From the Department of Neurology, University of Texas Houston Health
Science Center.
Correspondence to David Chiu, MD, Baylor College of Medicine, Department of Neurology, 6550 Fannin, Suite 1801, Houston, TX 77030. E-mail dchiu{at}bcm.tmc.edu
Methods—We initiated a prospective open-label study at a
university hospital and two community hospitals in Houston, Tex,
immediately after the publication of the National Institute of
Neurological Disorders and Stroke (NINDS) t-PA study. A total of 30
patients, age 32 to 90 years, were treated with 0.9 mg/kg of
intravenous t-PA (maximum dose, 90 mg) within 3 hours of
acute ischemic stroke between December 1995 and December
1996.
Results—Six percent (6%) of all patients hospitalized with
ischemic stroke received intravenous t-PA at the
university hospital and 1.1% at the community hospitals. The rates of
total, symptomatic, and fatal intracerebral
hemorrhage were 10%, 7%, and 3%. Thirty-seven percent (37%)
of patients recovered to fully independent function. The average time
from stroke onset to emergency department arrival was 57 minutes;
emergency department arrival to computed tomography scan 41 minutes;
and computed tomography scan to administration of treatment 59
minutes.
Conclusions—When treatment guidelines are carefully
followed in an urban hospital setting, intravenous t-PA for
acute ischemic stroke is feasible and shows safety and efficacy
comparable to the results of the NINDS study.
We initiated a postmarketing survey of t-PA for stroke immediately
after the publication of the NINDS study at a university hospital and
two community hospitals in Houston, Tex. The feasibility of evaluating
and treating patients in the emergency department within 3 hours of
stroke onset is examined. We assess the outcome of patients treated
with intravenous t-PA, including the incidence of
intracerebral hemorrhage and other adverse
events. Predictors of outcome are analyzed. The overall purpose
of our phase IV study of t-PA is to report the current clinical
practice of thrombolytic therapy for acute stroke.
We used paramedic, emergency department, and hospital records to
assess time of symptom onset, time of arrival in the emergency
department, time of CT examination, and time of t-PA administration.
Demographic characteristics, stroke risk factors, baseline CT scans,
and blood pressure measurements were recorded, and the baseline NIH
Stroke Scale was extrapolated from the recorded neurological
examination.
Each patient received 0.9 mg/kg of intravenous t-PA up to a
maximum of 90 mg, based on estimated or actual weight. Ten percent of
the dose was given as a bolus, and the remainder infused over 1 hour.
Heparin and aspirin were withheld for the first 24 hours after t-PA
administration in all patients. As a rule, systolic blood
pressures >185 mm Hg and diastolic blood pressures
>110 mm Hg were treated with intravenous
antihypertensive medications such as labetalol,
nicardipine, or enalapril.
Results of follow-up CT or MRI scans were recorded as well as use
of aspirin, ticlopidine, heparin, warfarin, or antihypertensive drugs
during hospitalization. Serious hemorrhages or transfusions
were noted, and the maximal blood pressure during t-PA infusion and the
first 24 hours was recorded. Stroke subtype, determined after
diagnostic evaluation, was classified as cardioembolic,
large vessel, small vessel, other determined pathogenesis, or
cryptogenic, using the TOAST criteria.7 We obtained
telephone or clinic follow-up with the patient (and caregiver, if
necessary) on all 30 cases in December 1996 and assessed the Barthel
Activities of Daily Living Index and Modified Rankin Disability Scale.
Use of the telephone interview for assessing stroke outcome has been
previously validated.8 9 Inquiry was made into the number
of weeks spent in acute inpatient rehabilitation, outpatient
rehabilitation, skilled nursing facilities, nursing homes, and
professional home care.
Logistic regression was performed to determine predictors of outcome.
For the purposes of the analysis, a good outcome was defined as
a Barthel Activities of Daily Living Index of
Fifty-three percent (53%) of the patients treated were male. The mean
age was 66±15 years, ranging from 32 to 90. Fifty-three percent (53%)
were white, 33% black, 7% Hispanic, and 3% Asian. Thirty percent
(30%) were taking aspirin at the time of the stroke. Other baseline
characteristics are listed in Table 1
More than half of patients had the onset of symptoms between noon and 6
PM (Table 2
The treating physician or radiologist recognized early ischemic
changes in four baseline CT scans (13%). In two cases, a hypodensity
limited to less than one third of the middle cerebral artery territory
was present, indicating a subacute infarct. In the other two
cases, the CT changes were subtle: loss of gray-white differentiation,
insular ribbon sign, indistinctness of the basal ganglia, and/or mild
sulcal effacement. No patient showed acute hypodensity that involved
greater than a third of the middle cerebral artery territory, that is,
two or more of the following regions: the basal ganglia, frontal,
parietal, and temporal lobes.
