bluuebunny/crossref_metadata_2025 huggingface dataset:
Operative Deliveries in Low‐Risk Pregnancies in The Netherlands: Primary versus Secondary Care
Authors: Maassen Marloes S. , Hendrix Marijke J. C. , Van Vugt Helena C. , Veersema Sebastiaan , Smits Frans , Nijhuis Jan G.
Published: November 2008

ABSTRACT:  Background:
In The Netherlands, 35 percent of births take place in “primary care” to women considered at low risk and during labor, approximately 30 percent are referred to “secondary care.” High‐risk women and some low‐risk women deliver in secondary care. This study sought to compare planned place of birth and incidence of operative delivery among women at low risk of complications at the time of onset of labor.
Methods:
A retrospective analysis was conducted of data about births in The Netherlands during 2003 that were recorded routinely in the Netherlands Perinatal Registry. Mode of delivery was analyzed for women classified as low risk at labor onset according to their planned place of birth (intention‐to‐treat analysis). The primary outcome was the rate of operative deliveries (vacuum or forceps extraction or cesarean section).
Results:
Women at low risk who planned to give birth, and therefore labored and delivered in secondary care, had a significantly higher rate of operative deliveries than women who began labor in primary care where they intended to give birth (18% [3,558/19,850] vs 9% [7,803/87,187]) (OR 2.25, 95% CI 2.00–2.52). For cesarean section, the rates were 12 percent (2,419/19,850) versus 3 percent (2,990/87,817) (OR 3.97, 95% CI 3.15–5.01), irrespective of parity.
Conclusions:
The rate of operative deliveries was significantly lower for low‐risk pregnant women who gave birth in a primary care setting compared with similar women who planned birth in secondary care. As with any retrospective analysis, it was not possible to eliminate bias, such as possible differences between primary and secondary care in assignment of risk status. In addition, known risk factors for interventions, technologies such as induction of labor and fetal monitoring, are only available in secondary care. These findings clearly demonstrate the need for a prospective study to examine the relationship between planned place of birth and mode of delivery and neonatal and maternal outcomes. (BIRTH 35:4 December 2008)
Attributions of Breastfeeding Determinants in a French Population
Authors: Hernández Paloma Trejo , Callahan Stacey
Published: November 2008

ABSTRACT:  Background:
The rates of initiation and duration of breastfeeding in France are low when compared with those in other European countries. The objective of this study was to determine attributions of breastfeeding determinants in a French population.
Methods:
A self‐report survey listing 68 reasons for or against breastfeeding was developed. Nine hundred nine participants from the general population rated their level of agreement with each reason by means of a Likert‐type scale. The survey explored gender, age, parenthood, decision to breastfeed, having friends who had breastfed, having family members who had breastfed, and having been breastfed themselves when younger. Exploratory factorial analyses extracted six factors for breastfeeding and five factors against breastfeeding. All the factors were entered in regression analyses to predict demographic variables that determined attributions for and against breastfeeding. Individuals were measured at two points in time to account for test‐retest reliability (28.1 days ± 6.95 day lapse).
Results:
Determinants varied significantly with respect to gender, age, parenthood, and breastfeeding history. High endorsement for breastfeeding involved breastfeeding to fulfill gender roles, to prevent health risks, and because of external encouragement; little endorsement was given for the physiological advantages for babies, pleasant sensations, and preference factors. In terms of not breastfeeding, high endorsement was observed in lack of support, negative attitudes, and infant formula reasoning factors; medical and physiological reasons for not breastfeeding showed low endorsement.
Conclusions:
The results of this study showed a strong impact of society and cultural norms on feeding choice. If breastfeeding initiation and duration rates are to be increased, we suggest approaching the rest of the population in addition to pregnant women and mothers since society as a whole influences the decision to breastfeed. (BIRTH 35:4 December 2008)
Effects of Contact with Stillborn Babies on Maternal Anxiety and Depression
Authors: Cacciatore Joanne , Rådestad Ingela , Frederik Frøen J.
Published: November 2008

Abstract:  Background:
Some guidelines encourage mothers to see and hold their babies after stillbirth, which might be traumatizing. The study objective was to investigate the effects of women seeing and holding their stillborn baby on the risk of anxiety and depression in a subsequent pregnancy and in the long term.
Methods:
Thirty‐seven organizations recruited women who had experienced stillbirth (N = 2,292 of whom 286 reported being pregnant). Anxiety and depressive symptoms were assessed by using the 25‐item Hopkins Symptom Check List. Results: Among nonpregnant women, seeing and holding their stillborn baby were associated with lower anxiety symptoms (OR 0.68, 95% CI 0.49–0.95) and a tendency toward fewer symptoms of depression (OR 0.72, 95% CI 0.51–1.02), compared with pregnant women. Participants who were pregnant also had less depressive symptomatology (OR 0.57, 95% CI 0.43–0.75), but more symptoms of anxiety if they had seen and held their baby (OR 3.79, 95% CI 1.42–10.1). Conclusions: Seeing and holding the baby are associated with fewer anxiety and depressive symptoms among mothers of stillborn babies than not doing so, although this beneficial effect may be temporarily reversed during a subsequent pregnancy. (BIRTH 35:4 December 2008)
Care in Labor: A Swedish Survey Using the Bologna Score
Authors: Sandin‐Bojö Ann‐Kristin , Kvist Linda J.
Published: November 2008

ABSTRACT:  Background:
An important part of midwives’ area of responsibility is to strive to keep birth normal. Interventions during childbirth are costly and may disrupt the course of normal labor. The aim of this study was to describe, by use of the Bologna Score, how birth is managed in Sweden.
Methods:
A prospective cross‐sectional study in a national sample was performed. All (n = 51) Swedish maternity units were invited to participate and 36 (70.6%) agreed. Midwives collected data, in accordance with the Bologna Score, for all deliveries occurring during a 2‐week period in 2007. Results:Qualified health personnel assisted at almost all deliveries (99.9%), and a vaginal birth was planned for 84 percent of the women. A Bologna Score of 5 signifies that birth has been managed using recommended evidence‐based practice, which was achieved for 22.7 percent of the planned vaginal births. Use of the supine position and some interventions were responsible for loss of points. The percentage of 5‐point scores varied greatly among units (0–53.1%). Conclusions: The findings suggest that in Sweden, birth is managed according to scientific evidence to a limited degree. Large differences among units also suggest that care in childbirth is based on attitudes rather than on scientific evidence. The Bologna Score was easy to use and gave a good picture of how care was given at the participating maternity units. We suggest that the instrument is useful as a quality indicator for intrapartum care. (BIRTH 35:4 December 2008)
Timing relationships between pegmatite emplacement, metamorphism and deformation during the intra‐plate Alice Springs Orogeny, central Australia
Authors: BUICK I. S. , STORKEY A. , WILLIAMS I. S.
Published: November 2008

In the Harts Range (central Australia), the upper amphibolite facies to lower granulite facies, c. 480–460 Ma Harts Range Metamorphic Complex (HRMC), and the upper amphibolite facies, c. 340–320 Ma Entia Gneiss Complex are cut by numerous, generally peraluminous pegmatites and their deformed equivalents. The pegmatites have previously been interpreted as locally derived partial melts. However, SHRIMP U–Pb monazite and zircon dating of 29 pegmatites or their deformed equivalents, predominantly from the HRMC, reveal that they were emplaced episodically throughout almost the entire duration of the polyphase, c. 450–300 Ma intra‐plate Alice Springs Orogeny. Episodes of pegmatite intrusion correlate with the age of major Alice Springs‐age structures and with deposition of syn‐orogenic sedimentary rocks in the adjacent Centralian Superbasin. Similar Alice Springs ages have not been obtained from anatectic country rocks in the HRMC, suggesting that the pegmatites were not locally derived. Instead, they are interpreted as highly fractionated granites, and imply that much larger parental Alice Springs‐age granites exist at depth. The mechanism to allow repeated felsic magmatism in an intraplate setting, where all exposed rock types had a previous high‐temperature history, is enigmatic. However, we suggest that episodic underthrusting and dehydration of unmetamorphosed Centralian Superbasin sedimentary rocks allowed crustal fertility to maintained over a c. 140 Ma interval during the intra‐plate Alice Springs Orogeny.
Aragonite and magnesite in eclogites from the Jæren nappe, SW Norway: disequilibrium in the system CaCO3–MgCO3 and petrological implications
Authors: SMIT M. A. , BRÖCKER M. , SCHERER E. E.
Published: November 2008

