Cytoprotective Agents in Stroke: Still Uncertainty in the Next Frontier.

INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Early Postmarket Results with EmboTrap II Stent Retriever for Mechanical Thrombectomy: A Multicenter Experience.

BACKGROUND AND PURPOSE: EmboTrap II is a novel stent retriever with a dual-layer design and distal mesh designed for acute ischemic stroke emergent large-vessel occlusions. We present the first postmarket prospective multicenter experience with the EmboTrap II stent retriever. MATERIALS AND METHODS: A prospective registry of patients treated with EmboTrap II at 7 centers following FDA approval was maintained with baseline patient characteristics, treatment details, and clinical/radiographic follow-up. RESULTS: Seventy patients were treated with EmboTrap II (mean age, 69.9 years; 48.6% women). Intravenous thrombolysis was given in 34.3%, and emergent large-vessel occlusions were located in the ICA (n = 18), M1 (n = 38), M2 or M3 (n = 13), and basilar artery (n = 1). The 5 × 33 mm device was used in 88% of cases. TICI ≥ 2b recanalization was achieved in 95.7% (82.3% in EmboTrap II-only cases), and first-pass efficacy was achieved in 35.7%. The NIHSS score improved from a preoperative average of 16.3 to 12.1 postprocedure and to 10.5 at discharge. An average of 2.5 [SD, 1.8] passes was recorded per treatment, including non-EmboTrap attempts. Definitive treatment was performed with an alternative device (aspiration or stent retriever) in 9 cases (12.9%). Some hemorrhagic conversion was noted in 22.9% of cases, of which 4.3% were symptomatic. There were no device-related complications. CONCLUSIONS: Initial postmarket results with the EmboTrap II stent retriever are favorable and comparable with those of other commercially available stent retrievers. Compared with EmboTrap II, the first-generation EmboTrap may have a higher first-pass efficacy; however, data are limited by retrospective case analysis, incomplete clinical follow-up, and small sample size, necessitating future trials.

Correlation between Clinical Outcomes and Baseline CT and CT Angiographic Findings in the SWIFT PRIME Trial.

BACKGROUND AND PURPOSE: Patient selection for endovascular therapy remains a great challenge in clinic practice. We sought to determine the effect of baseline CT and angiography on outcomes in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial and to identify patients who would benefit from endovascular stroke therapy. MATERIALS AND METHODS: The primary end point was a 90-day modified Rankin Scale score of 0-2. Subgroup and classification and regression tree analysis was performed on baseline ASPECTS, site of occlusion, clot length, collateral status, and onset-to-treatment time. RESULTS: Smaller baseline infarct (n = 145) (ASPECTS 8-10) was associated with better outcomes in patients treated with thrombectomy versus IV tPA alone (66% versus 41%; rate ratio, 1.62) compared with patients with larger baseline infarcts (n = 44) (ASPECTS 6-7) (42% versus 21%; rate ratio, 1.98). The benefit of thrombectomy over IV tPA alone did not differ significantly by ASPECTS. Stratification by occlusion location also showed benefit with thrombectomy across all groups. Improved outcomes after thrombectomy occurred in patients with clot lengths of ≥8 mm (71% versus 43%; rate ratio, 1.67). Outcomes stratified by collateral status had a benefit with thrombectomy across all groups: none-fair collaterals (33% versus 0%), good collaterals (58% versus 44%), and excellent collaterals (82% versus 28%). Using a 3-level classification and regression tree analysis, we observed optimal outcomes in patients with favorable baseline ASPECTS, complete/near-complete recanalization (TICI 2b/3), and early treatment (mean mRS, 1.35 versus 3.73), while univariate and multivariate logistic regression showed significantly better results in patients with higher ASPECTS. CONCLUSIONS: While benefit was seen with endovascular therapy across multiple subgroups, the greatest response was observed in patients with a small baseline core infarct, excellent collaterals, and early treatment.

Revascularization grading in endovascular acute ischemic stroke therapy.

BACKGROUND: Recanalization and angiographic reperfusion are key elements to successful endovascular and interventional acute ischemic stroke (AIS) therapy. Intravenous recombinant tissue plasminogen activator (rt-PA), the only established revascularization therapy approved by the US Food & Drug Administration for AIS, may be less effective for large artery occlusion. Thus, there is enthusiasm for endovascular revascularization therapies, which likely provide higher recanalization rates, and trials are ongoing to determine clinical efficacy and compare various methods. It is anticipated that clinical efficacy will be well correlated with revascularization of viable tissue in a timely manner. METHOD: Reporting, interpretation, and comparison of the various revascularization grading methods require agreement on measurement criteria, reproducibility, ease of use, and correlation with clinical outcome. These parameters were reviewed by performing a Medline literature search from 1965 to 2011. This review critically evaluates current revascularization grading systems. RESULTS AND CONCLUSION: The most commonly used revascularization grading methods in AIS interventional therapy trials are the thrombolysis in cerebral ischemia (TICI, pronounced "tissy") and thrombolysis in myocardial ischemia (TIMI) scores. Until further technical and imaging advances can incorporate real-time reliable perfusion studies in the angio-suite to delineate regional perfusion more accurately, the TICI grading system is the best defined and most widely used scheme. Other grading systems may be used for research and correlation purposes. A new scale that combines primary site occlusion, lesion location, and perfusion should be explored in the future.

Nicotine and estrogen synergistically exacerbate cerebral ischemic injury.

