(Stroke. 2000;31:610.)
© 2000 American Heart Association, Inc.
Original Contributions |
High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring
From the Center for Noninvasive Brain Perfusion Studies (A.V.A., R.A.F., I.C., W.S.B., M.M., A.W.W., J.C.G.), Stroke Treatment Team, University of Texas–Houston Medical School; and Department of Clinical Neurosciences (A.M.D., P.A.B.), University of Calgary, Alberta, Canada.
Correspondence to Dr A. Alexandrov, MSB 7.044 6431 Fannin St, University of Texas, Houston, TX 77030. E-mail avalexandrov{at}worldnet.att.net
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—Clot dissolution with tissue plasminogen activator (tPA) can lead to early clinical recovery after stroke. Transcranial Doppler (TCD) with low MHz frequency can determine arterial occlusion and monitor recanalization and may potentiate thrombolysis.
Methods—Stroke patients receiving intravenous tPA were monitored during infusion with portable TCD (Multigon 500M; DWL MultiDop-T) and headframe (Marc series; Spencer Technologies). Residual flow signals were obtained from the clot location identified by TCD. National Institutes of Health Stroke Scale (NIHSS) scores were obtained before and after tPA infusion.
Results—Forty patients were studied (mean age 70±16 years,
baseline NIHSS score 18.6±6.2, tPA bolus at 132±54 minutes from
symptom onset). TCD monitoring started at 125±52 minutes and continued
for the duration of tPA infusion. The middle cerebral artery was
occluded in 30 patients, the internal carotid artery was occluded in 11
patients, the basilar artery was occluded in 3 patients, and occlusions
were multiple in 7 patients; 4 patients had no windows; and 1 patient
had a normal TCD. Recanalization on TCD was found
at 45±20 minutes after tPA bolus: recanalization
was complete in 12 (30%) and partial in 16 (40%) patients. Dramatic
recovery during tPA infusion (total NIHSS score <3) occurred in 8
(20%) of all patients (baseline NIHSS range 6 to 22; all 8 had
complete recanalization). Lack of improvement or
worsening was associated with no recanalization,
late recanalization, or reocclusion on TCD
(C=0.811, P
0.01). Improvement by 
10 NIHSS points or
complete recovery was found in 30% of all patients at the end of tPA
infusion and in 40% at 24 hours. Improvement by 4 NIHSS points was
found in 62.5% of patients at 24 hours.
Conclusions—Dramatic recovery during tPA therapy occurred in 20%
of all patients when infusion was continuously monitored with TCD.
Recovery was associated with recanalization on TCD,
whereas no early improvement indicated persistent occlusion or
reocclusion. At 24 hours, 40% of all patients improved by 10 NIHSS
points or recovered completely. Ultrasonic energy transmission by TCD
monitoring may expose more clot surface to tPA and facilitate
thrombolysis and deserves a controlled trial as a way
to potentiate the effect of tPA therapy.
