsitive epilepsy. Wc performed 20 Hz red flicker and flickcring dot pattern half‐ficld stimulation to provoke PPR. In this method, the loci of gcnerators corresponding to the paroxysmal discharges were estimated as ECDs by I ‐ and 2‐dipole analyses. Each location of the ECDs was estimated by iterative calculation. Algorithms minimizing the squarcd difference betwccn the electrical potentials recorded from the scalp EEG and those calculated theoretically from the voluntary dipoles were uscd. In the SSB model, the scalp shell was reconstructed from the helmet mcasurements, and the shapc of the skull and brain was 3‐dimcnsionally reconstructed from CT images. A dipolarity larger than 98% w the accuracy of the estimation. We recorded thcir 2 I channel monopolar scalp EEG. Each spike was sampled analyzed at 10 points around the peaks of at least 10 spikes in each patient using the SSB‐DT method. The ECDs were then supcrimposed on thc MRI of each palient to idcntify the more cxact anatomical region.

Results: This study showed the location of cach focus and a dipolarity of greater than 98% in all cases, although the results from the 2‐dipole method showed scattered location. We considered that the analyzed signals were generated from single source. PPR was elicitcd cross‐lateral to the field stimulated. By red flicker half‐field stimulation, EEG revealed eithcr focal spikes and waves in the contralatcral occipital, temporo‐occipitel region, or diffuse spikes and wave complex bursts, sccn dominantly at the contralateral hcmisphere. The supcrimposed ESDs on MRI were located at the occipital or inferior temporal lobe. PPR, provoked by flickering dot pattern half‐field stimulation, werc focal spikes and waves, mainly in the occipital, parieto‐occipital region, or diffuse spikes and wave complcx bursts, seen dominantly at thc contralateral hcmiaphere. The ECDs of their PPRs were located in the occipital, inferior temporal, or inferior pirietal lobules on MRI.

Conclusion: Our findings suggest that the inferior temporal and inferior parictal lobules which are important for the processing sequence of the visual system in addition to the occipital lobc, might he responsible for thc mechanism of PPR by half‐ficld stimulation, espccially for electric source expansion.
A Sibling of a Patient with Familial Schizencephaly with Epileptic Spasms
Authors: Kimura Shigeru , Sakemi Kikuo , Makuta Masahiro
Published: August 2005

Case Report: Case 1 was a 5‐year old male with normal perinatal history. At 4 months he was noted to have left hemiparesis and microcephaly. Right schizencephaly was seen on CT. At 7 months he developed epileptic spasms. The interictal EEG showed right parietal focal sharp waves, but no hypsarhythmia. Epileptic spasms initially were controlled with phenobarbital and carhamazepine, but he relapsed. At 5 years and 9 months, he only could speak a few words and he had left hemiparesis. MRI showed right schizencephaly, bilateral cortical dysplasia, and presence of a septum pellucidum. Case 2 was a I‐year old male. Ultrasound in utero showed schizencephaly. He was born after a 39‐week gestation at a birth weight of 3,442 g. He presented poor activity and microcephaly at birth, and poor feeding and retardation of growth followed. At 4 months, he developed epileptic spasms. Interictal EEG showed bilateral focal sharp waves over bilateral occipital and frontopolar regions. Ictal EEG showed an electrodecremental pattern. Infantile spasms were controlled with zonisamide and the focal sharp waves resolved. At I year and 2 months, he exhibited severe mental retardation and quadriplegia. MRIshowed bilateral schizencephaly, cortical dysplasia, and presence of a septum pellucidum. Laboratory studies of blood and urine were normal except for mildly elevated serum ALT. Chromosomal G‐banding was normal with a 46XY karyotype. Parents and another sibling were clinically normal, but were not studied by neuroimaging.

Conclusions: Prior literature reports 4 cases of familial schizencephaly; this is the first in Japan. Those 10 cases in 5 families contained 4 pairs of sibs and 1 of half sibs, 5 males and 5 females. Six of 10 cases had bilateral cerebral clefts and 4 had right cerebral cleft, complicating absence of pellucidum in 4 cases, and cortical dysplasia in 8. Five cases developed bilateral paresis, 5 developed hemiparesis, 5 had severe mental retardation (MR), and 4 had moderate MR. Eight cases presented with generalized seizures and 2 had seizures of an unknown type. Among 6 patients with reported EEGs, 5 showed focal slow waves or focal seizure discharges. Several reported cases responded to seizure pharniacotherapy.

Barkovick and associates reported 20 cases of non‐familial schizencephaly with bilateral clefts, complicated other cerebral developmental anomalies, severe mental retardation, severe motor dysfunction, and epilepsy at a prevalence statistically lower than that of familial cases. Familial cases tended to have generalized seizures, non‐familial cases partial seizures. Two of the non‐familial cases developed infantile spasms and our cases developed epileptic spasm without EEG findings of hypsarhythmia.