Effect of balloon guide catheter on clinical outcomes and reperfusion in Trevo thrombectomy.

INTRODUCTION: The Solitaire stent retriever registry showed improved reperfusion, faster procedure times, and better outcome in acute stroke patients with large vessel occlusion treated with a balloon guide catheter (BGC) and Solitaire stent retriever compared with a conventional guide catheter. The goal of this study was to evaluate whether use of a BGC with the Trevo stent retriever improves outcomes compared with a conventional guide catheter. METHODS: The TRACK registry recruited 23 sites to submit demographic, clinical, and site adjudicated angiographic and outcome data on consecutive patients treated with the Trevo stent retriever. BGC use was at the discretion of the physician. RESULTS: 536 anterior circulation patients (of whom 279 (52.1%) had BGC placement) were included in this analysis. Baseline characteristics were notable for younger patients in the BGC group (65.4±15.3 vs 68.1±13.6, P=0.03) and lower rate of hypertension (72% vs 79%, P=0.06). Mean time from symptom onset to groin puncture was longer in the BGC group (357 vs 319 min, P=0.06).Thrombolysis in Cerebral Infarction 2b/3 scores were higher in the BGC cohort (84% vs 75.5%, P=0.01). There was no difference in reperfusion time, first pass effect, number of passes, or rescue therapy. Good clinical outcome at 3 months was superior in patients with BGC (57% vs 40%; P=0.0004) with a lower mortality rate (13% vs 23%, P=0.008). Multivariate analysis demonstrated that BGC use was an independent predictor of good clinical outcome (OR 2; 95% CI 1.3 to 3.1, P=0.001). CONCLUSIONS: In acute stroke patients presenting with anterior circulation large vessel occlusion, use of a BGC with the Trevo stent retriever resulted in improved reperfusion, improved clinical outcome, and lower mortality.

Factor VIII Level is Not Modifiable by Improved Glycemic Control in Patients with Ischemic Stroke.

AIMS: To determine whether the degree of glycemic control was related to change in Factor VIII (FVIII) level in patients with acute ischemic stroke (AIS). METHODS: From our stroke registry, all AIS patients admitted between 07/2008-05/2014 with baseline HbA1c and FVIII levels were eligible. Of these, patients with follow-up HbA1c and FVIII levels post-discharge were included. Elevation in FVIII was defined as level >150%. Diabetic control was categorized according to HbA1c levels:uncontrolled (>7.1%), controlled (5.7-7.0%), and normal (<5.7%) HbA1c and FVIII levels were further analyzed for evidence of a correlation as continuous variables. RESULTS: Among 1,631 AIS cases, 63 patients met inclusion criteria. Of these, 21 patients (33.3%) had uncontrolled diabetes, 27 patients (42.8%) had controlled diabetes, and 15 patients (23.4%) had normoglycemia. Baseline demographic characteristics differed only for history of hyperlipidemia (57.1% uncontrolled, 25.9% controlled, 26.7% normal, p=0.0443). Time between baseline and follow-up measures of both FVIII and HbA1c did not differ between groups (p=0.0812 and p=0.6969, respectively). There was no association between HbA1C group and FVIII level at baseline (p=0.2197) nor between change in HbA1c and change in FVIII from baseline to follow-up (r=0.0147, p=0.9092). Additionally, no statistically significant level at baseline or follow-up. CONCLUSIONS: While hyperglycemia and FVIII level are associated in the acute phase of AIS, long-term glycemic control before or subsequent to AIS was unrelated to FVIII level. Our results suggest that these stroke risk factors are independent of each other and that FVIII level cannot be modified by controlling diabetes.

Left Atrial Enlargement on Transthoracic Echocardiography Predicts Left Atrial Thrombus on Transesophageal Echocardiography in Ischemic Stroke Patients.

Background. Transesophageal echocardiogram (TEE) is superior to transthoracic echocardiogram (TTE) in detecting left atrial thrombus (LAT), a risk factor for stroke, but is costly and invasive, carrying a higher risk for complications. Aims. To determine the utility of using left atrial enlargement (LAE) on TTE to predict LAT on TEE. Methods. AIS patients who presented in 06/2008-7/2013 and underwent both TTE and TEE were identified from our prospective stroke registry. Analysis consisted of multivariate logistic regression with propensity score adjustment and receiver operating characteristic (ROC) area under the curve (AUC) analyses. Results. 219 AIS patients underwent both TTE and TEE. LAE on TTE was detected in 113 (51.6%) of AIS patients. Patients with LAE on TTE had higher proportion of LAT on TEE (8.4% versus 1.0%, p = 0.018). LAE on TTE predicted increased odds of LAT on TEE (OR = 8.83, 95% CI 1.04-74.83, p = 0.046). The sensitivity and specificity for LAT on TEE by LAE on TEE were 88.89% and 52.20%, respectively (AUC = 0.7054, 95% CI 0.5906-0.8202). Conclusions. LAE on TTE can predict LAT detected on TEE in nearly 90% of patients. This demonstrates the utility of LAE on TTE as a potential screening tool for LAT, potentially limiting unneeded costs and complications associated with TEE.

A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. METHODS: AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. RESULTS: Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. CONCLUSION: Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention.

Frontotemporal Dementia.

Frontotemporal dementia (FTD) is a not-uncommon explanation for progressive cognitive deficit in patients who often have a genetic susceptibility for such a neurodegenerative process. However, FTD does not seem to identify one particular pathogenetic mechanism but rather a spectrum of pathologies with particular predilection for the frontal and temporal lobes of the brain. There have been various subcategorizations of this form of dementia that have a tendency to be of earlier onset than typical Alzheimer disease and heralded by behavioral or communication manifestations. There is a behavioral variant and a language variant, referred to as primary progressive aphasia.

Resolution of internal carotid dissection with middle cerebral artery occlusion in pregnancy.

Introduction. Cervical artery dissection (CAD) is a common cause of stroke in younger patients. While the incidence of stroke in pregnancy is increasing, CAD remains a rare cause of ischemic stroke in the pregnant population, with only 30 cases described in the literature, most in the postpartum period. Methods. The case of a pregnant patient at 18 weeks of gestation presenting with CAD and ischemic stroke following intercourse is discussed. Discussion. CAD results from an intimal tear in the carotid artery, allowing accumulation of blood in the vessel wall. Stroke results from embolization of thrombogenic material in the wall. Etiology includes minor trauma, connective tissue disorders, or anatomic variations of the carotid artery. Most patients present with headache and/or neck pain, while ischemic symptoms are seen in at least 50% of patients. In the pregnant population, imaging with MRI or MRA of the head and neck aids in diagnosis. Once the diagnosis is made, patients are treated with either anticoagulation or antiplatelet medications. The optimal treatment in both pregnant and nonpregnant patients has not been well-studied. Conclusion. CAD is an important diagnosis to consider in a pregnant patient with persistent headache, especially if neurological symptoms are present. Imaging should be quickly obtained so treatment can be initiated.

Cryptogenic stroke: clinical consideration of a heterogeneous ischemic subtype.

BACKGROUND: Cryptogenic stroke can be subdivided into 3 distinct categories: stroke of no determined cause (CyNC), stroke due to multiple etiologies (Cy >1), and stroke etiology unclear due to incomplete evaluation. Although these subdivisions may be very different from one another with respect to baseline features and outcomes, they are often reported as a composite group in clinical trials. METHODS: Patients treated at our academic institution between July 2008 and June 2013 for acute ischemic stroke were retrospectively assessed in our prospective registry. CyNC and Cy >1 patients were compared to other Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes and to each other using univariate analyses and multivariate logistic regression. The primary outcome of interest was good functional outcome, defined as a discharge modified Rankin Scale score of 0-2. RESULTS: Of the 1311 included patients, 260 (19.8%) experienced a CyNC and 49 (3.7%) experienced a Cy >1. Cy >1 classification was associated with history of atrial fibrillation (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.16-6.12; P = .001). In comparison to other TOAST classifications, CyNC strokes were more likely to have good functional outcome (OR, 1.97; 95% CI, 1.38-2.82; P < .001) after adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, age, and intravenous tissue plasminogen activator (IV tPA). CONCLUSIONS: Even after adjusting for higher IV tPA treatment rates, ischemic stroke patients with no identified cause had better outcomes than other TOAST groups. Conversely, patients coded as cryptogenic with more than 1 likely cause represent a different patient subpopulation. These data argue against the consolidation of cryptogenic stroke subcategories in future investigations.

Trimming the fat in acute ischemic stroke: an assessment of 24-h CT scans in tPA patients.

BACKGROUND: International management of acute ischemic stroke patients treated with intravenous tissue plasminogen activator frequently includes 24-h head imaging. These recommendations stem from the National Institute of Neurological Disorders and Stroke (NINDS) clinical trial protocol regarding the risk of intracerebral hemorrhage post-tissue plasminogen activator administration. Follow-up computed tomography scans on select patients, however, may not effect clinical management, resulting in unnecessary radiation exposure and healthcare costs. AIMS: Our study questions the utility of routine 24-h computed tomography imaging and looks at the National Institute of Health Stroke Scale as a possible clinical screen for selecting candidates for 24-h imaging. Such a tool would result in decreased radiation exposure to the patient and decreased cost to the hospital. METHODS: Consecutive patients with acute ischemic stroke given intravenous tissue plasminogen activator between June 2008 and December 2011 were retrospectively identified and dichotomized based on change in 24-h National Institute of Health Stroke Scale from baseline. Initial analysis compared patients with National Institute of Health Stroke Scale worsening to those without worsening. Subsequent analysis was limited to patients with a baseline National Institute of Health Stroke Scale ≤10. Baseline demographics and medical history, baseline and 24-h computed tomography findings, medical and/or surgical orders within six-hours of imaging, and antithrombotic administration within 24-48-h postintravenous tissue plasminogen activator were compared between the two groups. RESULTS: Two-hundred patients met inclusion criteria: No 24-h National Institute of Health Stroke Scale worsening (n = 167) vs. 24-h National Institute of Health Stroke Scale worsening (n = 33). No baseline demographic or admission data differed significantly between the two groups. Patients without 24-h National Institute of Health Stroke Scale worsening had significantly lower incidence of hemorrhagic infarction (10·8% vs. 31·3%, P = 0·0014) on follow-up imaging. Less than 2% of all patients without 24-h National Institute of Health Stroke Scale worsening had a parenchymal hematoma. No patient with baseline National Institute of Health Stroke Scale ≤10 and without 24-h National Institute of Health Stroke Scale worsening had parenchymal hematoma. Patients with 24-h worsening were significantly less likely to receive timely antithrombotic therapy (60·6% vs. 77·8%, odds ratio 0·44, 95% confidence interval 0·20-0·96). CONCLUSIONS: Our results demonstrate that routine 24-h computed tomography scan in patients without 24-h National Institute of Health Stroke Scale worsening (especially those with baseline National Institute of Health Stroke Scale ≤10) is less likely to yield information that results in a deviation from standard acute stroke care. No patient without worsening and baseline National Institute of Health Stroke Scale ≤10 had parenchymal hematoma on 24-h computed tomography. Application of the National Institute of Health Stroke Scale to distinguish patients who should have 24-h follow-up imaging from those who will not benefit is a potential avenue for improving utilization of resources and warrants further study.

Decompressive hemicraniectomy with or without clot evacuation for large spontaneous supratentorial intracerebral hemorrhages.

OBJECTIVE: The management of patients with supra-tentorial intracerebral hemorrhage (ICH) remains controversial. Here we critically evaluate the safety, feasibility, and outcomes following decompressive hemicraniectomy (HC) with or without clot evacuation in the management of patients with large ICHs. METHODS: We analyzed data from 73 consecutive patients managed with a HC for a spontaneous ICH. All relevant patient variables at initial presentation and management were compiled. Variables were modeled as independent regressors against the three-month Glasgow Outcome Score using a multivariate logistic regression model. RESULTS: Over 7 years, HC was performed in 73 patients with clot evacuation in 86% and HC alone in 14%. The average ICH volume was 81 cc and the median HC surface area was 105 cm(2). 26 patients were comatose at initial presentation. Three-month functional outcomes were favorable in 29%, unfavorable in 44% and 27% of patients expired. Admission Glasgow Coma Scale (p = 0.003), dominant hemisphere ICH location (p = 0.01) and hematoma volume (p = 0.002) contributed significantly to the outcome, as estimated by a multivariate analysis. Eight surgical complications occurred. CONCLUSIONS: Early HC with or without clot evacuation is feasible and safe for managing spontaneous ICH. Our experience in this uncontrolled retrospective series, the largest such series in the modern era, suggests that it may be of particular benefit in patients with large non-dominant hemisphere ICH who are not moribund at presentation. Our findings suggest that a prospective randomized trial of HC vs. craniotomy for ICH be conducted.

Von Willebrand factor drives the association between elevated factor VIII and poor outcomes in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Despite clear roles of factor VIII (FVIII) and von Willebrand factor (vWF) in thrombosis, few studies have examined the relationship of these factors with acute ischemic stroke (AIS). We sought to determine whether concurrent elevation in FVIII and vWF was associated with adverse events and outcomes. METHODS: From our prospective stroke registry, patients consecutively admitted with AIS between July 2008 and October 2013 were included if both FVIII and vWF were measured during admission. The primary outcome was the modified Rankin Scale score on discharge. RESULTS: Among 1453 cases in our stroke registry, 148 patients with AIS met inclusion criteria; 62 patients (41.9%) had FVIII-/vWF-, 16 patients (10.8%) had FVIII+/vWF-, and 51 patients (34.5%) had FVIII+/vWF+. In the fully adjusted model, patients with FVIII+/vWF+ had increased odds of inpatient complications (odds ratio, 8.6; 95% confidence interval, 1.58-46.85; P=0.013) and neuroworsening (odds ratio, 3.2; 95% confidence interval, 1.18-8.73; P=0.022) than patients with FVIII-/vWF-. Adjusted for age, baseline stroke severity, and glucose, patients with FVIII+/vWF+ had increased odds of poor functional outcome (modified Rankin Scale>2; odds ratio, 2.87; 95% confidence interval, 1.16-7.06; P=0.021) than patients with FVIII-/vWF-. CONCLUSIONS: Concurrent FVIII/vWF elevation predicts higher odds of inpatient complications, neuroworsening, and worse functional outcomes for patients with AIS compared with patients with normal levels. Our findings suggest that FVIII and vWF levels may serve as clinically useful stroke biomarkers by providing risk profiles for patients with AIS.

Diagnosis and treatment of arterial dissections.

Dissections of the cervical and intracranial vessels represent an important source of stroke in those less than 50 years of age. This can occur spontaneously or following trauma, minor or major. Rapid diagnosis is essential to limit subsequent sequelae and modern computed tomographic angiography represents an appropriately sensitive modality. Treatment must be individualized to the patient and can consist of an antiplatelet regimen, anticoagulation, or endovascular intervention. No evidence demonstrates superiority of either medical modality and even aspirin alone may be efficacious. Consideration should be given to this in the multi-trauma population in which more aggressive anticoagulation is contraindicated. In addition, thrombolytic administration should not be withheld would it otherwise be indicated. Endovascular intervention is reserved for those with hemodynamically significant narrowing, enlarging pseudoaneurysms, fistulas formation, or subarachnoid hemorrhage.

New Thrombotic Events in Ischemic Stroke Patients with Elevated Factor VIII.

Background. Heightened levels of Factor VIII (FVIII) have been associated with both arterial and venous thrombosis. While elevated FVIII is common during acute ischemic stroke (AIS), whether elevated FVIII confers an increased risk for recurrent thrombotic events (RTEs) following AIS has not been previously explored. Methods. Consecutive AIS patients who presented to our center between July 2008 and September 2013 and had FVIII measured during admission were identified from our stroke registry. Baseline characteristics and the occurrence of RTE (recurrent or progressive ischemic stroke, DVT/PE, and MI) were compared in patients with and without elevated FVIII levels. Results. Of the 298 patients included, 203 (68.1%) had elevated FVIII levels. Patients with elevated FVIII had higher rates of any in-hospital RTE (18.7% versus 8.4%, P = 0.0218). This association remained after adjustment for baseline stroke severity and etiology (OR 1.01, 95% CI 1.00-1.01, P = 0.0013). Rates of major disability were also higher in patients who experienced a RTE (17.8% versus 3.2%, P < 0.0001). Conclusion. A significantly higher frequency of in-hospital RTEs occurred in AIS patients with elevated FVIII. The occurrence of such events was associated with higher morbidity. Further study is indicated to evaluate whether FVIII is a candidate biomarker for increased risk of RTEs following AIS.

Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC).

RATIONALE : Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. AIMS : The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. STUDY DESIGN : This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. OUTCOMES : The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

Overview of key factors in improving access to acute stroke care.

BACKGROUND: Despite recent advances in acute stroke therapy, only a small proportion of patients with acute ischemic stroke receive IV and endovascular revascularization therapies. This article provides an overview of factors influencing access to stroke therapy. METHODS: The key factors influencing access to stroke care highlighted during the Society of Vascular and Interventional Neurology (SVIN) roundtable meeting are summarized. Pertinent selected references on prehospital, hospital, and legislative and economic factors influencing access to stroke care, from the Medline database (between 1995 to 2011), are included. A brief summary of these key factors in improving access to stroke therapy is provided. RESULTS: Prehospital factors include the community; education of hospital administrators and health care personnel; dispatchers; the medical transport system; and preparedness and stroke education of emergency medical services (EMS). Stroke-ready hospitals and networking with other regional tertiary stroke hospitals play important roles in increasing access to stroke care. In addition, legislation at the state and federal levels is a key factor in providing high-quality, timely access to stroke care for the population in general. Strategies to facilitate access to stroke therapy are critical to improving mortality and functional outcome and increasing the proportion of patients treated by systemic thrombolysis and endovascular approaches. CONCLUSION: This is a brief overview and summary of selected factors influencing access to stroke care. These factors are divided into prehospital, hospital, legislative, and economic categories. Multilevel education of the population, public health care personnel, hospital preparedness, and legislative and economic factors are important in improving access to stroke care.

Acute ischemic stroke treated with intravenous tissue plasminogen activator in a patient taking dabigatran with radiographic evidence of recanalization.

Dabigatran etexelate is a new oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration to prevent stroke in patients with nonvalvular atrial fibrillation. A 51-year-old man with a history of atrial fibrillation who was taking dabigatran presented with an acute ischemic stroke. The patient had a normal international normalized ratio, activated partial thromboplastin time, and an elevated thrombin time of 26.4 seconds. Recanalization of the middle cerebral artery with intravenous tissue plasminogen activator was apparent on digital subtraction angiography, and there was no evidence of intracerebral hemorrhage on the repeat computed tomographic scan. This is the first report of a patient who was taking dabigatran etexilate and who had an ischemic stroke caused by a middle cerebral artery occlusion, with an elevated thrombin time and radiographic recanalization with intravenous tissue plasminogen activator without evidence of hemorrhagic transformation.

Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke.

BACKGROUND: Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. METHODS: SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. RESULTS: Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. DISCUSSION: In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients.

Intra-arterial delivery of cell therapies for stroke.

Cell therapy is a novel investigational approach to enhance stroke recovery. Intra-arterial (IA) delivery has the potential advantage of selectively targeting cell therapies to the ischemic brain tissue. Over the past 10 years, IA cell delivery has been under investigation in patients with cardiac and peripheral vascular disease, and these studies have reported promising results. This article reviews the trial methodology and procedural details of these studies and discusses the rationale and challenges in designing IA cell therapy trials for ischemic stroke.

Progenitor cell therapy for the treatment of central nervous system injury: a review of the state of current clinical trials.

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.

Current practice versus willingness to enroll in clinical trials: paradox among vascular neurologists about treatment for acute ischemic stroke.

BACKGROUND AND PURPOSE: Clinical trials are assessing the efficacy of fibrinolysis in extended time windows for acute ischemic stroke. METHODS: An Internet-based survey was sent to 400 US vascular neurologists affiliated with a university to assess whether there are consensus opinions on how they treat patients beyond 3 hours from symptom onset and which patients they are willing to enroll into clinical trials of fibrinolysis for acute ischemic stroke. RESULTS: We received 161 responses; 81% were male. Ninety-three percent of respondents treat patients with intravenous tissue plasminogen activator beyond 3 hours. More than 80% were treated beyond 3 hours with intra-arterial therapy (IAT). When asked if IAT improves stroke outcome, >50% selected the choice of "yes for middle cerebral artery and basilar occlusions" and only 2% selected the choice that "IAT does not improve outcome." Over half believe that imaging could be used to approximate the penumbra but with improvements to better identify salvageable tissue. Eighty-seven percent were willing to enroll patients into a placebo-controlled intravenous thrombolysis beyond 3 hours. For IAT trials, >80% would randomize beyond 3 hours with or without prior intravenous treatment. CONCLUSIONS: Vascular neurologists have been treating acute ischemic stroke beyond 3 hours with intravenous tissue plasminogen activator even before the American Heart Association guidelines supported extending the therapeutic window. There is a paradox among the respondents willing to enroll patients into trials involving IAT given that a majority is offering IAT as part of their practice. These results suggest that clinical practice may impair enrollment into trials testing reperfusion therapies for acute ischemic stroke.