Key Words: outcome • stroke, acute • thrombolysis • ultrasonography, Doppler, transcranial
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The intravenous administration of tissue plasminogen activator (tPA) can dissolve thrombi and improve the long-term outcome of patients with acute ischemic stroke.1 2 In the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, 47% of patients treated with tPA improved by
4 points on the National
Institutes of Health Stroke Scale (NIHSS) at 24 hours.2 In
the placebo group, 39% of patients showed a similar improvement
(P=0.06, NS).2 A post-hoc analysis
showed that by 24 hours, 27% of tPA-treated patients improved by 10
points or resolved their neurological deficit completely compared with
12% in the placebo group (P=0.002).3
The mechanism of early improvement is attributable to early brain
tissue reperfusion and arterial
recanalization.2 4 5 6 7
Transcranial Doppler (TCD) can be used to determine
arterial occlusion and to continuously monitor
recanalization during
thrombolysis.6 7 We previously established
the accuracy parameters of TCD diagnosis of intracranial
arterial occlusion and recanalization
compared with the use of angiographic studies.8 9 10 TCD
had a sensitivity of 91% and a specificity of 93% to determine
complete recanalization of the middle cerebral
artery (MCA) in tPA-treated patients.9 TCD had a
specificity of 90% for other arterial segments,
indicating that a normal TCD examination is highly predictive of
arterial patency at angiography.8 Furthermore,
continuous clot exposure to ultrasound frequencies in the kilohertz to
low megahertz range enhances tPA activity in vitro, and clot
degradation with 1-MHz ultrasound irradiation was 1.8 times greater
than that with tPA alone.11 12 13 14 15
In the present study, we prospectively applied TCD to identify the occlusion site before the tPA bolus and to continuously monitor the residual flow signals during tPA infusion. The goal was to establish the rate of complete arterial recanalization during tPA infusion and its possible correlation with an early dramatic clinical improvement.7
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Consecutive patients who were treated with intravenous tPA and received continuous TCD monitoring between July 1998 and September 1999 were included in the study. tPA was administered in a standard 0.9 mg/kg dose (10% bolus, 90% continuous infusion over 1 hour) to patients presenting within the first 3 hours after symptom onset. In selected patients presenting between 3 to 6 hours of onset or with other risk for hemorrhagic complications, tPA was administered in a dose of 0.6 mg/kg (15% bolus, 85% continuous infusion over 30 minutes). This experimental protocol was approved by the University of Texas Committee for Protection of Human Subjects.
A standard TCD examination was performed in the emergency department before tPA bolus with a single-channel portable unit (Multigon 500M or DWL MultiDop-T). No delay in tPA administration was experienced as a result of the ultrasound examination. TCD was used to identify the site of intracranial occlusion according to previously published diagnostic criteria.8 Once the occlusion was diagnosed with handheld examination, the presumed clot location and residual flow around it were determined through the presence of abnormal flow signals (minimal, blunted, or dampened waveforms).8
To select the depth for single gate monitoring, the following algorithm was used.
Distal M1–M2 MCA Occlusion
The residual flow signals had to be found at 40 to 45 mm
and the monitoring depth was set accordingly (Figure
, A).
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Proximal M1 MCA Occlusion
Monitoring was performed at 55 to 60 mm.
Asonic MCA Occlusion 1
If no signal could be obtained from the entire stem of an
occluded artery, the flow void depth closest to the normal signal was
selected. For example, monitoring depth was set at 60 to 65 mm if
no MCA signals were found in the presence of a normal anterior cerebral
artery.
Asonic MCA Occlusion 2
If no flow signals were detected from the distal part and the
abnormal signals were obtained at the proximal part of the MCA, the
monitoring depth was set at the depth that displayed the abnormal
signal closest to the signal void depths.
Internal Carotid Artery Occlusion
If the internal carotid artery (ICA) was occluded without tandem
proximal MCA occlusion, the distal MCA flow signal was monitored at 40
to 45 mm.
T-Type ICA Occlusion
If the terminal ICA was occluded with no or minimal signals from
M1 and A1 segments, the MCA origin was monitored at 65 mm.
Basilar Artery Occlusion
A similar algorithm was applied to select depths of 80 mm
(proximal basilar artery) or 100 mm (distal basilar artery).
Normal Pretreatment TCD
If a lacunar stroke was clinically suspected, a mid MCA depth of
56 mm was used for monitoring. If a small cortical stroke was
suspected, a distal MCA depth of 35 to 40 mm was used for
monitoring.
The sample volume (gate) was set at 11.8 mm (Multigon) or 15
mm (DWL). The power was set at a 100% level (Multigon) or 128 mW (DWL)
for the duration of monitoring. For patients with MCA occlusion, the
transducer was tightly fixed in position with a headframe (Marc series;
Spencer Technologies) to maximize sound energy transmission and to
maintain a constant angle of insonation (Figure
, B). For
patients with basilar artery occlusion, handheld monitoring was
performed through the transforaminal window.
