bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent progress in migraine pathophysiology: role of cortical spreading depression and magnetic resonance imaging
Authors: Bhaskar Sonu , Saeidi Kolsoum , Borhani Parvin , Amiri Houshang
Published: October 2013

Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among pain disorders in clinical conditions. We critically evaluate the scientific basis of various theories concerning migraine pathophysiology, and draw insights from brain imaging approaches that have unraveled the prevalence of cortical spreading depression (CSD) in migraine. The findings supporting the role of CSD as a physiological substrate in clinical pain are discussed. We also give an exhaustive overview of brain imaging approaches that have been employed to solve the genesis of migraine pain, and its possible links to the brainstem, the neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic hypersensitivity). Furthermore, a roadmap is proposed to provide a better understanding of pain pathophysiology in migraine, to enable the development of strategies using leads from brain imaging studies for the identification of early biomarkers, efficient prognosis, and treatment planning, which eventually may help in alleviating some of the devastating impact of pain morbidity in patients afflicted with migraine.
Multiple sessions of transcranial direct current stimulation to the intact hemisphere improves visual function after unilateral ablation of visual cortex
Authors: Rushmore R. J. , DeSimone C. , Valero‐Cabré A.
Published: October 2013

Damage to cerebral systems is frequently followed by the emergence of compensatory mechanisms, which serve to reduce the effects of brain damage and allow recovery of function. Intrinsic recovery, however, is rarely complete. Non‐invasive brain stimulation technologies have the potential to actively shape neural circuits and enhance recovery from brain damage. In this study, a stable deficit for detecting and orienting to visual stimuli presented in the contralesional visual hemifield was generated by producing unilateral brain damage of the right posterior parietal and contiguous visual cortical areas. A long regimen of inhibitory non‐invasive transcranial direct‐current stimulation (cathodal tDCS, 2 mA, 20 min) was applied to the contralateral (intact) posterior parietal cortex over 14 weeks (total of 70 sessions, one per day, 5 days per week) and behavioral outcomes were periodically assessed. In three out of four stimulated cats, lasting recovery of visuospatial function was observed. Recovery started after 2–3 weeks of stimulation, and recovered targets were located first in the periphery, and moved to more central visual field locations with the accrual of stimulation sessions. Recovery for moving tasks followed a biphasic pattern before reaching plateau levels. Recovery did not occur for more difficult visual tasks. These findings highlight the ability of multiple sessions of transcranial direct‐current stimulation to produce recovery of visuospatial function after unilateral brain damage.
Avoidance‐based human Pavlovian‐to‐instrumental transfer
Authors: Lewis Andrea H. , Niznikiewicz Michael A. , Delamater Andrew R. , Delgado Mauricio R.
Published: October 2013

The Pavlovian‐to‐instrumental transfer (PIT) paradigm probes the influence of Pavlovian cues over instrumentally learned behavior. The paradigm has been used extensively to probe basic cognitive and motivational processes in studies of animal learning. More recently, PIT and its underlying neural basis have been extended to investigations in humans. These initial neuroimaging studies of PIT have focused on the influence of appetitively conditioned stimuli on instrumental responses maintained by positive reinforcement, and highlight the involvement of the striatum. In the current study, we sought to understand the neural correlates of PIT in an aversive Pavlovian learning situation when instrumental responding was maintained through negative reinforcement. Participants exhibited specific PIT, wherein selective increases in instrumental responding to conditioned stimuli occurred when the stimulus signaled a specific aversive outcome whose omission negatively reinforced the instrumental response. Additionally, a general PIT effect was observed such that when a stimulus was associated with a different aversive outcome than was used to negatively reinforce instrumental behavior, the presence of that stimulus caused a non‐selective increase in overall instrumental responding. Both specific and general PIT behavioral effects correlated with increased activation in corticostriatal circuitry, particularly in the striatum, a region involved in cognitive and motivational processes. These results suggest that avoidance‐based PIT utilizes a similar neural mechanism to that seen with PIT in an appetitive context, which has implications for understanding mechanisms of drug‐seeking behavior during addiction and relapse.
Transporter‐mediated replacement of extracellular glutamate for GABA in the developing murine neocortex
Authors: Unichenko Petr , Dvorzhak Anton , Kirischuk Sergei
Published: October 2013

