Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis

BACKGROUND Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate VRS to their histopathologic signature. METHODS In a cohort study comprising 142 MS patients and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) outcomes. Findings were corroborated in a validation cohort comprising 63 MS patients. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. FINDINGS In our actively treated clinical cohort, the count of dilated centrum semiovale VRS was associated with increased T1 and T2 lesion volumes. There was no systematic spatial colocalization of dilated VRS with MS lesions. At tissue level, VRS mostly corresponded to arteries and were not associated with MS pathological hallmarks. Interestingly, in our ex vivo cohort comprising mostly progressive MS patients, dilated VRS in MS were associated with signs of small vessel disease. INTERPRETATION Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with an accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature. FUNDING NIH, Swedish Society for Medical Research, Swiss National Science Foundation and University of Zurich

Novel (Hetero)arylalkenyl propargylamine compounds are protective in toxin-induced models of Parkinson's disease

Background: Mitochondrial dysfunction, oxidative stress and their interplay are core pathological features of Parkinson's disease. In dopaminergic neurons, monoamines and their metabolites provide an additional source of reactive free radicals during their breakdown by monoamine oxidase or auto-oxidation. Moreover, mitochondrial dysfunction and oxidative stress have a supraadditive impact on the pathological, cytoplasmic accumulation of dopamine and its subsequent release. Here we report the effects of a novel series of potent and selective MAO-B inhibitory (hetero)arylalkenylpropargylamine compounds having protective properties against the supraadditive effect of mitochondrial dysfunction and oxidative stress. Results: The (hetero)arylalkenylpropargylamines were tested in vitro, on acute rat striatal slices, pretreated with the complex I inhibitor rotenone and in vivo, using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced acute, subchronic, and chronic experimental models of Parkinson's disease in mice. The compounds exhibited consistent protective effects against i) in vitro oxidative stress induced pathological dopamine release and the formation of toxic dopamine quinone in the rat striatum and rescued tyrosine hydroxylase positive neurons in the substantia nigra after rotenone treatment; ii) in vivo MPTP-induced striatal dopamine depletion and motor dysfunction in mice using acute and subchronic, delayed application protocols. One compound (SZV558) was also examined and proved to be protective in a chronic mouse model of MPTP plus probenecid (MPTPp) administration, which induces a progressive loss of nigrostriatal dopaminergic neurons. Conclusions: Simultaneous inhibition of MAO-B and oxidative stress induced pathological dopamine release by the novel propargylamines is protective in animal models and seems a plausible strategy to combat Parkinson's disease

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH

COVID-19 and Neurointerventional Service Worldwide: A Survey of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana De Neuroradiologia Diagnostica Y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN)

BACKGROUND This survey was focused on the provision of neurointerventional services, the current practices of managing patients under COVID-19 conditions, and the expectations for the future. METHODS Invitations for this survey were sent out as a collaborative effort of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana de Neuroradiologia Diagnostica y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN). RESULTS Overall, 475 participants from 61 countries responded (six from Africa (1%), 81 from Asia (17%), 156 from Europe (33%), 53 from Latin America (11%), and 172 from North America (11%)). The majority of participants (96%) reported being able to provide emergency services, though 26% of these reported limited resources. A decrease in emergency procedures was reported by 69% of participants (52% in ischemic and hemorrhagic stroke, 11% ischemic, and 6% hemorrhagic stroke alone). Only 4% reported an increase in emergency cases. The emerging need for social distancing and the rapid adoption of remote communication was reflected in the interest in establishing case discussion forums (43%), general online forums (37%), and access to angio video streaming for live mentoring and support (33%). CONCLUSION Neurointerventional emergency services are available in almost all centers, while the number of emergency patients is markedly decreased. Half of the participants have abandoned neurointerventions in non-emergent situations. There are considerable variations in the management of neurointerventions and in the expectations for the future

Crustal constraint through complete model space screening for diverse geophysical datasets facilitated by emulation

Deep crustal constraint is often carried out using deterministic inverse methods, sometimes using seismic refraction, gravity and electromagnetic datasets in a complementary or “joint” scheme. With increasingly powerful parallel computer systems it is now possible to apply joint inversion schemes to derive an optimum model from diverse input data. These methods are highly effective where the uncertainty in the system is small. However, given the complex nature of these schemes it is often difficult to discern the uniqueness of the output model given the noise in the data, and the application of necessary regularization and weighting in the inversion process means that the extent of user prejudice pertaining to the final result may be unclear. We can rigorously address the subject of uncertainty using standard statistical tools but these methods also become less feasible if the prior model space is large or the forward simulations are computationally expensive. We present a simple Monte Carlo scheme to screen model space in a fully joint fashion, in which we replace the forward simulation with a fast and uncertainty-calibrated mathematical function, or emulator. This emulator is used as a proxy to run the very large number of models necessary to fully explore the plausible model space. We develop the method using a simple synthetic dataset then demonstrate its use on a joint data set comprising first-arrival seismic refraction, MT and scalar gravity data over a diapiric salt body. This study demonstrates both the value of a forward Monte Carlo approach (as distinct from a search-based or conventional inverse approach) in incorporating all kinds of uncertainty in the modelling process, exploring the entire model space, and shows the potential value of applying emulator technology throughout geophysics. Though the target here is relatively shallow, the methodology can be readily extended to address the whole crust

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe