bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Expression of Ferritin, an Iron‐storage Protein, in Specific Regions of the Parahippocampal Cortex of Epileptic Rats
Authors: Gorter Jan A. , Mesquita Ana R.M. , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Aronica Eleonora 
Published: September 2005

Summary:  Purpose: Iron accumulation in the brain has been associated with neurodegenerative disorders, including epilepsy. In our previous SAGE study, we showed that ferritin, an iron‐storage protein, was one of the genes (Ferritin‐H) that showed overexpression before the chronic epileptic phase. In this study we used ferritin as indicator for disturbed iron homeostasis to acquire insight into whether this could play a role in the pathogenesis of temporal lobe epilepsy. Methods: With immunocytochemistry, we studied the regional and cellular distribution of ferritin protein in an animal model for temporal lobe epilepsy in which spontaneous seizures develop a few weeks after electrically induced status epilepticus (SE). Results: Increased ferritin expression was observed in regions known to be vulnerable to cell death, mainly in reactive microglial cells of epileptic rats. Ferritin expression after SE was initially high, especially throughout the hippocampus, but decreased over time. In the chronic epileptic phase, it was still upregulated in regions where extensive cell loss occurs during the early acute and latent period. Within the parahippocampal region, the most persistent ferritin overexpression was present in microglial cells in layer III of the medial entorhinal area. The upregulation was most extensive in rats that had developed a progressive form of epilepsy with frequent seizures (approximately five to 10 seizures per day). Conclusions: The fact that ferritin upregulation is still present in specific limbic regions in chronic epileptic rats, when neuronal loss is absent or minimal, suggests a role of iron in the pathogenesis and progression of epilepsy.
Characteristics of Male Veterans with Psychogenic Nonepileptic Seizures
Authors: Dworetzky Barbara A. , Strahonja‐Packard Andreja , Shanahan Christopher W. , Paz Jeanette , Schauble Barbara , Bromfield Edward B. 
Published: September 2005

Summary:  Purpose: To describe male patients (pts) with psychogenic nonepileptic seizures (PNESs) followed up in a Veteran's Administration (VA) seizure clinic and to compare them with those with epileptic seizures (ESs) by using clinical, and psychosocial variables. Methods: Adult male veterans seen between 1997 and 2000 with ESs were compared with those with PNESs with respect to clinical history (head trauma, antiepileptic drug exposure, depression, anxiety, substance abuse, seizure description), documented chronic pain, posttraumatic stress disorder (PTSD), compensation for diagnosis, neurologic examination, and test results including imaging and EEG data. Results: Men with PNESs were younger and reported more frequent events, and diagnoses of chronic pain, anxiety, and PTSD were significantly greater. Neuroimaging [computed tomography (CT) or magnetic resonance imaging (MRI) of the brain] and neurologic examination were significantly more likely to be normal or nonspecific in pts with PNESs, although history of ictal urinary incontinence or service‐connected compensation for diagnosis did not distinguish the groups. Conclusions: Male veterans with PNESs have characteristics similar to those reported in the literature, even though younger women have dominated previously studied populations. Compared with men with ESs, those with PNESs are more likely to have chronic pain, anxiety, and PTSD, as well as normal examinations and brain imaging.
Characterizing Magnetoencephalographic Spike Sources in Children with Tuberous Sclerosis Complex
Authors: Iida Koji , Otsubo Hiroshi , Mohamed Ismail S. , Okuda Chiyuki , Ochi Ayako , Weiss Shelly K. , Chuang Sylvester H. , Snead O. Carter 
Published: September 2005