During early development, cortical neurons migrate from their places of origin to their final destinations where they differentiate and establish synaptic connections. During corticogenesis, radially migrating cells move from deeper zone to the marginal zone, but they do not invade the latter. This “stop” function of the marginal zone is mediated by a number of factors, including glutamate and γ‐aminobutyric acid (GABA), two main neurotransmitters in the central nervous system. In the marginal zone, GABA has been shown to be released via GABA transporters (GAT)‐2/3, whereas glutamate transporters (EAATs) operate in the uptake mode. In this study, GABAergic postsynaptic currents (GPSCs) were recorded from Cajal‐Retzius cells in the marginal zone of murine neonatal neocortex using a whole‐cell patch‐clamp technique. Minimal electrical stimulation was applied to elicit evoked GPSCs using a paired‐pulse protocol. EAAT blockade with dl‐threo‐b‐benzyloxyaspartic acid (dl‐TBOA), a specific non‐transportable EAAT antagonist, abolishes constitutive GAT‐2/3‐mediated GABA release. In contrast to dl‐TBOA, d‐aspartate, an EAAT substrate, fails to block GAT‐2/3‐mediated GABA release. SNAP‐5114, a specific GAT‐2/3 antagonist, induced an elevation of intracellular sodium concentration ([Na+]i) under resting conditions and in the presence of d‐aspartate, indicating that GAT‐2/3 operates in reverse mode. In the presence of dl‐TBOA, however, SNAP‐5114 elicited a [Na+]i decrease, demonstrating that GAT‐2/3 operates in uptake mode. We conclude that EAATs via intracellular Na+ signaling and/or cell depolarization can govern the strength/direction of GAT‐mediated GABA transport.
Phagocytic microglial phenotype induced by glibenclamide improves functional recovery but worsens hyperalgesia after spinal cord injury in adult rats
Authors: Redondo‐Castro Elena , Hernández Joaquim , Mahy Nicole , Navarro Xavier
Published: October 2013

Microglial cell plays a crucial role in the development and establishment of chronic neuropathic pain after spinal cord injuries. As neuropathic pain is refractory to many treatments and some drugs only present partial efficacy, it is essential to study new targets and mechanisms to ameliorate pain signs. For this reason we have used glibenclamide (GB), a blocker of KATP channels that are over expressed in microglia under activation conditions. GB has already been used to trigger the early scavenger activity of microglia, so we administer it to promote a better removal of dead cells and myelin debris and support the microglia neuroprotective phenotype. Our results indicate that a single dose of GB (1 μg) injected after spinal cord injury is sufficient to promote long‐lasting functional improvements in locomotion and coordination. Nevertheless, the Randall–Selitto test measurements indicate that these improvements are accompanied by enhanced mechanical hyperalgesia. In vitro results indicate that GB may influence microglial phagocytosis and therefore this action may be at the basis of the results obtained in vivo.
Experimental evidence that evolutionary relatedness does not affect the ecological mechanisms of coexistence in freshwater green algae
Authors: Narwani Anita , Alexandrou Markos A. , Oakley Todd H. , Carroll Ian T. , Cardinale Bradley J.
Published: October 2013

The coexistence of competing species depends on the balance between their fitness differences, which determine their competitive inequalities, and their niche differences, which stabilise their competitive interactions. Darwin proposed that evolution causes species' niches to diverge, but the influence of evolution on relative fitness differences, and the importance of both niche and fitness differences in determining coexistence have not yet been studied together. We tested whether the phylogenetic distances between species of green freshwater algae determined their abilities to coexist in a microcosm experiment. We found that niche differences were more important in explaining coexistence than relative fitness differences, and that phylogenetic distance had no effect on either coexistence or on the sizes of niche and fitness differences. These results were corroborated by an analysis of the frequency of the co‐occurrence of 325 pairwise combinations of algal taxa in > 1100 lakes across North America. Phylogenetic distance may not explain the coexistence of freshwater green algae.
High frequency of intrathecal immunoglobulin synthesis in epilepsy so far classified cryptogenic
Authors: Kowski A. B. , Volz M. S. , Holtkamp M. , Prüss H.
Published: October 2013

Background and purpose

The influence of the immune system on seizures and epileptogenesis has been increasingly considered, in particular the role of autoantibodies. In this study, we aimed to determine the frequency of intrathecal antibody synthesis in the cerebrospinal fluid (CSF) compartment of patients with epilepsy.

Methods

In a retrospective cohort study trial in a university hospital neurology department, 164 well‐characterized patients with different etiologies of seizures and epilepsies, and 77 control patients were included.

Results

CSF‐specific immunoglobulin (IgG, IgM and IgA) synthesis was significantly (P < 0.0001) more frequent in patients with epilepsy (34.1%) compared with age‐ and sex‐matched controls (2.6%). The highest incidence of intrathecal Ig synthesis was detected in patients with encephalitis‐related acute symptomatic seizures (86.7%), but also in patients with focal epilepsy so far classified cryptogenic (45.2%). Antibody synthesis was not related to the number of CSF white blood cells.

Conclusions

Humoral immune activation in the CSF compartment was detected in one‐third of patients with epilepsy, besides acute symptomatic seizures particularly frequent in cryptogenic epilepsy – an etiology so far defined as not having a detectable cause. Systematic prospective clinical and experimental trials are required to identify antigenic targets and select appropriate patients for which immunotherapy might offer new causal therapeutic options.
Lipid profile and thyroid hormone concentrations in children with epilepsy treated with oxcarbazepine monotherapy: a prospective long‐term study
Authors: Garoufi A. , Koemtzidou E. , Katsarou E. , Dinopoulos A. , Kalimeraki I. , Fotinou A. , Drakatos A. , Attilakos A.
Published: October 2013

Background and purpose

To evaluate prospectively the changes and possible associations in lipid and thyroid profiles in children treated with oxcarbazepine (OXC) monotherapy.

