(Stroke. 1999;30:2280-2284.)
© 1999 American Heart Association, Inc.
Original Contributions |
Hemorrhagic Transformation Within 36 Hours of a Cerebral Infarct
Relationships With Early Clinical Deterioration and 3-Month Outcome in the European Cooperative Acute Stroke Study I (ECASS I) Cohort
From the Department of Neurological Science, University La Sapienza, Rome, Italy (M.F., S.B., S.L., L.B.); Department of Neuroradiology, University of Dresden, Dresden, Germany (R. von K.); Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif (G. del Z.); Department of Neurology, University of Toulouse, Toulouse, France (V.L.); Biostatistical Center for Clinical Trials, University of Leuven, Leuven, Belgium (E.L.); Department of Neurology, University of Heidelberg, Heidelberg, Germany (A.P.R.); and the Department of Neuroradiology, University of Toulouse, Toulouse, France (C.M.).
Correspondence to Marco Fiorelli, MD, PhD, Department of Neurological Sciences, University La Sapienza, Viale dell'Università 30, 00185 Rome, Italy. E-mail fiorelli{at}uniroma1.it
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke.
Methods—We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT.
Results—Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13.4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2.
Conclusions—Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.
Key Words: prognosis • stroke, hemorrhagic • tissue plasminogen activator
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Despite our improved understanding of the prevalence and pathogenesis of hemorrhagic transformation of an acute cerebral ischemic infarct, the prognostic implications of hemorrhage in this setting remain uncertain. Although pathological and radiological studies indicate that hemorrhagic transformation is a natural event in the evolution of a cerebral infarct,1 2 3 4 in the clinical setting it is often considered a complication. However, recent observations suggest that the prognosis may vary with the type of hemorrhagic transformation,4 5 6 challenging in particular the view that hemorrhagic infarction (HI) can be a direct cause of neurological deterioration. Regarding parenchymal hematoma (PH), daily clinical experience, as well as data from hospital cohorts4 and clinical trials,6 7 8 9 10 11 12 suggests that it can significantly worsen the clinical course of ischemic stroke.
The potential usefulness of thrombolytic agents in acute ischemic stroke has further increased the interest concerning the clinical correlates of hemorrhagic transformation as detected by CT and described in radiographic terms. Thrombolytic agents not only increase the risk of hemorrhage overall (systemic and central nervous system) but also tend to induce earlier hemorrhagic transformation of cerebral infarctions than is observed in spontaneous evolution, more often of the PH type.13 The cohort of patients recruited in the European Cooperative Acute Stroke Study I (ECASS I),7 a placebo-controlled trial of recombinant tissue plasminogen activator (rtPA) administered intravenously within the first 6 hours of an ischemic hemispheric stroke, was the object of an extensive clinical and radiological data collection. We exploited this database to assess the relationship of hemorrhagic transformation with early evolution of the neurological presentation and final outcome in placebo and rtPA patients. The objectives of this study were to investigate the clinical correlates of different subtypes of hemorrhagic transformation occurring within the first 36 hours from the clinical onset of the infarct.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The ECASS I study design and primary results have been reported in detail elsewhere.7 ECASS I was a double-blind, placebo-controlled trial evaluating safety and efficacy of 1.1 mg/kg rtPA by intravenous delivery in patients presenting within 6 hours from the onset of a hemispheric acute ischemic stroke. The use of intravenous heparin or oral anticoagulants within the first 24 hours was not allowed.
