bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early versus late remission in a cohort of patients with newly diagnosed epilepsy
Authors: Del Felice Alessandra , Beghi Ettore , Boero Giovanni , La Neve Angela , Bogliun Graziella , De Palo Alessia , Specchio Luigi M. 
Published: June 2009

SummaryPurpose:  To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission.Methods:  Children and adults with previously untreated epilepsy from two Italian tertiary centers (Monza, Bari) were the study population. All patients received monotherapy at treatment start; drug choice and schedule were left to the physician’s judgment. A retrospective audit was performed and the following prognostic predictors were identified: age, gender, putative etiology, first electroencephalography (EEG) record, neurologic and psychiatric examination, disease duration at diagnosis, seizure type(s) and number prior to starting treatment, epilepsy syndrome, and first antiepileptic drug. Early remission was defined by 2‐year seizure control immediately after treatment start. Late remission was defined by 2‐year seizure control achieved at least 24 months after treatment start. Prognostic predictors were assessed by logistic regression analysis, adjusting for age, gender, and center.Results:  One hundred seventy‐four women and 178 men (mean age 31.5 years) were included and followed for 2399.6 person‐years. The cumulative time‐dependent probability of 2‐year remission was 56.3% at 2 years after treatment start, and 62.6, 69.4, and 79.5% at 3, 5, and 10 years. One hundred fifteen patients (23.0%) achieved early remission and 38 patients (10.8%) achieved late remission. The interaction between partial seizures and number of seizures prior to treatment was the only independent predictor of late remission.Discussion:  The course of epilepsy and the chance of remission are together a complex and dynamic process, possibly explained by the diversity of the mechanisms underlying drug response and the use of an increasing number of drugs.
Behavioral depression induced by an amygdala seizure and the opioid fentanyl was mediated through the nucleus accumbens
Authors: Long Jennifer J. , Ma Jingyi , Stan Leung L. 
Published: June 2009

SummaryPurpose: To study the behavioral depression induced by a generalized limbic seizure and by an opioid. The hypothesis that an opioid fentanyl and an amygdala‐evoked seizure induced behavioral depression through the nucleus accumbens was tested.Methods: The behavioral depression induced by an amygdala‐kindled seizure was studied in fully kindled rats, with or without prior injection of fentanyl (0.05 mg/kg, s.c.). Local infusion of a nonspecific opioid antagonist, naloxone, or saline, was made bilaterally in the nucleus accumbens. The durations of loss of righting reflex (LORR), loss of tail‐pinch response, and catalepsy were assessed.Results: Fentanyl induced an LORR following a generalized kindled seizure. The combination of fentanyl and a generalized seizure, as compared to fentanyl alone or a generalized seizure alone, resulted in a prolonged duration of LORR, catalepsy, and loss of tail pinch response. Infusion of naloxone as compared to saline in the nucleus accumbens reduced the duration of catalepsy and LORR induced by fentanyl, with or without a generalized seizure.Conclusions: Postictal depression that follows a generalized kindled seizure enhanced the behavioral effects of the opioid fentanyl. Network synaptic depression induced by the seizure acted synergistically with fentanyl to produce analgesia, catalepsy, and LORR, in part through the nucleus accumbens.
Pregnancy, delivery, and outcome for the child in maternal epilepsy
Authors: Veiby Gyri , Daltveit Anne K. , Engelsen Bernt A. , Gilhus Nils E. 
Published: June 2009

