From the Departments of Neurology (S.W., T.B., R.W., W.H.) and
Neuroradiology (M.K., K.S.), University of Heidelberg, Heidelberg, Germany.
Correspondence to Susanne Wildermuth, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail susanne_wildermuth{at}krzmail.krz.uni-heidelberg.de
Methods—CTA was performed in 40 consecutive patients (11 women
and 29 men; age range, 19 to 80 years) with moderate or severe symptoms
(National Institutes of Health Stroke Scale score of
Results—Images and 3-dimensional reconstructions of
diagnostic quality could be obtained in all patients.
Thirty-four patients had a vessel occlusion. The extent of
leptomeningeal collaterals correlated significantly with the outcome
after thrombolytic therapy
(rs=0.46, P<0.05). The
evaluation of diagnostic accuracy showed a high agreement
with US (22 of 22) and DSA (6 of 7).
Conclusions—CTA can provide important information for the
initiation of therapy in patients with acute hemispheric
ischemia. Identification of patients with autolyzed thrombi,
occlusion of the internal carotid artery bifurcation, and poor
leptomeningeal collaterals is feasible with the use of CTA. These
patients may have little potential for benefit from
thrombolytic therapy.
Recent progress in CT technology, especially the spiral scanning
technique with intravenous bolus administration of contrast
agents, offers insight into the vascular status and the extent of the
parenchymal lesion. The purpose of this study was to determine the
feasibility of CTA in patients with clinically suspected acute
hemispheric ischemia and to evaluate its potential in the
decision for thrombolytic therapy. The extent of
leptomeningeal collaterals was determined and correlated with clinical
outcome. The diagnostic accuracy of CTA was compared with
those of US and DSA in a subgroup of patients.
A total of 1740 patients with ischemic stroke were admitted
from July 1995 through December 1996, and 44% of them were seen within
6 hours after onset. Of these 767 patients, 274 had an NIHSS score of
at least 8. Patients with aphasia (n=153) were excluded because of lack
of informed consent, and patients with symptoms of infratentorial
ischemia (n=34) were not included because of different
diagnostic and therapeutic strategies. Forty percent of the
remaining patients (n=35) were older than 80 years and were excluded as
well. Twelve patients did not agree to the CTA examination and
therefore were not included.
We included 11 women and 29 men (mean age, 58.2±13.7 years; range, 19
to 80 years). Thrombolytic therapy was considered in all.
After history and physical examination, all patients were referred to
CT and CTA. Informed consent was obtained from all patients or their
relatives. Patients with a known history of hyperthyroidism, allergy to
contrast agents, or acute renal failure were excluded. Additional
extracranial and transcranial Doppler and duplex
examinations were performed according to standard
procedures11 in 25 of the patients (CDS 2-4,
Medasonics Co). The Doppler examination was blinded regarding
results of CTA and DSA (extracranial cw 4-MHz pencil probe,
transcranial pw 2-MHz pencil probe; 5-MHz linear array, 128
XP4, Acuson Corp). On the basis of combined extracranial and
intracranial US and duplex sonographic findings, results were graded
into 4 groups: (1) complete ICA occlusions, (2) distal ICA occlusions
including the intracranial ICA bifurcation and the MCA origin, (3)
isolated M1 segment occlusions, and (4) distal M1 or M2 segment
occlusions.12 Most of these US examinations
lasted 10 to 20 minutes, and all were done within 3 hours of CT/CTA and
before initiation of thrombolytic therapy. In addition,
7 patients underwent conventional DSA.
A PQ 2000 CT (Picker International) was used for CT, with 8-mm slice
thickness, throughout the neurocranium. CTA, involving spiral scanning
with intravenous bolus administration of a nonionic
contrast medium (Omnipaque 300, Schering), was performed on the same
scanner immediately after the initial CT, without moving the patient.
Slice thickness was 1.5 mm, with an index of 1.0 mm. Patients
were scanned from the floor of the sella toward the vertex. The
following scan parameters were used in all patients: spiral
pitch, 1.25; 21 tube revolutions; tube voltage, 130 kV; and tube
amperage, 125 mA. Total scanning time was 21 seconds. We injected 130
mL contrast medium into an antecubital vein (intravenous
cannula >18 gauge) at an injection rate of 4 to 5 mL/s with a
mechanical injection pump. Scan delay was 20 seconds in all
patients.
