Perspective: Vagal nerve stimulation in the treatment of new-onset refractory status epilepticus

IntroductionResistance to drug therapy is a major hurdle in new-onset refractory status epilepticus (NORSE) treatment and there is urgent need to develop new treatment approaches. Non-drug approaches such as neuromodulation offer significant benefits and should be investigated as new adjunct treatment modalities. An important unanswered question is whether desynchronizing networks by vagal nerve stimulation (VNS) may improve seizure control in NORSE patients.Main textWe present a summary of published NORSE cases treated with VNS and our own data, discuss possible mechanisms of action, review VNS implantation timing, stimulation setting titration protocols and outcomes. Further, we propose avenues for future research.DiscussionWe advocate for consideration of VNS for NORSE both in early and late stages of the presentation and hypothesize a possible additional benefit from implantation in the acute phase of the disease. This should be pursued in the context of a clinical trial, harmonizing inclusion criteria, accuracy of documentation and treatment protocols. A study planned within our UK-wide NORSE-UK network will answer the question if VNS may confer benefits in aborting unremitting status epilepticus, modulate ictogenesis and reduce long-term chronic seizure burden

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In the present study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence

Language, Religion, and Ethnic Civil War

Are certain ethnic cleavages more conflict-prone than others? While only few scholars focus on the contents of ethnicity, most of those who do argue that political violence is more likely to occur along religious divisions than linguistic ones. We challenge this claim by analyzing the path from linguistic differences to ethnic civil war along three theoretical steps: (1) the perception of grievances by group members, (2) rebel mobilization, and (3) government accommodation of rebel demands. Our argument is tested with a new data set of ethnic cleavages that records multiple linguistic and religious segments for ethnic groups from 1946 to 2009. Adopting a relational perspective, we assess ethnic differences between potential challengers and the politically dominant group in each country. Our findings indicate that intrastate conflict is more likely within linguistic dyads than among religious ones. Moreover, we find no support for the thesis that Muslim groups are particularly conflict-prone

Craton Destruction 2:Evolution of Cratonic Lithosphere after a Rapid Keel Delamination Event

Cratonic lithosphere beneath the eastern North China Craton has undergone extensive destruction since early Jurassic times (approximately 190Ma). This is recorded in its episodic tectonic and magmatic history. In this time, its lithosphere changed thickness from approximately 200km to <60km. This change was associated with a peak time (approximately 120Ma) of lithospheric thinning and magmatism that was linked with high surface heat flow recorded in rift basins. We believe that these records are best explained by a two-stage evolutionary process. First, approximately 100km of cratonic keel underlying a weak midlithospheric discontinuity layer (approximately 80-100km) was rapidly removed in <10-20Ma. This keel delamination stage was followed by a protracted (approximately 50-100Ma) period of convective erosion and/or lithospheric extension that thinned the remaining lithosphere and continuously reworked the former cratonic lithospheric mantle. This study focuses on numerical exploration of the well-recorded second stage of the eastern North China Craton's lithospheric evolution. We find that (1) lithospheric mantle capped by thick crust can be locally replaced by deeper mantle material in 100Ma due to small-scale convective erosion; (2) asthenospheric upwelling and related extension can replace lithospheric mantle over horizontal length scales of 50-150km, and account for observed mushroom-shaped low-velocity structures; (3) modeling shows conditions that could lead to the multiple eastern North China Craton magmatic pulses between 190 and 115Ma that are associated with temporal and spatial changes in magma source petrology and a magmatic hiatus; and (4) a wet midlithospheric discontinuity layer provides a potential source material for on-craton magmatism

Modeling Craton Destruction by Hydration‐Induced Weakening of the Upper Mantle

Growing evidence shows that lithospheric mantle beneath cratons may contain a certain amount of water that originated from dehydration of subducted slabs or mantle metasomatism. As water can significantly reduce the viscosity of nominally anhydrous minerals such as olivine, hydration‐induced rheological weakening is a possible mechanism for the lithospheric thinning of cratons. Using 2‐D thermomechanical numerical models, we investigated the influence of water on dislocation and diffusion creep of olivine during the evolution of cratonic lithosphere. Modeling results indicate that dislocation creep of wet olivine alone is insufficient to trigger dramatic lithospheric thinning within a timescale of tens of millions of years, even with an extremely high water content. However, if diffusion creep is incorporated, significant convective instability will occur at the base of the lithosphere and drive lithospheric mantle dripping, which results in intense lithospheric thinning. We performed semianalytical models to better understand the influence of various parameters on the onset of convective instability. The convective instability promoted by hydration weakening drives lithospheric mantle dripping beneath cratons and thus provides a possible mechanism for cratonic thinning

Data_Sheet_1_Perspective: Vagal nerve stimulation in the treatment of new-onset refractory status epilepticus.PDF

IntroductionResistance to drug therapy is a major hurdle in new-onset refractory status epilepticus (NORSE) treatment and there is urgent need to develop new treatment approaches. Non-drug approaches such as neuromodulation offer significant benefits and should be investigated as new adjunct treatment modalities. An important unanswered question is whether desynchronizing networks by vagal nerve stimulation (VNS) may improve seizure control in NORSE patients.Main textWe present a summary of published NORSE cases treated with VNS and our own data, discuss possible mechanisms of action, review VNS implantation timing, stimulation setting titration protocols and outcomes. Further, we propose avenues for future research.DiscussionWe advocate for consideration of VNS for NORSE both in early and late stages of the presentation and hypothesize a possible additional benefit from implantation in the acute phase of the disease. This should be pursued in the context of a clinical trial, harmonizing inclusion criteria, accuracy of documentation and treatment protocols. A study planned within our UK-wide NORSE-UK network will answer the question if VNS may confer benefits in aborting unremitting status epilepticus, modulate ictogenesis and reduce long-term chronic seizure burden.</p