(Stroke. 2001;32:89.)
© 2001 American Heart Association, Inc.
Original Contributions |
From the Seaman Family MR Research Centre, Department of Clinical Neurosciences, University of Calgary, Calgary, Canada (A.M.D., P.A.B., M.D.H.), and Center for Noninvasive Brain Perfusion Studies, Stroke Program, Department of Neurology, University of TexasHouston (A.M.D., W.S.B., I.C., R.A.F., A.V.A.).
Correspondence to Dr Andrew M. Demchuk, Seaman Family MR Research Centre, Department of Clinical Neurosciences, University of Calgary, 1403 29 St NW, Calgary AB, Canada T2N 2T9. E-mail ademchuk{at}dcns.ucalgary.ca
| Abstract |
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MethodsTCD examination occurred acutely and on day 2. TIBI flows were determined at distal MCA and basilar artery depths, depending on occlusion site. TIBI waveforms were graded as follows: 0, absent; 1, minimal; 2, blunted; 3, dampened; 4, stenotic; and 5, normal. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours after administration of tPA.
ResultsOne hundred nine IV tPA patients were studied. Mean±SD age was 68±16 years; median NIHSS score before administration of tPA (pre-tPA) was 17.5. The tPA bolus was administered 143±58 minutes and the TCD examination 141±57 minutes after symptom onset. Pre-tPA NIHSS scores were higher in patients with TIBI grade 0 than TIBI grade 4 or 5 flow. TIBI flow improvement to grade 4 or 5 occurred in 35% of patients (19/54) with an initial grade of 0 or 1 and in 52% (12/23) with initial grade 2 or 3. The 24-hour NIHSS scores were higher in follow-up in patients with TIBI grade 0 or 1 than those with TIBI grade 4 or 5 flow. TIBI flow recovery correlated with NIHSS score improvement. Lack of flow recovery predicted worsening or no improvement. In-hospital mortality was 71% (5/7) for patients with posterior circulation occlusions; it was 22% (11/51) for patients with pre-tPA TIBI 0 or 1 compared with 5% (1/19) for those with pre-tPA TIBI 2 or 3 anterior circulation occlusions.
ConclusionsEmergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPAtreated stroke patients. A flow-grade improvement correlated with clinical improvement.
Key Words: stroke, acute thrombolysis ultrasound ultrasonography, Doppler, transcranial
| Introduction |
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| Subjects and Methods |
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In patients with evidence of anterior circulation occlusion
(internal carotid artery [ICA], MCA, or both), TIBI flow grade was
determined via a transtemporal window at a depth of
54 mm, corresponding to the distal MCA arterial bed.
In patients with evidence of posterior circulation occlusion (vertebral
artery or BA), TIBI flow grade was determined through the
transforaminal window at depth of 80 to 100 mm, corresponding to
BA stem location. For the purposes of this study, the worst flow signal
determined at the presumed occlusion site was
analyzed.
The 2 centers adopted similar approaches to performing and interpreting the TCD examinations. At both sites, a stroke neurologist performed the TCD study and interpreted the results immediately. At the Calgary site, a stroke nurse coordinator also was trained in TCD examination and performed some of the studies. Houston neurosonographers were generally more experienced than the Calgary counterparts with TCD examination.
The TIBI residual flow classification consists of 6 grades.
The individual flow grades are described and illustrated in
Figure 1
.
|
Patient age, sex, and baseline stroke severity (using the National Institutes of Health Stroke Scale [NIHSS] score) were prospectively collected on all patients. A follow-up NIHSS score was obtained at 24 hours after stroke onset. A follow-up TCD was repeated several hours after tPA infusion, usually the following day. All intracranial hemorrhages, including symptomatic intracerebral hemorrhage, were identified on the basis of review of the follow-up CT. In-hospital mortality was determined prospectively.