TCD monitoring was performed during the entire tPA infusion under direct visual control of the investigators. If any flow signal changes occurred, these data were interpreted on-line and the timing of change was documented. The flow signals at the proximal and distal arterial segments were documented at the end of tPA infusion, and TCD monitoring was discontinued at this point.
Recanalization was graded as complete, partial, or none according to previously validated criteria.9 Complete recanalization was diagnosed when a normal waveform or a low-resistance stenotic signal appeared at the selected depth of insonation. If a proximal arterial segment was monitored, the continuation of normal or low-resistance stenotic flow toward the distal arterial segment was confirmed. If the abnormal signals were still seen at the distal portion, partial recanalization was diagnosed. No change in the abnormal flow signals indicated that no recanalization has occurred. Reocclusion was diagnosed when the abnormal flow signals worsened in comparison with the baseline study or after a transient flow signal improvement during tPA infusion.
The NIHSS scores were obtained before and after tPA infusion by a
neurologist who was not involved in TCD. Outcome measurements included
the NIHSS scores at the end of tPA infusion and at 24 hours and
modified Rankin scale scores at follow-up.2 We used 4
measures of clinical recovery based on methods used in previous
studies.2 3 7 "Dramatic recovery" was defined as a
decrease in the total NIHSS score to <3 at the end of tPA
infusion.7 "Early neurological improvement" was
defined as a reduction in 10 points in the total NIHSS score or
complete recovery.3 "Improvement" was defined as a
reduction in the total NIHSS score by 4 points.2
"Worsening" was defined as an increase in the total NIHSS score by
4 points.2 At follow-up, a neurologist obtained modified
Rankin scores during an outpatient visit or during a structured
telephone interview. Statistical analysis included the
2 test and coefficient of contingency
(C) to establish an association between
recanalization and clinical recovery.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Forty patients were studied (mean age 70±16 years, range 32 to 93 years). Baseline stroke severity was 18.6±6.2 NIHSS points (median 19 points, range 6 to 33 points). tPA bolus was administered at 132±54 minutes from symptom onset, including 6 patients who were treated with a 0.6-mg/kg dose administered 120 to 360 minutes from time the patient was last known to be normal. At the prebolus TCD examination, the MCA was occluded in 30 patients (75%), the ICA was occluded in 11 patients (28%), and the basilar artery was occluded in 3 patients (8%). Multiple occlusions involving ICA and MCA were found in 7 (18%). Four patients had no windows of insonation (10%). Only 1 patient (2.5%) had a normal TCD examination before the tPA bolus.
TCD monitoring was started 125±52 minutes after symptom onset and
continued for the duration of tPA infusion in all patients. Evidence
for complete or partial recanalization on TCD was
found in 28 of 40 patients (70%) at 45±20 minutes after the tPA
bolus. Complete recanalization occurred in 12
patients (30%), and partial recanalization was
found in 16 patients (40%) (Table 1).
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Dramatic recovery during tPA infusion (total NIHSS score <3 by the end
of tPA infusion) was observed in 8 patients (20%), all of whom had
complete recanalization on TCD. Clinical recovery
was associated with recanalization
(2=26.3, C=0.811,
P<0.01; Table 1)). The baseline NIHSS score of
patients who experienced dramatic recovery was 13.3±5.6 points (median
13 points, range 6 to 22 points, age range 32 to 93 years). Complete
recanalization was common in patients with
cardioembolic occlusion (8 of 17, or 47%); however, this association
was not significant (Table 2). If partial
or complete recanalization was achieved by the end
of tPA infusion, 43% of these patients (12 of 28) improved by 10
NIHSS points or recovered completely at 24 hours.
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Overall, early improvement by 10 points or complete recovery was seen
in 12 of 40 patients (30%) at the end of tPA infusion and in 16
patients (40%) by 24 hours. An improvement by 4 points was observed
in 18 of 40 patients (45%) at the end of tPA infusion and in 25
patients (62.5%) by 24 hours.