Methods

Serum total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TGs), lipoprotein (a) [Lp(a)], free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and gamma‐glutamyltransferase (GGT) concentrations were measured in 23 children with epilepsy, before and at 8 and 18 months of OXC monotherapy.

Results

Total cholesterol was significantly increased at 8 months (P = 0.033), whereas LDL‐C was significantly increased at 8 and 18 months (P < 0.001 and P = 0.004, respectively) of treatment. Lp(a) was significantly increased at 8 months (P = 0.042) and borderline significantly increased at 18 months (P = 0.050) of treatment. FT4 was significantly decreased at 8 and 18 months (P < 0.001 and P = 0.002, respectively), and TSH levels were significantly increased at 8 and 18 months (P = 0.002 and P = 0.001, respectively) of OXC monotherapy. GGT levels were significantly increased at 8 and 18 months (P < 0.001) of treatment. There were no significant alterations in HDL‐C, TGs and FT3 levels during the study. Significant positive correlations were found between GGT and LDL‐C levels at 8 (r = 0.468, P = 0.024) and 18 months (r = 0.498, P = 0.016), and between TSH and TC at 18 months (r = 0.508, P = 0.013) of treatment.

Conclusions

OXC monotherapy may cause significant and persistent alterations in lipid and thyroid profiles in children with epilepsy. The increase in LDL‐C and TC levels may be associated with liver enzymes induction and thyroid dysfunction. Further long‐term prospective studies are required to confirm these findings and to determine their clinical significance.
Diabetes and thrombolysis for acute stroke: a clear benefit for diabetics
Authors: Reiter M. , Teuschl Y. , Matz K. , Seyfang L. , Brainin M. ,   the Austrian Stroke Unit Registry Collaborators
Published: October 2013

Background and purpose

Diabetes is a predictor for poor outcome after thrombolysis in stroke patients, and early post‐stroke glycaemia is associated with higher rates of post‐thrombolytic symptomatic intracerebral haemorrhages (SICHs). Diabetic stroke patients may nevertheless profit from thrombolysis. Here, we compared outcome data of matched thrombolysed and non‐thrombolysed diabetic and non‐diabetic stroke patients from a national database.

Methods

The outcomes of 1079 matched quadruples, each consisting of a thrombolysed diabetic, a non‐thrombolysed diabetic, a thrombolysed non‐diabetic and a non‐thrombolysed non‐diabetic case (a total of 4316 cases), enrolled in the Austrian Stroke Unit Registry (2004–2013), were compared. Patients were matched according to sex, age, stroke severity, pre‐stroke disability and prior stroke.

Results

A regression model with improvement as depending variable found no effect of diabetes (P = 0.158) or the interaction diabetes × thrombolysis (P = 0.507), whereas the effect of thrombolysis itself was highly significant (P < 0.001). Functional outcome (modified Rankin Scale) was significantly better in thrombolysed than in non‐thrombolysed diabetic patients at discharge from the stroke‐unit (P < 0.001) and 3 months later (P = 0.006). No significant differences were found in the number of SICHs after thrombolytic treatment between diabetic (4.9%) and non‐diabetic strokes (3.5%). Both groups had a higher risk of SICH compared with the non‐thrombolysed groups (diabetics 2.6%, non‐diabetics 2.5%). Due to lack of documentation, the effect of admission blood glucose on SICH was not investigated.

Conclusions

Data from this nationwide survey show that diabetic stroke patients receive a substantial benefit from thrombolysis, and therefore diabetic strokes should not be excluded from thrombolytic treatment.
Change in take‐off elevation angle after limb autotomy mitigates the reduction in jumping distance in rice grasshoppers Oxya yezoensis
Authors: Tsurui Kaori , Narita Shota , Iwatani Yasushi , Honma Atsushi
Published: October 2013

Autotomy is the ability to spontaneously self‐amputate a limb or other appendage, often as a reflexive action. This limb amputation typically occurs as a specialized defensive response to an attack from a predator and thereby enables the prey to escape from predation. Despite the benefits of escape, autotomized organisms lose the body part and its associated function. Here, we investigated the jumping behavior and performance of one‐leg‐autotomized and intact rice grasshoppers, Oxya yezoensis, to examine changes in jumping behavior after autotomy. The take‐off elevation of autotomized grasshoppers was 7.8° lower than in intact grasshoppers, resulting in nearly a 45° angle of take‐off, which maximized the jumping distance. Kinematic analyses of the jumping manner revealed that the angle of the femur during jumping differed between intact and autotomized grasshoppers, suggesting that the grasshoppers behaviorally change the take‐off elevation after autotomy. According to analyses of jumping performance, the degree of decline in performance differed between horizontal distance and vertical height. Even though they jumped on only one hind leg, one‐leg‐autotomized grasshoppers realized 69% performance along a horizontal distance relative to intact grasshoppers. In contrast, autotomized grasshoppers realized only a 44% performance in vertical height compared to intact grasshoppers. The difference in take‐off elevation between autotomized and intact grasshoppers is likely related to the observed difference in the magnitude of the decline in performance between horizontal distance and vertical height. These results suggest that rice grasshoppers may alter their take‐off elevation after limb autotomy to minimize the reduction in jumping distance.
Predictors of seizure‐free outcome after epilepsy surgery for pediatric tuberous sclerosis complex
Authors: Krsek Pavel , Jahodova Alena , Kyncl Martin , Kudr Martin , Komarek Vladimir , Jezdik Petr , Jayakar Prasanna , Miller Ian , Korman Brandon , Rey Gustavo , Resnick Trevor , Duchowny Michael
Published: October 2013

Purpose

Variable predictors of postsurgical seizure outcome have been reported in children with tuberous sclerosis complex (TSC). We analyzed a large surgical series of pediatricTSCpatients in order to identify prognostic factors crucial for selection of subjects for epilepsy surgery.

Methods

Thirty‐three children withTSCwho underwent excisional epilepsy surgery atMiamiChildren'sHospital were retrospectively reviewed. A total of 29 clinical, neuropsychological, electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical variables were analyzed and related to seizure outcomes. UnivariateBarnard's exact test,Wilcoxon's rank‐sum test, and multivariate statisticalCox's model were used to examine the significance of associations between the variables and seizure outcome.

Key Findings

Eighteen patients (55%) have been seizure‐free 2 years after (final) surgery; postoperative complications occurred in five subjects (15%). Complete removal of epileptogenic tissue detected by bothMRIand intracranialEEG, regional scalp interictalEEGpatterns, and agreement of interictal and ictalEEGlocalization were the most powerful predictors of seizure‐free outcome. Other significant predictors included occurrence of regional scalp ictalEEGpatterns, fewer brain regions affected by tubers, presence of preoperative hemiparesis, and one‐stage surgery. Remaining factors such as age at seizure onset, incidence of infantile spasms or other seizure types, duration of epilepsy, seizure frequency, mental retardation, as well as types and extent of resections did not influence outcome.

Significance

Perioperative features rather than preoperative variables are the most important determinants of postsurgical seizure outcome in patients withTSC. Our findings may assist in the surgical management of these patients.
Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages
Authors: Wellmer Jörg , Quesada Carlos M. , Rothe Lars , Elger Christian E. , Bien Christian G. , Urbach Horst
Published: October 2013

Purpose

Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, “standard head” MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy‐specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers.

Methods

Based on a large European presurgical epilepsy program comprising 2,740 patients we identified the spectrum of common epileptogenic lesions and determine the set of MRI sequences that are required for their reliable detection. Relying on a series of small, therapeutically particularly relevant lesions we determined the required slices thickness, slice angulations, and orientations for an epilepsy‐specific MRI protocol.

Key Findings

Indispensable for early outpatient epilepsy specific MRI are fluid attenuated inversion recovery (FLAIR), T2‐weighted, T1‐weighted, and hemosiderin/calcification‐sensitive sequences. Slice thickness for T2 and FLAIR must not exceed 3 mm. The T1 image should be acquired in three‐dimensional technique at 1 mm isotropic voxels size. For T2 and FLAIR, at least two slice orientations each must be demanded in hippocampal angulation. We suggest no adaption to a clinical focus hypothesis. The resulting “essential 6” sequence protocol allows the detection of virtually all common epileptogenic lesion entities.

Significance

The creation of a broadly accepted and abundantly applied MRI protocol for epilepsy outpatients can contribute to improved and earlier identification of potential candidates for epilepsy surgery. Our systematic analysis of MRI requirements for the detection of epileptogenic lesions can serve as basis for protocol negotiations between epileptologists, radiologists, and health care funders.
The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy
Authors: Mohamed Ismail S. , Gibbs Steve A. , Robert Manon , Bouthillier Alain , Leroux Jean‐Maxime , Khoa Nguyen Dang
Published: October 2013

Purpose

To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular‐onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures.

Methods

We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275‐channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin.

Key Findings

Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients.

Significance

MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.
AMPA Receptor antagonist NBQX attenuates later‐life epileptic seizures and autistic‐like social deficits following neonatal seizures
Authors: Lippman‐Bell Jocelyn J. , Rakhade Sanjay N. , Klein Peter M. , Obeid Makram , Jackson Michele C. , Joseph Annelise , Jensen Frances E.
Published: October 2013

Purpose

To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mammalian target of rapamycin (mTOR) pathway activation and long‐term sequelae following neonatal seizures in rats, including later‐life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic‐like social deficits.

