bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.