SummaryPurpose:  To investigate pregnancy, delivery, and child outcome in an unselected population of women with both treated and untreated epilepsy.Methods:  In the compulsory Medical Birth Registry of Norway, all 2,861 deliveries by women with epilepsy recorded from 1999–2005 were compared to all 369,267 nonepilepsy deliveries in the same period.Results:  The majority (66%, n = 1900) in the epilepsy group did not use antiepileptic drugs (AEDs) during pregnancy. A total of 961 epilepsy‐pregnancies were exposed to AEDs. Compared to nonepilepsy controls, AED‐exposed infants were more often preterm (p = 0.01), and more often had birth weight <2,500 g (p < 0.001), head circumference <2.5 percentile (p < 0.001), and low Apgar score (p = 0.03). Small‐for‐gestational‐age (SGA) infants (<10 percentile) occurred more frequently in both AED‐exposed (p = 0.05) and unexposed (p = 0.02) epilepsy‐pregnancies. Frequency of major congenital malformations (MCMs) was 2.8% (n = 81) in the epilepsy group versus 2.5% in controls (p = 0.3). Increased risk for MCMs could be demonstrated only for exposure to valproate (5.6%, p = 0.005) and AED polytherapy (6.1%, p = 0.02). Neonatal spina bifida was not significantly increased, but was a major indication for elective pregnancy termination among women with epilepsy. Cesarean section was performed more often in maternal epilepsy, regardless of AED‐exposure (p < 0.001).Discussion:  Adverse pregnancy and birth outcome in women with epilepsy is mainly confined to AED‐exposed pregnancies, although some risks are associated also with untreated epilepsy. The risk for congenital malformations was lower than previously reported. This could be due to a shift in AED selection, folic acid supplement, or possibly reflect the true risks in an unselected epilepsy population.
Rapid onset of seizure suppression with pregabalin adjunctive treatment in patients with partial seizures
Authors: Ramsay R. Eugene , Perucca Emilio , Robbins Jefferey , Barrett Jeannette A. , Spiegel Katharyn 
Published: June 2009

SummaryPurpose:  To determine the time at which pregabalin demonstrates seizure‐suppressing activity when given as adjunctive treatment to patients with refractory partial seizures.Methods:  Data from four similar 12‐week, randomized, double‐blind, placebo‐controlled, parallel‐group trials in patients with refractory partial seizures were pooled to provide an adequate sample to compare the proportion of patients free of seizures on each study day between pregabalin (combined 150–600 mg/day groups) and placebo (combined groups). A generalized estimating equation (GEE) statistical model was used to perform pairwise comparisons on each study day. In several pregabalin dosage groups the dosage was escalated during days 1–7, whereas in others pregabalin was initiated at a fixed dosage without escalation.Results:  The proportion of patients free of seizures on any treatment day was greater in the combined pregabalin groups compared with baseline. Differences were not observed between the placebo group and baseline. A significantly greater proportion of patients were free of seizures in the combined pregabalin 150–600 mg/day and the pregabalin 600 mg/day fixed‐dosage groups compared with the placebo groups from treatment day 2 onward (p < 0.05). From day 8 (coinciding with completion of the 1‐week dosage‐escalation period in two studies) onward, the proportion of patients free of seizures per day in the pregabalin groups remained relatively constant.Discussion:  This exploratory analysis of a refractory population using a rigorous endpoint demonstrates that pregabalin rapidly reduced the frequency of partial seizures. At the dosing schemes most commonly used in placebo‐controlled trials, significant seizure‐suppressing activity was observed after only 2 days of treatment.
Even a single seizure negatively impacts pediatric health‐related quality of life
Authors: Modi Avani C. , King Andrea S. , Monahan Sally R. , Koumoutsos Julie E. , Morita Diego A. , Glauser Tracy A. 
Published: June 2009

SummaryPurpose:  Both a single seizure and chronic recurrent seizures (epilepsy) occur commonly in childhood. Although several studies have documented the impact of pediatric epilepsy on psychosocial functioning, such as health‐related quality of life (HRQOL), no studies have examined the impact of a single seizure on HRQOL. The primary objectives of this study were: (1) to compare parent–proxy HRQOL in children with a single seizure and newly diagnosed untreated epilepsy to normative data and (2) to examine differences in parent–proxy HRQOL between children with single seizure and newly diagnosed untreated epilepsy.Methods:  A retrospective medical chart review was conducted on a consecutive cohort of children being evaluated for seizures at a New‐Onset Seizure Disorder Clinic. Information from the medical chart review included demographic data, seizure information, and the parent–proxy Pediatric Quality of Life Inventory (PedsQL), a well‐validated measure of HRQOL in pediatric chronic illnesses.Results:  Participants included 109 children (n = 53 single seizure; n = 56 newly diagnosed untreated epilepsy). Results indicated that both children with a single seizure and children with newly diagnosed untreated epilepsy had significant impairments in HRQOL compared to normative data. However, no significant HRQOL differences were found between the single seizure and the untreated epilepsy groups.Discussion:  Children diagnosed with a single seizure or epilepsy have similar clinically significant impairments in HRQOL. Evaluation of HRQOL, even after a first seizure, is important and will identify children at risk at the earliest opportunity, allowing for timely psychosocial intervention.
The social causes of inequality in epilepsy and developing a rehabilitation strategy: A U.K.‐based analysis
Authors: Ridsdale Leone 
Published: June 2009

