bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Interaction between Genetic Diversity and UV‐B Radiation on Wood Frog Fitness
Authors: WEYRAUCH SHAUNA L. , GRUBB THOMAS C.
Published: February 2006

Abstract:  Genetic diversity may buffer amphibian populations against environmental vicissitudes. We hypothesized that wood frogs ( Rana sylvatica) from populations with lower genetic diversity are more susceptible to ultraviolet‐B (UV‐B) radiation than those from populations with higher diversity. We used RAPD markers to obtain genetic diversity estimates for 12 wood frog populations. We reared larval wood frogs from these populations and exposed experimental groups of eggs and larvae to one of three treatments: unfiltered sunlight, sunlight filtered through a UV‐B‐blocking filter (Mylar), and sunlight filtered through a UV‐B‐transmitting filter (acetate). In groups exposed to UV‐B, larval mortality and deformity rates increased significantly, but egg mortality did not. We found a significant negative relationship between genetic diversity and egg mortality, larval mortality, and deformity rates. Furthermore, the interaction between UV‐B treatment and genetic diversity significantly affected larval mortality. Populations with low genetic diversity experienced higher larval mortality rates when exposed to UV‐B than did populations with high genetic diversity. This is the first time an interaction between genetic diversity and an environmental stressor has been documented in amphibians. Differences in genetic diversity among populations, coupled with environmental stressors, may help explain patterns of amphibian decline.
Impacts of Alternative Timber Harvest Practices on Leaf‐Chewing Herbivores of Oak
Authors: FORKNER REBECCA E. , MARQUIS ROBERT J. , LILL JOHN T. , LE CORFF JOSIANE
Published: February 2006

Abstract:  Studies of the effects of logging on Lepidoptera rarely address landscape‐level effects or effects on larval, leaf‐feeding stages. We examined the impacts of uneven‐aged and even‐aged logging on the abundance, richness, and community structure of leaf‐chewing insects of white (Quercus alba L.) and black (Q. velutina L.) oak trees remaining in unharvested areas by sampling 3 years before and 7 years after harvest. After harvest, white oaks in uneven‐aged sites had 32% fewer species of leaf‐chewing insects than control sites. This reduction in species richness may have resulted from changes in microclimate (reducing plant quality and/or changing leaf phenology) that affected a much larger total area of each site than did even‐aged cuts. For black oak after harvest, species richness in uneven‐ and even‐aged sites increased relative to levels before harvest. Harvesting did not alter total insect density or community structure in the unlogged habitat for either oak species with one exception: insect density on black oak increased in the oldest forest block. Community structure of herbivores of black and white oaks in clearcut gaps differed from that of oaks in intact areas of even‐aged sites. Furthermore, both richness and total insect density of black oaks were reduced in clearcut gaps. We suggest that low‐level harvests alter herbivore species richness at the landscape level. Treatment effects were subtle because we sampled untreated areas of logged landscapes, only one harvest had occurred, and large temporal and spatial variation in abundance and richness existed. Although the effects of logging were greater in uneven‐aged sites, the effects of even‐aged management are likely to increase as harvesting continues.
Ecological‐Economic Modeling for Biodiversity Management: Potential, Pitfalls, and Prospects
Authors: WÄTZOLD FRANK , DRECHSLER MARTIN , ARMSTRONG CLAIRE W. , BAUMGÄRTNER STEFAN , GRIMM VOLKER , HUTH ANDREAS , PERRINGS CHARLES , POSSINGHAM HUGH P. , SHOGREN JASON F. , SKONHOFT ANDERS , VERBOOM‐VASILJEV JANA , WISSEL CHRISTIAN
Published: February 2006

Abstract: Ecologists and economists both use models to help develop strategies for biodiversity management. The practical use of disciplinary models, however, can be limited because ecological models tend not to address the socioeconomic dimension of biodiversity management, whereas economic models tend to neglect the ecological dimension. Given these shortcomings of disciplinary models, there is a necessity to combine ecological and economic knowledge into ecological‐economic models. It is insufficient if scientists work separately in their own disciplines and combine their knowledge only when it comes to formulating management recommendations. Such an approach does not capture feedback loops between the ecological and the socioeconomic systems. Furthermore, each discipline poses the management problem in its own way and comes up with its own most appropriate solution. These disciplinary solutions, however, are likely to be so different that a combined solution considering aspects of both disciplines cannot be found. Preconditions for a successful model‐based integration of ecology and economics include (1) an in‐depth knowledge of the two disciplines, (2) the adequate identification and framing of the problem to be investigated, and (3) a common understanding between economists and ecologists of modeling and scale. To further advance ecological‐economic modeling the development of common benchmarks, quality controls, and refereeing standards for ecological‐economic models is desirable.
Influences of Microhabitat Constraints and Rock‐Climbing Disturbance on Cliff‐Face Vegetation Communities
Authors: KUNTZ KATHRYN LYNNE , LARSON DOUGLAS W.
Published: February 2006

Abstract:  Many researchers report that rock climbing has significant negative effects on cliff biota. Most work on climbing disturbance, however, has not controlled for variation in microsite characteristics when comparing areas with and without climbing presence. Additionally, some researchers do not identify the style or difficulty level of climbing routes sampled or select climbing routes that do not represent current trends in the sport. We solved these problems by sampling climbing areas used by advanced “sport” climbers and quantifying differences in microtopography between climbed and control cliffs. We determined whether differences in vegetation existed between pristine and sport‐climbed cliff faces when microsite factors were not controlled. We then determined the relative influence of the presence of climbing, cliff‐face microtopography, local physical factors, and regional geography on the richness, abundance, and community composition of cliff‐face vascular plants, bryophytes, and lichens. When we did not control for microsite differences among cliffs, our results were consistent with the majority of prior work on impacts of climbing (i.e., sport‐climbed cliff faces supported a lower mean richness of vascular plants and bryophytes and significantly different frequencies of individual species when compared with pristine cliff faces). When we investigated the relative influences of microtopography and climbing disturbance, however, the differences in vegetation were not related to climbing disturbance but rather to the selection by sport climbers of cliff faces with microsite characteristics that support less vegetation. Climbed sites had not diverged toward a separate vegetation community; instead, they supported a subset of the species found on pristine cliff faces. Prior management recommendations to restrict development of new climbing routes should be reevaluated based on our results.
Influence of Lamotrigine and Topiramate onMDR1Expression in Difficult‐to‐Treat Temporal Lobe Epilepsy
Authors: Wang‐Tilz Ying , Tilz Christian , Wang Bing , Tilz Gernot P. , Stefan Hermann
Published: February 2006

Summary: Purpose:Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue fromCoriarialactone (CL)‐kindled Sprague–Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).

Methods:Twenty‐five CL‐kindled SD rats were randomized into five groups (n = 5 for each group) to receive once‐daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage,or normal saline (NS control) for 1 month. The expression of P‐gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro‐plus 4.0). Mean area and mean integrated optical density (mean IOD) of P‐gp expression were calculated. In addition, the changes in seizure severity were analyzed via video‐camera monitoring.

Results:A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P‐gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).

Conclusions:TPM and LTG significantly inhibited seizures in this CL model. The expression of P‐gp was not significantly increased by TPM or LTG treatment in this study.
Serotonin Depletion Attenuates AY‐9944–Mediated Atypical Absence Seizures
Authors: Bercovici Eduard , Cortez Miguel A. , Wang Xiaomei , Snead O. Carter
Published: February 2006

Summary:  Purpose: To test the hypothesis that serotonin (5‐HT) plays a role in the modulation of experimental atypical absence seizures.

Methods: Male Long‐Evans hooded rats were treated from postnatal day (P) 2 to P20 with the cholesterol inhibitor AY‐9944 (AY). Epidural electrodes were implanted for electrocorticography (ECoG) followed by serotonin depletion by using para‐cholorophenylalanine (PCPA). High‐performance liquid chromatography (HPLC) was used to measure the levels of serotonin and its metabolite (5‐HIAA) in various brain regions. Serotonin metabolism was computed by using the 5‐HIAA/5‐HT ratio and used to ascertain differences between groups.

Results: PCPA treatment was associated with a significant decrease in the total slow spike‐and‐wave discharge (SSWD) duration in AY‐treated rats compared with controls (p < 0.01). HPLC data confirmed the PCPA depletion of 5‐HT and 5‐HIAA in cortex, thalamus, hippocampus, and brainstem compared with naïve rats. AY‐treated rats showed higher levels of 5‐HIAA and 5‐HT in the same brain regions, with a concomitant decrease in rates of serotonin turnover.

Conclusions: The data indicate that serotonin depletion protects against experimental atypical absence seizures. The increased levels of 5‐HIAA and 5‐HT and altered rates of serotonin turnover suggest that the serotonergic neurotransmission may be perturbed in the AY rat.
A Brief Period of Epileptiform Activity Strengthens Excitatory Synapses in the Rat Hippocampus in Vitro
Authors: Debanne Dominique , Thompson Scott M. , Gähwiler Beat H.
Published: February 2006

Summary:  Purpose: We examined here whether a very short period of epileptiform activity could produce lasting modifications of synaptic strength and network properties in the rat hippocampus in vitro.

Methods: Synaptic transmission at CA3‐CA1 and at CA3‐CA3 pyramidal cell synapses was monitored in hippocampal slice cultures before and after a very brief episode of epileptiform activity (20–180 s) induced with bicuculline methochloride.

Results: We show here that a brief period of epileptiform activity induces long‐lasting potentiation of glutamatergic transmission at CA3‐CA1 and at CA3‐CA3 pyramidal cell synapses. This potentiation also was observed at synapses formed by pairs of monosynaptically connected neurons. It was dependent on N‐methyl‐d‐aspartate (NMDA) receptors, occluded classic long‐term potentiation, and could be depotentiated by low‐frequency stimulation at 3 Hz. Recruitment of polysynaptic pathways within area CA3 was facilitated after epileptiform activity indicating that the induced potentiation enhanced overall hippocampal network excitability.

Conclusions: These changes in synaptic transmission may contribute to the genesis of epilepsy and to seizure‐associated memory deficits.
Reeler Homozygous Mice Exhibit Enhanced Susceptibility to Epileptiform Activity
Authors: Patrylo Peter R. , Browning Ronald A. , Cranick Scott
Published: February 2006

Summary:  Purpose: Seizures are observed frequently in humans with diffuse neuronal migration disorders. The reeler mutant mouse also exhibits a diffuse disruption of migration, yet no proepileptic phenotype has been reported for this model. Whether this disparity reflects a phenotypic difference that can be used to delineate the mechanisms associated with increasing seizure susceptibility or reflects a paucity of knowledge is unclear. Consequently, this study examined whether seizure susceptibility is altered in reeler mutant mice.

Methods: In vivo (minimal electroshock delivered transcorneally) and in vitro techniques (field‐potential recordings in neocortical and hippocampal brain slice preparations exposed to bicuculline methiodide) were used to determine whether the susceptibility to epileptiform activity is enhanced in reeler homozygous mice relative to controls. Adult (3–7 months) male reeler homozygotes (rl/rl) and controls (+/?) were identified based on their behavioral phenotype and were used in all experiments.

Results: Minimal electroshock revealed that rl/rl mice, compared with controls, exhibited a lower threshold for electroshock‐induced seizures (4.5 ± 0.52 vs. 6.7 ± 0.35 mA), and a higher incidence of behavioral seizures (median seizure score, class 4 vs. class 0) when animals were subjected to a 5‐mA electroshock stimulus. Additionally, neocortical and hippocampal slices from rl/rl mice were more likely to generate spontaneous epileptiform activity after bicuculline application, compared with controls, and the duration of the epileptiform events elicited in 10–30 μM bicuculline was longer in slices from rl/rl mice.

Conclusions: These data demonstrate that rl/rl mice have enhanced seizure susceptibility that is in part intrinsic to the malformed neocortex and hippocampus. Thus in contrast to prior belief, most animal models of diffuse neuronal migration disorders do exhibit a proepileptic phenotype.
Diacylglycerol Kinase Epsilon Modulates Rapid Kindling Epileptogenesis
Authors: Musto Alberto , Bazan Nicolas G.
Published: February 2006

Summary: Purpose:Diacylglycerol kinase epsilon (DGKε) regulates seizure susceptibility and long‐term potentiation through arachidonoyl‐inositol lipid signaling. We studied the significance of arachidonoyl‐diacylglycerol (20:4 DAG) in epileptogenesis in DGKε‐deficient mice undergoing rapid kindling epileptogenesis.

Methods:Tripolar electrode units were implanted in right dorsal hippocampi of male DGKε+/+and DGKε−/−mice. Ten days after surgery, kindling was achieved by stimulating 6 times daily for 4 days with a subconvulsive electrical stimulation (10‐s train of 50‐Hz biphasic pulses, 75–200 μA amplitude) at 30‐min intervals. After 1 week, mice were rekindled. EEGs were recorded and analyzed to characterize epileptogenic events as spikes, sharp waves, or abnormal amplitudes and rhythms. Right hippocampi were analyzed by histology [Timm's staining, neuropeptide Y (NPY) and glial fibrillary acidic protein immunoreactivity], and for DNA fragmentation (TUNEL).

Results:DGKε−/−mice had significantly fewer motor seizure and epileptic events compared with DGKε+/+mice from the second day of stimulation. These differences were maintained during rekindling. DGKε−/−mice also exhibited low‐amplitude spike–wave complexes, short spreading depression, and predominant lower‐frequency (1–4 Hz) bands throughout stimulation, whereas DGKε+/+mice exhibited increased high‐frequency bands (4–8 Hz; 8–15 Hz) from the second day of stimulation, as determined by power spectral analysis. DGKε−/−mice displayed no sprouting in the supragranular area or NPY inmunoreactivity in the hilus and had weak astrocyte reactivation in all hippocampal areas. No TUNEL‐positive cells were detected in any group of mice.

Conclusions:DGKε modulates kindling epileptogenesis through inositol lipid signaling. Because arachidonate‐containing diacylglycerol phosphorylation to phosphatidic acid is selectively blocked in DGKε−/−mice, we postulate that the shortage of arachidonoyl‐moiety inositol lipids and/or the messengers derived thereof is a key signaling event in epileptogenesis.
Decrease of Hippocampal GABAB Receptor–Mediated Inhibition after Hyperthermia‐induced Seizures in Immature Rats
Authors: Tsai Min‐Lan , Leung L. Stan
Published: February 2006

Summary:  Purpose: Whether febrile seizures have detrimental consequences on the brain is still controversial. We hypothesized that neuronal inhibition in the hippocampus is altered after hyperthermia‐induced seizures in immature rats.

Methods: Rats were given a single seizure by a heat lamp on postnatal day (PND) 15, or repeated seizures by heated air on PND 13 to 15. Fourteen or 30 days after the seizure(s), laminar field potentials were recorded by 16‐channel silicon probes in CA1 and the dentate gyrus (DG), in response to the paired‐pulse stimulation of the CA3 and medial perforant path, and analyzed as current source density. γ‐Aminobutyric acid (GABA)B‐receptor antagonist CGP35348 was injected intracerebroventricularly (icv).