Eclogites from the Jæren nappe in the Caledonian orogenic belt of SW Norway contain aragonite, magnesite and dolomite in quartz‐rich layers. The carbonates comprise composite grains that occur interstitially between phases of the eclogite facies assemblage: garnet + omphacite + zoisite + clinozoisite + quartz + apatite + rutile ± dolomite ± kyanite ± phengite. Pressure and temperature conditions for the main eclogite stage are estimated to be 2.3–2.8 GPa and 585–655 °C. Published ultrahigh pressure (UHP) experiments on CaO‐, MgO‐ and CO2‐bearing systems have shown that equilibrium assemblages of aragonite and magnesite form as a result of dolomite breakdown at pressures >5 GPa. As a result, recognition of magnesite and aragonite in eclogite facies rocks has been used as an indicator for UHP conditions. However, petrological testing showed that the samples studied here have not experienced such conditions. Aragonite and magnesite show disequilibrium textures that indicate replacement of magnesite by aragonite. This process is inferred to have occurred via a coupled dissolution–precipitation reaction. The formation of aragonite is constrained to eclogite facies conditions, which implies that the studied rocks have experienced metasomatic, reactive fluid flow during their residence at high pressure (HP) conditions. During decompression, the bimineralic carbonate aggregates were overgrown by rims of dolomite, which partially reacted with aragonite to form Mg‐calcite. The well‐preserved carbonate assemblages and textures observed in the studied samples provide a detailed record of the reaction series that affected the rocks during and after their residence at P–T conditions near the coesite stability field. Recognition of the HP mechanism of magnesite replacement by aragonite provides new insight into metasomatic processes that occur in subduction zones and illustrates how fluids facilitate HP carbonate reactions that do not occur in dry systems at otherwise identical physiochemical conditions. This study documents that caution is warranted in interpreting aragonite‐magnesite associations in eclogite facies rocks as evidence for UHP metamorphic conditions.
Graphitization of organic matter and fluid‐deposited graphite in Palaeoproterozoic (Birimian) black shales of the Kaya‐Goren greenstone belt (Burkina Faso, West Africa)
Authors: KŘÍBEK B. , SÝKOROVÁ I. , MACHOVIČ V. , LAUFEK F.
Published: November 2008

Palaeoproterozoic black shales form an essential part of the Birimian volcanosedimentary belt in Burkina Faso, West Africa. The meanRmaxvalues and the atomicH/Cvalues of the bulk carbonaceous matter (BCM), together with rock structures and mineral assemblages, indicate that these carbon‐rich rocks were metamorphosed to sub‐greenschist and low‐grade greenschist facies. X‐ray diffraction reveals that the (002) ‘graphite’ peak width in half maximum (FWHM) ranges from 0.43 to 0.71 °2θ in sub‐greenschist facies and from 0.27 to 0.41 °2θ in greenschist facies rocks, but thed(002) values in both groups of rocks are approximately the same (∼3.35 Å). The BCM of individual samples is composed of particles with very variable shape, reflectance and Raman spectra. Type I particles that predominate in sub‐greenschist facies are fine‐grained, irregular or elongate bodies 1 to 3 μm in size. Their maximum reflectance (Rmax) ranges between 2.5% and 8.2%, and Raman parameters R1 and R2 range from 0.5 to 1.4 and 0.5 to 0.8, respectively. Type II particles are lath‐shaped, up to 40 μm large bodies, commonly arranged parallel to white mica flakes. The number of these particles increases from sub‐greenschist to greenschist facies. Maximum reflectance varies between 6% and 11.2% and R1 and R2 Raman parameters range from 0.05 to 0.7 and from 0.1 to 0.5, respectively. Type III particles occur in hydrothermally altered and sheared rocks; these are nodular aggregates composed of grains up to 10 μm in size. This type of particles has very high reflectance (Rmax = 11–15%) and its Raman spectra indicate a very high degree of structural ordering corresponding to well‐ordered graphite. Type I particles represent original organic matter in the metasediments. Type II particles are believed to have been formed eitherin situby solid‐state transformation of Type I particles or by crystallization from metamorphic fluids. Gradual graphitization of the Type I organic particles and the growth of lath‐shaped Type II particles from a fluid phase is assumed to have taken place under the peak metamorphic conditions associated with the burial of Birimian sediments during thrust tectonism, progressive tectonic accretion and crustal thickening during the D1 event of the Eburnean orogeny. The growth of equant, high‐reflectance postkinematic nodular aggregates of Type III particles is ascribed to the reduction of CO2‐rich fluids during a hydrothermal event associated with Late Eburnean D2 exhumation and strike–slip movements. Type I carbonaceous particles were only slightly affected by high‐temperature, low‐pressure contact metamorphism during intrusion of Late Eburnean magmatic bodies, whereas formation of Type II or III particles was not recorded in contact‐metamorphosed rocks at all.
Phenotypic and Genetic Analysis of a Large Family With Migraine‐Associated Vertigo
Authors: Lee Hane , Jen Joanna C. , Cha Yoon‐Hee , Nelson Stanley F. , Baloh Robert W.
Published: November 2008

Objectives.— To describe a large multigenerational family with migraine‐associated vertigo (MAV) combining a detailed phenotypic and genetic analysis.

Background.— Migraine‐associated vertigo is said to be highly prevalent in the general population and, like other migraine syndromes, its etiology is felt to have a strong genetic component. However, so far, there have been no reports of large families with MAV.

Methods.— Detailed clinical study was conducted on a large multigenerational family with MAV. Genetic study using identical‐by‐descent analysis with dense single nucleotide polymorphism (SNP) arrays was performed to examine consistent inheritance pattern among the affecteds.

