bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of levetiracetam and valproate on reproductive endocrine function studied in human ovarian follicular cells
Authors: Taubøll Erik , Gregoraszczuk Ewa L. , Wojtowicz Anna K. , Milewicz Tomasz
Published: June 2009

Purpose:  Recent animal studies have indicated possible reproductive endocrine effects of levetiracetam (LEV). The aim of the present study was to investigate possible reproductive endocrine effects of LEV compared to valproate (VPA) using human ovarian follicular cells.

Methods:  Cell cultures of human granulosa cells were prepared. First, the effect of the drugs on basal and follicle‐stimulating hormone (FSH)–stimulated estradiol secretion was investigated at different concentrations of LEV (12, 20, 50, or 80 μg/ml) or VPA (75, 100, 250, or 350 μg/ml). Second, the effect of the drugs on CYP19 aromatase activity was studied. Third, the possible effect of the drugs on cell apoptosis was investigated by measuring caspase‐3 activity.

Results:  VPA significantly and concentration‐dependently decreased basal and FSH‐stimulated estradiol secretion. No effects on estradiol secretion were observed for LEV. Neither VPA nor LEV had any effect on CYP19 aromatase activity under basal conditions, but both drugs reduced CYP19 aromatase activity in FSH‐stimulated cells at the higher concentrations (VPA 100, 250, and 350 μg/ml; LEV 20, 50, and 80 μg/ml). Both drugs significantly increased caspase‐3 activity, the proapoptotic effect of LEV being more pronounced than VPA.

Discussion:  LEV acts differently from VPA on reproductive endocrine function when studied in human ovarian follicular cells. LEV does not affect estradiol secretion, although both drugs affect CYP19 aromatase activity after gonadotropin stimulation. Both drugs act as apoptotic agents in ovarian cells. The proapoptotic effect of LEV was more pronounced than that of VPA.
Interobserver agreement in neonatal seizure identification
Authors: Malone Aileen , Anthony Ryan C. , Fitzgerald Anthony , Burgoyne Louise , Connolly Sean , Boylan Geraldine B.
Published: June 2009

Objectives:  Accurate diagnosis of neonatal seizures is critically important and is often made clinically, without EEG (electroencephalography) monitoring. This observational study aimed to determine the accuracy and interobserver reliability of healthcare professionals in distinguishing clinically manifested seizures from other neonatal movements, when presented with clinical histories and digital video recordings only.

Methods:  Twenty digital video recordings of paroxysmal movements in term and preterm infants were selected from a video‐EEG database. The movements were categorized as seizure and nonseizure using EEG. Health care professionals (n = 137) from eight neonatal intensive care units (NICUs) were shown the video recordings with additional relevant clinical data, excluding EEG findings. The observers were asked to indicate which movements they considered to be seizure or nonseizure. A multirater Kappa statistic was used to assess agreement between observers and with the true diagnosis.

Results:  Twenty video clips (11 seizure, 9 nonseizure) were evaluated by 91 doctors and 46 other professionals. The average number of correctly identified events was 10/20. Clonic seizures were correctly identified most frequently (range 36.5–95.6% of observers). Subtle seizures were poorly identified (range 20.4–49.6% of observers). The interobserver agreement (Kappa) for doctors and other health care professionals was poor at 0.21 and 0.29, respectively. Agreement with the correct diagnosis was also poor at 0.09 for doctors and −0.02 for other healthcare professionals.

Discussion:  It is often impossible to accurately differentiate between seizure‐related and nonseizure movements in infants using clinical evaluation alone. In addition, doctors do not have a higher capacity for discriminating between neonatal paroxysmal events than other health care professionals. Until reliable continuous neurologic monitoring of newborn babies is available, it is likely that some babies with seizures will remain undetected and others with nonseizure movements will continue to be treated with potentially harmful anticonvulsants.
Underlying cause of death in incident unprovoked seizures in the urban community of Northern Manhattan, New York City
Authors: Benn Emma K.T. , Allen Hauser W. , Shih Tina , Leary Linda , Bagiella Emilia , Dayan Peter , Green Robert , Andrews Howard , Thurman David J. , Hesdorffer Dale C.
Published: June 2009

