bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community Leader Education to Increase Epilepsy Attendance at Clinics in Epworth, Zimbabwe
Authors: Ball D. E. , Mielke J. , Adamolekun B. , Mundanda T. , McLean J. 
Published: August 2005

Summary: Objective: To determine whether educating community leaders about epilepsy would lead to an increase in epilepsy cases being diagnosed and treated at primary health centers. Methods: This was a single‐arm cohort study performed in Epworth, a periurban township outside Harare, Zimbabwe. The subjects were Epworth community leaders (Local Board members, teachers, nurses, police officers, traditional healers, prophets). Educational workshops were given on epilepsy, its cause, and its management, and the number of new epilepsy cases on local primary health clinic registers 6 months after the workshops was measured. Results: Six new cases were recorded, all among patients previously diagnosed with epilepsy. This was a significant increase (p = 0.02) compared with the null hypothesis. Conclusion: Although there was a significant increase in new cases, these did not represent newly diagnosed patients. Significant prejudice within the community may still prevent identified patients with epilepsy from seeking treatment. Alternative methods must be sought to increase the awareness of epilepsy within low‐income communities and to reach “hidden” people with epilepsy.
Patient‐Based Assessments of Quality of Life in Newly Diagnosed Epilepsy Patients: Validation of the NEWQOL
Authors: Abetz Linda , Jacoby Ann , Baker Gus A. , McNulty Pauline 
Published: August 2005

Summary:Purpose: In epilepsy, patient‐based assessments are increasingly used as outcome measures in clinical trials of novel therapies alongside the traditional clinical measures of efficacy. The objective of this study was to validate psychometrically a quality of life (QOL) measure developed for use with recently diagnosed epilepsy patients.Methods: The NEWQOL (Quality of Life in Newly Diagnosed Epilepsy Instrument) is a 93‐item self‐administered battery designed to assess QOL in patients with new‐onset epilepsy. NEWQOL consists of eight multi‐item scales (13 subscales) measuring several health parameters: Anxiety, Depression, Social Activities, Symptoms, Locus of Control/Mastery, Neuropsychological Problems (includes the following subscales: Fatigue, Memory, Concentration, Motor Skills, and Reading), Social Stigma, Worry, Work Limitations, and several single‐item measures (General Health, Number of Seizures, Social Limitations, Social Support, Self Concept, Ambition Limitations, Health Transition, and General Limitations). The NEWQOL was collected at baseline and 1 week post‐baseline from 108 patients in the U.K. and U.S.Results: All of the multi‐item scales had high item discriminant validity, good test‐retest reliability, and acceptable levels of internal consistency reliability; all but the Reading and Stigma subscales had negligible floor and ceiling effects. General linear models were used to examine the known groups validity of NEWQOL. Significant differences were observed in the Worry, Symptoms, Summary Neuropsychological Scales, and all Neuropsychological subscales (Memory, Fatigue, Concentration, Motor Skills, and Reading), indicating poorer functioning in the more frequent or severe seizure groups.Conclusions: Results from this study offer supportive evidence that NEWQOL has good validity and reliability and can discriminate between patient groups, particularly in relation to symptoms and psychological problems. We conclude that NEWQOL represents a useful measure for future studies in this patient population.
A Population‐Based Study on Epilepsy in Mentally Retarded Children
Authors: Airaksinen Eila M. , Matilainen Riitta , Mononen Tarja , Mustonen Kirsi , Partanen Juhani , Jokela Veikko , Halonen Pirjo 
Published: August 2005