Summary:  Purpose: Tuberous sclerosis complex (TSC) often causes medically intractable seizures. Magnetoencephalography (MEG) localizes epileptiform discharges. To evaluate the use of MEG spike sources (MEGSSs) for localizing epileptic zones in TSC patients, we characterized MEGSSs and correlated them to EEG and magnetic resonance imaging (MRI) results. Methods: We analyzed data from seven children who underwent prolonged video‐EEG, MEG, and MRI. We classified MEGSSs as clusters (six or more spike sources, ≤1 cm between sources) and scatters (fewer than six spike sources regardless of distance between sources; sources with >1 cm between sources regardless of number of sources). Results: A single, unilateral cluster with additional scatters occurred in two patients; these predominantly lateralized dipoles correlated to prominent tubers on MRI and ictal/interictal EEG zones. Bilateral clusters with scatters existed in two patients; cluster locations partly overlapped multiple prominent tubers. These patients also had bilateral or diffuse interictal discharges, bilateral or generalized seizures, and changing seizure types and EEG findings. Only bilateral scatters occurred in three patients; scatters partly overlapped EEG interictal/ictal‐onset regions; one patient had coexisting generalized seizures. In one patient with equally bilateral scatters, scatters overlapped a prominent tuber and interictal/ictal‐onset zones in the right frontal region. Conclusions: MEG contributes to information from EEG and MRI for localizing epileptogenic zones in children with TSC. A single cluster with scatters in a unilateral hemisphere predicts a primary epileptogenic zone or hemisphere; bilateral or multiple clusters indicate bilateral primary or potential epileptogenic zones; and bilateral scatters without clusters may indicate epileptogenic zones that are hidden within extensive areas of scattered MEGSSs.
Pregabalin Drug Interaction Studies: Lack of Effect on the Pharmacokinetics of Carbamazepine, Phenytoin, Lamotrigine, and Valproate in Patients with Partial Epilepsy
Authors: Brodie Martin J. , Wilson Elaine A. , Wesche David L. , Alvey Christine W. , Randinitis Edward J. , Posvar Edward L. , Hounslow Neil J. , Bron Nicola J. , Gibson G. L. , Bockbrader Howard N. 
Published: September 2005

Summary:  Purpose: Pregabalin (PGB) is an α2‐δ ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures. Methods: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open‐label, multiple‐dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ). Results: Trough steady‐state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady‐state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB–AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug–drug interactions.
Modulation of CaM Kinase II Activity Is Coincident with Induction of Status Epilepticus in the Rat Pilocarpine Model
Authors: Singleton Michael W. , Holbert William H. , Lee Anh Tuyet , Bracey James M. , Churn Severn B. 
Published: September 2005

Summary:  Purpose: This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE). Methods: The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II–specific substrate, autocamtide III, was used to determine kinase activity. Results: After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus. Conclusions: The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.
Photic‐ and Pattern‐induced Seizures: Expert Consensus of the Epilepsy Foundation of America Working Group
Authors: Harding Graham , Wilkins Arnold J. , Erba Giuseppe , Barkley Gregory L. , Fisher Robert S. 
Published: September 2005

Summary:  Purpose: In August, 2004, the Epilepsy Foundation of America convened a workshop to begin to develop an expert consensus on photosensitive seizures. Methods: Literature and data were reviewed, and consensus was derived from discussion. Results: A flash is a potential hazard if it has luminance ≥20 cd/m2, occurs at a frequency of ≥3 Hz, and occupies a solid visual angle of ≥0.006 steradians (∼10% of the central visual field or 25% of screen area at typical viewing distances). A transition to or from saturated red also is considered a risk. A pattern with the potential for provoking seizures contains clearly discernible stripes, numbering more than five light–dark pairs of stripes in any orientation. When the light–dark stripes of any pattern collectively subtend at the eye from the minimal‐expected viewing distance a solid angle of >0.006 steradians, the luminance of the lightest stripe is >50 cd/m2, and the pattern is presented for ≥0.5 s, then the pattern should display no more than five light–dark pairs of stripes, if the stripes change direction, oscillate, flash, or reverse in contrast; if the pattern is unchanging or smoothly drifting in one direction, no more than eight stripes. These principles are easier to apply in the case of fixed media, for example, a prerecorded TV show, which can be analyzed frame‐by‐frame, as compared with interactive media. Conclusions: A consensus view of stimuli likely to provoke visually evoked seizures can be developed.
Predicting Posttraumatic Epilepsy with MRI: Prospective Longitudinal Morphologic Study in Adults
Authors: Messori Anna , Polonara Gabriele , Carle Flavia , Gesuita Rosaria , Salvolini Ugo 
Published: September 2005