According to the study protocol, all patients were submitted to a CT
scan before randomization. A CT scan was repeated after 24 to 36 hours
(or earlier in case of rapid and severe clinical deterioration) and
again between days 4 and 10. All CT scans were read by an independent
committee of 3 neuroradiologists with extensive experience in acute
stroke. The 3 observers were blinded to both the rtPA/placebo
allocation and the clinical course. After the exclusion of 11 patients
(6 rtPA, 5 placebo) whose CT scans were judged of too poor quality to
allow unequivocal assessment of hemorrhagic changes, 609 patients
remained for the analysis. With the adaptation of preexisting
criteria6 14 to the purposes of ECASS I protocol, HI was
defined as a petechial infarction without space-occupying effect, and
PH was defined as a hemorrhage (coagulum) with mass effect. HIs
were of 2 subtypes: HI1 (small petechiae) and HI2 (more confluent
petechiae). Similarly, there were 2 subtypes of PH: PH1 (
30% of the
infarcted area with some mild space-occupying effect) and PH2 (>30%
of the infarcted area with significant space-occupying effect, or clot
remote from infarcted area). Potential determinants of HI and PH in
ECASS I patients have been investigated and reported in a companion
article.13
The 2-by-2 interrater agreement for the diagnosis of hemorrhagic
transformation (either HI or PH) compared with no hemorrhagic
transformation was good,15 with a 
of 0.77 (95% CI,
0.75 to 0.79). The diagnosis of PH compared with no PH (either HI or no
hemorrhagic transformation) was also characterized by good interrater
agreement (=0.75; 95% CI, 0.72 to 0.77). When the 5-type
classification (no hemorrhagic transformation, HI1, HI2, PH1, or PH2)
was used, the 2-by-2 weighted ranged from 0.67 (95% CI, 0.62 to
0.71) to 0.72 (95% CI, 0.67 to 0.76). The 2-by-2 agreement in
diagnosis of a specific subtype (no hemorrhagic transformation, HI1,
HI2, PH1, or PH2) versus any other diagnostic possibility
was always 
90%. For the purpose of this study, the agreement of at
least 2 of the 3 raters was required to label each scan as showing no
hemorrhagic transformation or a given subtype of
hemorrhage.
For each patient, we retrieved from the database of the trial the
following variables: age, sex, allocation to placebo/rtPA
treatment, severity of neurological deficit on admission as quantified
with the National Institutes of Health Stroke Scale (NIHSS) score, and
presence of early focal hypodensity or swelling due to developing
infarction in the baseline CT. Odds ratios (ORs) and their 95% CIs
were used to evaluate the association of hemorrhagic transformation
with the risk of (1) early deterioration of neurological
presentation (increase of 4 points on the NIHSS score
after 24 hours from baseline assessment),16 (2) death, or
(3) disability (Rankin17 score 1 in survivors within 3
months of stroke). ORs were adjusted by age and extent of initial
ischemic damage on baseline CT scan (0=none, 1=<33% of the
middle cerebral artery territory, and 2=>33% of the middle cerebral
artery territory). Analyses were performed with BMDP
statistical software.18
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Prototypes of the 4 subtypes of hemorrhagic transformation are presented in Figure 1
. Figure 2 illustrates changes in NIHSS score at
24 hours according to presence and type of hemorrhagic transformation.
Two-way ANOVA (factor 1=group, factor 2=allocation to rtPA or placebo
arm) demonstrated a significant (P<0.00001) global
difference in mean baseline-to-24-hour NIHSS score change across the 5
groups exhibiting, respectively, no hemorrhagic transformation
(mean±SD change, -1.6±6.5), HI1 (-1.8±5.5), HI2 (-2.3±6.8), PH1
(-0.6±7.7), and PH2 (16.8±12.3). There was no effect of rtPA or
placebo allocation (P=0.7) on the relationship between
subtype of hemorrhagic transformation and clinical evolution. The
group-by-arm interaction term was also not significant
(P=0.3), which allowed the pooling of placebo and rtPA data
for further comparisons. Two-by-two post hoc t tests
revealed similar changes in NIHSS score at 24 hours across types of
hemorrhagic transformation, except for PH2, whose score was greatly
increased (indicating severe neurological deterioration) compared with
each of the other 4 categories (P=0.00001 or lower).