Methods

Long‐Evans rats experienced hypoxia‐induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12 h × 4 doses). Twelve hours post‐HS, we assessed mTOR activation marker phosphorylated p70‐S6 kinase (p‐p70S6K) in hippocampus and cortex of vehicle (HS + V) or NBQX‐treated post‐HS rats (HS + N) versus littermate controls (C + V). Spontaneous seizure activity was compared between groups by epidural cortical electroencephalography (EEG) at P70–100. Aberrant mossy fiber sprouting was measured using Timm staining. Finally, we assessed behavior between P30 and P38.

Key Findings

Postseizure NBQX treatment significantly attenuated seizure‐induced increases in p‐p70S6K in the hippocampus (p < 0.01) and cortex (p < 0.001). Although spontaneous recurrent seizures increased in adulthood in HS + V rats compared to controls (3.22 ± 1 seizures/h; p = 0.03), NBQX significantly attenuated later‐life seizures (0.14 ± 0.1 seizures/h; p = 0.046). HS + N rats showed less aberrant mossy fiber sprouting (115 ± 8.0%) than vehicle‐treated post‐HS rats (174 ± 10%, p = 0.004), compared to controls (normalized to 100%). Finally, NBQX treatment prevented alterations in later‐life social behavior; post‐HS rats showed significantly decreased preference for a novel over a familiar rat (71.0 ± 12 s) compared to controls (99.0 ± 15.6 s; p < 0.01), whereas HS + N rats showed social novelty preference similar to controls (114.3 ± 14.1 s).

Significance

Brief NBQX administration during the 48 h postseizure in P10 Long‐Evans rats suppresses transient mTOR pathway activation and attenuates spontaneous recurrent seizures, social preference deficits, and mossy fiber sprouting observed in vehicle‐treated adult rats after early life seizures. These results suggest that acute AMPAR antagonist treatment during the latent period immediately following neonatal HS can modify seizure‐induced activation of mTOR, reduce the frequency of later‐life seizures, and protect against CA3 mossy fiber sprouting and autistic‐like social deficits.
Enhancing medical compliance of patients with convulsive epilepsy in rural community: A randomized intervention trial
Authors: Li Juan , Si Yang , Hu Jia , Liu Ling , Deng Ying , He Jun , Zhang Ning‐Mei , Zhou Dong
Published: October 2013

Purpose

This randomized intervention trial was to determine whether the implementation of a practical intervention was effective in enhancing medical compliance and improving seizure control among patients with convulsive epilepsy in rural communities in western China.

Methods

Two of four areas were randomly selected for this study and assigned to be the intervention group (IG) and the control group (CG), respectively. An intervention package with four components (intensive education, consultation services, maintenance of an epilepsy tracking card, and repeated reminders) was formulated. Medical compliance included antiepileptic drug (AED) adherence and lifestyle; each was graded on a 6‐point scale with possible scores. Medical compliance and seizure control were measured and compared between the groups before and after the intervention. In addition, correlation of both changes in medical compliance and seizure frequency were investigated.

Key Findings

After 1‐year follow‐up, 183 patients in the IG (105 male) and 177 in the CG (99 male) remained for the analysis. At the end of the study, the average number of seizures in the IG declined 18.3% compared to that prior to the intervention (after 6‐month phenobarbital monotherapy), nearly twice as much as in CG (9.1%) with statistical difference (p = 0.023). The proportion of patients with a reduction in seizures >50% (including those who were seizure‐free) rose to 79.8% in the IG compared to 61.0% in the CG (p < 0.05). With regard to medical compliance, the majority of the IG members were rated as excellent or very good, but medical compliance remained nearly unchanged for the CG. A moderate correlation was found between the changes in AED adherence and seizure control (r = 0.4, p < 0.05), and a weaker correlation was found between lifestyle and seizure control (r = 0.328, p < 0.05).

Significance

This intervention package proved to be efficient in enhancing medical compliance and improving seizure control in rural communities of resource‐poor areas.
Clinical features, proximate causes, and consequences of active convulsive epilepsy inAfrica
Authors: Kariuki Symon M. , Matuja William , Akpalu Albert , Kakooza‐Mwesige Angelina , Chabi Martin , Wagner Ryan G. , Connor Myles , Chengo Eddie , Ngugi Anthony K. , Odhiambo Rachael , Bottomley Christian , White Steven , Sander Josemir W. , Neville Brian G. R. , Newton Charles R. J. C. ,   SEEDS writing group
Published: October 2013

Purpose

Epilepsy is common in sub‐SaharanAfrica (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital‐based, and few studies have compared different ecological sites inSSA. We described active convulsive epilepsy (ACE) identified in cross‐sectional community‐based surveys inSSA, to understand the proximate causes, features, and consequences.