The greater incidence of myocardial infarction, cardiac arrest, and ischemic stroke among women who smoke and use oral contraception (OC) compared to women who do not smoke and who do or do not use OC may be due in part to how nicotine influences endocrine function in women. For example, we recently demonstrated that chronic exposure to nicotine, the addictive agent in tobacco smoke responsible for the elevated risk of cardiac arrest, abolishes the endogenous or exogenous 17ß-estradiol-conferred protection of the hippocampus against global cerebral ischemia (a potential outcome of cardiac arrest) in naive or ovariectomized female rats. In the current study we examined the hypotheses that (1) a synergistic deleterious effect of nicotine plus oral contraceptives exacerbates post-ischemic hippocampal damage in female rats, and (2) nicotine directly inhibits estrogen-mediated intracellular signaling in the hippocampus. To test first hypothesis and to simulate smoking behavior-induced nicotine levels in the human body, we implanted osmotic pumps containing nicotine in the female rats for 16 days. Furthermore, we mimicked the use of oral contraceptives in females by administering oral contraceptives orally to the rat. Rats exposed to either nicotine alone or in combination with oral contraceptives were subjected to an episode of cerebral ischemia and the resultant brain damage was quantified. These results showed for the first time that nicotine with oral contraceptives did indeed exacerbate post-ischemic CA1 damage as compared to nicotine alone in naive female rats. In ex vivo hippocampal slice cultures, we found that nicotine alone or with 17ß-estradiol directly hinders estrogen receptors-mediated phosphorylation of cyclic-AMP element binding protein, a process required for neuronal survival and also exacerbates ischemic damage. Thus, nicotine can affect the outcome of cerebral ischemia by influencing brain endocrine function directly rather than through indirect systemic effects.

Endovascular mechanical thrombectomy of an occluded superior division branch of the left MCA for acute cardioembolic stroke.

Cardiac embolism accounts for a large proportion of ischemic stroke. Revascularization using systemic or intra-arterial thrombolysis is associated with increasing risks of cerebral hemorrhage as time passes from stroke onset. We report successful mechanical thrombectomy from a distal branch of the middle cerebral artery (MCA) using a novel technique. A 72-year old man suffered an acute ischemic stroke from an echocardiographically proven ventricular thrombus due to a recent myocardial infarction. Intraarterial administration of 4 mg rt-PA initiated at 5.7 hours post-ictus failed to recanalize an occluded superior division branch of the left MCA. At 6 hours, symptomatic embolic occlusion persisted. Mechanical extraction of the clot using an Attracter-18 device (Target Therapeutics, Freemont, CA) resulted in immediate recanalization of the MCA branch. Attracter-18 for acute occlusion of MCA branches may be considered in selected patients who fail conventional thrombolysis or are nearing closure of the therapeutic window for use of thrombolytic agents.

Metoclopramide for preventing pneumonia in critically ill patients receiving enteral tube feeding: a randomized controlled trial.

OBJECTIVE: To determine whether metoclopramide prevents nosocomial pneumonia in intensive care unit (ICU) patients receiving enteral feeding by a nasogastric tube. DESIGN: Prospective, randomized, controlled trial. SETTING: ICU of a university hospital. PATIENTS: A total of 305 consecutive patients requiring placement of a nasogastric tube for >24 hrs. INTERVENTIONS: Patients were randomized to receive either 10 mg of metoclopramide or placebo at 8-hr intervals through the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: A total of 174 patients received placebo and 131 received metoclopramide. Baseline characteristics in the two treatment groups were comparable. Of the 305 patients, 46 developed nosocomial pneumonia, which was 24 patients (13.7%) in the placebo group and 22 (16.8%) in the metoclopramide group (p > .05). Patients in the placebo group developed pneumonia earlier than patients receiving metoclopramide (4.46+/-1.72 days [mean +/- SD[rsqb] after ICU admission compared with 5.95+/-1.78 days; p = .006). Subgroup analysis showed that metoclopramide did not reduce the frequency rate of pneumonia in patients with tracheal intubation (19 [25.3%] of 75 patients receiving metoclopramide vs. 21 [21.2%] of 99 patients receiving placebo) or those receiving mechanical ventilation (17 [25.6%] of 58 patients receiving metoclopramide vs. 20 [29.3%] of 78 patients receiving placebo). The mortality rate also did not differ in the two treatments groups (56% in the metoclopramide group vs. 53% in the placebo group; p > .05). CONCLUSIONS: Although metoclopramide delayed the development of nosocomial pneumonia, it did not decrease its frequency rate and had no effect on the mortality rate in critically ill patients receiving nasogastric enteral feeding.

Ultrastructural, cell culture and karyotype study of bone marrow in a patient with congenital dyserythropoietic anaemia (CDA)-type III presenting with recurrent still-births.

A 28 year old female patients presented with refractory anaemia since childhood and recurrent still-births at 28-30 weeks of gestation. One still-born child was hydropic at birth. Bone marrow showed characteristic morphological changes of congenital dyserythropoietic anaemia (CDA)-Type III. Electron microscopy showed disruption of the nuclear membrane, spongy appearance of nuclei, stacks of microtubules in intermediate normoblasts and myelin figures in erythroid cells. In vitro culture and karyotype data from the bone marrow of the patient is presented. Recurrent still-births in association with congenital dyserythropoietic anaemia has rarely been reported in the literature.

A patient with congenital dyserythropoietic anaemia type III presenting with stillbirths.

A 28-year-old female patient presented with recurrent stillbirths between 28 and 30 weeks of gestation. At least one of the stillborn was hydropic at birth; alpha-thalassaemia and Rh isoimmunisation were ruled out. The patient was found to be suffering from congenital dyserythropoietic anaemia (CDA) type III, a rare form of congenital anaemia inherited as an autosomal dominant character in some families. It is tempting to speculate that at least the hydropic stillborn inherited the same disorder from the mother. CDA type III as a cause of hydrops fetalis has not been reported in the literature. The patient, who was transfusion-dependent, underwent splenectomy. Subsequently she did not need any transfusion for the last 6 months.