Summary: Purpose: This study presents data on cumulative risk of seizures, cause, comorbidity, and remission of epilepsy among mentally retarded (MR) children followed until the age of 22 years. Methods: A total of 151 MR children were identified at the age of 8 or 9 years by screening four birth cohorts of 12,882 children born from 1969 to 1972 in the Finnish province of Kuopio. Information about epilepsy was gathered longitudinally when children were 9 to 10, 17, and 22 years old. The guidelines for epidemiological studies on epilepsy proposed by the International League Against Epilepsy were followed. Results: By the age of 10 years, 29 of the 151 MR children (19%) had epilepsy. The cumulative risk for epilepsy at 22 years was 21%. The probability of developing epilepsy was increased fivefold in severely MR children compared with mildly MR children, i.e., in 27 of the 77 severely MR children (35%) versus 5 of the 74 mildly MR children (7%). Postnatal causes of mental retardation or association with cerebral palsy increased the risk for epilepsy, especially in the mildly MR children. When these risk factors were not present, the mildly MR children exhibited only a 3% risk for epilepsy, whereas the respective risk was about 10‐fold in severe mental retardation. The cumulative probability of epilepsy being in remission for 5 years by the age of 22 was 32%. Conclusions: The cumulative risk of epilepsy varies according to the severity and the cause of the retardation as well as the presence of additional disabilities. The cumulative probability of epilepsy remission tended to increase with age.
Discriminating Between Epileptic and Nonepileptic Events: The Utility of Hypnotic Seizure Induction
Authors: Barry John J. , Atzman Orit , Morrell Martha J. 
Published: August 2005

Summary: Purpose: To determine the validity of the Hypnotic Induction Profile (HIP) followed by seizure induction during continuous video‐electroencephalographic (EEG) monitoring to discriminate between epileptic (EE) and nonepileptic events (NEE). Methods: Eighty‐two patients admitted to the Stanford Comprehensive Epilepsy Center for differential diagnosis of seizure‐like events were evaluated. Exclusion criteria included inability or refusal to complete the HIP, lack of a “typical”event, an IQ <70, present evidence of psychosis, or a physiological cause for NEE. Sixty‐nine patients met these criteria. While undergoing continuous video‐EEG monitoring, the patient completed an HIP, an inventory designed to measure the degree of hypnotizability. An attempt was then made to induce the patient's typical events under hypnosis by using a splitscreen technique. An event without an EEG correlate was thought to represent an NEE. A diagnosis of NEE was made independently by the neurology team and was compared with results obtained with the hypnotic evaluation. Results: Results for patients with EE were compared with those with NEE and a group consisting of both EE/NEE. All patients with NEE were then contrasted with the EE group. HIP scores for the EE patients indicated lower hypnotizability than the NEE group and were statistically significant when NEE patients and those with NEE/EE were combined. The sensitivity of seizure induction in the diagnosis of NEE was 77%, with a specificity of 95%. Conclusions: The HIP coupled with seizure induction is a useful technique to aid in the diagnosis of patients with NEE. It is sensitive and specific, and it may provide the patient with a useful behavioral tool to control NEEs. It may also furnish a conduit for long‐term treatment.
Association Between the Density of Mossy Fiber Sprouting and Seizure Frequency in Experimental and Human Temporal Lobe Epilepsy
Authors: Pitkänen Asla , Nissinen Jari , Lukasiuk Katarzyna , Jutila Leena , Paljärvi Leo , Salmenperä Tuuli , Karkola Kari , Vapalahti Matti , Ylinen Aarne 
Published: August 2005

Summary: Purpose: If the sprouting of granule cell axons or mossy fibers in the dentate gyrus is critical for the generation of spontaneous seizures in temporal lobe epilepsy (TLE), one could hypothesize that epileptic animals or humans with increased sprouting would have more frequent seizures. This hypothesis was tested by analyzing the data gathered from experimental and human epilepsy. Methods: In experiment I (rats with “newly diagnosed” TLE), self‐sustained status epilepticus was induced in rats by electrically stimulating the amygdala. Thereafter, the appearance of spontaneous seizures was monitored by continuous video‐electroencephalography (EEG) until the animal developed two spontaneous seizures and for 11 d thereafter. Rats were perfused for histology, and mossy fibers were stained using the Timm method. In experiment II (rats with “recently diagnosed” TLE), status epilepticus was induced in rats and the development of seizures was monitored by video‐EEG for 24 h/d every other day for 60 days. All animals were then perfused for histology. In experiment III (rats with “chronic” TLE), animals were monitored by video‐EEG for 24 h/d every other day for 6 months before histologic analysis. To assess mossy fiber sprouting in human TLE, hippocampal sections from 31 patients who had undergone surgery for drug‐refractory TLE were stained with an antibody raised against dynorphin. Results and Conclusions: Our data indicate that the density of mossy fiber sprouting is not associated with the total number of lifetime seizures or the seizure frequency in experimental or human TLE.
Does Status Epilepticus Influence the Motor Development of Immature Rats?
Authors: Kubová Hana , Haugvicová Renata , Suchomelová Lucie , Mareš Pavel 
Published: August 2005

Summary: Purpose: To study the effect of severe status epilepticus (SE) on the motor development of rats. Methods: SE was induced in 12‐day‐old rats (P12 group) and 25‐day‐old rats (P25 group) using the lithium‐pilocarpine model. Seizures were interrupted after 2 hours by paraldehyde with an intraperitoneal dose of 0.3 or 0·6 mL/kg, respectively. Starting 3 days after SE, all animals were repeatedly exposed to a battery of motor and behavioral tests, including the bar‐holding test, rotarod test, and open field test. Results: In P12 animals, motor impairment occurred 2 months after SE, when significantly worse performance in the rotarod test was found. No difference between controls and experimental rats was found in any other test used. In contrast, P25 animals were significantly poorer in the bar‐holding test from postnatal day 34 until adulthood. In open field study, P25 rats were found to be hyperactive during the whole period of testing, whereas P12 animals exhibited an initial period of hypoactivity (in the first test) that was replaced by hyperactivity that lasted until 2 months of age. In the last test performed at the age of 98 days, experimental P12 animals were again less active than age‐matched controls. Conclusions: Animals of both age groups exhibited permanent changes of motor performance; however, both the pattern and the time course of these changes was related to age when SE was elicited.
Morphological Plasticity in an Infant Monkey Model of Temporal Lobe Epilepsy
Authors: Wenzel H. Jürgen , Born Donald E. , Dubach Mark F. , Gunderson Virginia M. , Maravilla Kenneth R. , Robbins Carol A. , Szot Partrizia , Zierath Danielle , Schwartzkroin Philip A. 
Published: August 2005

Summary: Purpose/Methods: Seizures in early life are thought to contribute to the development of human temporal lobe epilepsy. To examine the consequences of early seizures, we elicited status epilepticus in immature, 5.5‐ to 7.0‐month‐old pigtailed macaques by unilateral microinfusion of bicuculline methiodide into the entorhinal cortex. Results: This report focuses on neuropathological changes in the hippocampus. Bicuculline infusion consistently elicited limbic‐like seizures with prolonged, relatively localized electrographic activity. Magnetic resonance imaging revealed enhanced signal intensity in the ipsilateral hippocampus after seizures; in some cases, there was also progressive hippocampal atrophy. Histological changes were variable; in two of five monkeys, there was significant hippocampal neuron loss, gliosis, granule cell dispersion, and mossy fiber reorganization. Conclusions: The histopathological findings and associated magnetic resonance imaging abnormalities after bicuculline‐induced status epilepticus in infant monkeys mimic common aspects of human temporal lobe epilepsy.
Brain Plasticity and Cellular Mechanisms of Epileptogenesis in Human and Experimental Cortical Dysplasia
Authors: Babb Thomas L. , Ying Zhong , Mikuni Nobuhiro , Nishiyama Kazuotoshi , Drazba Judy , Bingaman William , Wyllie Elaine , Wylie Christi J. , Yacubova Karina 
Published: August 2005

Summary: Purpose: The cellular mechanisms that may contribute to epilepsy in resected human cortical dysplasia (CD) were compared with the in utero radiated rat CD model. In human and rat focal hippocampal epilepsy, postsynaptic N‐methyl‐d‐aspartate receptors are up‐regulated and presynaptic axon collaterals hyperinnervate them. We hypothesized that in both human and rat CD: (a) the N‐methyl‐d‐aspartate receptor subunits NR1 and NR2A/B would be increased and coassembled, and (b) aberrant axons would be in regions of CD. Methods: Tests for presynaptic and postsynaptic changes in human and rat CD included the following: (a) cytology, (b) immunocytochemistry, (c) coimmunoprecipitation, (d) double‐labeled immunofluorescence, and (e) Timm histochemistry of hippocampal mossy fibers. Within‐patient comparisons were made between epileptic tissue, identified by subdural electro‐encephalographic seizure onsets, and nonepileptic tissue remote from the focus but within the therapeutic resection. Rats were radiated at embryonic day 17, and offspring were studied postnatally. Statistical comparisons were made against normal rats matched for age and tissue processing. Results: In focal CD patients, NR2A/B subunits and their coassemblies with NR1 were increased significantly more than for the remote nonepileptic cortex. Confocal microscopy showed that NR1‐NR2A/B colabeled single dysplastic neurons in both human and rat. In CD rats, mossy fibers innervated the anomalously oriented hippocampal neurons. Conclusions: Human epileptic CD exhibits a spectrum of abnormal cell orientations and laminations that must require plastic axodendritic changes during development. These altered circuits and receptors could account for the seizures and cognitive deficits found in patients with CD. The radiated rat CD model with cortical dyslaminations and NR2A/B subunit increases would allow the development and testing of drugs targeted at only the NR2A/B subunit or at decoupling the NR1‐NR2 coassembly, which could provide a specific antiepileptic drug for dysplastic circuits without inducing general depression of all brain neurons.
Hippocampal Neurons Express GABAAReceptor Insensitive to Diazepam in Hyperexcitable Conditions
Authors: Kapur Jaideep 
Published: August 2005