Results.— Clinical features of MAV were variable although most had other migraine symptoms with at least some of their attacks. We did not find a region of the genome shared by all eight subjects with MAV indicating a polygenetic inheritance for MAV even in this single large family.

Conclusions.— A region on 11q shared by most affected females may contain a susceptibility allele for MAV that is expressed exclusively or predominantly by women.
Divalproex Sodium Extended‐Release for the Prophylaxis of Migraine Headache in Adolescents: Results of a Stand‐Alone, Long‐Term Open‐Label Safety Study
Authors: Apostol George , Lewis Donald W. , Laforet Genevieve A. , Robieson Weining Z. , Fugate Julie M. , Abi‐Saab Walid M. , Saltarelli Mario D.
Published: November 2008

Objective.—The objective of this long‐term open‐label study in adolescents was to assess the safety and tolerability of divalproex sodium extended‐release in the prophylaxis of migraine headaches.

Background.—Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long‐term safety data on agents for migraine prevention are lacking for this younger population. Therefore, the current study was conducted to assess the long‐term safety and tolerability of divalproex extended‐release in adolescents with migraine headaches.

Methods.—This was a 12‐month, phase 3, open‐label, multicenter study of adolescents aged 12 to 17 years with migraine headaches diagnosed by International Headache Society criteria. Divalproex sodium extended‐release was initiated at 500 mg/day for 15 days then increased to 1000 mg daily, with subsequent adjustments permitted within a dosing range of 250‐1000 mg daily. Study visits were conducted at days 1 and 15 and months 1, 2, 3, 6, 9, and 12. Safety was evaluated by adverse event collection, laboratory assessments, physical and neurological examinations, vital signs, electrocardiograms, the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, the Wechsler Abbreviated Scale of Intelligence, and the Behavioral Assessment Scale for Children. Efficacy was evaluated by following the number of migraine headache days reported in subjects' headache diaries over sequential 4‐week intervals for the duration of the trial.

Results.—A total of 241 subjects were enrolled and treated. The most frequently reported adverse events were nausea (19%), vomiting (18%), weight gain (12%), nasopharyngitis (11%), migraine (10%), and upper respiratory tract infection (10%). Ten (4%) subjects experienced serious adverse events, and 40 (17%) subjects discontinued because of an adverse event. Increases in ammonia levels were observed. No other clinically significant changes were observed in laboratory values, vital signs, rating scales, or electrocardiograms. Median 4‐week migraine headache days decreased 75% between the first and the fourth months of the study (from 4.0 to 1.0) and remained at or below this level for the remainder of the study.

Conclusions.—In this long‐term open‐label study of adolescents with migraine, the safety and tolerability profile of divalproex sodium extended‐release was consistent with findings from previous trials in adults, as well as 2 studies recently completed in adolescents. In general, divalproex sodium extended‐release was well‐tolerated in adolescents with migraine.
Multilocus Analyses Reveal Involvement of the ESR1, ESR2, and FSHR Genes in Migraine
Authors: Oterino Agustin , Toriello Maria , Cayón Amalia , Castillo Jesus , Colas Rafael , Alonson‐Arranz Ana , Ruiz‐Alegria Carlos , Quintela Estrella , Monton Fernando , Ruiz‐Lavilla Nuria , Gonzalez Felix , Pascual Julio
Published: November 2008

Objective.— Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view.

Methods.— We investigated 5 polymorphisms implicated in female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of 730 subjects matched for age and sex. The effect of gene–gene interaction was assessed using the set association approach, and the corresponding haplotypes were studied with PM Plus software. To corroborate initial results, we analyzed the selected markers using a cohort of 134 families in which 168 trios were suitable for transmission‐disequilibrium test (TDT) analysis under the migraine with aura (MA) phenotype.

Results.— A total of 356 consecutive migraine patients (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and 374 matched controls [71% females]) were genotyped. In the 2‐point analyses, the ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and this association was higher with the FSHR polymorphism in MA females (P = .004, uncorrected). Using the SUMSTAT program, we observed ESR2‐ESR1‐FSHR significant gene–gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females). We corroborated that ESR2‐ESR1‐FSHR haplotypes interacted for migraine under a model‐free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e‐4, under the heterogeneity model; P = .001 for females). These results were corroborated using family‐based association approaches. We observed nominal association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study, and significant association for ESR1 using family‐based association test statistics. Haplotype‐TDT analyses showed further significant gene–gene interaction for ESR1‐ESR2 (global P = .009), ESR2‐FSHR (global P = .011), and nominally significant interaction for ESR2‐ESR1‐FSHR genes (global P = .037).