SummaryA rehabilitation approach has been adopted for many long‐term neurologic conditions, but not for epilepsy. The disabilities associated with epilepsy are cognitive, psychological, and social, which are not as readily identified by medical doctors as are physical disabilities. A rehabilitation approach moves the emphasis from a medically driven process to a focus on the personal, social, and physical context of long‐term illness. It is suggested that a missed opportunity for education and support for self‐management occurs after diagnosis. This results in disadvantage to those whose educational level and knowledge of epilepsy are low. People who do not achieve epilepsy control may then experience higher levels of psychological distress, and a negative cycle of loss of self‐efficacy, poor epilepsy control, social disadvantage, and disability. Rehabilitation services have benefited communities surrounding centers of excellence. Not so in epilepsy. Despite centers of excellence, areas with deprivation have higher than national average levels of patients reporting a seizure in the prior year, and higher emergency hospital admissions. Specialists working in partnership with general practitioners (GPs) and practice nurses can do more to increase participation and reduce distress for people with epilepsy. When available, GPs and nurses with special interest in epilepsy promote integrated services. Primary–secondary networks are likely to be more effective in preventing downward drift. This requires evaluation.
The Personality Assessment Inventory as a tool for diagnosing psychogenic nonepileptic seizures
Authors: Thompson Alexander W. , Hantke Nathan , Phatak Vaishali , Chaytor Naomi 
Published: June 2009

SummaryUsing 184 subjects with valid personality assessment interview (PAI) profiles and video–electroencephalography (VEEG)–confirmed diagnoses of epileptic seizures (ES; n = 109) or psychogenic nonepileptic seizures (PNES; n = 75), we present the diagnostic test performance of the PAI PNES Indicator and other PAI scales when used to differentiate PNES from ES. Subjects with PNES reported significantly higher somatic, conversion, depressed, anxious, and suicidal symptoms. As a diagnostic tool, the PNES Indicator does not add additional accuracy beyond the conversion subscale (SOM‐C). The somatization (SOM‐S) and physiological depression (DEP‐P) subscales perform as well as the SOM‐C subscale. The SOM‐C scale (cut point ≥70) was 58.7% sensitive and 83.5% specific at diagnosing PNES. Assuming a 30% prevalence of PNES, the SOM‐C scale has a positive predictive value (PPV) of 60.4% and negative predictive value (NPV) of 82.5%. Overall, the PAI SOM‐C subscale does not appear more accurate than other psychometric tests used to differentiate PNES from ES.
Sequential analysis of fMRI images: A new approach to study human epileptic networks
Authors: Donaire Antonio , Falcón Carlos , Carreno Mar , Bargallo Nuria , Rumià Jordi , Setoain Javier , Maestro Iratxe , Boget Teresa , Pintor Luis , Agudo Rolando , Falip Merce , Fernández Santiago 
Published: June 2009