Summary:Purpose: To define the properties of γ‐aminobutyric acid‐type A (GABAA) receptors expressed on dentate granule cells in neonatal rats and to define the impact of prolonged seizures on GABAAreceptors in 28‐ to 35‐day‐old rats.Methods: Whole GABAAreceptor currents were recorded from acutely isolated dentate granule cells. Cells were isolated from 7‐ to 14‐day‐old rats for the first experiment. For the second experiment, cells were isolated from 28‐ to 35‐day‐old naive rats and rats that had undergone 45 minutes of status epilepticus. Modulation of GABAAreceptor currents by diazepam (DZP), zinc, and zolpidem was studied.Results: In 7‐ to 14‐day‐old rats, dentate granule cells express DZP‐ and zolpidem‐insensitive, zinc‐sensitive GABAAreceptors. In 28‐ to 35‐day‐old rats, dentate granule cells express DZP‐sensitive GABAAreceptors. At the latter age, prolonged seizures render GABAAreceptors DZP‐insensitive.Conclusion: Hippocampal dentate granule cells express DZP‐insensitive receptors in hyperexcitable states. These receptors are likely to contain α4 subunit.
Neurons Recorded from Pediatric Epilepsy Surgery Patients with Cortical Dysplasia
Authors: Mathern Gary W. , Cepeda Carlos , Hurst Raymond S. , Flores‐Hernandez Jorge , Mendoza Delia , Levine Michael S. 
Published: August 2005

Summary: Purpose: Cortical dysplasia (CD) is a common pathological substrate in patients with early‐onset childhood epilepsy. In CD tissue, little is known about the mechanisms responsible for cellular hyperexcitability. In this study, we report initial electrophysiological and morphological observations from normal and dysmorphic cells in pediatric CD patients. Methods: Neocortical “most” and “least” epileptogenic areas were sampled based on neuroimaging and electrocorticography from 15 CD patients (ages 0.3 to 14 years). Whole‐cell voltage clamp recordings combined with infrared videomicroscopy sampled abnormal cells (cytomegalic neurons, cells with bifurcated dendrites, disoriented pyramidal cells, etc.) compared with normal‐appearing neurons from the same patient. Cells were filled with biocytin, and adjacent tissue blocks were stained for neuronal and glial markers. Results: About 15% of the 161 recorded cells were abnormal in appearance. Abnormal cells showed electrophysiological irregularities ranging from intrinsic cellular hyperexcitability to hyposensitivity after application of ionotropic receptor agonists. Other findings included increased excitatory postsynaptic currents and alterations in γ‐aminobutyric acid reversal potentials. Conclusions: In pediatric CD tissue, these preliminary results indicate that abnormal‐appearing cells showed abnormalities in electrophysiological measures compared with normal‐appearing neurons. The abnormalities varied from hyperexcitability to hypoexcitability. More detailed results and conclusions will be forthcoming as additional patient material is analyzed.
Loss of Hilar Mossy Cells in Ammon's Horn Sclerosis
Authors: Blümcke I. , Suter B. , Behle K. , Kuhn R. , Schramm J. , Elger C. E. , Wiestler O. D. 
Published: August 2005