We determined underlying cause‐specific mortality for incident unprovoked seizures from Northern Manhattan, New York City. We calculated the case fatality, proportionate mortality, and the underlying cause‐specific standardized mortality ratios (SMRs), with U.S. death rates as the standard. Thirty‐two deaths were observed between 2003 and 2007 among 209 participants. Case fatality was significantly lower for idiopathic/cryptogenic seizures versus symptomatic seizures. About 31.3% of the deaths were attributed to malignant neoplasms, 25.0% to diseases of the heart, 15.6% to influenza and pneumonia, 3.1% to cerebrovascular diseases, and 25.0% to other causes. Significant SMRs were observed for all causes (SMR = 1.6), influenza and pneumonia (SMR = 7.1), and malignant neoplasms (SMR = 2.9). Younger cases (<65 years) had increased SMRs for all causes, malignant neoplasms, and other causes. Older cases (≥65 years) had increased SMRs for influenza and pneumonia. Underlying cause of death paralleled the underlying cause of seizure in patients with symptomatic etiologies.
Foramen ovale electrodes in the preoperative evaluation of temporal lobe epilepsy in children
Authors: Nilsson Daniel , Fohlen Martine , Jalin Claude , Dorfmuller George , Bulteau Christine , Delalande Olivier
Published: June 2009

Purpose:  Foramen ovale electrodes (FOEs) can localize the epileptogenic zone in adults with mesial temporal lobe epilepsy (TLE). Our aim was to investigate the feasibility and safety of using FOEs to investigate refractory TLE in children.

Methods:  Thirty‐eight children with seizure semiology and video‐EEG (electroencephalography) consistent with medically refractory TLE, and/or the presence of a lesion in the temporal lobe, had FOEs inserted. Complications occurring during the monitoring and up to 3 months after surgery and the long‐term seizure outcome were registered.

Results:  Forty electrodes were placed in 38 patients. The mean age of the patients was 9.8 years (range 2.3–15.4 years). FOEs confirmed a unilateral mesial temporal lobe seizure onset in 14 patients, onset in both FOEs and lateral electrodes in two patients, and onset in the anterior temporal electrodes in only one patient. Six patients had seizures recorded but were not considered surgical candidates; four patients had no seizures recorded, and 11 patients were further investigated with depth electrodes. One patient (2.6%) developed a hematoma in the cheek, and in two patients the electrodes were extracranial but could still be used for recording. Twenty‐eight children had a temporal resection; 25 were Engel class I at follow‐up.

Discussion:  FOEs are safe to use in children and provide valuable information on the mesial temporal lobe structures in the preoperative investigation of pediatric TLE. Patient selection for FOE investigation is, however, essential for a conclusive result.
Language lateralization in epilepsy patients: fMRI validated with the Wada procedure
Authors: Arora Jagriti , Pugh Kenneth , Westerveld Michael , Spencer Susan , Spencer Dennis D. , Todd Constable R.
Published: June 2009

Purpose:  This work examines the efficacy of functional magnetic resonance imaging (fMRI) for language lateralization using a comprehensive three‐task language‐mapping approach. Two localization methods and four different metrics for quantifying activation within hemisphere are compared and validated with Wada testing. Sources of discordance between fMRI and Wada lateralization are discussed with respect to specific patient examples.

Methods:  fMRI language mapping was performed in patients with epilepsy (N = 40) using reading sentence comprehension, auditory sentence comprehension, and a verbal fluency task. This was compared with the Wada procedure using both whole‐brain and midline exclusion–based analyses. Different laterality scores were examined as a function of statistical threshold to investigate the sensitivity to threshold effects.

Results:  For the lateralized patients categorized by Wada, fMRI laterality indices (LIs) were concordant with the Wada procedure results in 83.87% patients for the reading task, 83.33% patients for the auditory task, 76.92% patients for the verbal fluency task, and in 91.3% patients for the conjunction analysis. The patients categorized as bilateral via the Wada procedure showed some hemispheric dominance in fMRI, and discrepancies between the Wada test findings and the functional laterality scores arose for a range of reasons.

Discussion:  Discordance was dependent upon whether whole‐brain or midline exclusion method–based lateralization was calculated, and in the former case the inclusion of the occipital and other midline regions often negatively influenced the lateralization scores. Overall fMRI was in agreement with the Wada test in 91.3% of patients, suggesting its utility for clinical use with the proper consideration given to the confounds discussed in this work.
Ondansetron and seizures
Authors: Singh Niranjan N. , Rai Ajitesh , Selhorst John B. , Acharya Jayant N.
Published: June 2009

Experimental studies suggest that 5‐hydroxytryptamine (5‐HT) receptors play a role in epileptogenesis and seizure propagation. Ondansetron, a 5‐HT3receptor antagonist, has been reported to have proconvulsant and anticonvulsant effects in animals. We describe three patients who developed seizures after receiving ondansetron. There were two females and one male. Ages ranged from 38–56 years. None had a previous or family history of seizures. Four milligrams (mg) of ondansetron was given intravenously for severe nausea and vomiting in association with migraine, gastritis, and diabetic ketoacidosis. A generalized tonic–clonic seizure occurred in each patient—12, 15, and 22 min after injection. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) were normal in all patients. Although no antiepileptic drugs were given, none had seizure recurrence subsequently. The temporal relationship between ondansetron administration and seizures, lack of EEG or MRI abnormalities, and absence of seizure recurrence suggest that the seizures were causally related to ondansetron in our patients.
Prevalence of epilepsy and seizures in the Navajo Nation 1998–2002
Authors: Parko Karen , Thurman David J.
Published: June 2009

Purpose:  To determine the prevalence of epilepsy and seizures in the Navajo.

Methods:  We studied 226,496 Navajo residing in the Navajo Reservation who had at least one medical encounter between October 1, 1998 and September 30, 2002. We ascertained and confirmed cases in two phases. First, we identified patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes signifying epilepsy or seizures using Indian Health Service (IHS) administrative data. Second, we reviewed medical charts of a geographic subpopulation of identified patients to confirm diagnoses and assess the positive predictive value of the ICD‐9‐CM codes in identifying patients with active epilepsy.

Results:  Two percent of Navajo receiving IHS care were found to have an ICD‐9‐CM code consistent with epilepsy or seizures. Based on confirmed cases, the crude prevalence for the occurrence of any seizure (including febrile seizures and recurrent seizures that may have been provoked) in the geographic subpopulation was 13.5 per 1,000 and the crude prevalence of active epilepsy was 9.2 per 1,000. Prevalence was higher among males, children under 5 years of age, and older adults.

Discussion:  The estimated prevalence of active epilepsy in the Navajo Nation is above the upper limit of the range of reported estimates from other comparable studies of U.S. communities.
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

Purpose:  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

Purpose: 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

Purpose:  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

Purpose:  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

Purpose:  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

A 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

Using 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

Purpose: 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

Purpose:  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

Purpose:  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

Introduction:  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

Purpose:  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

We 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.
Seizure frequency in pregnant women treated with lamotrigine monotherapy
Authors: Sabers Anne , Petrenaite Vaiva
Published: June 2009

Previous studies have demonstrated that the pharmacokinetics of the new antiepileptic drug (AED) lamotrigine (LTG) are substantially influenced by pregnancy and are more likely to be associated with seizure deterioration in pregnancy compared to other AEDs. This is of great concern, as LTG has developed into a first‐line AED for women of childbearing age. In this study we evaluated the risk of seizure deterioration in a cohort of women treated with LTG monotherapy (n = 42) who were closely monitored with frequent dose adjustments based on monthly routine plasma level determinations. It was demonstrated that with this close monitoring set‐up, the risk of increased seizure frequency (19%) was not higher than that reported for other AED treatment regimens.
Anoxia–ischemia: A mechanism of seizure termination in ictal asystole
Authors: Schuele Stephan U. , Bermeo Adriana C. , Alexopoulos Andreas V. , Burgess Richard C.
Published: June 2009

Cerebral anoxia–ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self‐termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia–ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously.
AGROBACTERIUM‐MEDIATED TRANSFORMATION IN THE GREEN ALGA HAEMATOCOCCUS PLUVIALIS (CHLOROPHYCEAE, VOLVOCALES)1
Authors: Kathiresan S. , Chandrashekar A. , Ravishankar G. A. , Sarada R.
Published: June 2009