No improvement was noted in 16 patients (40%) during tPA infusion and in 7 patients (17.5%) by 24 hours. Worsening of the neurological deficit occurred in 6 patients (15%) during tPA infusion and in 8 patients (20%) by 24 hours.
Digital subtraction angiography was performed in 10 patients, magnetic resonance angiography was performed in 9 patients, and CT-angiography was performed in 2 patients (total 53%). Angiography was performed at a median time of 34 hours after stroke onset, with 50% of angiograms obtained within the first 24 hours. In all of these patients, angiography results confirmed TCD findings at the end of tPA infusion: 8 patients had normal vessels, 3 had intracranial stenoses, and 11 had persisting occlusion.
On TCD, 12 patients had persisting occlusion (30%), and 3 patients had late recanalization that occurred by 5 to 8 hours after stroke onset (7.5%). All these patients either worsened or had no clinical improvement within the first 24 hours. Symptomatic intracerebral hemorrhage occurred in 3 of 40 patients (7.5%). TCD detected complete recanalization in all 3 of these patients between 348 and 720 minutes preceding neurological deterioration.
Eight patients died within the first 3 months after therapy (overall
mortality rate 20%), and 22 patients were available for long-term
follow-up (1.5±1.2 months). Of these, 11 patients achieved modified
Rankin scores of 3 (50%), including 6 patients with modified Rankin
scores of 1 who sustained early dramatic improvement. Two other
patients who completely recanalized and improved dramatically during
tPA infusion did not sustain the improvement in the long term because
of a subsequent reocclusion. In the first patient, MCA recanalized 20
minutes after the tPA bolus, but reocclusion occurred at 40 minutes,
and repeat CT scan at 65 minutes showed new cortical edema formation.
Several hours later, this patient had late
recanalization, developed a massive
intracerebral hemorrhage, and died. The second
patient had a 50% residual basilar artery stenosis and
despite receiving warfarin sodium had a recurrent fatal basilar
artery thrombosis 2 weeks after tPA treatment. Of 16 patients who
recovered completely or improved by 10 NIHSS points by 24 hours, 3
(19%) did not sustain early improvement (2 died and 1 had late
worsening of the neurological deficit with an outcome Rankin score of 4
points).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Our study showed that dramatic improvement during tPA therapy occurred in 20% of all patients and that resolution of the neurological deficit was associated with complete recanalization on TCD. Early improvement by
10
points or complete recovery at 24 hours was seen in 40% of all
patients; this finding was also associated with either complete or
partial recanalization. No clinical improvement or
worsening during tPA therapy and at 24 hours indicated persistent
arterial occlusion, reocclusion, or late
recanalization.
The response rate to tPA therapy at 24 hours was higher in our study
than was expected on the basis of the results of the NINDS rt-PA Stroke
Study. The NINDS trial showed that 27% of tPA-treated patients
improved by 10 points or recovered completely at 24 hours, whereas
40% of our patients had the same amount of recovery. Also, 47% of
tPA-treated patients in the NINDS rt-PA Stroke Study improved by 4
points at 24 hours, whereas in our study, 62.5% of patients had such
an improvement. Different sample sizes, patient selection, and
treatment regimens in the present small study compared with the
NINDS trial preclude any conclusive comparison. For instance, the
pretreatment median NIHSS score was 14 in the NINDS trial versus 19 in
our study, and therefore the expected outcome in our study might have
been worse than that in the NINDS trial. In addition, angiographic and
sonographic studies showed that arterial occlusion and poor
collateral flow are adverse prognostic factors in patients with
ischemic stroke.6 10 16 Because 39 of 40 patients
in our study had occlusions on TCD before treatment, the early
improvement rate observed at 24 hours in the present study of 40%
versus the rate of 27% in the NINDS trial is somewhat surprising.
The recanalization rate (30% complete, 40%
partial) in the present study is higher than that previously
reported by del Zoppo et al,1 who also used
intravenous tPA. With digital subtraction angiography, a
26% complete and partial recanalization rate for
MCA stem occlusion was seen after 60 minutes of tPA
infusion.1 Again, caution must be exercised in a
comparison of the present study with this report. Among other
differences, del Zoppo et al1 used a continuous infusion
of duteplase that was initiated 
5.5 hours after stroke onset without
a bolus. Although we did not have a control group in the present
study, complete recanalization was achieved in 30%
of patients within 1 hour compared with previously reported 26% rate
of spontaneous MCA recanalization seen over 4
hours.10
The present study had rates of recanalization and recovery after tPA therapy that were greater than those previously reported. One difference, of course, between the present study and previous trials is that we used continuous TCD monitoring throughout the tPA infusion. This raises the intriguing possibility that TCD somehow augments tPA-induced clot lysis. The synergistic effect of ultrasound and tPA has been documented in vitro and in vivo experiments for frequencies up to 1.03 MHz.10 11 12 13 14 We hypothesize that continuous ultrasonic energy transmission focused on clot location by TCD monitoring may expose more clot surface to tPA. Ultrasound becomes scattered at the clot/residual flow interface, and the pressure gradients that were created may force more tPA molecules to lodge into the clot, thus facilitating thrombolysis. Although these comments remain speculative, our study supports further evaluation of the potential for TCD to promote thrombolysis through a prospective randomized trial.
Our data also indicate that patients who do not effectively lyse the clot during tPA infusion may be at a higher risk of remaining disabled or experiencing further stroke progression. These patients may be an ideal target group for a trial of more aggressive therapy such as combined intravenous and intra-arterial thrombolysis. In addition, a subgroup of patients with large vessel occlusion may benefit from early anticoagulation,17 and the use of ultrasound monitoring in this setting may be also be tested.
In conclusion, dramatic recovery during tPA therapy occurred in 20% of
all patients when the infusion was continuously monitored with TCD.
Recovery is associated with recanalization, while
no early improvement indicated persistent occlusion or reocclusion. At
24 hours, 40% of all treated patients improved by 10 NIHSS points or
recovered completely. Ultrasonic energy transmission by TCD monitoring
may expose more clot surface to tPA and facilitate
thrombolysis, and a controlled trial should be
undertaken to determine whether TCD enhances reperfusion.
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Acknowledgments |
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Drs Burgin and Felberg are supported by NIH Fellowship Training Grant 1-T32-NS07412-O1A1 for the Stroke Program, University of Texas–Houston Medical School. Dr Christou is supported by a Hellenic Ministry of Defense Visiting Clinician Grant, Athens, Greece. The authors gratefully acknowledge technical support provided by Multigon Industries, DWL/Neuroscan, and Spencer Technologies during the project.
Received November 3, 1999; revision received December 17, 1999; accepted December 17, 1999.
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References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, Alberts MJ, Zivin JA, Wechsler L, Busse O, Greenlee R, Brass L, Mohr JP, Feldmann E, Hacke W, Kase CS, Biller J, Gress D, Otis SM. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992;32:78–86.[Medline] [Order article via Infotrieve]
2.
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.
3. Haley EC, Lewandowski C, Tilley BC. Myths regarding NINDS rt-PA Stroke Trial: setting the record straight. Ann Emerg Med. 1997;30:676–682.[Medline] [Order article via Infotrieve]
4.
Grotta JC, Alexandrov AV. tPA-associated reperfusion
in acute ischemic stroke demonstrated by SPECT.
Stroke. 1998;29:429–432.
5. Heiss W-D, Grond M, Thiel A, von Stockhausen H-M, Rudolf J, Ghaemi M, Lottgen J, Stenzel C, Pawlik G. Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke. J Cereb Blood Flow Metab. 1998;18:1298–1307.[Medline] [Order article via Infotrieve]
6.
Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte
PN, Thron A. Type and extent of hemispheric brain infarctions and
clinical outcome in early and delayed middle cerebral artery
recanalization. Neurology. 1992;42:289–298.
7.
Demchuk AM, Felberg RA, Alexandrov AV. Clinical
recovery from acute ischemic stroke after early reperfusion of
the brain with intravenous thrombolysis.
N Engl J Med. 1999;340:894–895.
8. Demchuk AM, Christou I, Wein TH, Felberg RA, Malkoff M, Grotta JC, Alexandrov AV. The accuracy and criteria for localizing arterial occlusion with transcranial Doppler. J Neuroimaging. 1999;9:57. Abstract.
9. Burgin SW, Felberg RA, Demchuk AM, Christou I, Grotta JC, Alexandrov AV. Ultrasound criteria for middle cerebral artery recanalization: an angiographic correlation. Stroke. 2000;31:329. Abstract.
10. Alexandrov AV. Bladin CF, Norris JW. Intracranial blood flow velocities in acute ischemic stroke. Stroke. 1994;25:1378–1383.[Abstract]
11.
Lauer CG, Burge R, Tang DB, Bass BG, Gomez ER, Alving
BM. Effect of ultrasound on tissue-type plasminogen
activator-induced thrombolysis.
Circulation. 1992;86:1257–1264.
12. Kimura M, Iijima S. Kobayashi K, Furuhata H. Evaluation of the thrombolytic effect of tissue-type plasminogen activator with ultrasound irradiation: in vitro experiment involving assay of the fibrin degradation products from the clot. Biol Pharm Bull. 1994;17:126–130.[Medline] [Order article via Infotrieve]
13. Akiyama M, Ishibashi T, Yamada T, Furuhata H. Low-frequency ultrasound penetrates the cranium and enhances thrombolysis in vitro. Neurosurgery. 1998;43:828–832.[Medline] [Order article via Infotrieve]
14.
Suchkova V, Siddiqi FN, Carstensen EL, Dalecki D, Child
S, Francis CW. Enhancement of fibrinolysis with 40-kHz
ultrasound. Circulation. 1998;98:1030–1035.
15. Behrens S, Daffertshoffer M, Spiegel D, Hennerici M. Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull. Ultrasound Med Biol. 1999;25:269–273.[Medline] [Order article via Infotrieve]
16. Fieschi C, Argentino C, Lenzi GL, Sacchetti ML, Toni D, Bozzao L. Clinical and instrumental evaluation of patients with ischemic stroke within six hours. J Neurol Sci. 1989;91:311–322.[Medline] [Order article via Infotrieve]
17.
Adams HP, Bendixen BH, Leira E, Chang KC, Davis PH,
Woolson RF, Clarke WR, Hansen MD. Antithrombotic treatment of
ischemic stroke among patients with occlusion or severe
stenosis of the internal carotid artery: a report of the Trial
of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999;53:122–125.
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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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E. A. Noser, H. M. Shaltoni, C. E. Hall, A. V. Alexandrov, Z. Garami, E. D. Cacayorin, J. K. Song, J. C. Grotta, and M. S. Campbell III Aggressive Mechanical Clot Disruption: A Safe Adjunct to Thrombolytic Therapy in Acute Stroke? Stroke, February 1, 2005; 36(2): 292 - 296. [Abstract] [Full Text] [PDF]
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S. Pfaffenberger, B. Devcic-Kuhar, C. Kollmann, S. P. Kastl, C. Kaun, W. S. Speidl, T. W. Weiss, S. Demyanets, R. Ullrich, H. Sochor, et al. Can a Commercial Diagnostic Ultrasound Device Accelerate Thrombolysis?: An In Vitro Skull Model Stroke, January 1, 2005; 36(1): 124 - 128. [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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A. Berlis, H. Lutsep, S. Barnwell, A. Norbash, L. Wechsler, C. A. Jungreis, A. Woolfenden, G. Redekop, M. Hartmann, and M. Schumacher Mechanical Thrombolysis in Acute Ischemic Stroke With Endovascular Photoacoustic Recanalization Stroke, May 1, 2004; 35(5): 1112 - 1116. [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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 B. M. Hardig, H. W. Persson, G. Gido, and S. B. Olsson Does Low-Energy Ultrasound, Known to Enhance Thrombolysis, Affect the Size of Ischemic Brain Damage? J. Ultrasound Med., December 1, 2003; 22(12): 1301 - 1308. [Abstract] [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. Nedelmann, B. M. Eicke, E. G. Lierke, A. Heimann, O. Kempski, and H. C. Hopf Low-Frequency Ultrasound Induces Nonenzymatic Thrombolysis In Vitro J. Ultrasound Med., June 1, 2002; 21(6): 649 - 656. [Abstract] [Full Text] [PDF]
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R. A. Felberg, N. J. Okon, A. El-Mitwalli, W. S. Burgin, J. C. Grotta, and A. V. Alexandrov Early Dramatic Recovery During Intravenous Tissue Plasminogen Activator Infusion: Clinical Pattern and Outcome in Acute Middle Cerebral Artery Stroke Stroke, May 1, 2002; 33(5): 1301 - 1307. [Abstract] [Full Text] [PDF]
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T. Ishibashi, M. Akiyama, H. Onoue, T. Abe, and H. Furuhata Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator? Stroke, May 1, 2002; 33(5): 1399 - 1404. [Abstract] [Full Text] [PDF]
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 H. A. Taylor, G. D. Hughes, and R. J. Garrison Cardiovascular Disease Among Women Residing in Rural America: Epidemiology, Explanations, and Challenges Am J Public Health, April 1, 2002; 92(4): 548 - 551. [Abstract] [Full Text]
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F. Schlachetzki, T. Holscher, H. J. Koch, B. Draganski, A. May, G. Schuierer, and U. Bogdahn Observation on the Integrity of the Blood-Brain Barrier After Microbubble Destruction by Diagnostic Transcranial Color-Coded Sonography J. Ultrasound Med., April 1, 2002; 21(4): 419 - 429. [Abstract] [Full Text] [PDF]
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P. Cintas, A. P. Le Traon, and V. Larrue High Rate of Recanalization of Middle Cerebral Artery Occlusion During 2-MHz Transcranial Color-Coded Doppler Continuous Monitoring Without Thrombolytic Drug Stroke, February 1, 2002; 33(2): 626 - 628. [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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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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W. Scott Burgin and A. V. Alexandrov Deterioration following improvement with tPA therapy: Carotid thrombosis and reocclusion Neurology, February 27, 2001; 56(4): 568 - 570. [Full Text] [PDF]
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A. M. Demchuk, W. S. Burgin, I. Christou, R. A. Felberg, P. A. Barber, M. D. Hill, and A. V. Alexandrov Thrombolysis in Brain Ischemia (TIBI) Transcranial Doppler Flow Grades Predict Clinical Severity, Early Recovery, and Mortality in Patients Treated With Intravenous Tissue Plasminogen Activator Stroke, January 1, 2001; 32(1): 89 - 93. [Abstract] [Full Text] [PDF]
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D. D. Blacker and A. V. Alexandrov High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring Response Stroke, December 1, 2000; 31 (12): 3079 - 3083. [Full Text]
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 TCD Monitors, Perhaps Aids Recovery During t-PA Infusion Journal Watch Neurology, August 9, 2000; 2000(809): 4 - 4. [Full Text]
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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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W. S. Burgin, M. Malkoff, R. A. Felberg, A. M. Demchuk, I. Christou, J. C. Grotta, and A. V. Alexandrov Transcranial Doppler Ultrasound Criteria for Recanalization After Thrombolysis for Middle Cerebral Artery Stroke Stroke, May 1, 2000; 31(5): 1128 - 1132. [Abstract] [Full Text] [PDF]
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