Summary: Purpose: Hilar mossy cells represent an important excitatory subpopulation of the hippocampal formation. Several studies have identified this cell type as particularly vulnerable to seizure activity in rat models of limbic epilepsy. Here we have subjected hilar mossy cell loss in the hippocampus of patients with chronic temporal lobe epilepsy (TLE) to a systematic morphological and immunohistochemical analysis. Methods: Hippocampal specimens from 30 TLE patients were included; 21 patients presented with segmental neuronal cell loss [Ammon's horns clerosis (AHS)] and 8 with focal lesions (tumors, scars, malformations) not involving the hippocampus proper. In one additional TLE patient, no histopathological alteration could be observed. Surgical specimens from tumor patients without epilepsy (n = 2) and nonepileptic autopsy brains (n = 8) were used as controls. Hilar mossy cells in the human hippocampus were visualized using a novel polycloncal antiserum directed against the metabotropic glutamate receptor subtype mGluR7b or by intracellular Lucifer Yellow injection, confocal laser scanning microscopy, and three‐dimensional morphological reconstruction. Results: Compared with controls, a significant loss of mGluR7 immunoreactive mossy cells was observed in patients with AHS (p < 0·05). In contrast, TLE patients with focal lesions but structurally intact hippocampus demonstrated only a discrete, nonsignificant reduction of this neuronal subpopulation. This observation was confirmed by analysis of 62 randomly injected hilar neurons from AHS patients, in which we were unable to detect neurons with a morphology like that of hilar mossy cells. Conclusion: Our present data indicate significant hilar mossy cell loss in TLE patients with AHS. In contrast, hilar mossy cells appear to be less vulnerable in patients with lesion‐associated TLE. Although the significance of mGluR7 immunoreactivity in mossy cells remains to be studied, loss of this cell population is compatible with alterations in hippocampal networks and regional hyperexcitability as pathogenic mechanism of AHS and TLE.
Role of Nitric Oxide in the Epileptogenesis of EL Mice
Authors: Murashima Yoshiya L. , Yoshii Mitsunobu , Suzuki Jiro 
Published: August 2005

Summary: Purpose: To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis. Methods: EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8·33 to 8·43 μg) were separated by sodium dodecyl sulfate—polyacrylamide gel electrophoresis and identified by immunoblotting. Results: EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable. Conclusions: Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium‐derived relaxing factor) may work together to form a focus complex.
Cellular Actions of Topiramate: Blockade of Kainate‐Evoked Inward Currents in Cultured Hippocampal Neurons
Authors: Gibbs John W. , Sombati Sompong , DeLorenzo Robert J. , Coulter Douglas A. 
Published: August 2005

Summary: Purpose: This study was undertaken to evaluate the effects of topiramate (TPM) on excitatory amino acid‐evoked currents. Methods:Kainate and N‐methyl‐d‐aspartate (NMDA) were applied to cultured rat hippocampal neurons by using a concentration‐clamp apparatus to selectively activate the AMPA (α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid)/kainate and NMDA receptor subtypes, respectively. The evoked membrane currents were recorded by using perforated‐patch whole‐cell voltage‐clamp techniques. Results:TPM partially blocked kainate‐evoked currents with an early‐onset reversible phase (phase I) and a late‐onset phase (phase II) that occurred after a 10‐ to 2‐min delay and did not reverse during a 2‐h washout period. Application of dibutyryl cyclic adenosine monophosphate (cAMP; 2 mM) during washout after phase II block enhanced reversal, with the kainate current amplitude being restored by =50%. Phase II but not phase I block was prevented by prior application of okadaic acid (1 μM), a broad‐spectrum phosphatase inhibitor, suggesting that phase II block may be mediated through interactions with intracellular intermediaries that alter the phosphorylation state of kainate‐activated channels. Topiramate at 100 μM blocked kainate‐evoked currents by 90% during phase II, but had no effect on NMDA‐evoked currents. The median inhibitory concentration (IC50) values for phase I and II block of kainate currents were 1·6 and 4·8 μM, respectively, which are within the range of free serum levels of TPM in patients. Conclusions:The specific blockade of the kainate‐induced excitatory conductance is consistent with the ability of TPM to reduce neuronal excitability and could contribute to the anti‐convulsant efficacy of this drug.