The spiral data were transferred to an independent workstation (Picker
Voxel Q), and the circle of Willis was reconstructed 3 dimensionally,
as previously published.13 Since the 3-D
volume–rendering algorithm does not require data segmentation, 3-D
evaluation of the CTA data set took less than 10 minutes (including
data transfer from the scanner to the workstation). Two experienced
neuroradiologists (M.K. and K.S.), blinded to the other imaging
modalities, evaluated independently occlusion site and presence and
extent of LCBS. LCBS was graded according to the technique used by
Knauth et al.14 Filling of the MCA branches in
the Sylvian fissure was rated as "good" LCBS. "Moderate" LCBS
meant that collaterals were visible but that the Sylvian MCA branches
remained unchanged. No visible arteries beyond the occlusion was rated
as "absent."
The source images and the 3-D reconstructions were both used for the
diagnosis of vessel obstruction and assessment of collaterals.
In 20 patients we performed thrombolytic therapy in the
following manner: local application of up to 1.5 million IU of
urokinase in 4 patients and systemic application of recombinant tissue
plasminogen activator (rtPA; 1.1 mg/kg body wt)
in 16 patients. The remaining 20 patients received
intravenous heparin (20 000 to 40 000 U IV qd). Clinical
improvement was assessed at discharge according to the NIHSS and graded
as no recovery (NIHSS score
Thrombolytic therapy was initiated in 20 patients, and the
other 20 patients received intravenous heparin. Recovery
from the ischemic insult was judged clinically according to the
NIHSS. One patient receiving heparin died from
intracerebral hemorrhage, and 3 patients
receiving it were lost to follow-up. Of the remaining 36 patients, 10
showed no recovery, 12 a moderate recovery, and 14 a good to
complete recovery (see Table 1
US was performed in 25 patients by an experienced sonographer. US
examinations of 3 patients were technically insufficient because of
poor ultrasound penetration. Twenty-two of 22 US results showed
findings identical to those of CTA.
DSA showed results identical to those of CTA in 6 of 7 patients. In the
seventh patient CTA and US both showed an ICA occlusion at the common
carotid artery bifurcation. DSA was performed 1 hour after CTA and
showed only wall irregularities consistent with embolic
remainders but no occlusion.
Additional vascular studies would be helpful to determine site and
extent of the vascular occlusion when a treatment plan is being
determined, especially with respect to thrombolytic
therapy.1 Today, there are several
modalities for vascular assessment available that differ greatly in
availability, invasiveness, time requirement, applicability, and cost.
MRA yields high-quality images of the cerebral circulation. However, it
is time consuming and may be hampered by movement artifacts in acutely
ill stroke patients. The clinical value of novel functional MR
techniques (eg, perfusion and diffusion MR) remains to be evaluated in
the future. US is comparatively time-consuming, examiner dependent, and
sometimes technically infeasible (eg, in 12% of our cases).
Intra-arterial DSA remains the gold standard for vascular
assessment up to now. However, it is invasive and time consuming, and
it sometimes requires sedation and intubation. Complications with
permanent neurological deficits cannot be avoided totally, even by a
skillful technique and an experienced
angiographer.15 Although DSA is an integral part
of local thrombolytic therapy, cost effectiveness, risk
reduction, and the need to save time strongly favor other modes of
vascular assessment, provided they reveal reasonably accurate
information.
CTA is readily available and minimally invasive. It can be
performed on all CT scanners with spiral
capability16 and can be done immediately after
standard CT imaging without moving the patient. Because of the narrow
time window for initiation of successful thrombolytic
therapy, it is important to note that CTA is a very fast procedure,
requiring only an additional 5 minutes of examination time in the CT
scanner and about 10 minutes of reconstruction time. The application of
130 mL nonionic contrast agent for CTA is no contraindication for a
subsequent diagnostic or therapeutic DSA. Idiosyncratic
reactions to iodinated contrast agents have been reported,
but the use of nonionic agents minimizes the risk of moderate or severe
incidents.17 There is no risk of
arterial injury or embolization. In our experience, CTA can
even be applied to severely ill and uncooperative patients owing to the
speed of imaging. Patients who would have required general
anesthesia for DSA have undergone CTA with no sedation or
only mild sedation. Contrary to DSA and US, CTA yields only static
images, but hemodynamic or functional information can
be inferred by indirect parameters such as visibility of
collaterals.