The first successful Agrobacterium‐mediated transformation of the green alga Haematococcus pluvialis Flot. using the binary vectors hosting the genes coding for GUS (β‐glucuronidase), GFP (green fluorescent protein), and hpt (hygromycin phosphotransferase) is reported here. Colonies resistant to hygromycin at 10 mg · L−1 expressed β‐glucuronidase. The greenish yellow fluorescence of GFP was observed when the hygromycin‐resistant cells were viewed with a fluorescent microscope. PCR was used to successfully amplify fragments of the hpt (407 bp) and GUS (515 bp) genes from transformed cells, while Southern blots indicated the integration of the hygromycin gene into the genome of H. pluvialis. SEM indicated that the cell wall of H. pluvialis was altered on infection with Agrobacterium. The transformation achieved here by Agrobacterium does not need treatment with acetosyringone or the wounding of cells. A robust transformation method for this alga would pave the way for manipulation of many important pathways relevant to the food, pharmaceutical, and nutraceutical industries.
HIGH‐LIGHT AND SODIUM CHLORIDE STRESS DIFFERENTIALLY REGULATE THE BIOSYNTHESIS OF ASTAXANTHIN IN CHLORELLA ZOFINGIENSIS (CHLOROPHYCEAE)1
Authors: Li Yantao , Huang Junchao , Sandmann Gerhard , Chen Feng
Published: June 2009

Although light and salt stresses are known to enhance the biosynthesis of astaxanthin in certain green algae, the mechanism of their action remains largely unknown. Here we report the regulation of the genes encoding phytoene desaturase (PDS), carotenoid hydroxylase (CHYb), and carotenoid ketolase (BKT) in the green alga Chlorella zofingiensis Dönz under light or sodium chloride (NaCl) stress. High‐light illumination (150 μmol photons · m−2 · s−1) up‐regulated the transcripts of PDS, CHYb, and BKT and greatly enhanced the biosynthesis of zeaxanthin, canthaxanthin, and astaxanthin. In contrast, sodium chloride stress only up‐regulated the transcript of BKT and enhanced the biosynthesis of canthaxanthin and astaxanthin. High‐light and NaCl stresses were revealed to result in an increase in the intracellular reactive oxygen species (ROS) level. By applying chemically generated ROS to the algal cells, we determined that 1O2 specifically up‐regulated the CHYb gene, whereas •OH up‐regulated the PDS and BKT genes. We suggest that high‐light and NaCl stresses may stimulate the generation of different ROS, which in turn trigger the up‐regulation of specific carotenogenic genes and the enhanced biosynthesis of carotenoids in C. zofingiensis.
PHYLOGENETIC ANALYSIS OF PSEUDOCHLORODESMIS STRAINS REVEALS CRYPTIC DIVERSITY ABOVE THE FAMILY LEVEL IN THE SIPHONOUS GREEN ALGAE (BRYOPSIDALES, CHLOROPHYTA)1
Authors: Verbruggen Heroen , Vlaeminck Caroline , Sauvage Thomas , Sherwood Alison R. , Leliaert Frederik , De Clerck Olivier
Published: June 2009

The genus Pseudochlorodesmis (Bryopsidales) is composed of diminutive siphons of extreme morphological simplicity. The discovery of Pseudochlorodesmis‐like juveniles in more complex Bryopsidales (e.g., the Halimeda microthallus stage) jeopardized the recognition of this genus. Confronted with this uncertainty, taxonomists transferred many simple siphons into a new genus, Siphonogramen. In this study, we used a multimarker approach to clarify the phylogenetic and taxonomic affinities of the Pseudochlorodesmis‐Siphonogramen (PS) complex within the more morphologically complex bryopsidalean taxa. Our analyses reveal a new layer of diversity largely distinct from the lineages containing the structurally complex genera. The PS complex shows profound cryptic diversity exceeding the family level. We discuss a potential link between thallus complexity and the prevalence and profundity of cryptic diversity. For taxonomic simplicity and as a first step toward clarifying the taxonomy of these simple siphons, we propose to maintain Pseudochlorodesmis as a form genus and subsume Siphonogramen and Botryodesmis therein.
SENSITIVITY OF ANTARCTIC UROSPORA PENICILLIFORMIS (ULOTRICHALES, CHLOROPHYTA) TO ULTRAVIOLET RADIATION IS LIFE‐STAGE DEPENDENT1
Authors: Roleda Michael Y. , Campana Gabriela L. , Wiencke Christian , Hanelt Dieter , Quartino Maria Liliana , Wulff Angela
Published: June 2009