Summary: Purpose:Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments ≤2 years after traumatic brain injury (TBI).Methods:Brain MRI hyperintense (gliosis) or hypointense (hemosiderin) areas or both were assessed in the images of 135 adult TBI inpatients who completed a 2‐year clinical, EEG, and MRI study protocol. Overall clinical follow‐up for the development of PTE was 5–10 years (median, 102 months). Morphologic risk factors for PTE were evaluated by using Kaplan–Meier curves and Cox regression analysis.Results:In 20 patients, PTE developed. Kaplan–Meier curves showed that gliomesenchymal sequelae of focal brain lesions (subdural hematomas/contusions) that required surgical treatment (sSDH‐C) were a PTE risk factor (p < 0.001), as were sequelae of nonsurgical hemorrhagic contusions with gliosis wall incompletely surrounding hemosiderin dregs (IW) (p = 0.039) and mainly those with time‐related changes from incomplete to complete gliosis wall around hemosiderin (I/CW) (p = 0.005); those with early hemosiderin completely surrounded by gliosis (CW) were not (p = 0.821). Cox regression analysis showed that for patients with sequelae of sSDH‐C, the PTE risk was 4.38 (p = 0.023) times higher than for those who did not require surgical treatment or underwent surgery because of purely extradural hematoma; for those with IW and I/CW lesions, considered pooled, it was 6.61 times higher (p = 0.014) than for those with CW lesions.Conclusions:MRI follow‐up examination in the early chronic stage can differentiate among low‐, intermediate‐, and high‐risk sequelae of TBI. These findings yield new evidence for, but do not resolve, the debate on posttraumatic epileptogenesis.
Cerebral Damage in Epilepsy: A Population‐based Longitudinal Quantitative MRI Study
Authors: Liu Rebecca S. N. , Lemieux Louis , Bell Gail S. , Sisodiya Sanjay M. , Bartlett Philippa A. , Shorvon Simon D. , Sander Josemir W. A. S. , Duncan John S. 
Published: September 2005

Summary:  Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community‐based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy‐nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age‐related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures.
Hemispherectomy for Catastrophic Epilepsy in Infants
Authors: González‐Martínez Jorge A. , Gupta Ajay , Kotagal Prakash , Lachhwani Deepak , Wyllie Elaine , Lüders Hans O. , Bingaman William E. 
Published: September 2005

Summary:  Purpose: To report our experience with hemispherectomy in the treatment of catastrophic epilepsy in children younger than 2 years. Methods: In a single‐surgeon series, we performed a retrospective analysis of 18 patients with refractory epilepsy undergoing hemispherectomy (22 procedures). Three different surgical techniques were performed: anatomic hemispherectomy, functional hemispherectomy, and modified anatomic hemispherectomy. Pre‐ and postoperative evaluations included extensive video‐EEG monitoring, magnetic resonance imaging, and positron emission tomography scanning. Seizure outcome was correlated with possible variables associated with persistent postoperative seizures. The Generalized Estimation Equation (GEE) and the Barnard's exact test were used as statistical methods. Results: The follow‐up was 12–74 months (mean, 34.8 months). Mean weight was 9.3 kg (6–12.3 kg). The population age was 3–22 months (mean, 11.7 months). Thirteen (66%) patients were seizure free, and four patients had >90% reduction of the seizure frequency and intensity. The overall complication rate was 16.7%. No deaths occurred. Twelve (54.5%) of 22 procedures resulted in incomplete disconnection, evidenced on postoperative images. Type of surgical procedure, diagnosis categories, persistence of insular cortex, and bilateral interictal epileptiform activity were not associated with persistent seizures after surgery. Incomplete disconnection was the only variable statistically associated with persistent seizures after surgery (p < 0.05). Conclusions: Hemispherectomy for seizure control provides excellent and dramatic results with a satisfactory complication rate. Our results support the concept that early surgery should be indicated in highly selected patients with catastrophic epilepsy. Safety factors such as an expert team in the pediatric intensive care unit, neuroanesthesia, and a pediatric epilepsy surgeon familiar with the procedure are mandatory.
Consequences of Prolonged Caffeine Administration and Its Withdrawal on Pilocarpine‐ and Kainate‐induced Seizures in Rats
Authors: Hoexter Marcelo Q. , Rosa Pedro S. , Tufik Sergio , Mello Luiz E. 
Published: September 2005

Summary:  Purpose: To investigate the consequences of caffeine consumption on epileptic seizures, we used the pilocarpine and the kainate models of epilepsy. We hypothesized that prolonged caffeine consumption or its withdrawal would alter adenosine levels and hence alter seizure susceptibility. Methods: We administered a 0.1% caffeine solution in the drinking water of adult male Wistar rats over a 2‐week period. We challenged another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine‐administration protocol. Results: This did not alter the threshold for the induction of seizures by a subconvulsant dose of pilocarpine (200 mg/kg, i.p.) or kainic acid (8 mg/kg, i.p.). Similarly, challenging another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine‐administration protocol did not lead to any significant changes in seizures. Conclusions: With the pilocarpine model of epilepsy, we were not able to find any significant difference in seizure profile that could stem from either caffeine administration or its withdrawal. Despite the extensive laboratory evidence on the convulsant properties of xanthine derivatives in animal models of epilepsy, such strong evidence is lacking in clinical settings. Our current findings with the administration of caffeine at doses similar to those of daily life both support and confirm the clinical experience.
Clinical Features of Patients with Posterior Cortex Epilepsies and Predictors of Surgical Outcome
Authors: Dalmagro Charles L. , Bianchin Marino M. , Velasco Tonicarlo R. , Alexandre Veriano , Walz Roger , Terra‐Bustamante Vera C. , Inuzuka Luciana M. , Wichert‐Ana Lauro , Araújo David , Serafini Luciano N. , Carlotti Carlos G. , Assirati João A. , Machado Hélio R. , Santos Antonio C. , Sakamoto Américo C. 
Published: September 2005

Summary:  Purpose: Posterior cortex epilepsies (PCEs) encompass a group of epilepsies originating from the occipital, parietal, or occipital border of the temporal lobe, or from any combination of these regions. When their seizures are refractory to pharmacologic treatment, these patients are usually referred for surgery. The aim of our study was to analyze clinical characteristics of all PCE patients referred for surgery from 1994 to 2003, and to search for predictors of surgical outcome. Methods: We performed a retrospective analysis of clinical and laboratory data from 81 consecutive refractory PCE patients referred for surgery. Surgical and nonsurgical groups of patients were compared, and detailed analyses of all variables of the surgical cases were performed in the search for predictors of seizure outcome. Results: Risk factors for PCEs included gliosis (34.56%), malformations of cortical development (33.33%), tumors (8.64%), brain trauma (3.70%), Sturge–Weber disease (4.93%), vascular malformations (3.70%), family history of epilepsy (3.70%), history of CNS infections (2.46%), and low IQ (2.46%). Of the 81 patients, 44 were submitted to surgery at the time of the completion of this study. Surgical treatment was highly effective in improving seizures (p < 0.001) when compared with previous pharmacologic treatment alone. Twenty‐eight (65.11%) patients became seizure free after surgery versus none in the nonsurgical group. Regarding outcome predictors, patients with shorter duration of epilepsy and those without neurologic abnormalities on clinical examination had higher chances of favorable evolution. Conclusions: Surgical treatment is effective for the treatment of PCEs and superior to pharmacologic therapy alone. In our series, shorter duration of epilepsy and normal neurologic examination were the only independent variables that predicted better surgical outcome.
A Comparison of Case‐Control and Family‐Based Association Methods: The Example of Sickle‐Cell and Malaria
Authors: Ackerman H. , Usen S. , Jallow M. , Sisay‐Joof F. , Pinder M. , Kwiatkowski D. P. 
Published: September 2005

SummaryThere has been much debate about the relative merits of population‐ and family‐based strategies for testing genetic association, yet there is little empirical data that directly compare the two approaches. Here we compare case‐control and transmission/disequilibrium test (TDT) study designs using a well‐established genetic association, the protective effect of the sickle‐cell trait against severe malaria. We find that the two methods give similar estimates of the level of protection (case‐control odds ratio = 0.10, 95% confidence interval 0.03–0.23; family‐based estimate of the odds ratio = 0.11, 95% confidence interval 0.04–0.25) and similar statistical significance of the result (case‐control: χ2= 41.26, p= 10−10, TDT: χ2= 39.06, p= 10−10) when 315 TDT cases are compared to 583 controls. We propose a family plus population control study design, which allows both case‐control and TDT analysis of the cases. This combination is robust against the respective weaknesses of the case‐control and TDT study designs, namely population structure and segregation distortion. The combined study design is especially cost‐effective when cases are difficult to ascertain and, when the case‐control and TDT results agree, offers greater confidence in the result.
Fishing for Pleiotropic QTLs in a Polygenic Sea
Authors: Bauman L. E. , Almasy L. , Blangero J. , Duggirala R. , Sinsheimer J. S. , Lange K. 
Published: September 2005

SummaryThe application of factor analysis to human genetics has the potential to discover the coordinated control of multiple traits by common environment, common polygenes, or a single major gene. Classical factor analysis explains the covariation among the components of a random vector by approximating the vector by a linear transformation of a small number of uncorrelated factors. In the current paper we show how factor analysis dovetails with the classical variance decompositions of biometrical genetics. To explore the relationships between related quantitative variables, and avoid complicated positive definiteness constraints, we employ Cholesky and factor analytic decompositions. We derive an ECM algorithm and a competing quasi‐Newton algorithm for estimating parameters by maximum likelihood and propose tactics for selecting initial parameter values. We also show how parameter asymptotic standard errors under these parameterizations propagate to asymptotic standard errors of the underlying variance components. Our genetic analysis program Mendel, which now incorporates the program Fisher, has performed well on a variety of data sets. We illustrate our methods, algorithms, and models on two data sets: a bivariate quantitative genetic example using total finger ridge count data and a multivariate linkage example using insulin resistance data.