Patients NIHSS scores were grouped according to their TIBI
grade, and mean scores were compared, by group, with the Kruskal-Wallis
test. Trends were assessed by using the Wilcoxon rank sum
extension method of Cuzick.9
Improvement was assessed by categorizing the change from baseline to
24-hour NIHSS score as <5 or
5 and by categorizing the improvement
in TIBI grade as true or false. All comparisons of proportions were
done with the Fisher exact test.
| Results |
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Baseline NIHSS scores were strongly associated with baseline
TIBI grades (P=0.004;
Figure 2A
). The 24-hour NIHSS scores were strongly
associated with follow up TIBI grades
(P=0.002)
(Figure 2B
). Similarly strong trends were observed with
increasing NIHSS scores associated with poorer TIBI flow grades at both
the baseline and 24-hour time points
(P<0.001).
|
TIBI flow improvement to grades 4 or 5 occurred in 35% of patients (19/54) with an initial grade of 0 or 1 and 52% (12/23) with initial grade 2 or 3. No patient with an initial TIBI grade of 4 or 5 deteriorated in flow grade. Flow-grade improvement occurred in 2 of 2 isolated ICA occlusions, 22 of 49 isolated MCA occlusions (45%), and only 4 of 20 tandem ICA/MCA occlusions (20%).
The change in TIBI flow grade between baseline and follow-up
examinations was significantly associated with change in NIHSS score
(P<0.001)
(Figure 2C
). Improvement by baseline TIBI category is shown
in the
Table
.
Flow that did not improve was matched with little or not improvement in
the NIHSS score at 24 h.
|
In-hospital mortality was 71% (5/7) for posterior circulation occlusion and 17% (12/70) for anterior circulation occlusion (Fisher exact test, P=0.005). Among anterior circulation occlusions, there was 22% mortality (11/51) in patients with baseline TIBI grades 0 or 1 and 5.3% (1/19) in those with baseline grades 2 or 3. Symptomatic intracerebral hemorrhage occurred in 6 patients (6.4%). Among patients who suffered symptomatic ICH, 3 had poor flow (baseline TIBI grade 1 to 3) and 3 had good flow (baseline grade 4 to 5). Of 4 patients who died of symptomatic hemorrhage, 3 had baseline TIBI grade 4 or 5 flow. However, 1 of these patients died of a remote hemorrhage into the brain stem rather than into the area of MCA ischemia.
| Discussion |
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Vascular imaging is currently lacking in the standard emergent evaluation of acute stroke. Critics of the across-the-board use of systemic tPA suggest that vascular imaging is needed to better identify patients who will and will not benefit from this treatment.11 Several studies12 13 have previously shown that TCD findings in the setting of acute stroke have utility through their prediction of clinical outcome. Patients with acutely normal TCD results appear to have favorable prognosis.14 An abnormal TCD study, defined as no or asymmetrical MCA flow signal, is associated with poor outcome.15 Development of the TIBI classification is an extension of previous work that examined the potential value of TCD as a vascular study for acute stroke, particularly in the setting of thrombolytic treatment.6 16 We have previously developed diagnostic TCD criteria for each site of arterial occlusion and recanalization that is accurate and correlates with angiographic occlusion and recanalization.7 17
Because mortality was significantly higher in patients with a poor TIBI grade at baseline, the TIBI grading system may be prognostically useful early in the course of hospitalization. Equally, the group with very poor TIBI grades (TIBI 0 and 1) may be an ideal target for additional intra-arterial thrombolytic or mechanical interventions. Similarly, the change in TIBI flow from baseline to follow-up may aid physicians in providing an early assessment of outcome and facilitating disposition planning.