Conclusion.— We found significant association of female hormone metabolism polymorphisms under the perspective of multigene approach.
Epidemiology and Biology of Menstrual Migraine
Authors: Martin Vincent T. , Lipton Richard B.
Published: November 2008

Migraine is frequently associated with menstruation in female migraineurs, and consequently it is commonly referred to as menstrually associated migraine. The trigger thought to be partially responsible for menstrually associated migraine is a significant drop in circulating estrogen that is noted during 2‐3 days prior to onset of menses. It is estimated that approximately 50% of women have an increased risk of experiencing migraine during the premenstrual phase of decreasing estrogen levels. Understanding the biological basis of migraine associated with menses will facilitate an accurate diagnosis and help patients recognize time susceptible to migraine exacerbations. This paper will review the biological bases for the hormonal changes that occur during the menstrual cycle and review the prevalence and burden of menstrual migraine among female headache sufferers.
Menstrual Migraine: Case Studies of Women with Estrogen‐Related Headaches
Authors: Hutchinson Susan L. , Silberstein Stephen D.
Published: November 2008

This paper presents 2 case scenarios that illustrate the complexity of diagnosing and managing migraine associated with hormonal changes. Migraine is commonly associated with comorbidies such as depression, anxiety, obesity, cardiovascular disease, as well as other conditions, thereby making management more challenging for the physician and the patient. The first case is a 35‐year‐old woman who has migraine almost exclusively during menstruation. She is under a physician's care for long‐term management of premenstrual dysphoric disorder (PMDD). Achieving a differential diagnosis of pure menstrual migraine is illustrated, and a detailed treatment plan including use of a migraine miniprophylaxis protocol, management of her PMDD, and prescription of acute treatment medications is reviewed. The second case scenario describes the diagnosis of menstrually associated migraine in a woman who suffers from a frequent disabling migraine along with work‐related anxiety and depression. This paper reviews her differential diagnosis, laboratory testing, treatment plan, including management of her comorbid anxiety and depressive symptoms.
Assessment of seizure susceptibility in pilocarpine epileptic and nonepileptic Wistar rats and of seizure reinduction with pentylenetetrazole and electroshock models
Authors: Blanco Miriam Marcela , Dos Santos Jr Jair Guilherme , Perez‐Mendes Patrícia , Kohek Silvia R. B. , Cavarsan Clarissa Fantin , Hummel Michele , Albuquerque Cristovão , Mello Luiz E.
Published: November 2008

Purpose:  Pentylenetetrazole (PTZ) and maximal electroshock (MES) models are often used to induce seizures in nonepileptic control animals or naive animals. Despite being widely used to screen antiepileptic drugs (AEDs), both models have so far failed to detect potentially useful AEDs for treating drug‐resistant epilepsies. Here we investigated whether the acute induction of MES and PTZ seizures in epileptic rats might yield a distinct screening profile for AEDs.

Methods:  Status epilepticus (SE) was induced in adult male Wistar rats by intraperitoneal pilocarpine injection (Pilo, 320 mg/kg, i.p.). One month later, controls or naive animals (Cont) that did not develop SE postpilocarpine (N‐Epi) and pilocarpine‐epileptic rats (Epi) received one of the following: phenobarbital (PB, 40 mg/kg), phenytoin (PHT, 50 mg/kg), or valproic acid (VPA, 400 mg/kg). Thirty min later the animals were challenged with either subcutaneous MES or PTZ (50 mg/kg, s.c.).

Results:  VPA, PB, and PHT were able to prevent MES in all groups tested (Cont, N‐Epi, and Epi groups), whereas for the PTZ model, only the Cont group (naive animals) had seizure control with the same AEDs. In addition, Epi and N‐Epi groups when challenged with PTZ exhibited a higher incidence of severe seizures (scores IV‐IX) and SE (p < 0.05, Fisher's exact test).

Conclusions:  Our findings suggest that the induction of acute seizures with PTZ, but not with MES, in animals pretreated with pilocarpine (regardless of SE induction) might constitute an effective and valuable method to screen AEDs and to study mechanisms involved in pharmacoresistant temporal lobe epilepsy (TLE).
Lamotrigine–valproic acid combination therapy for medically refractory epilepsy
Authors: Moeller Jeremy J. , Rahey Susan R. , Sadler R. Mark
Published: November 2008

Purpose:  A retrospective study of lamotrigine (LTG)–valproic acid (VPA) combination therapy in medically refractory epilepsy.

Methods:  Patients were identified with an adult epilepsy clinic database and were included if they had been on LTG–VPA combination therapy for at least 6 months. Patient demographics and information about epilepsy type, severity, and degree of medical intractability were obtained by retrospective chart review. The primary outcome measure was change in baseline seizure frequency, and patients were stratified into three groups: (i) seizure‐free, (ii) improved (at least 50% reduction in baseline seizure frequency), and (iii) not improved.