SummaryPurpose: The aim of this study was to introduce a new approach for analysis of functional magnetic resonance imaging (fMRI) data in order to illustrate the temporal development of the blood oxygenation level–dependent (BOLD) signal changes induced by epileptic seizures.Method: In order to sequentially analyze the fMRI images acquired during epileptic seizures, a continuous series of echo planar imaging (EPI) scans covering the complete period of a seizure was acquired. Data were segmented into 10‐s blocks. Each block, representing a unique experimental condition, was contrasted with a neutral (no seizure) baseline condition. Visual comparison of the activations from one block to the next highlighted the course of activations and deactivations during the seizure event. This analysis was applied to three independent seizures of one patient with peri‐rolandic epilepsy secondary to chronic encephalitis: one seizure before epilepsy surgery and two after unsuccessful tailored resection. Observations were compared to results from invasive subdural electroencephalography (EEG) monitoring, single‐photon emission computed tomography (SPECT) coregistered to MRI (SISCOM), and independent component analysis (ICA), a model‐free method of BOLD‐signal analysis.Results: The initial increase in BOLD signal occurred 10–40 s before clinical onset in the same location compared to the seizure‐onset zone determined by invasive subdural evaluation and SISCOM. Sequential involvement of cortical and subcortical structures was in agreement with SISCOM, intracranial EEG recordings, and ICA results.Discussion: In selected patients, sequential analysis of changes in BOLD signal induced by epileptic seizures might represent a useful approach for investigating the temporal development of brain activity during epileptic seizures, thereby allowing imaging of those cerebral structures involved in seizure generation and propagation.
Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: A randomized placebo‐controlled trial
Authors: Brodie Martin J. , Rosenfeld William E. , Vazquez Blanca , Sachdeo Rajesh , Perdomo Carlos , Mann Allison , Arroyo Santiago 
Published: June 2009

SummaryPurpose:  To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged ≥16 years with refractory partial seizures.Methods:  This double‐blind, placebo‐controlled, randomized, parallel‐group, multicenter trial included an 8‐week baseline phase and a 13‐week double‐blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a ≥50% reduction in partial seizure frequency.Results:  Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide‐treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo‐treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide‐treated subjects, 28.2% experienced a ≥50% decrease in partial seizure frequency versus 18.6% of placebo‐treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase.Discussion:  Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.
Modulation of androgen and estrogen receptor expression by antiepileptic drugs and steroids in hippocampus of patients with temporal lobe epilepsy
Authors: Killer Nina , Hock Monika , Gehlhaus Marcel , Capetian Philipp , Knoth Rolf , Pantazis Georgios , Volk Benedikt , Meyer Ralf P. 
Published: June 2009

SummaryPurpose:  Many of the antiepileptic drugs (AED) used in therapy of temporal lobe epilepsy (TLE) are known as cytochrome P450 (CYP, P450) inducers. These AEDs are thought to modulate androgen and estrogen pathways in hippocampus, and therefore cause mental and reproductive disorders found in TLE patients. In the present study, we analyzed expression of androgen receptor (AR), estrogen receptor α (ERα), and CYP3A in the hippocampus of TLE patients and in murine hippocampal cell line HN25.1.Methods:  Patients and cell lines had been treated with P450‐inducing or noninducing AEDs, or with prednisolone, applied to prevent oedema formation prior to neurosurgical resection of the epileptic hippocampus. Human patient samples were analyzed by immunohistochemical approach, the HN25.1 cell line by quantitative RT‐PCR, CAT reporter gene assay, and immunoblot.Results:  In both, humans and cell lines, the expression of testosterone metabolising CYP3A4 (human) or CYP3A11 (mouse) and AR was up‐regulated when P450‐inducing AEDs and/or prednisolone had been applied. AR responsive CAT reporter gene assay indicated an increase of AR‐signalling after treatment of the HN25.1 cells with the P450‐inducers phenytoin and carbamazepine. ERα expression was increased only by the P450‐inducing AEDs, but not by prednisolone, which indicates that pathways different from CYP3A4/11 led to ERα enhancement.Discussion:  We conclude that P450‐inducing AEDs influence AR expression and signalling in hippocampus most likely via CYP3A4/11‐induction. The HN25.1 cell line holds promise to investigate the correlation between drug application and AR regulation, and to specifically address issues that are relevant to human TLE patients.
Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1‐null mice
Authors: Fenoglio‐Simeone Kristina A. , Wilke Julianne C. , Milligan Heather L. , Allen Charles N. , Rho Jong M. , Maganti Rama K. 
Published: June 2009

