Epileptic falls and gait disturbance in two young children with a sharp wave focus at the vertex: a variant of benign partial epilepsy of childhood?

We describe two young children who presented with frequent falls and myoclonic jerks affecting the trunk and legs associated with a sharp and slow wave epileptic focus at the vertex. The initial neurological examination and brain magnetic resonance imaging were normal. Both patients had a persistent gait dysfunction, sometimes asymmetrical, fluctuating with the intensity of the epilepsy and the electroencephalogram abnormalities. The localization of the epileptic focus at the vertex, corresponding to the motor control of the legs and trunk, can explain this peculiar semiology. The seizures were difficult to treat, but one patient is currently in remission. Although epileptic falls are most often a feature of severe epilepsies of childhood, we think that these two patients present a variant of benign partial epilepsy of childhood.     

Therapeutic gîtes in child psychiatry

Therapeutic g?tes in child psychiatry. A therapeutic stay in a g?te is a project led by a multidisciplinary team. It enables children to experiment with the notion of pleasure and to develop their level of socialisation, their personality and their independence, outside the family environment. For caregivers, it provides a rich source of clinical material and strengthens the team dynamics.     

Enhanced visual functioning in autism: an ALE meta-analysis

Autistics often exhibit enhanced perceptual abilities when engaged in visual search, visual discrimination, and embedded figure detection. In similar fashion, while performing a range of perceptual or cognitive tasks, autistics display stronger physiological engagement of the visual system than do non-autistics. To account for these findings, the Enhanced Perceptual Functioning Model proposes that enhanced autistic performance in basic perceptual tasks results from stronger engagement of sensory processing mechanisms, a situation that may facilitate an atypically prominent role for perceptual mechanisms in supporting cognition. Using quantitative meta-analysis of published functional imaging studies from which Activation Likelihood Estimation maps were computed, we asked whether autism is associated with enhanced task-related activity for a broad range of visual tasks. To determine whether atypical engagement of visual processing is a general or domain-specific phenomenon, we examined three different visual processing domains: faces, objects, and words. Overall, we observed more activity in autistics compared to non-autistics in temporal, occipital, and parietal regions. In contrast, autistics exhibited less activity in frontal cortex. The spatial distribution of the observed differential between-group patterns varied across processing domains. Autism may be characterized by enhanced functional resource allocation in regions associated with visual processing and expertise. Atypical adult organizational patterns may reflect underlying differences in developmental neural plasticity that can result in aspects of the autistic phenotype, including enhanced visual skills, atypical face processing, and hyperlexia.     

Neuropeptide Y promotes neurogenesis and protection against methamphetamine-induced toxicity in mouse dentate gyrus-derived neurosphere cultures

Methamphetamine (METH) is a psychostimulant drug of abuse that causes severe brain damage. However, the mechanisms responsible for these effects are poorly understood, particularly regarding the impact of METH on hippocampal neurogenesis. Moreover, neuropeptide Y (NPY) is known to be neuroprotective under several pathological conditions. Here, we investigated the effect of METH on dentate gyrus (DG) neurogenesis, regarding cell death, proliferation and differentiation, as well as the role of NPY by itself and against METH-induced toxicity. DG-derived neurosphere cultures were used to evaluate the effect of METH or NPY on cell death, proliferation or neuronal differentiation. Moreover, the role of NPY and its receptors (Y(1), Y(2) and Y(5)) was investigated under conditions of METH-induced DG cell death. METH-induced cell death by both apoptosis and necrosis at concentrations above 10 nM, without affecting cell proliferation. Furthermore, at a non-toxic concentration (1 nM), METH decreased neuronal differentiation. NPY's protective effect was mainly due to the reduction of glutamate release, and it also increased DG cell proliferation and neuronal differentiation via Y(1) receptors. In addition, while the activation of Y(1) or Y(2) receptors was able to prevent METH-induced cell death, the Y(1) subtype alone was responsible for blocking the decrease in neuronal differentiation induced by the drug. Taken together, METH negatively affects DG cell viability and neurogenesis, and NPY is revealed to be a promising protective tool against the deleterious effects of METH on hippocampal neurogenesis.     

Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer

We performed a phase I trial of FANG vaccine, an autologous tumor-based product incorporating a plasmid encoding granulocyte-macrophage colony-stimulating factor (GMCSF) and a novel bifunctional short hairpin RNAi (bi-shRNAi) targeting furin convertase, thereby downregulating endogenous immunosuppressive transforming growth factors (TGF) β1 and β2. Patients with advanced cancer received up to 12 monthly intradermal injections of FANG vaccine (1 × 10(7) or 2.5 × 10(7) cells/ml injection). GMCSF, TGFβ1, TGFβ2, and furin proteins were quantified by enzyme-linked immunosorbent assay (ELISA). Safety and response were monitored. Vaccine manufacturing was successful in 42 of 46 patients of whom 27 received ≥1 vaccine. There were no treatment-related serious adverse events. Most common grade 1, 2 adverse events included local induration (n = 14) and local erythema (n = 11) at injection site. Post-transfection mean product expression GMCSF increased from 7.3 to 1,108 pg/10(6) cells/ml. Mean TGFβ1 and β2 effective target knockdown was 93.5 and 92.5% from baseline, respectively. Positive enzyme-linked immunospot (ELISPOT) response at month 4 was demonstrated in 9 of 18 patients serially assessed and correlated with survival duration from time of treatment (P = 0.025). Neither dose-adverse event nor dose-response relationship was noted. In conclusion, FANG vaccine was safe and elicited an immune response correlating with prolonged survival. Phase II assessment is justified.     

Drug safety evaluation of rotigotine

INTRODUCTION: Rotigotine, a non-ergolinic dopamine-receptor agonist, is currently approved as monotherapy in early idiopathic Parkinson's disease (IPD), in moderate to severe idiopathic restless legs syndrome (RLS) and as adjunct therapy to levodopa in advanced IPD. Randomized, double-blind, placebo-controlled, as well as open-label studies were conducted in IPD and RLS patients to evaluate the efficacy, tolerability and safety of rotigotine in dosages up to 16 mg/24 h. Overall, these trials have shown that rotigotine has a similar adverse event (AE) profile as other non-ergolinic dopamine agonists such as pramipexole or ropinirole, inducing typical dopaminergic effects like nausea, daytime somnolence, peripheral edema or impulse control disorders. In addition, the most common AE seen with transdermal delivery of rotigotine are local skin reactions, which may lead to a treatment discontinuation in approximately 8% of patients. AREAS COVERED: This review outlines Phase II and III trials that were published between 2003 and 2011. The focus of this review is on the safety profile of rotigotine but it also goes into detail about clinical trial data, pharmacokinetics and pharmacodynamics. EXPERT OPINION: The emergent safety profile is similar to other non-ergolinic dopamine agonists. In addition, transdermal delivery is associated with local skin reactions, which are usually mild but may lead to a treatment discontinuation in a minority of patients.     

A new model for preclinical testing of dermal substitutes for human skin reconstruction

Background

Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage.

Methods

Bioengineered grafts consisting of collagen type I hydrogels with incorporated human fibroblasts and human keratinocytes seeded on these gels were produced. Two different dermal substitutes, namely Matriderm^®, and an acellular collagen type I hydrogel, were applied onto full-thickness skin wounds created on the back of immuno-incompetent rats. As control, no dermal substitute was used. As coverage for the dermal substitutes either the bioengineered grafts were used, or, as controls, human split-thickness skin or neonatal rat epidermis were used. Grafts were excised 21 days post-transplantation. Histology and immunofluorescence was performed to investigate survival, epidermis formation, and vascularization of the grafts.

Results

The bioengineered grafts survived on all tested dermal substitutes. Epidermis formation and vascularization were comparable to the controls.

Conclusion

We could successfully use human bioengineered grafts to test different dermal substitutes. This novel model can be used to investigate newly designed dermal substitutes in detail and in a standardized way.