Results:  Thirty‐five patients met all inclusion–exclusion criteria. Epilepsy type was generalized in 25 patients (71%) and partial in 10 patients (29%). Before LTG–VPA treatment, 27 of 35 (77%) experienced disabling seizures on a monthly basis, and 17 of 35 (49%) of patients had at least one disabling seizure per week. Patients had previously failed treatment with a median of five antiepileptic drugs (AEDs), alone or in combination. With LTG–VPA therapy, 18 (51.4%) remained completely seizure‐free, four (11.4%) were improved, and 13 (37.1%) were unimproved. Median follow‐up was 42 months. Of the 22 patients who improved, 11 had previously failed LTG and VPA monotherapy. There was no significant difference between improved and unimproved patients with respect to demographics, epilepsy type or severity, or number of previously failed AEDs.

Discussion:  The combination of LTG and VPA should be considered in patients with medically refractory epilepsy. The effectiveness of this combination appears to be independent of epilepsy type or patient demographics.
A case report of a family with overlapping features of autosomal dominant febrile seizures and GEFS+
Authors: Hindocha Neeti , Nabbout Rima , Elmslie Frances , Makoff Andrew , Al‐Chalabi Ammar , Nashef Lina
Published: November 2008

Familial febrile seizures occur in both generalized epilepsy with febrile seizures plus (GEFS+) and autosomal dominant febrile seizures (ADFS). The literature largely separates families with GEFS+ from those with ADFS. However, there is clinical overlap, and families with ADFS also include individuals with afebrile seizures. The phenotypic spectrum of GEFS+ is broader now than when first described, resulting in unclear boundaries between these two familial syndromes. The purpose of this report is to highlight the phenotypic similarities of GEFS+ and ADFS. A multigenerational family with febrile and afebrile seizures is described and the clinical features are compared to those of previously reported GEFS+ and ADFS families. This family meets the requirements for both ADFS and the broader definition of GEFS+. Linkage analysis has shown no clear linkage to known febrile seizure or GEFS+ loci. Despite locus heterogeneity, identified mutations in reported GEFS+ have so far all been in sodium channel or γ‐aminobutyric acid (GABA)–receptor genes, with other modifier genes postulated to affect individual phenotypes. The two mutations identified in families with ADFS are in genes implicated in GEFS+, SCN1A, and GABRG2. We conclude that it is inappropriate to separate GEFS+ and ADFS at present given the clinical and genotypic overlap.
Status epilepticus in children with Alpers’ disease caused byPOLG1mutations: EEG and MRI features
Authors: Wolf Nicole I. , Rahman Shamima , Schmitt Bernhard , Taanman Jan‐Willem , Duncan Andrew J. , Harting Inga , Wohlrab Gabriele , Ebinger Friedrich , Rating Dietz , Bast Thomas
Published: November 2008

Purpose: Refractory convulsive status epilepticus in infancy and childhood is a rare emergency situation. Metabolic disorders frequently underlie this condition, in particular Alpers' disease caused byPOLG1mutations. Status epilepticus may be the first symptom. A pathognomonic electroencephalography (EEG) signature may facilitate diagnosis of Alpers' disease and allow timely avoidance of valproic acid, which is contraindicated in this disorder because it may trigger fatal liver failure.

Patients: We present five patients with Alpers' disease caused by mutations inPOLG1. Age of onset ranged from 7 months to 10 years. Three of the five children died after 3 to 12 months after onset of status epilepticus. Two of these had liver failure associated with use of valproic acid; liver transplantation in one child did not prevent a fatal neurologic outcome.

Results: Convulsive status epilepticus was the first obvious sign of Alpers' disease in all children. All had focal clonic and complex‐focal seizures; four of them developed epilepsia partialis continua. In four children, initial EEG showed unilateral occipital rhythmic high‐amplitude delta with superimposed (poly)spikes (RHADS). Magnetic resonance imaging (MRI) revealed cortical and thalamic involvement in all, although there were only discrete abnormalities in one child. Metabolic investigations remained normal in three children.

Conclusion: Alpers' disease is an important differential diagnosis in childhood refractory convulsive status epilepticus. Its EEG hallmark of RHADS is important for timely diagnosis, management, and counseling.
Three‐dimensional hippocampal atrophy maps distinguish two common temporal lobe seizure–onset patterns
Authors: Ogren Jennifer A. , Bragin Anatol , Wilson Charles L. , Hoftman Gil D. , Lin Jack J. , Dutton Rebecca A. , Fields Tony A. , Toga Arthur W. , Thompson Paul M. , Engel Jr. Jerome , Staba Richard J.
Published: November 2008

Purpose:  Current evidence suggests that the mechanisms underlying depth electrode–recorded seizures beginning with hypersynchronous (HYP) onset patterns are functionally distinct from those giving rise to low‐voltage fast (LVF) onset seizures. However, both groups have been associated with hippocampal atrophy (HA), indicating a need to clarify the anatomic correlates of each ictal onset type. We used three‐dimensional (3D) hippocampal mapping to quantify HA and determine whether each onset group exhibited a unique distribution of atrophy consistent with the functional differences that distinguish the two onset morphologies.