SummaryIntroduction:  Seizures are known to perturb circadian rhythms in humans as well as in animal models of epilepsy. However, it is unknown whether treatment of the underlying epilepsy restores normal biologic rhythms. We asked whether: (1) seizure activity is characterized by diurnal rhythmicity, (2) chronically epileptic mice exhibit impaired rest–activity rhythms, and (3) treatment with the anticonvulsant ketogenic diet (KD) improves such perturbations.Methods:  Chronically epileptic Kcna1‐null mice were fed either a standard diet (SD) or KD for 4 weeks and subjected to continuous video‐EEG (electroencephalography) and actigraphy monitoring for 3–5 days to assess seizure activity and rest–activity cycles.Results:  Seizure activity in Kcna1‐null mice demonstrated diurnal rhythmicity, peaking at zeitgeber (ZT)2.30 ± 1.52. Rest–activity rhythms of epileptic mice were significantly disrupted. Whereas locomotor activity for wild‐type mice peaked at ZT15.45 ± 0.28 (ZT14:26–ZT16:51), peak activity of epileptic mice was more unpredictable, occurring over a 12.4 h range (ZT06:33–ZT18:57). In six of nine epileptic mice, peak activity was delayed to ZT17.42 ± 0.38, whereas peak activity was advanced to ZT10.00 ± 1.26 in the remaining mice. Treatment with the KD abolished seizure periodicity and restored the rest–activity rhythm to values resembling those of wild‐type mice (i.e., activity peaking at ZT16.73 ± 0.67).Conclusions:  Kcna1‐null mice experience seizures with 24‐h periodicity and impaired circadian behavior. KD reduces the number and periodicity of seizures and restores normal behavioral rhythms, suggesting that this nonpharmacologic therapy may benefit biologic rhythm disturbances in epileptic patients.
Role of the superior colliculus in the expression of acute and kindled audiogenic seizures in Wistar audiogenic rats
Authors: Doretto Maria C. , Cortes‐de‐Oliveira José A. , Rossetti Franco , Garcia‐Cairasco Norberto 
Published: June 2009

SummaryPurpose:  The role of the superior colliculus (SC) in seizure expression is controversial and appears to be dependent upon the epilepsy model. This study shows the effect of disconnection between SC deep layers and adjacent tissues in the expression of acute and kindling seizures.Methods:  Subcollicular transections, ablation of SC superficial and deep layers, and ablation of only the cerebral cortex were evaluated in the Wistar audiogenic rat (WAR) strain during acute and kindled audiogenic seizures. The audiogenic seizure kindling protocol started 4 days after surgeries, with two acoustic stimuli per day for 10 days. Acute audiogenic seizures were evaluated by a categorized seizure severity midbrain index (cSI) and kindled seizures by a severity limbic index (LI).Results:  All subcollicular transections reaching the deep layers of the SC abolished audiogenic seizures or significantly decreased cSI. In the unlesioned kindled group, a reciprocal relationship between limbic and brainstem pattern of seizures was seen. The increased number of stimuli provoked an audiogenic kindling phenomenon. Ablation of the entire SC (ablation group) or of the cerebral cortex only (ctx‐operated group) hampered the acquisition of limbic behaviors. There was no difference in cSI and LI between the ctx‐operated and ablation groups, but there was a difference between ctx‐operated and the unlesioned kindled group. There was also no difference in cSI between SC deep layer transection and ablation groups. Results of histologic analyses were similar for acute and kindled audiogenic seizure groups.Conclusions:  SC deep layers are involved in the expression of acute and kindled audiogenic seizure, and the cerebral cortex is essential for audiogenic kindling development.
Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy
Authors: Lacey Cameron J. , Salzberg Michael R. , Roberts Helene , Trauer Tom , D’Souza Wendyl J. 
Published: June 2009

SummaryWe aimed to determine the level of psychological distress in community‐treated patients with epilepsy and to determine if this distress is associated with increased health service use. The Australian National prescription database was used to recruit patients with epilepsy onto the Tasmanian Epilepsy Register (TER). Psychological distress was measured using the K10 in the TER patients and compared to the Tasmanian population using the National Health Survey 2004–5. Of the 1,180 on the TER, 43 withdrew, 36 died, and 262 were excluded. Of 839 patients, 652 completed the K10 (78%). High–very high levels of psychological distress were observed in patients with epilepsy compared with the general population [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.79–2.56]. Patients with high–very high psychological distress had increased attendance at general practitioners (p < 0.001), specialists (p = 0.02), and emergency departments (p = 0.004). Psychological distress is increased in community‐treated patients with epilepsy compared to the general population, and is associated with increased health service use.