Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma.

Background: Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear.

Methods: In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for surgical evacuation to undergo middle meningeal artery embolization plus surgery (treatment group) or surgery alone (control group).

Thrombectomy With the pRESET vs Solitaire Stent Retrievers as First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial.

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking.

Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever.

Infarct Evolution on MR-DWI After Thrombectomy in Acute Stroke Patients Randomized to Nerinetide or Placebo: The REPERFUSE-NA1 Study.

Background And Objectives: The neuroprotectant nerinetide has shown promise in reducing infarct volumes in primate models of ischemia reperfusion. We hypothesized that early secondary infarct growth after endovascular therapy (EVT) (1) may be a suitable surrogate biomarker for testing neuroprotective compounds, (2) is feasible to assess in the acute setting using sequential MRI, and (3) can be modified by treatment with nerinetide.

Methods: REPERFUSE-NA1 was a prospective, multisite MRI substudy of the randomized controlled trial ESCAPE-NA1 (ClinicalTrials.

Assessment of Discrepancies Between Follow-up Infarct Volume and 90-Day Outcomes Among Patients With Ischemic Stroke Who Received Endovascular Therapy.

Importance: Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes.

Objective: To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome.

COVID-19 Impact on Acute Ischemic Stroke Treatment at 9 Comprehensive Stroke Centers across Los Angeles.

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC).

Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution.

Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection.

Background: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

Rationale: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery.

Aim: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window.

Feasibility and utility of an integrated medical imaging and informatics smartphone system for management of acute stroke.

Background Rapid dissemination and coordination of clinical and imaging data among multidisciplinary team members are essential for optimal acute stroke care. Aim To characterize the feasibility and utility of the Synapse Emergency Room mobile (Synapse ERm) informatics system. Methods We implemented the Synapse ERm system for integration of clinical data, computerized tomography, magnetic resonance, and catheter angiographic imaging, and real-time stroke team communications, in consecutive acute neurovascular patients at a Comprehensive Stroke Center.

Use of perfusion imaging and other imaging techniques to assess risks/benefits of acute stroke interventions.

The advent of multimodal neuroimaging has provided acute stroke care providers with an armamentarium of sophisticated imaging options to utilize for guidance in clinical decision-making and management of acute ischemic stroke patients. Here, we propose a framework and potential algorithm-based methodology for imaging modality selection and utilization for the purpose of achieving optimal stroke clinical care. We first review imaging options that may best inform decision-making regarding revascularization eligibility, with a focus on the imaging modalities that best identify critical inclusion and exclusion criteria.

Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray.

A form of aversively motivated learning called fear conditioning occurs when a neutral conditioned stimulus is paired with an aversive unconditioned stimulus (UCS). UCS-evoked depolarization of amygdala neurons may instruct Hebbian plasticity that stores memories of the conditioned stimulus-unconditioned stimulus association, but the origin of UCS inputs to the amygdala is unknown. Theory and evidence suggest that instructive UCS inputs to the amygdala will be inhibited when the UCS is expected, but this has not been found during fear conditioning.

Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats.

Several sodium channel blockers are used clinically to treat neuropathic pain. However, many patients fail to achieve adequate pain relief from these highly brain-penetrant drugs because of dose-limiting central nervous system side effects. Here, we describe the functional properties of trans-N-{[2'-(aminosulfonyl)biphenyl-4-yl]methyl}-N-methyl-N'-[4-(trifluoromethoxy)benzyl]cyclopentane-1,2-dicarboxamide (CDA54), a peripherally acting sodium channel blocker.

Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain.

A new series of voltage-gated sodium channel blockers with potential for treatment of chronic pain is reported. Systematic structure-activity relationship studies, starting with compound 1, led to identification of potent analogs that displayed use-dependent block of sodium channels, were efficacious in pain models in vivo, and most importantly, were devoid of activity against the cardiac potassium channel hERG.

Unilateral storage of fear memories by the amygdala.

Pavlovian fear conditioning is an associative learning task in which subjects are trained to respond defensively to a neutral conditioned stimulus (CS) by pairing it with an aversive unconditioned stimulus (US). This type of learning depends critically on the amygdala, and evidence suggests that synaptic plasticity within the lateral nucleus of the amygdala (LA) may be responsible for storing memories of the CS-US association. In the present study, we trained rats to fear an auditory CS by pairing it with a shock US delivered to one eyelid.

The behavioral and neuroanatomical effects of IB4-saporin treatment in rat models of nociceptive and neuropathic pain.

One distinguishing feature of primary afferent neurons is their ability to bind the lectin IB(4). Previous work suggested that neurons in the inner part of lamina II (IIi), onto which IB(4)-positive sensory neurons project, facilitate nociceptive transmission following tissue or nerve injury. Using an IB(4)-saporin conjugate (IB(4)-SAP), we examined the contribution of IB(4)-positive neurons to nociceptive processing in rats with and without nerve injury.