The mean baseline NIH Stroke Scale was 14 (range, 3 to 36). Stroke
subtype by final diagnosis was cardioembolic in 30%, large vessel in
27%, small vessel in 7%, cryptogenic in 17%, undetermined in 10%,
and other in 10%. The other etiologies—established after hospital
admission—included bacterial endocarditis in one patient, concomitant
large vessel and cardiac disease in one patient, and suspected
psychogenic hemiparesis in the third. Seventeen percent (17%) were
vertebrobasilar strokes.
Follow-up CT or MRI was performed in all patients except one who had
complete resolution of symptoms by 24 hours. Sixty-three percent (63%)
showed an ischemic infarct (Table 3
The mean duration of follow-up in our study was 5 months (SD, 4).
Thirty-seven percent of patients recovered to fully independent
function in activities of daily living (Barthel Index, 100; Table 4
All three intracerebral hemorrhages occurred in
women with cardioembolic stroke who had early ischemic changes
on initial CT. ICH occurred in 1 of 23 patients treated by fellows, 2
of 5 patients treated by faculty, and none of 2 patients treated by
emergency physicians or neurology residents. The incidence of
hemorrhage was 2 of 23 in patients treated at the university
hospital and 1 of 7 in patients treated at a community hospital. None
of the 3 patients treated beyond the 180-minute mark developed ICH. The
two factors significantly associated with ICH by Fisher's exact test
were early CT ischemic changes (P=.002) and
cardioembolic stroke (P=.04).
An obvious difference between our study and the NINDS trial is that
half of the patients randomized in the NINDS study were treated within
90 minutes of stroke onset as mandated by the protocol, whereas the
earliest treatment in our study was 97 minutes. Of note, the response
to t-PA in the NINDS trial was the same for patients who received
treatment under 90 minutes and those who received treatment between 90
and 180 minutes. Over half of our patients had the onset of symptoms in
the afternoon despite the fact that consultation with the stroke
treatment team was readily available 24 hours a day, a major reason
being the exclusion of patients who developed symptoms during
sleep.
Patients arrived in the emergency department an average of 57 minutes
after onset of symptoms. The CT scan was performed an average of 41
minutes after arrival in the emergency department. Another 59 minutes
elapsed on average between the CT and initiation of
thrombolysis. The most common reasons for delay of
treatment were queues in the CT scanner, travel by the stroke team
member to the hospital, marked acute hypertension requiring treatment,
drug preparation, agitation of patients requiring sedation for CT scan,
delays in laboratory results, difficulty in obtaining venous access,
consultations with other physicians, and locating family members.
Recent NIH consensus guidelines recommend a door-to-needle time of 60
minutes or less for acute stroke patients.12
The NINDS trial excluded patients with acute myocardial infarction,
significant neurological deficits residual from previous strokes, or
any illness that would interfere with assessment of patient outcome,
whereas FDA guidelines did not bar us from treating such patients. We
administered thrombolysis to 4 individuals (13%) who
had baseline disability (Modified Rankin Scale
The 3-month mortality in our study was 20% (one subject died after 3
months), compared with 17% in the NINDS trial. The number of patients
left severely impaired was similar (17% with Barthel Index 0-50 in
both studies). The proportion of patients who made a complete or
near-complete recovery in our study was somewhat less than that of the
NINDS t-PA patients, but this is not surprising given our inclusion of
patients with previous disability. Excluding these subjects, 35% of
our patients achieved a Modified Rankin Scale of 0 or 1, compared with
39% of the NINDS t-PA group. Only one patient (3%) was admitted to a
skilled nursing facility and one patient (3%) to a nursing home,
consistent with the finding in the NINDS study that patients
receiving t-PA required less chronic care.13
The variables that had the most significant effect on outcome in
multivariate logistic regression were the NIH Stroke
Scale, the mean arterial pressure, age, and a cardioembolic
stroke subtype. Adjusting for the other variables in the model, a
five-point increase in the NIH Stroke Scale decreases the odds of a
favorable outcome by 69%. A cardiac cause of stroke increases the odds
of a poor outcome, as do a high pretreatment mean arterial
pressure and advanced age. Patients with cardioembolic strokes had
poorer outcomes independent of stroke severity and age largely because
of cardiac comorbidity (eg, congestive heart failure). We found that
these patients as a group had lengthier hospital stays, often because
of cardiac complications. The effect sizes have wide confidence
intervals because of the relatively small sample size, but our findings
are consistent with known predictors of stroke outcome in
general and do not indicate which patients should not receive t-PA. An
elderly patient or one with a severe stroke may have a poorer overall
prognosis, but it is irrational to withhold therapy if the margin of
benefit is the same. Post hoc analysis of the NINDS data showed
t-PA to be beneficial for patients in all strata of age, stroke
severity, and stroke subtype.14
Attempting to predict hemorrhagic conversion in our study is hazardous
because of the small numbers of ICH (n=3), but early CT
ischemic changes and a cardioembolic causes proved to be
significant risk factors in univariate analysis.