Methods

We performed a detailed clinical and neurophysiologic description ofACEcases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites inAfrica:SouthAfrica;Tanzania;Uganda;Kenya; andGhana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities.

Key Findings

Half (51%) of the 2,170 people withACEwere children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% ofACEcases, and these varied significantly with site. Status epilepticus occurred in 25% of people withACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes ofACEwere adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences ofACEwere burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy.

Significance

There were significant differences in the comorbidities across sites. Focal features are common inACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people withACEand should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed.
Vertical perithalamic hemispherotomy: A single‐center experience in 40 pediatric patients with epilepsy
Authors: Dorfer Christian , Czech Thomas , Dressler Anastasia , Gröppel Gudrun , Mühlebner‐Fahrngruber Angelika , Novak Klaus , Reinprecht Andrea , Reiter‐Fink Edith , Traub‐Weidinger Tatjana , Feucht Martha
Published: October 2013

Purpose

The current concept for hemispherotomy includes various lateral techniques and the vertical perithalamic hemispherotomy introduced by Delalande in 1992. We have chosen the vertical approach because of advantages that possibly influence outcome: the possibility to completely disconnect the hemisphere at the level of the thalamus obviating both the need to resect the insula and the need to open and dissect the subarachnoid space of the Sylvian fissure.

Methods

We retrospectively analyzed prospectively collected data of all patients who underwent vertical hemispherotomy at the Vienna pediatric epilepsy center. Seizure outcome was classified according to the International League Against Epilepsy (ILAE) proposal 2001.

Key Findings

Follow‐up data of 40 patients (22 male/18 female; median age 5.5 years; range 4.4 months to 20.1 years) were analyzed. Hemispherotomy was left in 26 and right in 14 patients. The underlying pathology was ischemic vascular in 19, malformation of cortical development (MCD) in 11, and other pathology in 10. No serious intraoperative complications were encountered. Only two infants (5.0%) needed blood replacement. There was one death on the fourth day after surgery caused by intractable hyponatremic brain edema. Three patients developed cerebrospinal fluid (CSF) disturbances, but only one needed a permanent ventriculoperitoneal (VP) shunt (2.5%). For outcome analysis we included 37 of 40 children with at least 12 months of follow‐up. Thirty‐four (91.9%) of 37 children were seizure‐free (class 1a) after a median follow‐up time of 3.7 years (range 12 month to 14.8 years).

Significance

We confirm the efficacy and safety of vertical parasagittal hemispherotomy as described by Delalande in a consecutive series of patients treated at our center since 1998. In addition, complete disconnection of the hemisphere in patients with MCD and/or patients with significant involvement of the insula was possible without the complications usually reported with other techniques.
Evaluation of focus laterality in temporal lobe epilepsy: A quantitative study comparing double inversion‐recovery MR imaging at 3T with FDG‐PET
Authors: Morimoto Emiko , Okada Tomohisa , Kanagaki Mitsunori , Yamamoto Akira , Fushimi Yasutaka , Matsumoto Riki , Takaya Shigetoshi , Ikeda Akio , Kunieda Takeharu , Kikuchi Takayuki , Paul Dominik , Miyamoto Susumu , Takahashi Ryosuke , Togashi Kaori
Published: October 2013

Purpose

To quantitatively compare the diagnostic capability of double inversion‐recovery (DIR) with F‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE).

Methods

This study was approved by the institutional review board, and written informed consent was obtained. Fifteen patients with TLE and 38 healthy volunteers were enrolled. All magnetic resonance (MR) images were acquired using a 3T‐MRI system. Voxel‐based analysis (VBA) was conducted for FDG‐PET images and white matter segments of DIR images (DIR‐WM) focused on the whole temporal lobe (TL) and the anterior part of the temporal lobe (ATL). Distribution of hypometabolic areas on FDG‐PET and increased signal intensity areas on DIR‐WM were evaluated, and their laterality was compared with clinically determined seizure focus laterality. Correct diagnostic rates of laterality were evaluated, and agreement between DIR‐WM and FDG‐PET was assessed using κ statistics.

Key Findings

Increased signal intensity areas on DIR‐WM were located at the vicinity of the hypometabolic areas on FDG‐PET, especially in the ATL. Correct diagnostic rates of seizure focus laterality for DIR‐WM (0.80 and 0.67 for the TL and the ATL, respectively) were slightly higher than those for FDG‐PET (0.67 and 0.60 for the TL and the ATL, respectively). Agreement of laterality between DIR‐WM and FDG‐PET was substantial for the TL and almost perfect for the ATL (κ = 0.67 and 0.86, respectively).