The sensitivity of different life stages of the eulittoral green alga Urospora penicilliformis (Roth) Aresch. to ultraviolet radiation (UVR) was examined in the laboratory. Gametophytic filaments and propagules (zoospores and gametes) released from filaments were separately exposed to different fluence of radiation treatments consisting of PAR (P = 400–700 nm), PAR + ultraviolet A (UVA) (PA, UVA = 320–400 nm), and PAR + UVA + ultraviolet B (UVB) (PAB, UVB = 280–320 nm). Photophysiological indices (ETRmax, Ek, and α) derived from rapid light curves were measured in controls, while photosynthetic efficiency and amount of DNA lesions in terms of cyclobutane pyrimidine dimers (CPDs) were measured after exposure to radiation treatments and after recovery in low PAR; pigments of propagules were quantified after exposure treatment only. The photosynthetic conversion efficiency (α) and photosynthetic capacity (rETRmax) were higher in gametophytes compared with the propagules. The propagules were slightly more sensitive to UVB‐induced DNA damage; however, both life stages of the eulittoral inhabiting turf alga were not severely affected by the negative impacts of UVR. Exposure to a maximum of 8 h UVR caused mild effects on the photochemical efficiency of PSII and induced minimal DNA lesions in both the gametophytes and propagules. Pigment concentrations were not significantly different between PAR‐exposed and PAR + UVR–exposed propagules. Our data showed that U. penicilliformis from the Antarctic is rather insensitive to the applied UVR. This amphi‐equatorial species possesses different protective mechanisms that can cope with high UVR in cold‐temperate waters of both hemispheres and in polar regions under conditions of increasing UVR as a consequence of further reduction of stratospheric ozone.
NITZSCHIA ALICAESP. NOV. ANDN. PURIFORMISSP. NOV., NEW DIATOMS FROM EUROPEAN RIVERS AND COMPARISON WITH THE TYPE MATERIAL OFN. SUBLINEARISANDN. PURA1
Authors: Hlúbiková Daša , Blanco Saúl , Falasco Elisa , Gomà Joan , Hoffmann Lucien , Ector Luc
Published: June 2009

Nitzschia sublinearisHustedt andN. puraHustedt are common oligosaprobic freshwater diatom species that frequently occur in diatom inventories, thus being important in water quality studies. Both are considered as species with overlapping diagnostic criteria in several floras, which is typical of the whole genusNitzschia. The type material of Hustedt ofN. sublinearisandN. purawas examined using LM and EM in order to document the range of variation within the type populations and to compare it with populations occurring in different European rivers. Detailed observations allowed recognition of two new freshwater diatom species:N. alicaesp. nov., occurring in mesotrophic up to eutrophic conditions, andN. puriformissp. nov., mostly occurring in oligotrophic habitats, both in rivers and streams at middle and high altitudes. The most reliable taxonomic features that separate both new species from the most similar taxa are the density of fibulae and striae, valve shape, and valve width as well as the shape of areolae. Morphological examination of different populations indicates thatN. puriformisis relatively common in European rivers and has been overlooked to date and confounded withN. puraby several researchers. By contrast,N. alicaehas, to date, been collected only in Slovakia and Northern Italy, but with a high frequency of occurrence and sometimes in high abundance at sites.
MOLECULAR CHARACTERIZATION AND ANTIBODY DETECTION OF A NITROGEN‐REGULATED CELL‐SURFACE PROTEIN OF THE COCCOLITHOPHORE EMILIANIA HUXLEYI (PRYMNESIOPHYCEAE)1
Authors: Landry Dori M. , Kristiansen Svein , Palenik Brian P.
Published: June 2009

Dissolved organic nitrogen (DON) can account for a significant portion of total nitrogen in some aquatic environments, and many species of phytoplankton are able to scavenge nitrogen from this pool especially when inorganic nitrogen is limiting. Emiliania huxleyi (Lohmann) H. W. Hay et H. Mohler is able to use various forms of DON for growth, including several amino acids, purines, and pyrimidines. A cell‐surface protein up‐regulated in the absence of inorganic nitrogen, NRP1, is hypothesized to play a role in the metabolism of one or more of these organic nitrogen forms. Here, the genomic and cDNA sequence of NRP1 is reported. Structural predictions based on the amino acid sequence suggest a pyridoxal‐5′‐phosphate‐dependent enzyme that may have a role in acquiring nitrogen from amino acids. Further evidence for the function of NRP1 is measured in spent media from nitrogen‐limited cultures, which contain NRP1 and have glutaminase and formamidase activity. Field studies using an antibody to NRP1 show that it is expressed in E. huxleyi during bloom conditions in a Norwegian fjord.