The fatal ICH occurred in a patient who, in retrospect, had relatively
advanced ischemic changes on baseline CT. Stroke severity,
pulse pressure, and early CT changes were predictors of ICH in post hoc
analysis of the NINDS data.15 The occurrence of
hemopericardium in two of our patients indicates that caution should be
exercised when treating patients with acute myocardial infarction or
recent coronary artery bypass graft surgery. Hemopericardium
should be suspected in patients who develop unexplained hypotension
after receiving t-PA.
Our data reflect the outcome of patients managed in urban hospitals by
a stroke team experienced in treating acute stroke patients with t-PA.
While there is no particular reason to believe that the same results
could not be duplicated in other practice settings, the
generalizability of our findings in other environments remains to be
established. There can be no doubt, however, that the ability to
perform rapid and accurate neurological assessment, CT examination, and
cardiovascular monitoring are essential to the success
of thrombolytic therapy for stroke.
Our experience in Houston with intravenous t-PA for acute
ischemic stroke in the first year of FDA approval demonstrates
that the therapy is feasible and safe in an urban hospital setting.
Patients can be successfully triaged, selected, and treated outside the
scope of a randomized clinical trial, although the present
door-to-needle time of 100 minutes leaves room for improvement.
Approximately 6% of stroke patients currently receive t-PA at our
university hospital, a considerably higher percentage than that in the
community.
Received August 7, 1997;
revision received October 7, 1997;
accepted October 28, 1997.
2.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von
Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH, Hennerici M,
for the ECASS Study Group. Intravenous
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ischemic stroke: the European Cooperative Acute Stroke Study
(ECASS). JAMA.. 1995;274:1017-1025.
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Donnan GA, Davis SM, Chambers BR, Gates PC, Hankey GJ,
McNeil JJ, Rosen D, Stewart-Wynne EG, Tuck RR, for the Australian
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administration. JAMA.. 1996;276:961-966.
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The Multicenter Acute Stroke Trial–Europe Study
Group. Thrombolytic therapy with streptokinase in
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The Multicentre Acute Stroke Trial–Italy (MAST-I)
Group. Randomised controlled trial of streptokinase, aspirin,
and combination of both in treatment of acute ischemic
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Fieschi C, Bluhmki E for the ECASS Study Group. Rt-PA in acute
ischemic stroke: results from the ECASS three-hour
cohort. Stroke.. 1997;28:272. Abstract.
7.
Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB,
Gordon DL, Marsh EE, and the TOAST Investigators. Classification
of subtype of acute ischemic stroke: definitions for use in a
multicenter clinical trial. Stroke.. 1993;24:35-41.
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Shinar D, Gross CR, Bronstein KS, Licata-Gehr EE, Eden
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Candelise L, Pinardi G, Aritzu E, Musicco M.
Telephone interview for stroke outcome assessment.
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10.
Hosmer DW, Lemeshow S. Model-building strategies
and methods for logistic regression. In: Hosmer DW, Lemeshow S,
eds. Applied Logistic Regression. New York, NY: John Wiley &
Sons; 1989:82-134.
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Bratina P, Greenberg L, Pasteur W, Grotta JC.
Current emergency department management of stroke in Houston,
Texas. Stroke.. 1995;26:409-414.
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The National Institute of Neurological Disorders and
Stroke. A National Symposium on Rapid Identification and
Treatment of Acute Stroke, December 12-13, 1996, Arlington, Va.
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Fagan SC, Morgenstern LB, Petitta A, Ward RE, Tilley
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© 1998 American Heart Association, Inc.
Original Contributions
Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke
Feasibility, Safety, and Efficacy in the First Year of Clinical Practice
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—The feasibility, safety, and
efficacy of intravenous tissue plasminogen
activator (t-PA) for patients with acute ischemic
stroke in clinical practice need to be assessed.
Key Words: cerebral hemorrhage • cerebral infarction • emergency medical services • thrombolytic therapy
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Tissue plasminogen
activator (t-PA) was demonstrated to be effective in the
first 3 hours after acute ischemic stroke in a pivotal
randomized clinical trial sponsored by the National Institutes of
Neurological Disorders and Stroke (NINDS).1 Questions
regarding the safety and efficacy of t-PA in clinical practice still
persist, in part because a number of other multicenter trials, using
alternative thrombolytic protocols and time windows >3
hours, failed to replicate the results of the NINDS
study,2 3 4 5 mainly because of high rates of
intracerebral hemorrhage (ICH) and/or
ICH-related mortality. The incidence of ICH may be influenced by the
time to treatment, the presence of CT hypodensity,6 the
thrombolytic agent and dose, and the combination of
thrombolysis with heparin or aspirin.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We prospectively studied all patients (n=30) who were treated
with intravenous t-PA for stroke at a university hospital
and two community hospitals in Houston between December 1995 and
December 1996. The three hospitals were linked by a communication
system to a single stroke treatment team made up of four neurology
faculty members, three fellows, and a nurse coordinator. In 28 of 30
cases, a member of the stroke team examined the patient before the
decision to administer thrombolysis. The stroke team
provided consultation by telephone for the other two patients. The
treating physician was a stroke fellow in 23 cases, a stroke faculty
member in 5 cases, an emergency physician in 1 case, and a neurology
resident in 1 case. 
75. Potential
predictors were tested first in univariate regression. A
stepwise model-building procedure was then carried out,10
and covariates significant at the .10 level were included in the final
multivariate regression model. Significance was
calculated by the likelihood ratio test. Potential predictors of
intracerebral hemorrhage were analyzed
by Fisher's exact test (for dichotomous variables) or
univariate logistic regression.
Multivariate regression for ICH was not performed
because of the small number of such patients.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Thirty patients received intravenous t-PA for stroke
between December 1995 and December 1996. The stroke team was notified
of 267 patients suspected of having an acute stroke during this
period.11 The most common reasons for disqualification
from thrombolytic therapy were the time limit (37%),
intracerebral hemorrhage (22%), minor or
rapidly resolving symptoms (19%), and a nonstroke diagnosis (12%).
Several patients met multiple criteria for exclusion, but only one was
tabulated per patient. In many cases, patients could be excluded by
telephone. Twenty-three patients were treated with t-PA at the
university hospital out of 405 discharged with an ICD-9 diagnosis of
ischemic stroke during the same period (6%). The rates of t-PA
use at the two community hospitals were 5 of 302 and 2 of 328 (1.7%
and 0.6%, respectively). Risks and benefits were discussed with the
family of all candidates before t-PA was given. There were no refusals
of treatment for patients who were otherwise eligible. 
.
View this table:
[in a new window]
Table 1. Demographic and Pretreatment Characteristics
(n=30) ). The average
time from onset of symptoms to arrival in the emergency department was
57 minutes. Mean duration from arrival in the emergency department to
CT scanning was 41 minutes (39 minutes at the university hospital, 47
minutes at the affiliate hospitals). The average "door-to-needle"
time was 100 minutes (94 minutes at the university hospital, 118
minutes at the affiliate hospitals). The average total time from stroke
onset to administration of t-PA was 157 minutes (range, 97 to 220).
Although the intention was to treat within 3 hours in each case, t-PA
was actually administered beyond the 180-minute mark in 3 patients
(10%) at 192, 200, and 220 minutes. Two of the time violations
occurred in a community hospital.
View this table:
[in a new window]
Table 2. Time Parameters (n=30) ). Three developed ICH: one fatal
intrainfarct hematoma (3%), one nonfatal symptomatic
hemorrhage (3%) in a location remote from the initial infarct,
and one mild hemorrhagic infarct conversion unaccompanied by
neurological worsening (3%). The symptomatic
hemorrhages developed 3 and 13 hours after
thrombolytic treatment and were managed
conservatively.
View this table:
[in a new window]
Table 3. Outcome (n=30) ). Thirty percent of patients had no
disability at follow-up (Modified Rankin Scale 0-1). Another 33% had
mild or moderate disability but were ambulatory (Modified Rankin Scale
2-3). Thirteen percent (13%) were moderately to severely disabled and
unable to walk (Modified Rankin Scale 4-5), and 23% were dead. Of the
deaths, two were caused by bleeding complications: an
intracerebral hemorrhage and a hemorrhagic
pericardial tamponade. The patient with fatal hemopericardium had no
previous cardiac history. The other causes of death were neurological
in three patients (two with basilar artery infarcts and one with a
malignant middle cerebral artery stroke) and nonneurological in two
(pneumonia and ischemic heart disease). There was one serious
nonfatal hemorrhagic event, also a hemopericardium, occurring in a
patient who received thrombolysis 16 days after
coronary artery bypass surgery. A total of three patients
(10%) received blood transfusions. The effects of various risk factors
on the likelihood of a favorable outcome in a
multivariate model are shown in Table 5.
View this table:
[in a new window]
Table 4. Functional (Barthel Index) and Disability (Modified
Rankin Scale) Outcomes (n=30)
View this table:
[in a new window]
Table 5. Adjusted Effects on Odds of Favorable Outcome
(Barthel Index 75) by Multivariate Logistic
Regression (n=30)
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
There were notable similarities between the results of this study
and those of the NINDS t-PA trial. The mean NIH Stroke Scale in our
study was 14, identical to the average stroke severity score in the
NINDS study. The mean age was 66 years, compared with 67 in the NINDS
study. The rates of total, symptomatic, and fatal
intracerebral hemorrhage in our study were
10%, 7%, and 3%, respectively, compared with 10%, 6%, and 3% in
the treated group in the NINDS trial. The safety of t-PA demonstrated
in the multicenter NINDS clinical trial can be replicated in clinical
practice when the guidelines are observed. 2) resulting from
prior strokes or impaired cardiac function. The overall outcome scores
on the Barthel Activities of Daily Living Index and Modified Rankin
Disability Scale are compared with those of the t-PA patients in the
NINDS trial in Table 4
.
Acknowledgments
We gratefully acknowledge the physicians, nurses, and staff of
Hermann Hospital, Memorial Southwest Hospital, and Memorial Northwest
Hospital in Houston, Tex, and the Houston Fire Department and Emergency
Medical Services.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
The National Institute of Neurological Disorders
and Stroke rt-PA Stroke Study Group. Tissue
plasminogen activator for acute
ischemic stroke. N Engl J
Med.. 1995;333:1581-1587.
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M. K. Kapral, A. Laupacis, S. J. Phillips, F. L. Silver, M. D. Hill, J. Fang, J. Richards, J. V. Tu, and for the Investigators of the Registry of the Canad Stroke Care Delivery in Institutions Participating in the Registry of the Canadian Stroke Network Stroke, July 1, 2004; 35(7): 1756 - 1762. [Abstract] [Full Text] [PDF]
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S. Straub, U. Junghans, V. Jovanovic, H. J. Wittsack, R. J. Seitz, and M. Siebler Systemic Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Acute Middle Cerebral Artery Occlusion Stroke, March 1, 2004; 35(3): 705 - 709. [Abstract] [Full Text] [PDF]
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R. Handschu, R. Littmann, U. Reulbach, C. Gaul, J. G. Heckmann, B. Neundorfer, and M. Scibor Telemedicine in Emergency Evaluation of Acute Stroke: Interrater Agreement in Remote Video Examination With a Novel Multimedia System Stroke, December 1, 2003; 34(12): 2842 - 2846. [Abstract] [Full Text] [PDF]
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J. M. Provenzale, R. Jahan, T. P. Naidich, and A. J. Fox Assessment of the Patient with Hyperacute Stroke: Imaging and Therapy Radiology, November 1, 2003; 229(2): 347 - 359. [Abstract] [Full Text] [PDF]
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J.M. Wardlaw, P.A.G. Sandercock, and E. Berge Thrombolytic Therapy With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke: Where Do We Go From Here? A Cumulative Meta-Analysis Stroke, June 1, 2003; 34(6): 1437 - 1442. [Abstract] [Full Text] [PDF]
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L. C. Shih, J. L. Saver, J. R. Alger, S. Starkman, M. C. Leary, F. Vinuela, G. Duckwiler, Y. P. Gobin, R. Jahan, J. P. Villablanca, et al. Perfusion-Weighted Magnetic Resonance Imaging Thresholds Identifying Core, Irreversibly Infarcted Tissue Stroke, June 1, 2003; 34(6): 1425 - 1430. [Abstract] [Full Text] [PDF]
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P. U. Heuschmann, K. Berger, B. Misselwitz, P. Hermanek, C. Leffmann, M. Adelmann, H.-J. Buecker-Nott, J. Rother, B. Neundoerfer, and P. L. Kolominsky-Rabas Frequency of Thrombolytic Therapy in Patients With Acute Ischemic Stroke and the Risk of In-Hospital Mortality: The German Stroke Registers Study Group Stroke, May 1, 2003; 34(5): 1106 - 1112. [Abstract] [Full Text] [PDF]
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N. Nighoghossian Editorial Comment--tPA in Daily Clinical Practice Stroke, May 1, 2003; 34(5): 1112 - 1113. [Full Text] [PDF]
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H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]
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R. Handschu, R. Poppe, J. Rauss, B. Neundorfer, and F. Erbguth Emergency Calls in Acute Stroke Stroke, April 1, 2003; 34(4): 1005 - 1009. [Abstract] [Full Text] [PDF]
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R. C. Lisboa, B. D. Jovanovic, and M. J. Alberts Analysis of the Safety and Efficacy of Intra-Arterial Thrombolytic Therapy in Ischemic Stroke Stroke, December 1, 2002; 33(12): 2866 - 2871. [Abstract] [Full Text] [PDF]
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J. W. Sturm, R. H. Osborne, H. M. Dewey, G. A. Donnan, R. A.L. Macdonell, and A. G. Thrift Brief Comprehensive Quality of Life Assessment After Stroke: The Assessment of Quality of Life Instrument in the North East Melbourne Stroke Incidence Study (NEMESIS) Stroke, December 1, 2002; 33(12): 2888 - 2894. [Abstract] [Full Text] [PDF]
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H. J. Cloft, T. A. Tomsick, D. F. Kallmes, J. H. Goldstein, and J. J. Connors Assessment of the Interventional Neuroradiology Workforce in the United States: A Review of the Existing Data AJNR Am. J. Neuroradiol., November 1, 2002; 23(10): 1700 - 1705. [Full Text] [PDF]
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P. A. Scott, A. M. Pancioli, L. A. Davis, S. M. Frederiksen, and J. Eckman Prevalence of Atrial Fibrillation and Antithrombotic Prophylaxis in Emergency Department Patients Stroke, November 1, 2002; 33(11): 2664 - 2669. [Abstract] [Full Text] [PDF]
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J. P. Broderick and W. Hacke Treatment of Acute Ischemic Stroke: Part I: Recanalization Strategies Circulation, September 17, 2002; 106(12): 1563 - 1569. [Full Text] [PDF]
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J. G. Merino, B. Silver, E. Wong, B. Foell, B. Demaerschalk, A. Tamayo, F. Poncha, and V. Hachinski Extending Tissue Plasminogen Activator Use to Community and Rural Stroke Patients Stroke, January 1, 2002; 33(1): 141 - 146. [Abstract] [Full Text] [PDF]
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L. Derex, P. Adeleine, N. Nighoghossian, J. Honnorat, and P. Trouillas Factors Influencing Early Admission in a French Stroke Unit Stroke, January 1, 2002; 33(1): 153 - 159. [Abstract] [Full Text] [PDF]
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L. B. Morgenstern, L. Staub, W. Chan, T. H. Wein, L. K. Bartholomew, M. King, R. A. Felberg, W. S. Burgin, J. Groff, S. L. Hickenbottom, et al. Improving Delivery of Acute Stroke Therapy: The TLL Temple Foundation Stroke Project Stroke, January 1, 2002; 33(1): 160 - 166. [Abstract] [Full Text] [PDF]
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 J. C. Grotta, W. S. Burgin, A. El-Mitwalli, M. Long, M. Campbell, L. B. Morgenstern, M. Malkoff, and A. V. Alexandrov Intravenous Tissue-Type Plasminogen Activator Therapy for Ischemic Stroke: Houston Experience 1996 to 2000 Arch Neurol, December 1, 2001; 58(12): 2009 - 2013. [Abstract] [Full Text] [PDF]
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C. S. Kase, A. J. Furlan, L. R. Wechsler, R. T. Higashida, H. A. Rowley, R. G. Hart, G. F. Molinari, L. S. Frederick, H. C. Roberts, J. M. Gebel, et al. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: The PROACT II trial Neurology, November 13, 2001; 57(9): 1603 - 1610. [Abstract] [Full Text] [PDF]
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 J. Huang, D. B. Agus, C. J. Winfree, S. Kiss, W. J. Mack, R. A. McTaggart, T. F. Choudhri, L. J Kim, J Mocco, D. J. Pinsky, et al. Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke PNAS, September 25, 2001; 98(20): 11720 - 11724. [Abstract] [Full Text] [PDF]
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C. Fieschi and A. Falcou Keynote address Neurology, September 1, 2001; 57(90002): S82 - 86. [Abstract] [Full Text]
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A. M. Demchuk, D. Tanne, M. D. Hill, S. E. Kasner, S. Hanson, M. Grond, and S. R. Levine Predictors of good outcome after intravenous tPA for acute ischemic stroke Neurology, August 14, 2001; 57(3): 474 - 480. [Abstract] [Full Text] [PDF]
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D. J. Gladstone and S. E. Black Update on intravenous tissue plasminogen activator for acute stroke: from clinical trials to clinical practice Can. Med. Assoc. J., August 1, 2001; 165(3): 311 - 317. [Abstract] [Full Text] [PDF]
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S. D. Reed, S. C. Cramer, D. K. Blough, K. Meyer, J. G. Jarvik, and D. Z. Wang Treatment With Tissue Plasminogen Activator and Inpatient Mortality Rates for Patients With Ischemic Stroke Treated in Community Hospitals Editorial Comment Stroke, August 1, 2001; 32(8): 1832 - 1840. [Abstract] [Full Text] [PDF]
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C. Berger, M. Fiorelli, T. Steiner, W.-R. Schabitz, L. Bozzao, E. Bluhmki, W. Hacke, and R. von Kummer Hemorrhagic Transformation of Ischemic Brain Tissue : Asymptomatic or Symptomatic? Stroke, June 1, 2001; 32(6): 1330 - 1335. [Abstract] [Full Text] [PDF]
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H.-C. Koennecke, R. Nohr, S. Leistner, and P. Marx Intravenous tPA for Ischemic Stroke Team Performance Over Time, Safety, and Efficacy in a Single-Center, 2-Year Experience Stroke, May 1, 2001; 32(5): 1074 - 1078. [Abstract] [Full Text] [PDF]
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R.J. Riopelle, D.C. Howse, C. Bolton, S. Elson, D.L. Groll, D. Holtom, D.G. Brunet, A.C. Jackson, M. Melanson, and D.F. Weaver Regional Access to Acute Ischemic Stroke Intervention Stroke, March 1, 2001; 32(3): 652 - 655. [Abstract] [Full Text] [PDF]
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 A C Pereira, P J Martin, and E A Warburton Thrombolysis in acute ischaemic stroke Postgrad. Med. J., March 1, 2001; 77(905): 166 - 171. [Full Text]
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A. M. Lopez-Yunez, A. Bruno, L. S. Williams, E. Yilmaz, C. Zurru, and J. Biller Protocol Violations in Community-Based rTPA Stroke Treatment Are Associated With Symptomatic Intracerebral Hemorrhage Stroke, January 1, 2001; 32(1): 12 - 16. [Abstract] [Full Text] [PDF]
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G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke Chest, January 1, 2001; 119 (2009): 300S - 320S. [Full Text] [PDF]
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P.T. Akins, C. Delemos, D. Wentworth, J. Byer, S.J. Schorer, and a. R.P. Atkinson Can emergency department physicians safely and effectively initiate thrombolysis for acute ischemic stroke? Neurology, December 26, 2000; 55(12): 1801 - 1805. [Abstract] [Full Text] [PDF]
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K. M. Chapman, A. R. Woolfenden, D. Graeb, D. C. C. Johnston, J. Beckman, M. Schulzer, and P. A. Teal Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke : A Canadian Hospital's Experience Stroke, December 1, 2000; 31(12): 2920 - 2924. [Abstract] [Full Text] [PDF]
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 M. Fisher and W. Schaebitz An Overview of Acute Stroke Therapy: Past, Present, and Future Arch Intern Med, November 27, 2000; 160(21): 3196 - 3206. [Full Text] [PDF]
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D. L. Morris, W. Rosamond, K. Madden, C. Schultz, and S. Hamilton Prehospital and Emergency Department Delays After Acute Stroke : The Genentech Stroke Presentation Survey Stroke, November 1, 2000; 31(11): 2585 - 2590. [Abstract] [Full Text] [PDF]
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J. A. Hinchey and C. Benesch Thrombolytic Therapy in Patients With Acute Ischemic Stroke Arch Neurol, October 1, 2000; 57(10): 1430 - 1436. [Full Text] [PDF]
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L. Robinson, A. V. Alexandrov, and J. C. Grotta Clototripsy? Response Stroke, August 1, 2000; 31(8): 2024 - 2025. [Full Text] [PDF]
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 M. J. Alberts, G. Hademenos, R. E. Latchaw, A. Jagoda, J. R. Marler, M. R. Mayberg, R. D. Starke, H. W. Todd, K. M. Viste, M. Girgus, et al. Recommendations for the Establishment of Primary Stroke Centers JAMA, June 21, 2000; 283(23): 3102 - 3109. [Abstract] [Full Text] [PDF]
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H. J. M. Barnett and A. M. Buchan The Imperative to Develop Dedicated Stroke Centers JAMA, June 21, 2000; 283(23): 3125 - 3126. [Full Text] [PDF]
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Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke Can. Med. Assoc. J., May 1, 2000; 162(11): 1589 - 1593.
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G. W. Albers, V. E. Bates, W. M. Clark, R. Bell, P. Verro, and S. A. Hamilton Intravenous Tissue-Type Plasminogen Activator for Treatment of Acute Stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) Study JAMA, March 1, 2000; 283(9): 1145 - 1150. [Abstract] [Full Text] [PDF]
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I. L. Katzan, A. J. Furlan, L. E. Lloyd, J. I. Frank, D. L. Harper, J. A. Hinchey, J. P. Hammel, A. Qu, and C. A. Sila Use of Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: The Cleveland Area Experience JAMA, March 1, 2000; 283(9): 1151 - 1158. [Abstract] [Full Text] [PDF]
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J. P. Mohr Thrombolytic Therapy for Ischemic Stroke: From Clinical Trials to Clinical Practice JAMA, March 1, 2000; 283(9): 1189 - 1191. [Full Text] [PDF]
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A. M. Buchan, P. A. Barber, N. Newcommon, H. G. Karbalai, A. M. Demchuk, K. M. Hoyte, G. M. Klein, and T. E. Feasby Effectiveness of t-PA in acute ischemic stroke: Outcome relates to appropriateness Neurology, February 8, 2000; 54(3): 679 - 679. [Abstract] [Full Text] [PDF]
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C. S. Kidwell, S. Starkman, M. Eckstein, K. Weems, and J. L. Saver Identifying Stroke in the Field : Prospective Validation of the Los Angeles Prehospital Stroke Screen (LAPSS) Stroke, January 1, 2000; 31(1): 71 - 76. [Abstract] [Full Text] [PDF]
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D. Z. Wang, J. A. Rose, D. S. Honings, D. J. Garwacki, and J. C. Milbrandt Treating Acute Stroke Patients With Intravenous tPA : The OSF Stroke Network Experience Stroke, January 1, 2000; 31(1): 77 - 81. [Abstract] [Full Text] [PDF]
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S. E. Kasner, J. A. Chalela, J. M. Luciano, B. L. Cucchiara, E. C. Raps, M. L. McGarvey, M. B. Conroy, and A. R. Localio Reliability and Validity of Estimating the NIH Stroke Scale Score from Medical Records Stroke, August 1, 1999; 30(8): 1534 - 1537. [Abstract] [Full Text] [PDF]
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 J. Huang, L. J. Kim, R. Mealey, H. C. Marsh Jr., Y. Zhang, A. J. Tenner, E. S. Connolly Jr., and D. J. Pinsky Neuronal Protection in Stroke by an sLex-Glycosylated Complement Inhibitory Protein Science, July 23, 1999; 285(5427): 595 - 599. [Abstract] [Full Text]
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D. Tanne, V. E. Bates, P. Verro, S. E. Kasner, J. R. Binder, S. C. Patel, H. H. Mansbach, S. Daley, L. R. Schultz, P. N. Karanjia, et al. Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: A multicenter survey Neurology, July 1, 1999; 53(2): 424 - 424. [Abstract] [Full Text]
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A. Jaillard, C. Cornu, A. Durieux, T. Moulin, F. Boutitie, K. R. Lees, and M. Hommel Hemorrhagic Transformation in Acute Ischemic Stroke : The MAST-E Study Stroke, July 1, 1999; 30(7): 1326 - 1332. [Abstract] [Full Text] [PDF]
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T. G. Kwiatkowski, R. B. Libman, M. Frankel, B. C. Tilley, L. B. Morgenstern, M. Lu, J. P. Broderick, C. A. Lewandowski, J. R. Marler, S. R. Levine, et al. Effects of Tissue Plasminogen Activator for Acute Ischemic Stroke at One Year N. Engl. J. Med., June 10, 1999; 340(23): 1781 - 1787. [Abstract] [Full Text] [PDF]
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J. E. Riggs, Z. Nadareishvili, P. Oh, L. T. Smurawska, C. Tran, J. W. Norris, and S. C. Fagan Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke Neurology, March 1, 1999; 52(4): 894 - 894. [Full Text]
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S. R. Levine and M. Gorman "Telestroke" : The Application of Telemedicine for Stroke Stroke, February 1, 1999; 30(2): 464 - 469. [Abstract] [Full Text] [PDF]
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K. D. Flemming and R. D. Brown Jr Acute Cerebral Infarction Caused by Aortic Dissection: Caution in the Thrombolytic Era Stroke, February 1, 1999; 30(2): 477 - 478. [Full Text] [PDF]
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A. M. Demchuk, L. B. Morgenstern, D. W. Krieger, T. Linda Chi, W. Hu, T. H. Wein, R. J. Hardy, J. C. Grotta, and A. M. Buchan Serum Glucose Level and Diabetes Predict Tissue Plasminogen Activator–Related Intracerebral Hemorrhage in Acute Ischemic Stroke Stroke, January 1, 1999; 30(1): 34 - 39. [Abstract] [Full Text] [PDF]
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M. Grond, C. Stenzel, S. Schmulling, J. Rudolf, M. Neveling, A. Lechleuthner, S. Schneweis, and W.-D. Heiss Early Intravenous Thrombolysis for Acute Ischemic Stroke in a Community-Based Approach Stroke, August 1, 1998; 29(8): 1544 - 1549. [Abstract] [Full Text] [PDF]
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L. Robinson and D. Chiu Ischemic Strokes Arriving Too Late for tPA Are an Ideal and Ethical Control Group for Continuing Studies of tPA Efficacy • Response Stroke, July 1, 1998; 29(7): 1476 - 1477. [Full Text]
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