A surprising and alarming finding of this study was that was 3 symptomatic intracerebral hemorrhages occurred in patients with normal baseline TIBI flow grades (25% symptomatic ICH rate among initial TIBI grade 5 patients). This finding raises the question of whether tPA could be harmful in a setting of "freshly" reperfused brain. Recent animal studies18 19 have suggested that alteplase may enhance blood-brain barrier disruption. An animal study20 of embolic focal cerebral ischemia revealed a significant increase in hemorrhage volumes when tPA was administered at the time of late mechanical reperfusion compared with no hemorrhage with late mechanical reperfusion alone. Further scrutiny of this subgroup of patients is needed to understand whether alteplase benefits patients with open arteries and "stunned brain" and whether alteplase increases the risk of hemorrhage.
There are potential limitations of the TIBI classification. First, TIBI grade 0 (or absent flow) could have been inappropriately concluded because of technical problems, such as inadequate bony windows, inconsistent technical skill, or absence of imaging control with TCD. We feel that this source of error was minimized by the considerable effort that was made in each instance to find the bony window. In most cases, a good posterior cerebral artery waveform or proximal MCA/anterior cerebral artery waveforms were identified to ensure that a good window had been identified. The second limitation is that TIBI flow grades were not compared with gold-standard imaging techniques that may visualize residual flow. Studies are required to evaluate the relationship between TIBI grades and gold-standard imaging, such as high-resolution contrast angiography. Our group has utilized aspects of the TIBI classification to develop TCD criteria for recanalization. With use of these criteria, TCD has excellent correlation with angiography for complete recanalization (sensitivity 91%, specificity 93%).17 (The number of tPA patients also undergoing angiography was too small to include in this study.)
The third limitation is the lack of information regarding importance of TIBI in arterial segments other than those affected by ischemia. TCD can directly insonate proximal vascular structures such as M1 MCA, A1 anterior cerebral artery, and P1-P2 posterior cerebral artery. TCD can only indirectly provide information about more distal vascularity. In this study, only MCA and BA segments were evaluated to concentrate on the perfusion status in the critical brain areas most often affected by ischemia. A further study of the TIBI classification in other proximal arterial segments is needed.
This study introduces a novel TCD flow grading system that is prognostically useful, and a companion paper will describe reliability of the scale. TIBI correlates with clinical deficit, clinical improvement, and mortality in a series of thrombolytically treated stroke patients. An improvement in TIBI flow during TCD monitoring is an important positive predictor. In the future, this scale could be used as an inexpensive, real-time surrogate marker of thrombolytic effectiveness to enable rapid assessment of various thrombolytic treatments and delivery strategies in stroke. We feel the TIBI classification should be incorporated into the standard acute stroke TCD examination and interpretation. The real advantage of TCD is lost if only flow velocity differences are reported and other hemodynamic findings are left behind. TIBI flow grades show information that can be obtained through waveform analysis and provide a convenient way to communicate the results similar to other angiographic scales. After residual flow waveform is identified, this information can be incorporated into TCD interpretation targeted to provide assessment of vessel patency.
Future studies should examine the prognostic role of TIBI flow in patients not receiving thrombolytic therapy. Such a quantitative score, once shown valid and reliable, could have important implications in assisting clinical investigation and treatment of acute stroke.
| Acknowledgments |
|---|
Received June 16, 2000;
revision received August 22, 2000;
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M. Ribo, C. Molina, J. Montaner, M. Rubiera, R. Delgado-Mederos, J. F. Arenillas, M. Quintana, and J. Alvarez-Sabin Acute Hyperglycemia State Is Associated With Lower tPA-Induced Recanalization Rates in Stroke Patients Stroke, August 1, 2005; 36(8): 1705 - 1709. [Abstract] [Full Text] [PDF] |
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O. O. Zaidat, J. I. Suarez, J. L. Sunshine, R. W. Tarr, M. J. Alexander, T. P. Smith, D. S. Enterline, W. R. Selman, and D. M. D. Landis Thrombolytic Therapy of Acute Ischemic Stroke: Correlation of Angiographic Recanalization with Clinical Outcome AJNR Am. J. Neuroradiol., April 1, 2005; 26(4): 880 - 884. [Abstract] [Full Text] [PDF] |
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M. Saqqur, A. Shuaib, A. V. Alexandrov, M. D. Hill, S. Calleja, T. Tomsick, J. Broderick, and A. M. Demchuk Derivation of Transcranial Doppler Criteria for Rescue Intra-arterial Thrombolysis: Multicenter Experience From the Interventional Management of Stroke Study Stroke, April 1, 2005; 36(4): 865 - 868. [Abstract] [Full Text] [PDF] |
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J. Eggers, G. Seidel, B. Koch, and I. R. Konig Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA Neurology, March 22, 2005; 64(6): 1052 - 1054. [Abstract] [Full Text] [PDF] |
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M. Ribo, C. A. Molina, A. Rovira, M. Quintana, P. Delgado, J. Montaner, E. Grive, J. F. Arenillas, and J. Alvarez-Sabin Safety and Efficacy of Intravenous Tissue Plasminogen Activator Stroke Treatment in the 3- to 6-Hour Window Using Multimodal Transcranial Doppler/MRI Selection Protocol Stroke, March 1, 2005; 36(3): 602 - 606. [Abstract] [Full Text] [PDF] |
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O. Y. Chernyshev, Z. Garami, S. Calleja, J. Song, M. S. Campbell, E. A. Noser, H. Shaltoni, C.-I Chen, Y. Iguchi, J. C. Grotta, et al. Yield and Accuracy of Urgent Combined Carotid/Transcranial Ultrasound Testing in Acute Cerebral Ischemia Stroke, January 1, 2005; 36(1): 32 - 37. [Abstract] [Full Text] [PDF] |
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A. V. Alexandrov, C. A. Molina, J. C. Grotta, Z. Garami, S. R. Ford, J. Alvarez-Sabin, J. Montaner, M. Saqqur, A. M. Demchuk, L. A. Moye, et al. Ultrasound-Enhanced Systemic Thrombolysis for Acute Ischemic Stroke N. Engl. J. Med., November 18, 2004; 351(21): 2170 - 2178. [Abstract] [Full Text] [PDF] |
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A. V. Alexandrov Ultrasound Identification and Lysis of Clots Stroke, November 1, 2004; 35(11_suppl_1): 2722 - 2725. [Abstract] [Full Text] [PDF] |
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G. Saposnik, B. Young, B. Silver, S. Di Legge, F. Webster, V. Beletsky, V. Jain, Y. Nilanont, and V. Hachinski Lack of Improvement in Patients With Acute Stroke After Treatment With Thrombolytic Therapy: Predictors and Association With Outcome JAMA, October 20, 2004; 292(15): 1839 - 1844. [Abstract] [Full Text] [PDF] |
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G. Seidel, K. Meyer-Wiethe, G. Berdien, D. Hollstein, D. Toth, and T. Aach Ultrasound Perfusion Imaging in Acute Middle Cerebral Artery Infarction Predicts Outcome Stroke, May 1, 2004; 35(5): 1107 - 1111. [Abstract] [Full Text] [PDF] |
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E. Stolz, S. Trittmacher, A. Rahimi, T. Gerriets, C. Rottger, R. Siekmann, and M. Kaps Influence of Recanalization on Outcome in Dural Sinus Thrombosis: A Prospective Study Stroke, February 1, 2004; 35(2): 544 - 547. [Abstract] [Full Text] [PDF] |
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A. V. Alexandrov, C. E. Hall, L. A. Labiche, A. W. Wojner, and J. C. Grotta Ischemic Stunning of the Brain: Early Recanalization Without Immediate Clinical Improvement in Acute Ischemic Stroke Stroke, February 1, 2004; 35(2): 449 - 452. [Abstract] [Full Text] [PDF] |
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M. Ribo, Z. Garami, K. Uchino, J. Song, C. A. Molina, and A. V. Alexandrov Detection of Reversed Basilar Flow With Power-Motion Doppler After Acute Occlusion Predicts Favorable Outcome Stroke, January 1, 2004; 35(1): 79 - 82. [Abstract] [Full Text] [PDF] |
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D. L. Brown, K. C. Johnston, D. P. Wagner, and E. C. Haley Jr Predicting Major Neurological Improvement With Intravenous Recombinant Tissue Plasminogen Activator Treatment of Stroke Stroke, January 1, 2004; 35(1): 147 - 150. [Abstract] [Full Text] [PDF] |
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T. Neumann-Haefelin, R. du Mesnil de Rochemont, J.B. Fiebach, A. Gass, C. Nolte, T. Kucinski, J. Rother, M. Siebler, O.C. Singer, K. Szabo, et al. Effect of Incomplete (Spontaneous and Postthrombolytic) Recanalization After Middle Cerebral Artery Occlusion: A Magnetic Resonance Imaging Study Stroke, January 1, 2004; 35(1): 109 - 114. [Abstract] [Full Text] [PDF] |
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R. T. Higashida and A. J. Furlan Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke Stroke, August 1, 2003; 34 (8): e109 - e137. [Abstract] [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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C Foerch, R Du Mesnil de Rochemont, O Singer, T Neumann-Haefelin, M Buchkremer, F E Zanella, H Steinmetz, and M Sitzer S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion J. Neurol. Neurosurg. Psychiatry, March 1, 2003; 74(3): 322 - 325. [Abstract] [Full Text] [PDF] |
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L. A. Labiche, F. Al-Senani, A. W. Wojner, J. C. Grotta, M. Malkoff, and A. V. Alexandrov Is the Benefit of Early Recanalization Sustained at 3 Months?: A Prospective Cohort Study Stroke, March 1, 2003; 34(3): 695 - 698. [Abstract] [Full Text] [PDF] |
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J. Rother, P.D. Schellinger, A. Gass, M. Siebler, A. Villringer, J.B. Fiebach, J. Fiehler, O. Jansen, T. Kucinski, V. Schoder, et al. Effect of Intravenous Thrombolysis on MRI Parameters and Functional Outcome in Acute Stroke <6 Hours Stroke, October 1, 2002; 33(10): 2438 - 2445. [Abstract] [Full Text] [PDF] |
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A. V. Alexandrov and J. C. Grotta Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator Neurology, September 24, 2002; 59(6): 862 - 867. [Abstract] [Full Text] [PDF] |
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M. D. Hill, P. A. Barber, A. M. Demchuk, N. J. Newcommon, A. Cole-Haskayne, K. Ryckborst, L. Sopher, A. Button, W. Hu, M. E. Hudon, et al. Acute Intravenous-Intra-Arterial Revascularization Therapy for Severe Ischemic Stroke Stroke, January 1, 2002; 33(1): 279 - 282. [Abstract] [Full Text] [PDF] |
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C. A. Molina, J. Montaner, S. Abilleira, J. F. Arenillas, M. Ribo, R. Huertas, F. Romero, and J. Alvarez-Sabin Time Course of Tissue Plasminogen Activator-Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study Stroke, December 1, 2001; 32(12): 2821 - 2827. [Abstract] [Full Text] [PDF] |
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M. Ma, J. Berger, and A. M. Demchuk A Novel TCD Grading System for Residual Flow in Stroke Patients Stroke, October 1, 2001; 32(10): 2446 - 2446. [Full Text] [PDF] |
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A. V. Alexandrov, W. S. Burgin, A. M. Demchuk, A. El-Mitwalli, and J. C. Grotta Speed of Intracranial Clot Lysis With Intravenous Tissue Plasminogen Activator Therapy : Sonographic Classification and Short-Term Improvement Circulation, June 19, 2001; 103(24): 2897 - 2902. [Abstract] [Full Text] [PDF] |
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