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The Table shows the frequency of
24-hour neurological deterioration, 3-month death, and 3-month
disability in the ECASS I cohort according to presence and type of
hemorrhagic transformation on 24-hour CT and according to rtPA/placebo
allocation. Figure 3 shows the ORs for
24-hour neurological deterioration, 3-month death, and 3-month
disability according to presence and type of hemorrhagic transformation
and placebo/rt-PA allocation. ORs were adjusted for age and extent of
initial ischemic damage as assessed on baseline CT. After
adjustment, neither HI1 and HI2 (pooled for this analysis to
avoid empty cells) nor PH1 influenced significantly the risks of early
deterioration, 3-month death, or 3-month disability, whereas PH2 was
still associated with a significantly increased risk of 24-hour
deterioration and of 3-month death. Since here again the relationship
between hemorrhagic transformation and outcome was similar in placebo
and rtPA groups, it was possible to estimate the ORs and their 95% CIs
in the whole cohort. Compared with patients without hemorrhagic
transformation, patients with a PH2 had a strongly increased risk of
24-hour deterioration (OR, 32.3; 95% CI, 13.4 to 77.7), and of 3-month
death (OR, 18.0; 95% CI, 8.05 to 40.1). PH2 survivors had a
nonsignificantly higher risk of disability (placebo: OR, 1.8; 95% CI,
0.2 to 20.5; rtPA: OR, 5.4; 95% CI, 0.6 to 47.4).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The results of this retrospective analysis confirm the clinical impression that the outcome after HI differs markedly from PH, when the events are established within the first 36 hours. Patients exhibiting an early HI did not a have a higher risk of neurological deterioration compared with patients without hemorrhagic transformation. Among patients treated with rtPA, HI was even loosely associated with early improvement. Overall, 3-month mortality and disability were also not influenced by HI. These findings may seem in contrast to the observation that hemorrhagic transformation of the HI type is often a proxy for large infarction4 5 and hence a marker of bad outcome in ischemic stroke patients. However, a HI detected within the first 36 hours of ischemic stroke might not be comparable to a HI occurring at a later time, since early petechial changes may indicate that reperfusion occurred when the ischemic tissue was still at least partially viable. Accordingly, in a small-scale, placebo-controlled pilot trial of rtPA (duteplase) conducted by Mori et al19 in 31 ischemic stroke patients, 8 (39%) developed early hemorrhagic transformation without influence on the clinical evolution. As summarized by Lyden and Zivin,20 the relationships between reperfusion and hemorrhagic transformation of a cerebral infarction remain unclear. Experimental studies in the nonhuman primate clearly demonstrate a correlation between petechial (and microscopic) hemorrhage and the loss of microvascular basal lamina/extracellular matrix antigens within the first 24 hours after middle cerebral artery occlusion,21 22 providing a theoretical basis for blood extravasation. However, for a correct appraisal of the functional correlates of early HI, we need further studies on the mechanism of bleeding within the infarcted area and its relationships with reperfusion and clinical status at different times after stroke.
The univariate excess risk of 3-month death shown by patients with PH1 was neither associated with a higher risk of early deterioration nor still evident after adjustment for age and initial severity. This suggests that in most cases early small hematomas can have little if no influence on the clinical course. In contrast to the outcomes of other subtypes of bleeding, PH2 significantly increased the risk of early deterioration and 3-month death even after adjustment for possible confounders, which confirms that clinical and experimental research must focus on the prevention of this type of hemorrhagic transformation. Roughly, 3 of 4 patients with early PH2 deteriorated and died. Compared with patients without any hemorrhagic transformation, survivors from PH2 had a nonsignificantly higher risk of disability, which indicates that, taken alone, disability in survivors does not reflect faithfully the risk-benefit ratio of thrombolytics in acute ischemic stroke. These results need confirmation, since they cannot be compared with those of the retrospective review of intracerebral hemorrhages that occurred in the NINDS rt-PA Stroke Study,23 in which HI and PH were not analyzed separately, or with the analysis made on the cohort of the Multicenter Acute Stroke Trial–Italy, in which only 5-day scans were available.10
Clinical deterioration during the first 24 hours was frequent in the ECASS I cohort, even among patients with no evidence of bleeding on 24-hour CT. This finding suggests that care should be taken in creating mixed clinical/CT definitions such as "symptomatic hemorrhagic transformation" since, for example, in petechial infarction this association of bleeding with clinical worsening is coincidental. A classification of hemorrhages based on radiological criteria might be a more objective tool to characterize hemorrhagic transformation after an ischemic stroke. However, although the classification used in ECASS I proved reliable in the hands of experienced neuroradiologists, its reliability in a less specialized setting has to be assessed. Additionally, if studies in different populations confirm that PH2 is the only clinically relevant subtype of hemorrhagic transformation, the number of categories of ECASS I classification might be reduced accordingly, from the original 5 to 4 or 3. For this reason, we are planning to exploit the database of ECASS II,12 a trial that used a protocol similar to that of ECASS I but recruited patients with milder strokes on average and tested a lower dosage of rtPA (0.9 instead of 1.1 mg/kg).