Significance

High agreement in localization between DIR‐WM and FDG‐PET and nearly equivalent detectability of them show us an additional role of MRI in TLE.
Resting state networks in temporal lobe epilepsy
Authors: Cataldi Mauro , Avoli Massimo , de Villers‐Sidani Etienne
Published: October 2013

Temporal lobe epilepsy (TLE) is typically described as a neurologic disorder affecting a cerebral network comprising the hippocampus proper and several anatomically related extrahippocampal regions. A new level of complexity was recently added to the study of this disorder by the evidence that TLE also appears to chronically alter the activity of several brain‐wide neural networks involved in the control of higher order brain functions and not traditionally linked to epilepsy. Recently developed brain imaging techniques such as functional magnetic resonance imaging (fMRI) analysis of resting state connectivity, have greatly contributed to these observations by allowing the precise characterization of several brain networks with distinct functional signatures in the resting brain, and therefore also known as “resting state networks.” These significant advances in imaging represent an opportunity to investigate the still elusive origins of the disabling cognitive and psychiatric manifestations of TLE, and could have important implications for its pathophysiology and, perhaps, its therapy. Herein we review recent studies in this field by focusing on resting state networks that have been implicated in the pathophysiology of psychiatric disorders and cognitive impairment in patients with epilepsy: the default mode network, the attention network, and the reward/emotion network.
Preserving Socioemotional Wealth in Family Firms: Asset or Liability? The Moderating Role of Business Context
Authors: Naldi Lucia , Cennamo Carmelo , Corbetta Guido , Gomez–Mejia Luis
Published: October 2013

We ask whether choices aimed at preserving socioemotional wealth (SEW) represent an asset or a liability in family–controlled firms. Specifically, we consider one major SEW–preserving mechanism—having as chief executive officer (CEO) a member of the controlling family—and hypothesize that this choice is (1) an asset in business contexts, such as industrial districts, in which tacit rules and social norms are relatively more important, but (2) a potential liability in contexts like stock exchange markets, where formal regulations and transparency principles take center stage. The results from our empirical analysis confirm these hypotheses.
Family Business Survival and the Role of Boards
Authors: Wilson Nick , Wright Mike , Scholes Louise
Published: October 2013

We explore the vexing question of whether family firms are more likely to survive than nonfamily firms, focusing on the role of board composition. Utilizing a unique data set of over 700,000 private family and nonfamily firms in the U.K. during 2007–2010, we find that family firms are significantly less likely to fail than nonfamily firms. We identify the board characteristics associated with survival/failure in all firms and determine that it is these characteristics that are important in explaining the lower failure probability of family firms. We conclude with an agenda for further research on boards and family firm survival.
International Entrepreneurship and the Theory of the (Long–Lived) International Firm: A Capabilities Perspective
Authors: Al–Aali Abdulrahman , Teece David J.
Published: October 2013

This paper expands on the Oviatt–McDougall framework of sustainable international ventures. It does so by relating the elements of the framework to existing scholarship on the multinational enterprise (MNE), a category that encompasses foreign direct–invested new ventures (FDINVs). The paper then incorporates entrepreneurship and capabilities into MNE theory and applies them to the FDINV. Strong dynamic capabilities coupled with good strategy work together to generate and sustain superior enterprise performance in fast–moving global environments. The resulting framework is used to revisit key questions in MNE/FDINV research such as the timing and mode of FDI.
Evidence for Caste Differences in Anal Droplet Alarm Pheromone Production and Responses in the Eusocial Thrips Kladothrips intermedius
Authors: De Facci Monica , Svensson Glenn P. , Chapman Thomas W. , Anderbrant Olle
Published: October 2013

Thrips (Thysanoptera) are tiny insects that produce anal secretions when threatened. Several studies have shown that, depending on the species, the droplets may contain alarm pheromones and/or repellents against enemies. In the eusocial gall‐inducing thrips Kladothrips intermedius both larvae and adults produce such droplets. There are two castes of adults in this species, soldiers (the sub‐fertile and gall‐bound defenders) and dispersers (winged and capable of initiating a gall). We tested the proclivity of secreting anal droplets by the two castes and whether the anal droplets induce different behavioural responses in relation to the emitter–receiver's caste in a contact chemoreception bioassay. Although secretion patterns were similar between castes, exposure to anal droplets emitted by different castes elicited different behavioural responses in adults in the bioassay. When exposed to soldiers’ anal droplets, dispersers significantly reduced the distance moved while soldiers significantly increased the distance moved, compared to when they were exposed to hexane control. In contrast, no differences in the distance moved were observed for any caste when exposed to dispersers’ anal droplets versus hexane control. Increased activity in soldiers when exposed to their own anal droplets is a predicted response to enhance the overall defence of the gall when under threat, whereas dispersers should slow down their activity when exposed to such ‘warning signal’. Thus, the behavioural data indicate that the anal droplets emitted by soldiers are likely to contain an alarm pheromone.
Interpopulation Comparisons of Antipredator Defense Behavior of the Thorn‐Tailed Rayadito (Aphrastura spinicauda)
Authors: Ippi Silvina , van Dongen Wouter F. D. , Lazzoni Ilenia , Venegas Cristóbal I. , Vásquez Rodrigo A.
Published: October 2013