Results: At 14 but not at 30 days after a single or after repeated hyperthermia‐induced seizures, paired‐pulse facilitation (PPF) of the CA1 population spikes at 100 to 200 ms interpulse intervals (IPIs) was significantly increased in seizure as compared with control rats, irrespective of the types of induced seizures. CGP35348 icv also resulted in PPF at 100 to 200 ms IPIs in CA1 of control rats, but CGP35348 had no effect on PPF in seizure rats. At 30 days after repeated seizures, paired‐pulse inhibition in the DG was significantly increased at 30‐ms IPI, and PPF was increased at 200‐ms IPI. CGP35348 increased paired‐pulse inhibition in the DG in repeated‐seizure rats but not in control rats.

Conclusions:We conclude that hyperthermia‐induced seizures in immature rats induced a decrease of GABAB receptor–mediated inhibition in CA1 and DG that lasted ≥14 to 30 days after hyperthermic seizure(s).
Neocortical Microenvironment in Patients with Intractable Epilepsy: Potassium and Chloride Concentrations
Authors: Gorji Ali , Stemmer Nina , Rambeck Bernhard , Jürgens Uwe , May Theodor , Pannek Heinz Wolfgang , Behne Friedrich , Ebner Alois , Straub Hiedrun , Speckmann Erwin‐Josef
Published: February 2006

Summary:  Purpose: The regulation of extracellular ion concentrations plays an important role in neuronal function and epileptogenesis. Despite the many studies into the mechanisms of epileptogenesis in human experimental models, no data are available regarding the fluctuations of extracellular potassium ([K+]o) and chloride ([Cl−]o) concentrations, which could underlie seizure susceptibility in human chronically epileptic tissues in vivo.

Methods: By using cerebral microdialysis during surgical resection of epileptic foci, the basic [K+]o and [Cl−]o as well as their changes after epicortical electric stimulation were studied in samples of dialysates obtained from 11 patients by ion‐selective microelectrodes.

Results: The mean basal values of [K+]o and [Cl−]o in all patients were 3.83 ± 0.08 mM and 122.9 ± 2.6 mM, respectively. However, significant differences were observed in the basal levels of both [K+]o and [Cl−]o between different patients. Statistically, no correlation was found between basal [K+]o or [Cl−]o and electrocorticogram (ECoG) spike activity, but in one patient, dramatically lowered baseline [Cl−]o was accompanied by enhanced ECoG spike activity. Application of epicortical electrical stimulation increased [K+]o but not [Cl−]o in all cases. According to the velocity as well as spatial distribution of [K+]o reduction to the prestimulation levels, three different types of responses were observed: slow decline, fast decline, and slow and fast declines at adjacent sites.

Conclusions: These data may represent abnormalities in ion homeostasis of the epileptic brain.
Ginkgo biloba Use in Nursing Home Elderly with Epilepsy or Seizure Disorder
Authors: Harms Susan L. , Garrard Judith , Schwinghammer Paul , Eberly Lynn E. , Chang Yanping , Leppik Ilo E.
Published: February 2006

Summary:  Purpose: Ginkgo biloba, among the most widely used herbs, possesses the capacity both to induce and to inhibit seizures. The purpose of this study was to describe the prevalence of ginkgo and other common herb prescribing in a sample of nursing home (NH) elderly diagnosed with epilepsy/seizure (Epi/Sz) disorder and to determine demographic, clinical, and functional factors associated with ginkgo use.

Methods: This was a 1‐year prevalence study of 68,403 NH residents living in 557 nursing facilities throughout the United States.

Results: Overall, herb use in the NHs was very low (0.41%). Ginkgo was prescribed 162 times, more than any other herb. St. John's wort was prescribed 40 times; garlic, 29 times; and all others, <20 times, for a total of 307 herb orders. Among all residents with an herb order, ginkgo was prescribed for 61.9% of residents with an Epi/Sz diagnosis and 58.0% (p = 0.820) of residents without an Epi/Sz diagnosis. Dementia, educational level, and the interaction of age group with cognitive impairment were all significantly associated with herb use among Epi/Sz residents. Cognitive impairment and the interaction of Epi/Sz disorder with dementia were associated specifically with ginkgo use.

Conclusions: Ginkgo is the most frequently prescribed herb in this population in which >50% of all herb orders were written for ginkgo. The concern with ginkgo use among elderly with Epi/Sz is the lack of standardization that characterizes ginkgo products. In the absence of standardization, the likelihood is increased that ginkgo products may be adulterated with the Ginkgo biloba plant parts most commonly associated with seizure provocation.
Temporal and Extratemporal BOLD Responses to Temporal Lobe Interictal Spikes
Authors: Kobayashi Eliane , Bagshaw Andrew P. , Bénar Christian‐George , Aghakhani Yahya , Andermann Frederick , Dubeau François , Gotman Jean
Published: February 2006

Summary: Purpose:Simultaneous EEG and functional MRI (fMRI) allows measuring metabolic changes related to interictal spikes. Our objective was to investigate blood oxygenation level–dependent (BOLD) responses to temporal lobe (TL) spikes by using EEG‐fMRI recording.

Methods:We studied 35 patients who had a diagnosis of temporal lobe epilepsy (TLE) and active TL spiking on routine scalp EEG recording. Two‐hour sessions of continuous EEG‐fMRI were recorded, and spikes were identified after offline artifact removal and used as events in thefMRI analysis. Each type of spike was analyzed separately, as one EEG‐fMRI study. We determined significant (p < 0.05) positive (activation) and negative (deactivation) BOLD responses for each study.

Results:Twenty‐seven patients had spikes during scanning (19 unilateral and eight bilateral). From a total of 35fMRI studies, 29 (83%) showed BOLD responses: 14 had both activations and deactivations; 12, activations only; and three, deactivations only. Six (17%) showed no responses. Nineteen studies had mainly neocortical TL activation: Sixteen (84%) of 19 concordant with spikes, 12 of 16 with concomitant activation of the contralateral TL, and 16 of 19 with additional extratemporal activation; few showed exclusively mesial TL activation. Seventeen studies showed deactivation, either extratemporal plus temporal (n = 8) or exclusively extratemporal (n = 9).

Conclusions:BOLD responses to TL spikes occurred in 83% of studies, predominated in the spiking temporal lobe, and manifested as activation or deactivation. Responses often involved the contralateral homologous cortex at the time of unilateral spikes and were frequently observed in extratemporal regions, suggesting that TL epileptic spikes can affect neuronal activity at a distance through synaptic connections.
Single and Multiple Clusters of Magnetoencephalographic Dipoles in Neocortical Epilepsy: Significance in Characterizing the Epileptogenic Zone
Authors: Oishi Makoto , Kameyama Shigeki , Masuda Hiroshi , Tohyama Jun , Kanazawa Osamu , Sasagawa Mutsuo , Otsubo Hiroshi
Published: February 2006

Summary:  Purpose: To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG).

Methods: We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal‐onset zones (IOZs) from subdural electroencephalography (SDEEG), resected areas, and postsurgical outcomes of 20 patients who underwent cortical resection for medically intractable NE.

Results: Fourteen patients had single clusters; six had multiple clusters. Overlap of clusters and IOZs defined group A (nine patients), in which a single cluster coincided with the IOZ; group B1 (four patients), in which a single cluster was within or partially overlapped the IOZ; group B2 (five patients), in which multiple‐cluster sections overlapped IOZs; group C (two patients; one single; one multiple), in which no overlap was seen. More single clusters (nine of 14) than multiple clusters (none of six) coincided with the IOZ (p = 0.014). More patients with single clusters (10 of 14) than patients with multiple clusters (one of six) had seizure‐free outcomes (p = 0.049). Eight of nine patients in group A, versus three of 11 in groups B1, B2, and C, achieved seizure‐free outcomes (p = 0.0098). Correlations between MRI findings and postsurgical outcomes were not statistically significant; eight of 13 patients with single lesions, one of four with no lesions, and two of three with multifocal lesions had seizure‐free outcomes.

Conclusions: In neocortical epilepsy, MEG ECD clusters correlated with SDEEG IOZs. Single clusters indicated discrete epileptogenic zones that required complete resection for seizure‐free outcome. Multiple clusters necessitated that the multiple or extensive epileptogenic zones be completely identified and delineated by SDEEG.
Epileptogenicity of Supratentorial Medullary Venous Malformation
Authors: Morioka Takato , Hashiguchi Kimiaki , Nagata Shinji , Miyagi Yasushi , Yoshida Fumiaki , Mihara Futoshi , Sakata Ayumi , Sasaki Tomio
Published: February 2006

Summary:  Purpose: The purpose of this study was to evaluate the epileptogenicity of supratentorial medullary venous malformation (MVM). Special consideration was given to any associations with intracerebral hemorrhage with or without other vascular malformations, including cavernous angioma (CA).

Methods: In total, 10 patients with angiographically or histologically verified MVMs were examined. The patients were divided into two groups with or without intracerebral hemorrhage, and their clinical, neuroradiologic, and interictal and ictal EEG findings were reviewed retrospectively.

Results: Although three of five patients in the nonhemorrhagic group had epilepsy, no topographic concordance was found between the MVM location and the EEG focus. On the contrary, in four of five patients in the hemorrhagic group, epilepsy developed, and topographic concordance between the hemorrhagic MVM location and the EEG focus was noted. One patient with a hemorrhagic MVM and an associated CA in the hippocampus had electroclinical pictures of intractable medial temporal lobe epilepsy on this side.

Conclusions: Although a supratentorial MVM itself is not epileptogenic, the development of an intracerebral hemorrhage may cause epilepsy. In particular, an associated CA may be highly epileptogenic.
Extended, One‐stage Callosal Section for Treatment of Refractory Secondarily Generalized Epilepsy in Patients with Lennox–Gastaut and Lennox‐like Syndromes
Authors: Cukiert Arthur , Burattini Jose Augusto , Mariani Pedro Paulo , Câmara Ródio Brandão , Seda Lauro , Baldauf Cristine Mella , Argentoni Meire , Baise‐Zung Carla , Forster Cássio Roberto , Mello Valeria Antakli
Published: February 2006

Summary: Purpose:We report on the efficacy and safety of extended one‐stage callosal section performed in a large and homogeneous series of patients.

Methods:Seventy‐six patients with Lennox–Gastaut (n = 28) and Lennox‐like (n = 48) syndrome were studied (42 male patients; mean age, 11.2 years). All patients had multiple seizure types per day, including atonic, tonic–clonic, atypical absence, myoclonic, and tonic seizures. All of them were developmentally impaired. The EEG showed intense secondary bilateral synchrony in all of them. All patients were submitted to an extended, one‐stage, callosal section, leaving only the splenium intact. Mean follow‐up time was 4.7 years.

Results:Worthwhile improvement (>50%) was noted in 69 of 76 patients; 52 patients had a ≥90% reduction in seizure frequency. Seven patients were seizure free after surgery. The seizure patterns most responsive to surgery were atonic (92%), atypical absence (82%), and tonic–clonic (57%) seizures. All patients had some degree of a transient acute postoperative disconnection syndrome. A consistent increase in attention level was observed postoperatively.

Conclusions:We report one of the larger homogeneous series of patients submitted to callosotomy and are the first to report on the effectiveness and safety of performing extended callosal section in a single stage in this patient group. Extended callosal section should be considered a good palliative surgical option for suitable candidates. The increase in attention level was as useful as seizure control in improving quality of life of these patients.
Seizure Recurrence and Risk Factors after Antiepilepsy Drug Withdrawal in Children with Brain Tumors
Authors: Khan Raja B. , Onar Arzu
Published: February 2006

Summary: Purpose:To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence.

Methods:Brain tumor patients with seizures and at least one attempt at AED discontinuation were identified from the hospital database and neurology clinic records. After defining study variables, patient charts were abstracted for clinical and demographic data. Statistical analyses used log‐rank tests and multivariable Cox proportional hazards models.

Results:Sixty‐two patients discontinued AEDs at a median time of 5.6 years from the first seizure (range, 1.2–19.6 years). Median time since AED withdrawal was 2.3 years (range, 0.4–15.1 years). Seizures recurred in 17 (27%) patients within a median time of 0.8 years (range, 0.06–7.7 years). Median seizure‐free period before AED withdrawal was 1.3 years (range, 0.1–11 years). More than one tumor resection and whole‐brain radiation treatment (WBRT) were associated with seizure recurrence, whereas posterior fossa tumor location was correlated with reduced seizure recurrence risk. At seizure recurrence, control was easily reestablished in 10 patients with AED reinstitution and after dose adjustment in five; two patients with poor drug compliance continue to have seizures. In 48 patients who had an EEG before AED withdrawal, spikes or slow waves did not correlate with seizure recurrence.

Conclusions:AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.
Epilepsy in Menkes Disease: Analysis of Clinical Stages
Authors: Bahi‐Buisson Nadia , Kaminska Anna , Nabbout Rima , Barnerias Christine , Desguerre Isabelle , De Lonlay Pascale , Mayer Michele , Plouin Perrine , Dulac Olivier , Chiron Catherine
Published: February 2006

Summary: Purpose:Epilepsy is one of the main features of Menkes disease (MD), although it is not described in depth. To determine the spectrum of epilepsy, we studied its main characteristics.

Methods:Based on clinical charts, we retrospectively analyzed the evolution of electroclinical features of 12 patients with confirmed MD.

Results:Epilepsy could be divided into three periods: (a) an early stage (median age, 3 months), characterized by focal clonic status epilepticus, usually triggered by fever (10 patients). Ictal EEG showed runs of slow spike–waves and slow waves in the posterior regions, and interictal EEG multifocal and polymorphic slow waves (three cases), or mixed slow spike–waves and slow waves (seven cases). Partial seizure control was obtained in nine patients during 5.9 months; (b) an intermediate stage (median age, 10 months) with intractable infantile spasms (11 patients) in which interictal EEG demonstrated modified hypsarrhythmia (seven cases), diffuse irregular slow waves and spike–waves (four cases). Six patients died at the median age of 15 months; and (c) a late stage in the six remaining patients (median age, 25 months), with multifocal seizures, tonic spasms, and myoclonus in four patients, whereas two patients became seizure free. Interictal EEG showed multifocal high‐amplitude activity, mixed with irregular slow waves in all six cases. These patients died at the median age of 3.6 years.

Conclusions:Based on a relatively large series of MD patients with a quite prolonged survival, we individualized three successive periods in the course of epilepsy: early focal status, then infantile spasms, and then myoclonic and multifocal epilepsy after age 2 years.
Benign Myoclonic Epilepsy in Infants: Electroclinical Features and Long‐term Follow‐up of 34 Patients
Authors: Auvin Stéphane , Pandit Florence , De Bellecize Jullita , Badinand Nicole , Isnard Hervé , Motte Jacques , Villeneuve Nathalie , Lamblin Marie‐Dominique , Vallée Louis ,   Epilepsy Study Group of the French Pediatric Neurology Society
Published: February 2006

Summary: Purpose:Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the electroclinical features and the follow‐up of this syndrome.

Methods:BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and electroencephalographic findings at diagnosis and during the follow‐up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations.

Results:We report 34 patients with BMEI characterized by MSs occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes‐and‐waves, or spikes‐and‐waves. The interictal EEG was usually normal. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FSs was noted in 11 patients. Eleven patients had reflex MSs. Monotherapy with valproic acid was effective in 23 of 30 treated patients. The onset of epilepsy was known in all patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with the Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others.

Conclusions:BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes‐and‐waves, or spikes‐and‐waves. The interictal EEG was usually normal. Reflex MSs were frequently observed, suggesting that two distinctive syndromes are not necessary. BMEI may be followed by juvenile myoclonic epilepsy. Despite a generally favorable neuropsychological outcome, mental retardation can be observed more frequently than in the general population.
Postsurgical Outcome in Pediatric Patients with Epilepsy: A Comparison of Patients with Intellectual Disabilities, Subaverage Intelligence, and Average‐Range Intelligence
Authors: Gleissner Ulrike , Clusmann Hans , Sassen Robert , Elger Christian E. , Helmstaedter Christoph
Published: February 2006

Summary: Purpose:Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents.

Methods:Pediatric patients with intellectual disabilities (IQ ≤ 70), subaverage intelligence (IQ between 71 and 85), or average‐range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66).

Results:No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I).

Conclusions:IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average‐range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent.
A Modified Atkins Diet Is Effective for the Treatment of Intractable Pediatric Epilepsy
Authors: Kossoff Eric H. , McGrogan Jane R. , Bluml Renee M. , Pillas Diana J. , Rubenstein James E. , Vining Eileen P.
Published: February 2006

Summary:  Purpose: The Atkins diet may induce ketosis as does the ketogenic diet, without restrictions on calories, fluids, protein, or need for an inpatient fast and admission. Our objective was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy.

Methods: Twenty children were treated prospectively in a hospital‐based ambulatory clinic from September 2003 to May 2005. Children aged 3–18 years, with at least three seizures per week, who had been treated with at least two anticonvulsants, were enrolled and received the diet over a 6‐month period. Carbohydrates were initially limited to 10 g/day, and fats were encouraged. Parents measured urinary ketones semiweekly and recorded seizures daily. All children received vitamin and calcium supplementation.

Results: In all children, at least moderate urinary ketosis developed within 4 days (mean, 1.9). Sixteen (80%) completed the 6‐month study; 14 chose to remain on the diet afterward. At 6 months, 13 (65%) had >50% improvement, and seven (35%) had >90% improvement (four were seizure free). Mean seizure frequency after 6 months was 40 per week (p = 0.005). Over a 6‐month period, mean serum blood urea nitrogen increased from 12 to 17 mg/dl (p = 0.01); creatinine was unchanged. Cholesterol increased from 192 to 221 mg/dl, (p = 0.06). Weight did not change significantly (34.0–33.7 kg); only six children lost weight. A stable body mass index over time correlated with >90% improvement (p = 0.004).

Conclusions: A modified Atkins diet is an effective and well‐tolerated therapy for intractable pediatric epilepsy.
The Outcome of Children with Intractable Seizures: A 3‐ to 6‐Year Follow‐up of 67 Children Who Remained on the Ketogenic Diet Less Than One Year
Authors: Marsh Elisabeth B. , Freeman John M. , Kossoff Eric H. , Vining Eileen P. G. , Rubenstein James E. , Pyzik Paula L. , Hemingway Cheryl
Published: February 2006

Summary: Purpose:To determine the long‐term outcome of children with difficult‐to‐control seizures who remained on the ketogenic diet for <1 year.

Methods:Between 1994 and 1996, 150 children with epilepsy, refractory to at least two medications, initiated the ketogenic diet according to the Hopkins protocol. Three to six years after diet initiation, all the families were contacted by telephone or questionnaire to assess their child's current seizure status, medications, and therapies.

Results:Sixty‐seven children discontinued the diet within 1 year of initiation. Follow‐up data were available for 54 of these children. Ten subsequently had surgery, and three underwent VNS implantation. These operated‐on children were significantly more likely to be >50% controlled at follow‐up than were those managed with medications alone (p < 0.05). A statistically significant difference in long‐term outcome was noted between those who responded while on the diet, even if they discontinued it before 1 year, and those who did not (p < 0.05), but no statistical correlation was found between length of time that they had remained on the diet and long‐term prognosis.

Conclusions:Almost half of the children who discontinued the diet during the first year had a decrease in seizures when assessed 3–6 years later. Twenty‐two percent of these had become seizure free without surgery. We were unable to ascertain whether this may have been due to new medications. Those who saw some improvement while on the diet were more likely to have a favorable long‐term outcome. Resective surgery, in children who were candidates, or vagal nerve stimulation (VNS) implantation, was more likely to result in significant seizure improvement than was management with medications alone. Whether or not the diet was effective, most families did not regret trying it and would recommend it to others.
Lack of Association between a GABAB Receptor 1 Gene Polymorphism and Temporal Lobe Epilepsy
Authors: Stogmann Elisabeth , Zimprich Alexander , Baumgartner Christoph , Gleiss Andreas , Zimprich Fritz
Published: February 2006

Summary:  Purpose: Recently a coding nonsynonymous single‐nucleotide polymorphism (SNP; G1465A) in the GABBR1 gene was reported to be associated with the incidence and severity of temporal lobe epilepsy (TLE). To clarify the role of this polymorphism in TLE, we attempted to replicate this study.

Methods: We genotyped 188 unrelated patients with TLE (110 women, 78 men) and 259 controls of middle European descent by a restriction‐length polymerase chain reaction (PCR) assay.

Results: Only two (0.5%) patients and none of the controls exhibited the heterozygous A/G genotype, which was previously reported to be overrepresented among patients as compared with controls.

Conclusions: Although our study was sufficiently powered, we could not replicate the original association. Potential reasons for this failure could lie in subtle genetic differences between the studied populations or differences in the TLE phenotypes.
Linking Generalized Spike‐and‐Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures
Authors: Laufs Helmut , Lengler Ulrike , Hamandi Khalid , Kleinschmidt Andreas , Krakow Karsten
Published: February 2006

Summary:  Purpose: To illustrate a functional interpretation of blood oxygen level–dependent (BOLD) signal changes associated with generalized spike‐and‐wave discharges in patients with absence seizures and to demonstrate the reproducibility of these findings in one case.

Methods: In a 47 year‐old patient with frequent absence seizures, BOLD signal changes during generalized spike‐and‐wave discharges (GSWD) were mapped by using simultaneous and continuous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) at 1.5 T and 6 months later at 3 T. GSWDs were modeled as individual events and as blocks.

Results: The patient studied exhibited frequent generalized spike–wave activity with temporal properties ideal for study with EEG/fMRI. Highly reproducible GSWD‐associated fMRI signal decreases (deactivations) were seen in bilateral frontal and temporoparietal cortices and the precuneus, in addition to activations in occipital cortex and, at 3 T, the posterior thalamus.

Conclusions: The GSWD‐associated changes seen here involve cortical regions that have been shown to be more active at conscious rest compared with sleep and with various types of extroverted perception and action. These regions have been proposed to constitute the core of a functional “default mode” system. We propose that the findings of deactivation of this distributed brain system during GSWDs mirrors the clinical manifestation of GSWDs (i.e., absence seizures). Furthermore, we suggest that these deactivations may reflect the functional consequences of GSWDs on physiologic brain activity at rest rather than direct hemodynamic correlates of epileptic discharges.
Structural Constraints for Alcohol‐Stimulated Ca2+Release in Neural Crest, and Dual Agonist/Antagonist Properties ofn‐Octanol
Authors: Garic‐Stankovic Ana , Hernandez Marcos , Flentke George R. , Smith Susan M.
Published: February 2006

Background:Prenatal ethanol exposure is a leading cause of mental retardation. Alcohol damages susceptible neuronal populations through its alteration of signaling pathways that direct cellular activity and survival. In early neural crest cells, ethanol elicits an intracellular Ca2+transient that is necessary and sufficient to cause apoptosis. We tested the hypothesis that ethanol's activity represents a saturable and selective effect of alcohols upon this pathway.

Methods:Fura‐2–loaded chick embryos, at the 3‐somite stage, were exposed ton‐alcohols ranging in size from ethanol (C2) to decanol (C10). Thereafter, Ca2+mobilization was measured using Fura‐2 and ratiometric imaging. Apoptosis was assessed using acridine orange uptake.

Results:Ethanol caused the dose‐dependent mobilization of intracellular Ca2+within neural crest populations, with an EC50of 52.0 mM.n‐Alcohols displayed increasing potency for Ca2+mobilization through pentanol. Hexanol and heptanol were inactive. Unexpectedly, micromolarn‐octanol concentrations triggered significant Ca2+release and apoptosis in a G‐protein–dependent manner. Decanol was inactive. Coaddition of either octanol or decanol antagonized the ability of ethanol to stimulate Ca2+release.

Conclusions:The selective, saturable effect ofn‐alcohols upon Ca2+mobilization in neural crest is consistent with a hypothesis that ethanol stimulates these signals through specific interaction with one or more alcohol‐binding sites on a target protein. Octanol may overcome structural constraints imposed upon C6 and C7 in interacting with this protein target; alternatively, it may interact through a unique binding site.
Understanding and Treating Alcohol Dependence
Authors: Johnson Bankole A. , Koob George F. , Schuckit Marc A. , Mason Barbara J. , Ait‐Daoud Nassima
Published: February 2006

This article represents the proceedings of a symposium presented at the 158th Annual Meeting of the American Psychiatric Association held in Atlanta, Georgia, on May 24, 2005. The organizer/chairman was Bankole A. Johnson, DSc, MD, PhD. The presentations included the following: (1) Neuropharmacological Basis of Alcohol Dependence, by George F. Koob, PhD; (2) Recent Developments in the Genetics of Alcohol Dependence, by Marc A. Schuckit, MD; (3) New Pharmacological Strategies for Treating Alcohol Dependence, by Barbara J. Mason, PhD; (4) New Medications: The Use of Anticonvulsants, Both Alone and in Combination, with Various Forms of Psychotherapy, by Bankole A. Johnson, DSc, MD, PhD; and (5) Differential Effects of Pharmacological Agents on Craving, by Nassima Ait‐Daoud, MD.