In conclusion, in the ECASS I cohort, early hemorrhagic transformation after ischemic stroke was associated with a wide range of clinical patterns. Large hematomas, significantly more frequent after rtPA than after placebo, had an ominous prognosis in the vast majority of cases, whereas the clinical outcome of cerebral infarction did not appear to be modified by the occurrence of other subtypes of hemorrhagic transformation within the first 36 hours from onset.
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Acknowledgments |
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ECASS I was supported exclusively by Dr Karl Thomae, GmbH, a member of Boehringer Ingelheim, Biberach, Germany. Jim Koziol, PhD, kindly provided helpful comments. The advice and support of Dieter Meier, MD, were greatly appreciated.
Received June 17, 1999; revision received July 19, 1999; accepted July 30, 1999.
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R. L. Sacco, R. Adams, G. Albers, M. J. Alberts, O. Benavente, K. Furie, L. B. Goldstein, P. Gorelick, J. Halperin, R. Harbaugh, et al. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke, February 1, 2006; 37(2): 577 - 617. [Abstract] [Full Text] [PDF]
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J. H. Choi, B. T. Bateman, S. Mangla, R. S. Marshall, S. Prabhakaran, J. Chong, J. P. Mohr, H. Mast, and J. Pile-Spellman Endovascular Recanalization Therapy in Acute Ischemic Stroke Stroke, February 1, 2006; 37(2): 419 - 424. [Abstract] [Full Text] [PDF]
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P. Trouillas and R. von Kummer Classification and Pathogenesis of Cerebral Hemorrhages After Thrombolysis in Ischemic Stroke Stroke, February 1, 2006; 37(2): 556 - 561. [Abstract] [Full Text] [PDF]
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 C. Tanaka, T. Ueguchi, E. Shimosegawa, N. Sasaki, T. Johkoh, H. Nakamura, and J. Hatazawa Effect of CT Acquisition Parameters in the Detection of Subtle Hypoattenuation in Acute Cerebral Infarction: A Phantom Study AJNR Am. J. Neuroradiol., January 1, 2006; 27(1): 40 - 45. [Abstract] [Full Text] [PDF]
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R. J. Seitz, S. Meisel, P. Weller, U. Junghans, H.-J. Wittsack, and M. Siebler Initial Ischemic Event: Perfusion-weighted MR Imaging and Apparent Diffusion Coefficient for Stroke Evolution Radiology, December 1, 2005; 237(3): 1020 - 1028. [Abstract] [Full Text] [PDF]
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T. G. Jovin, R. Gupta, K. Uchino, C. A. Jungreis, L. R. Wechsler, M. D. Hammer, A. Tayal, and M. B. Horowitz Emergent Stenting of Extracranial Internal Carotid Artery Occlusion in Acute Stroke Has a High Revascularization Rate Stroke, November 1, 2005; 36(11): 2426 - 2430. [Abstract] [Full Text] [PDF]
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M S Mouradian, A Senthilselvan, G Jickling, J A McCombe, D J Emery, N Dean, and A Shuaib Intravenous rt-PA for acute stroke: comparing its effectiveness in younger and older patients J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1234 - 1237. [Abstract] [Full Text] [PDF]
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M. Daffertshofer, A. Gass, P. Ringleb, M. Sitzer, U. Sliwka, T. Els, O. Sedlaczek, W. J. Koroshetz, and M. G. Hennerici Transcranial Low-Frequency Ultrasound-Mediated Thrombolysis in Brain Ischemia: Increased Risk of Hemorrhage With Combined Ultrasound and Tissue Plasminogen Activator: Results of a Phase II Clinical Trial Stroke, July 1, 2005; 36(7): 1441 - 1446. [Abstract] [Full Text] [PDF]
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H. J. Audebert, C. Kukla, S. Clarmann von Claranau, J. Kuhn, B. Vatankhah, J. Schenkel, G. W. Ickenstein, R. L. Haberl, M. Horn, and on behalf of the TEMPiS Group Telemedicine for Safe and Extended Use of Thrombolysis in Stroke: The Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria Stroke, February 1, 2005; 36(2): 287 - 291. [Abstract] [Full Text] [PDF]