Methods:  Sixteen nonconsecutive patients with medically refractory epilepsy were assigned to HYP or LVF groups according to ictal onset patterns recorded with intracranial depth electrodes. Using preimplant magnetic resonance imaging (MRI), levels of volumetrically defined HA were determined by comparison with matched controls, and the distribution of local atrophy was mapped onto 3D hippocampal surface models.

Results:  HYP and LVF groups exhibited significant and equivalent levels of HA ipsilateral to seizure onset. Patients with LVF onset seizures also showed significant contralateral volume reductions. On ipsilateral contour maps HYP patients exhibited an atrophy pattern consistent with classical hippocampal sclerosis (HS), whereas LVF atrophy was distributed more laterally and diffusely. Contralateral LVF maps also showed regions of subicular atrophy.

Discussion:  The HS‐like distribution of atrophy and the restriction of HA to the ipsilateral hippocampus in HYP patients are consistent with focal hippocampal onsets, and suggest a mechanism utilizing intrahippocampal circuitry. In contrast, the bilateral distribution of nonspecific atrophy in the LVF group may reflect mechanisms involving both hippocampal and extrahippocampal networks.
Safety and pharmacokinetics of intravenous levetiracetam infusion as add‐on in status epilepticus
Authors: Uges Joris W.F. , Van Huizen Marc D. , Engelsman Jeroen , Wilms Erik B. , Touw Daniel J. , Peeters Els , Vecht Charles J.
Published: November 2008

Purpose: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE.

Methods: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24‐h follow‐up, patients were observed for any clinically relevant side‐effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two‐stage Bayesian analysis and compared to PK data of healthy volunteers.

Results: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized‐convulsive SE, five as partial‐convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two‐compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k12): 0.24 (0.12)/h, and peripheral to central (k21): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L.

Discussion: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two‐compartment population model.
Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES)
Authors: Kramer Uri , Sagi Liora , Goldberg‐Stern Hadassa , Zelnik Nathanel , Nissenkorn Andreea , Ben‐Zeev Bruria
Published: November 2008

Purposes: To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES).

Methods: Clinical data of all patients with ESES (not including patients with Landau‐Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007.

Results: Eleven (37%) children had benign partial epilepsies of childhood, five (17%) had cerebral palsy, five (17%) had hydrocephalus, one (3%) had schizencephaly, one (3%) had prenatal parenchymal bleeding, and the etiology was unclear in seven (23%). The duration of ESES ranged between 2 and 60 months. The antiepileptic drugs that were found to be efficacious were: levetiracetam (41%), clobazam (31%), and sulthiame (17%). Valproic acid, lamotrigine, topiramate, and ethosuximide showed no efficacy. Steroids were efficacious in 65%; immunoglobulins were efficacious in 33%. High‐dose diazepam was efficacious in 37%, but all the children had temporary response. Seventeen patients (57%) had cognitive deterioration, whereas the rest presented with regression in attention, speech, communication, and behavior. Fourteen children had permanent cognitive deficit. There was a significant correlation (p = 0.029) between the duration of ESES and residual intellectual deficit at follow‐up.

Conclusions: ESES reflects an evolution of benign partial epilepsy of childhood in more than one‐third of the patients, whereas there is an underlying structural brain anomaly in another one‐third. The most efficacious antiepileptic drugs (AEDs) are levetiracetam and clobazam. The duration of ESES correlated significantly with residual intellectual deficit at follow‐up.
Cognitive complaints after a first seizure in adulthood: Influence of psychological adjustment
Authors: Velissaris Sarah L. , Wilson Sarah J. , Newton Mark R. , Berkovic Samuel F. , Saling Michael M.
Published: November 2008

Purpose:  To examine the nature and determinants (biologic and psychological) of cognitive complaints in first‐seizure patients. We analyzed this in the context of our previous findings that a sense of loss of control after a newly diagnosed seizure (limited or pervasive) predicts subsequent psychological adjustment trajectories.

Methods:  Eighty‐five consecutive First Seizure Clinic patients were assessed at 1 and 3 months. Cognitive complaints were evaluated qualitatively, with a semistructured interview, and quantitatively, with the A‐B Neuropsychological Assessment Schedule (ABNAS). Objective attentional processing was assessed with reaction time tasks and the Wechsler Adult Intelligence Scale‐3rd edition (WAIS‐III) Processing Speed Index. Mood was assessed with the Hospital Anxiety and Depression Scale (HADS). Psychological adjustment trajectories were represented by previous classification of patients into limited and pervasive groups, as derived from semistructured interview.

Results:  Cognitive complaints at 1 and 3 months were strongly associated with mood, and unrelated to objective attentional processing. Psychological adjustment trajectories influenced the longitudinal course of cognitive complaints, and these effects were partially mediated by mood differences between the limited and pervasive groups. The course of cognitive complaints was also altered by commencing antiepileptic drugs. Patients experiencing seizure recurrence reported greater cognitive complaints, even before their seizure recurred. Mediation analyses showed this effect was likely attributable to increased mood disturbance in the seizure recurrence group, and was unrelated to objective attentional processing.

Discussion:  Understanding cognitive complaints in first‐seizure patients requires a longitudinal perspective that takes into account the patients’ changing psychological and medical contexts. Patients presenting with extensive cognitive complaints may warrant assessment for mood and adjustment issues.
Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy
Authors: Wheless James W. , Carmant Lionel , Bebin Martina , Conry Joan A. , Chiron Catherine , Elterman Roy D. , Frost Michael , Paolicchi Juliann M. , Donald Shields W. , Thiele Elizabeth A. , Zupanc Mary L. , Collins Stephen D.
Published: November 2008

Purpose:  Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS).

Methods:  Medical records and 332 cranial MRIs from 205 infants (aged ≤24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2–16 years) and adults (aged >16 years) with CPS were re‐reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T2‐weighted or fluid‐attenuated inversion‐recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well‐characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with vigabatrin were estimated.

Results:  Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin‐treated versus vigabatrin‐naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)—vigabatrin was discontinued in four. Among adults and children treated with vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between vigabatrin‐exposed and vigabatrin‐naive subjects.

Discussion:  Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on vigabatrin therapy.
Sociodemographic disparities in epilepsy care: Results from the Houston/New York City health care use and outcomes study
Authors: Begley Charles E. , Basu Rituparna , Reynolds Thomas , Lairson David R. , Dubinsky Stephanie , Newmark Michael , Barnwell Forbes , Hauser Allen , Hesdorffer Dale , Hernandez Nora , Karceski Steven C. , Shih Tina
Published: November 2008

Purpose:  The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care.

Methods:  Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One‐half of the patients were from a Houston site and two NYC sites that serve predominantly low‐income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care.

Results:  Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model.

Discussion:  There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.
Stress, the hippocampus, and epilepsy
Authors: Joëls Marian
Published: November 2008

Stress is among the most frequently self‐reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin‐releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress mediators in the rodent hippocampus are highlighted. Overall, corticosterone—with other stress hormones—rapidly enhances CA1/CA3 hippocampal activity shortly after stress. At the same time, corticosterone starts gene‐mediated events, which enhance calcium influx several hours later. This later effect serves to normalize activity but also imposes a risk for neuronal injury if and when neurons are concurrently strongly depolarized, for example, during epileptic activity. In the dentate gyrus, stress‐induced elevations in corticosteroid level are less effective in changing membrane properties such as calcium influx; here, enhanced inhibitory tone mediated through neurosteroid effects on γ‐aminobutyric acid (GABA) receptors might dominate. Under conditions of repetitive stress (e.g., caused from experiencing repetitive and unpredictable seizures) and/or early life stress, hormonal influences on the inhibitory tone, however, are diminished; instead, enhanced calcium influx and increased excitation become more important. In agreement, perinatal stress and elevated steroid levels accelerate epileptogenesis and lower seizure threshold in various animal models for epilepsy. It will be interesting to examine how curtailing the effects of stress in adults, for example, by brief treatment with antiglucocorticoids, may be beneficial to the treatment of epilepsy.
Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men
Authors: Han Ling , Agostini Joseph V. , Allore Heather G.
Published: November 2008

OBJECTIVES: To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men.

DESIGN: Prospective cohort study.

SETTING: A Department of Veterans Affairs primary care clinic.

PARTICIPANTS: Five hundred forty‐four community‐dwelling men aged 65 and older with diagnosed hypertension.

MEASUREMENTS: The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short‐term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow‐up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician‐rated anticholinergic score.

RESULTS: Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1‐unit increase in the total anticholinergic burden per 3 months was associated with a 0.32‐point (95% confidence interval (CI)= 0.05–0.58) and 0.10‐point (95% CI=0.04–0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI=0.01–0.56) and executive function (0.08, 95% CI=0.02–0.15) after further adjustment for concomitant non‐anticholinergic medications.

CONCLUSION: Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects.