[Show abstract][Hide abstract] ABSTRACT: This retrospective study addresses for the first time the differences in clinical features and outcomes between those individuals with a cerebellar infarct who were correctly diagnosed on initial presentation compared to those who experienced delayed diagnosis.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 09/2014; 41(5):568-71. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess the incidence of deterioration, fluctuation, and associated risk of poor outcome in patients with subcortical stroke (SCS).METHODS: We conducted a prospective observational study, enrolling patients admitted with SCS based on their clinical examination and imaging studies. An NIH Stroke Scale evaluation was performed daily and whenever deterioration in examination was detected. Neurologic deterioration was defined as a motor score increase of at least 1 on the NIH Stroke Scale. Modified Rankin Scale scores at discharge were used to assess outcome.RESULTS: Among 90 enrolled patients, 37 (41%) deteriorated, 75% of them in the first 24 hours after enrollment. Administration of tissue plasminogen activator was significantly associated with deterioration (hazard ratio 2.25; 95% confidence interval [CI]: 1.13-4.49) even after controlling for the association of deterioration with the early poststroke period. Deterioration conferred an increased risk of poor outcome (modified Rankin Scale scores 3-6) at discharge (relative risk: 1.80; 95% CI: 1.71-1.93). Reversion back to predeterioration deficits occurred in 38% of patients, and was associated with reduced risk of poor outcome at discharge (relative risk: 0.12; 95% CI: 0.02-0.83). Treatment with tissue plasminogen activator conferred better chances of spontaneous recovery to predeterioration deficits after initial deterioration (hazard ratio: 4.36; 95% CI: 1.36-14.01).CONCLUSION: More than 40% of patients with SCS deteriorate neurologically. Deterioration tends to occur early after stroke, spontaneously reverses in approximately one-third of cases, and poses an increased risk of poor outcome. Therapies are needed to prevent, arrest, or reverse deterioration in patients with SCS.
[Show abstract][Hide abstract] ABSTRACT: Prehospital evaluation using telemedicine may accelerate acute stroke treatment with tissue-type plasminogen activator. We explored the feasibility and reliability of using telemedicine in the field and ambulance to help evaluate acute stroke patients.
[Show abstract][Hide abstract] ABSTRACT: To examine the impact of telemedicine on access to acute stroke care and expertise in the state of Texas.
Texas hospitals were surveyed using a standard questionnaire and categorized as: (1) stand-alone Primary Stroke Centers not using telemedicine for acute stroke care, (2) Primary Stroke Centers using telemedicine for acute stroke care, (3) non-Primary Stroke Center hospitals using telemedicine for acute stroke care, or (4) non-Primary Stroke Center hospitals not using telemedicine for acute stroke care. Population data were obtained from the US Census Bureau and the Neilson Claritas Demographic Estimation Program. Access within 60 minutes to a designated facility was calculated at the block group level.
Over 75% of Texans had 60-minute access to a stand-alone Primary Stroke Center. Including Primary Stroke Centers using telemedicine increased access by 6.5%. Adding non- Primary Stroke Centers that use telemedicine for acute stroke care provided 60-minute access for an additional 2% of Texans, leaving 16% of Texans without 60-minute access to acute stroke care. Approximately 62% of Texans had 60-minute access to more than one type of facility that provided acute stroke care.
The use of telemedicine in the state of Texas brought 60-minute access to >2 million Texans who otherwise would not have had access to acute stroke expertise. Our findings demonstrate that using telemedicine for acute stroke has the ability to provide neurologically underserved areas access to acute stroke care.
Annals of clinical and translational neurology. 06/2014; 1(1):27-33.
[Show abstract][Hide abstract] ABSTRACT: Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS.
AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA.
Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P < .0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P = .0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] = .85, 95% confidence interval [CI] .72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI .92-1.46, P = .22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR = .66, 95% CI .44-.99, P = .0433).
Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 01/2014;
[Show abstract][Hide abstract] ABSTRACT: Background
The use of bone marrow–derived mesenchymal stromal cells (MSCs) as a cellular therapy for various diseases, such as graft-versus-host disease, diabetes, ischemic cardiomyopathy and Crohn's disease, has produced promising results in early-phase clinical trials. However, for widespread application and use in later phase studies, manufacture of these cells must be cost-effective, safe and reproducible. Current methods of manufacturing in flasks or cell factories are labor-intensive, involve a large number of open procedures and require prolonged culture times.
We evaluated the Quantum Cell Expansion System for the expansion of large numbers of MSCs from unprocessed bone marrow in a functionally closed system and compared the results with a flask-based method currently in clinical trials.
After only two passages, we were able to expand a mean of 6.6 × 108 MSCs from 25 mL of bone marrow reproducibly. The mean expansion time was 21 days, and cells obtained were able to differentiate into all three lineages: chondrocytes, osteoblasts and adipocytes. The Quantum was able to generate the target cell number of 2.0 × 108 cells in an average of 9 fewer days and in half the number of passages required during flask-based expansion. We estimated that the Quantum would involve 133 open procedures versus 54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs infused into an ischemic stroke rat model were therapeutically active.
The Quantum is a novel method of generating high numbers of MSCs in less time and at lower passages when compared with flasks. In the Quantum, the risk of contamination is substantially reduced because of the substantial decrease in open procedures.
[Show abstract][Hide abstract] ABSTRACT: Background
Computerized Tomography Perfusion (CTP) has been widely studied in assessing physiological brain tissue parameters in patients with acute ischemic stroke (AIS). The utility of (CTP to predict clinical outcome in patients with AIS treated with intravenous tissue plasminogen activator (IV t-PA) is controversial. We reviewed CTP data in AIS patients treated with IV t-PA to uncover potential predictors of clinical outcome.
We retrospectively identified AIS patients from our stroke registry (7/07 to 2/10), underwent CTP on arrival and then received IV t-PA. A neuro-radiologist blinded to outcome performed all CTP parameter measurements on a commercially available Siemens Neuro PCT workstation. Tissue at risk (TAR) was defined as the area of infarct territory with a relative time to peak (rTTP) greater than 4 seconds. Non-viable tissue (NVT) was defined as the area of infarct territory with absolute cerebral blood volume (CBV) less than 2 ml/100 g and cerebral blood flow (CBF) less than 12.7 ml/100 g/min. Penumbra was defined as the area of (TAR) minus the area of (NVT). Excellent clinical outcome was defined as mRS (0-1), good clinical outcome was defined as mRS (0-2), and poor clinical outcome was defined as mRS (4–6) all measured at hospital discharge and 90 days if available. Recanalization data was obtained when available, by comparing pre-thrombolytic CTA data and post treatment MRA/CTA images by a single blinded radiologist.
We identified 61 patients that met out inclusion criteria with a mean age of 68 (29-94), median NIHSS on admission of 13 (1-40), and median discharge mRS of 4 (0-6). Using multivariate logistic regression and ordinal logistic regression controlling for age and admission NIHSS, none of the CTP parameters were statistically associated with excellent or good clinical outcome. (mRS < 2). Using multivariate analysis controlling for age and admission NIHSS, NVT area > 30 cm2 (OR = 5.12, CI: 0.95- 27, p = 0.05) was statistically associated with poor clinical outcome at discharge. NVT area ≥ 30 cm2 was a potential predictor of poor outcome at discharge even when controlling for age and NIHSS.
CTP parameters derived from commercially available software and published thresholds yield little predictive value for good clinical outcomes for AIS patients treated with IV tPA but may be useful in predicting poor clinical outcome especially if the area of non-viable tissue is greater than 30 cm2.
Journal of the neurological sciences 01/2014; · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option.
To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH.
We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion.
Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups.
We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 12/2013;
[Show abstract][Hide abstract] ABSTRACT: The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health-sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion.
All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days.
Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows: 14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5-29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows: 8 of 20 (40%; 95% confidence interval, 19%-64%) complete and 2 of 20 (10%; 95% confidence interval, 1%-32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate: 8 of 14 (57%; 95% confidence interval, 29%-82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%-49) patients had a modified Rankin scale of 0 to 1.
Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial.
http://www.clinicaltrials.gov. Unique identifier: CLOTBUST-HF NCT01240356.
[Show abstract][Hide abstract] ABSTRACT: It is unknown which patient will benefit most from hospital admission after transient ischemic attack (TIA). Our aim was to define predictors of a positive hospital outcome.
We used two cohorts of TIA patients: the University of Texas at Houston Stroke Center (UTH); and Tel-Aviv Sourasky Medical Center in Israel (TASMC) for external validation. We retrospectively reviewed medical records and imaging data. We defined positive yield (PY) of the hospital admission as identification of stroke etiologies that profoundly changes clinical management.
The UTH cohort included 178 patients. 24.7% had PY. In the multivariate analysis, the following were associated with PY: coronary disease (CAD); age; and acute infarct on DWI. We then derived a composite score termed the PY score to predict PY. One point is scored for: age>60, CAD, and acute infarct on DWI. The proportion of PY by PY score was as follows: 0-6%; 1-22%; 2-47%; 3-67% (p<0.001). In the validation cohort PY score was highly predictive of PY and performed in a very similar manner.
Our data suggest, the PY score may enable physicians to make better admission decisions and result in better, safer and more economical care for TIA patients.
Journal of the neurological sciences 10/2013; · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone marrow-derived mononuclear cells (MNCs) are an investigational autologous cell-based therapy for acute ischemic stroke. Both intravenous (IV) and intra-arterial (IA) administration routes have been used in clinical trials. However, the route of administration to optimize the effect of MNCs is unknown. In this study, we compared the effect of IV versus IA route of administration of MNCs in the rat stroke model.
Long Evans rats were subjected to transient middle cerebral artery occlusion. At 24 hours after stroke, animals were randomly assigned to receive autologous bone marrow-derived MNCs using either the IV or IA delivery route. IV saline served as control. One million cells/kg (low dose) and 30 million cells/kg (high dose) were assessed. Neurological testing, cavity size, serum cytokines, neuroregenerative end points, and MNC biodistribution were evaluated.
High-dose MNCs improved functional recovery, reduced lesion size and proinflammatory cytokines, and increased vessel density and neurogenesis markers compared with saline treatment (P<0.05). However, there were no significant differences between IV and IA MNC-treated groups, although IV MNCs reduced serum interleukin-1β levels compared with IA MNCs (P<0.05). IA MNCs at high dose led to a greater number of cells in the brain at 1 and 6 hours after injection but not in the lungs and spleen. Low-dose MNCs (by IV or IA) did not improve any functional or structural end point compared with saline.
At low and high doses of MNCs, we found that IV or IA achieves similar structural and functional outcomes after stroke.
[Show abstract][Hide abstract] ABSTRACT: Neuroprotective agents have the potential to reduce ischemia to penumbra of the cortex, but are time-sensitive. To quickly determine whether a cortical stroke is present without imaging, we created a scoring system based on the NIH stroke scale (NIHSS) that can accurately predict cortical damage in an acute ischemic stroke (AIS).
Patients treated with tPA for AIS were retrospectively assessed through prospectively acquired databases at two stroke centers. Stroke was classified as cortical vs. non-cortical stroke. The total NIHSS score, cortical components (gaze, visual fields, language, and neglect) and cortical score (sum of cortical components) were analyzed for site 1 and then validated for site 2 for sensitivity and positive predictive value (PPV) for a cortical stroke.
An acute infarct was detected in 194/239 (81%) patients at site 1 and 122/174 (70%) at site 2 on diffusion-weighted MRI. Cortical involvement was found in 71% (site 1) and 75% (site 2). The median cortical score was 25% of the total NIHSS score at both sites. NIHSS ≥ 4 had the highest sensitivity; PPV was 90% for any cortical sign with ≥ 2 points. The best combination of sensitivity and PPV was cortical score/NIHSS score ≥10%.
If a trial targeting cortical stroke required that the cortical score represent at least 10% of the total NIHSS score with no imaging, less than 10% of patients with cortical stroke would be missed and less than 18% of patients would be misclassified as having a cortical stroke.
Journal of neurological disorders & stroke. 09/2013; 2(1):1026.
[Show abstract][Hide abstract] ABSTRACT: The incidence of acute ischaemic stroke with mild neurological deficits (called mild ischaemic stroke [MIS]) is increasing, and studies show that a large percentage of untreated patients have poor long-term outcomes. Many physicians do not, however, routinely treat patients with MIS with intravenous recombinant tissue plasminogen activator (rtPA)-the only thrombolytic therapy currently approved by the FDA. Here, we discuss the reasons why physicians do not treat patients with MIS and we review the studies published to date regarding the potential risks and benefits of administering rtPA in this patient population. We then provide our perspective on why patients with MIS should be treated with intravenous rtPA and we highlight the need for a randomized clinical trial to address treatment of MIS.
[Show abstract][Hide abstract] ABSTRACT: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions.
Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University.
A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score ≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score ≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores.
The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Heat stress results in multiorgan failure and CNS injury. There a few case reports in the literature on the neurological consequences of heat stress. CASE PRESENTATION: We describe a patient with heat stress presenting with encephalopathy and bilateral cerebral, cerebellar, and thalamic lesions and intraventricular hemorrhage on MRI. CONCLUSION: Heat stress should be in the differential diagnosis of patients presenting with encephalopathy and elevated serum inflammatory markers especially if the history suggests a preceding episode of hyperthermia.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Limited information has been published regarding standard quality assurance (QA) procedures for stroke registries. We share our experience regarding the establishment of enhanced QA procedures for the University of Texas Houston Stroke Registry (UTHSR) and evaluate whether these QA procedures have improved data quality in UTHSR. METHODS: All 5093 patient records that were abstracted and entered in UTHSR, between January 1, 2008 and December 31, 2011, were considered in this study. We conducted reliability and validity studies. For reliability and validity of data captured by abstractors, a random subset of 30 records was used for re-abstraction of select key variables by two abstractors. These 30 records were re-abstracted by a team of experts that included a vascular neurologist clinician as the "gold standard". We assessed inter-rater reliability (IRR) between the two abstractors as well as validity of each abstractor with the "gold standard". Depending on the scale of variables, IRR was assessed with Kappa or intra-class correlations (ICC) using a 2-way, random effects ANOVA. For assessment of validity of data in UTHSR we re-abstracted another set of 85 patient records for which all discrepant entries were adjudicated by a vascular neurology fellow clinician and added to the set of our "gold standard". We assessed level of agreement between the registry data and the "gold standard" as well as sensitivity and specificity. We used logistic regression to compare error rates for different years to assess whether a significant improvement in data quality has been achieved during 2008--2011. RESULTS: The error rate dropped significantly, from 4.8% in 2008 to 2.2% in 2011 (P < 0.001). The two abstractors had an excellent IRR (Kappa or ICC >= 0.75) on almost all key variables checked. Agreement between data in UTHSR and the "gold standard" was excellent for almost all categorical and continuous variables. CONCLUSIONS: Establishment of a rigorous data quality assurance for our UTHSR has helped to improve the validity of data. We observed an excellent IRR between the two abstractors. We recommend training of chart abstractors and systematic assessment of IRR between abstractors and validity of the abstracted data in stroke registries.