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M. Hermier and N. Nighoghossian Contribution of Susceptibility-Weighted Imaging to Acute Stroke Assessment Stroke, August 1, 2004; 35(8): 1989 - 1994. [Abstract] [Full Text] [PDF]
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M.-C. Arnould, C. B. Grandin, A. Peeters, G. Cosnard, and T. P. Duprez Comparison of CT and Three MR Sequences for Detecting and Categorizing Early (48 Hours) Hemorrhagic Transformation inHyperacute Ischemic Stroke AJNR Am. J. Neuroradiol., June 1, 2004; 25(6): 939 - 944. [Abstract] [Full Text] [PDF]
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P. Trouillas, L. Derex, F. Philippeau, N. Nighoghossian, J. Honnorat, M. Hanss, P. Ffrench, P. Adeleine, and M. Dechavanne Early Fibrinogen Degradation Coagulopathy Is Predictive of Parenchymal Hematomas in Cerebral rt-PA Thrombolysis: A Study of 157 Cases Stroke, June 1, 2004; 35(6): 1323 - 1328. [Abstract] [Full Text] [PDF]
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A. Montavont, N. Nighoghossian, L. Derex, M. Hermier, J. Honnorat, F. Philippeau, M. Belo, F. Turjman, P. Adeleine, J. C. Froment, et al. Intravenous r-TPA in vertebrobasilar acute infarcts Neurology, May 25, 2004; 62(10): 1854 - 1856. [Abstract] [Full Text] [PDF]
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P H Lee, S H Oh, O Y Bang, I S Joo, and K Huh Isolated middle cerebral artery disease: clinical and neuroradiological features depending on the pathogenesis J. Neurol. Neurosurg. Psychiatry, May 1, 2004; 75(5): 727 - 732. [Abstract] [Full Text] [PDF]
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D. M. Kent, J. Hinchey, L. L. Price, S. R. Levine, and H. P. Selker In Acute Ischemic Stroke, Are Asymptomatic Intracranial Hemorrhages Clinically Innocuous? Stroke, May 1, 2004; 35(5): 1141 - 1146. [Abstract] [Full Text] [PDF]
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R. J. Seitz, M. Hamzavi, U. Junghans, P. A. Ringleb, C. Schranz, and M. Siebler Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Stroke: Preliminary Observations Stroke, August 1, 2003; 34(8): 1932 - 1935. [Abstract] [Full Text] [PDF]
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M. D. Hill, H. A. Rowley, F. Adler, M. Eliasziw, A. Furlan, R. T. Higashida, L. R. Wechsler, H. C. Roberts, W. P. Dillon, N. J. Fischbein, et al. Selection of Acute Ischemic Stroke Patients for Intra-Arterial Thrombolysis With Pro-Urokinase by Using ASPECTS Stroke, August 1, 2003; 34(8): 1925 - 1931. [Abstract] [Full Text] [PDF]
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V. S. Caviness, N. Makris, E. Montinaro, N. T. Sahin, J. F. Bates, L. Schwamm, D. Caplan, and D. N. Kennedy Anatomy of Stroke, Part I: An MRI-Based Topographic and Volumetric System of Analysis Stroke, November 1, 2002; 33(11): 2549 - 2556. [Abstract] [Full Text] [PDF]
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A.K. Gilligan, R. Markus, S. Read, V. Srikanth, T. Hirano, G. Fitt, M. Arends, B.R. Chambers, S.M. Davis, and G.A. Donnan Baseline Blood Pressure but Not Early Computed Tomography Changes Predicts Major Hemorrhage After Streptokinase in Acute Ischemic Stroke Stroke, September 1, 2002; 33(9): 2236 - 2242. [Abstract] [Full Text] [PDF]
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R. von Kummer Brain Hemorrhage After Thrombolysis: Good or Bad? Stroke, June 1, 2002; 33(6): 1446 - 1447. [Full Text] [PDF]
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C. A. Molina, J. Alvarez-Sabin, J. Montaner, S. Abilleira, J. F. Arenillas, P. Coscojuela, F. Romero, and A. Codina Thrombolysis-Related Hemorrhagic Infarction: A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion Stroke, June 1, 2002; 33(6): 1551 - 1556. [Abstract] [Full Text] [PDF]
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C. Neumann-Haefelin, G. Brinker, U. Uhlenkuken, F. Pillekamp, K-A. Hossmann, and M. Hoehn Prediction of Hemorrhagic Transformation After Thrombolytic Therapy of Clot Embolism: An MRI Investigation in Rat Brain Stroke, May 1, 2002; 33(5): 1392 - 1398. [Abstract] [Full Text] [PDF]
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P.A. Ringleb, P.D. Schellinger, C. Schranz, and W. Hacke Thrombolytic Therapy Within 3 to 6 Hours After Onset of Ischemic Stroke: Useful or Harmful? Stroke, May 1, 2002; 33(5): 1437 - 1441. [Abstract] [Full Text] [PDF]
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N. Nighoghossian, M. Hermier, P. Adeleine, K. Blanc-Lasserre, L. Derex, J. Honnorat, F. Philippeau, J.F. Dugor, J.C. Froment, and P. Trouillas Old Microbleeds Are a Potential Risk Factor for Cerebral Bleeding After Ischemic Stroke: A Gradient-Echo T2*-Weighted Brain MRI Study Stroke, March 1, 2002; 33(3): 735 - 742. [Abstract] [Full Text] [PDF]
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H. P. Adams Jr Emergent Use of Anticoagulation for Treatment of Patients With Ischemic Stroke Stroke, March 1, 2002; 33(3): 856 - 861. [Abstract] [Full Text] [PDF]
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L. Zhang, Z. G. Zhang, R. L. Zhang, M. Lu, J. Adams, P. J. Elliott, and M. Chopp Postischemic (6-Hour) Treatment With Recombinant Human Tissue Plasminogen Activator and Proteasome Inhibitor PS-519 Reduces Infarction in a Rat Model of Embolic Focal Cerebral Ischemia Stroke, December 1, 2001; 32(12): 2926 - 2931. [Abstract] [Full Text] [PDF]
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S. Nakano, T. Iseda, H. Kawano, T. Yoneyama, T. Ikeda, and S. Wakisaka Parenchymal Hyperdensity on Computed Tomography After Intra-Arterial Reperfusion Therapy for Acute Middle Cerebral Artery Occlusion: Incidence and Clinical Significance Stroke, September 1, 2001; 32(9): 2042 - 2048. [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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C. A. Molina, J. Montaner, S. Abilleira, B. Ibarra, F. Romero, J. F. Arenillas, and J. Alvarez-Sabin Timing of Spontaneous Recanalization and Risk of Hemorrhagic Transformation in Acute Cardioembolic Stroke Stroke, May 1, 2001; 32(5): 1079 - 1084. [Abstract] [Full Text] [PDF]
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Y. Fujii, S. Takeuchi, A. Harada, H. Abe, O. Sasaki, and R. Tanaka Hemostatic Activation in Spontaneous Intracerebral Hemorrhage Stroke, April 1, 2001; 32(4): 883 - 890. [Abstract] [Full Text] [PDF]
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S. Leistner, F. Boegner, P. Marx, and H.-C. Koennecke Transtentorial Herniation After Unilateral Infarction of the Anterior Cerebral Artery Stroke, March 1, 2001; 32(3): 649 - 651. [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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V. Larrue, R. von Kummer, A. Muller, and E. Bluhmki Risk Factors for Severe Hemorrhagic Transformation in Ischemic Stroke Patients Treated With Recombinant Tissue Plasminogen Activator : A Secondary Analysis of the European-Australasian Acute Stroke Study (ECASS II) Stroke, February 1, 2001; 32(2): 438 - 441. [Abstract] [Full Text] [PDF]
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L. Candelise, A. Ciccone, C. Motto, M. Fiorelli, R. v. Kummer, S. Bastianello, and L. Bozzao Extraparenchymal Bleeding Predicts an Unfavorable Outcome in Patients With Hemorrhagic Transformation Response Stroke, July 1, 2000; 31(7): 1785 - 1790. [Full Text] [PDF]
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 Larger Hematomas Are Associated with Poor Outcome in Ischemic Stroke Journal Watch Neurology, February 1, 2000; 2000(201): 3 - 3. [Full Text]
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