The high impact of predators on breeding success has favored the evolution of diverse behavioral strategies that enhance both individual survivorship and reproductive success. Self‐ and nest‐defense against predators are inter‐related behaviors that vary according to life history traits and the risks involved in defense. In addition, interpopulation differences in the composition of predator guilds, and hence predation pressures, may result in geographic variation in antipredator defense strategies. It is generally accepted that the absence of predators could drive the loss of antipredator behavior. However, it is unclear how species respond if one type of predator (e.g., a specialized nest predator) is absent but others are present. The multipredator hypothesis suggests that the absence of only a few predators is not sufficient to drive a change or loss of antipredator behavior in a species. We examined interpopulation variation in defense behavior in the thorn‐tailed rayadito (Aphrastura spinicauda), a suboscine bird inhabiting a wide latitudinal range in southern South America. In populations where nest predators were either present or absent, we examined the responses of rayaditos to an adult predator (an owl) and to a nest predator (a marsupial). Owl‐defense behavior involved more intense and longer responses than marsupial‐defense. This suggests that adult rayaditos may allocate more energy to defend themselves than their young. However, because the presence of adult predators near the nest also prevents parents from feeding the nestlings, owl‐defense may simultaneously represent a form of nest‐defense. No differences in marsupial‐defense were found among the three sampled populations, despite the absence of native mammalian nest predators in one population. The lack of variation in nest‐defense behavior provides some support for the multipredator hypothesis, although the high interpopulation gene flow in this species could also contribute to this behavior's maintenance.
Diagnosis, treatment and outcome of spinal lymphoma in a pony
Authors: Finding E. J. T. , Ciasca T. , Pinilla M. J. , Driver C. J. , Johns I. C. , Weller R. , Volk H. A.
Published: October 2013

This report describes the diagnostic approach to, and treatment of, a case of severe pelvic limb ataxia in a MiniatureShetland pony. Diagnosis of an intradural‐extramedullary lesion at the level ofT11–12 was made usingCTmyelography. Dorsolateral hemilaminectomy allowed surgical debulking of an intradural mass, diagnosed histopathologically asTcell richBcell lymphoma. Post operative treatment with prednisolone, cytarabine and cyclophosphamide was tolerated well and the degree of ataxia reduced markedly, allowing the pony to return to normal management.
Abortogenic viruses in horses
Authors: Bażanów B. A. , Jackulak N. A. , Frącka A. B. , Staroniewicz Z. M.
Published: October 2013

Viral causes of abortion include equine viral arteritis (EVA) and infection with equine herpesviruses‐1 and ‐4 (EHV‐1 andEHV‐4). Transmission of equine arteritis virus (EAV) occurs through respiratory, venereal or transplacental routes. Horizontal respiratory transmission ofEAVresults from exposure to infective nasopharyngeal secretions from acutely infected horses. For this transmission to occur, direct and close contact between horses is necessary. Venereal infection is an efficient method of transmission, with seroconversion of 85 to 100% of seronegative mares bred to virus shedding stallions. Asymptomatic carrier stallions are the essential natural reservoir of equine arteritis virus. Equine herpesviruses‐1 and ‐4 infect a susceptible host, replicate and establish a lifelong latent infection without any associated clinical signs. Reactivation of latent infections can result from factors such as stress and intercurrent disease. The control of these diseases is by implementation of appropriate management and hygiene measures, supplemented by vaccination and, in the case ofEVA, by the identification of persistently infected stallions, which can be removed from breeding or continue to be bred to if managed under controlled conditions to prevent the risk of an outbreak of the disease.
Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo
Authors: Steingräber Annika Kathrin , Schelhaas Sonja , Faust Andreas , Jacobs Andreas Hans , Schäfers Michael , Goerge Tobias
Published: October 2013

Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in vivo imaging. First, we analysed skin sections from patients suffering from leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked LcV in mice in a well‐studied model of immune complex‐mediated vasculitis (ICV). This acute inflammatory process was serially visualized in vivo using the fluorescence‐labelled MMP tracer Cy5.5‐AF443. The deposition of fluorescence‐labelled immune complexes and MMP tracer distribution was visualized repeatedly and non‐invasively by fluorescence reflectance imaging. In correlation with the presence of MMP‐2 and MMP‐9 in immunofluorescence stainings, Cy5.5‐AF443 accumulated in ICV spots in the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice equipped with a dorsal skinfold chamber, where microscopic observations revealed an increased recruitment of fluorescence‐labelled leucocytes during ICV. The specificity of the MMP tracer was supported by (i) analysis of mice deficient in functional β2‐integrins (CD18−/−) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β2‐mediated leucocyte recruitment. In summary, we show that MMPs are involved in ICV as determined by Cy5.5‐AF443, a new optical marker to longitudinally and non‐invasively follow MMP activity in acute skin inflammation in vivo.