The analysis of the European multicenter
study1 on systemic thrombolytic
therapy identified the extent of collateral circulation as a strong
predictor for outcome after therapy, with poor collaterals associated
with a high risk of secondary hemorrhage and space-occupying
infarction.1 Our data show that it is possible to
determine the extent of leptomeningeal collateral circulation using CTA
in patients with acute hemispheric ischemia. The highly
significant correlation between the outcome after
thrombolytic therapy and the extent of collateral
circulation estimated by CTA in this study confirms the usefulness of
this parameter in estimating outcome.
On the basis of the available clinical data on
thrombolytic therapy, it is not yet clear whether
systemic or local therapy will become state-of-the-art therapy.
However, should systemic therapy yield the same results as local
thrombolytic therapy, one may limit
diagnostic DSA to those cases in which CTA is inconclusive.
In our department CTA has been incorporated as part of the routine
workup of patients with suspected acute cerebral ischemia.
Furthermore, as a minimally invasive imaging modality, CTA can be
repeated to monitor recanalization after
thrombolytic therapy and to assess follow-up.
In a subset of patients we compared vascular diagnosis obtained by CTA
with results of standard modalities. Although this was not the primary
purpose of this study, the numbers are still small, and the data are
not fully comparable, the diagnostic accuracy of CTA in
this emergency setting was high compared with the standard methods of
DSA and US.18 19 CTA clearly detected all 6
occlusions found by DSA. Results were different in 1 patient in whom
CTA showed an ICA occlusion not confirmed by DSA 1 hour later. This
mismatch was most likely due to spontaneous lysis between the two
studies. This view is supported by wall irregularities displayed in DSA
at the site of the presumed previous occlusion. Agreement between CTA
and US was 100%.
In conclusion, our data demonstrate that CTA is feasible in patients
with acute hemispheric ischemia. The extent of leptomeningeal
collateral circulation, which has been confirmed as a predictor for
outcome after thrombolytic therapy in other studies,
can be determined by CTA. Identification of patients with autolyzed
thrombi or occlusion of the ICA bifurcation is feasible with the use of
CTA. Such patients may have little potential for benefit from
thrombolytic therapy.
Received November 24, 1997;
revision received February 12, 1998;
accepted February 12, 1998.
2.
von Kummer R, Holle R, Rosin L, Forsting M, Hacke W.
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outcome in carotid territory stroke? Stroke. 1995;26:581–587.
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plasminogen activator administered within 90
minutes. Stroke. 1992;23:632–640.
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Sacchetti ML, Pace A, Rasura M, Bastianello S, Bozzao L, Zanette E.
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Thrombolysis in Stroke Group. Intravenous
tissue plasminogen activator ameliorates the
outcome of hyperacute embolic stroke. Cerebrovasc Dis. 1993;3:269–272.
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Thrombolytic therapy in acute occlusion of the intracranial
internal carotid artery bifurcation. Am J Neuroradiol. 1995;16:1977–1986.[Abstract]
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intravenous tissue plasminogen
activator and heparin in acute middle cerebral artery
stroke. Stroke. 1992;23:646–652.
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Ohsumi Y, Kilano K, Tsutsumi A, Yamadori A. Intravenous
recombinant tissue plasminogen activator in
acute carotid artery territory stroke. Neurology. 1992;42:976–982.
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The prognostic value of collateral blood flow in acute middle cerebral
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Thrombolytic Therapy in Acute Ischemic Stroke
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© 1998 American Heart Association, Inc.
Original Contributions
Role of CT Angiography in Patient Selection for Thrombolytic Therapy in Acute Hemispheric Stroke
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—It has been
shown that thrombolytic therapy can improve clinical
outcome in a subgroup of patients with acute cerebral ischemia.
This subgroup was characterized by certain clinical and imaging
findings (eg, moderate to severe neurological deficit for less than 3
to 6 hours, occlusion of the middle cerebral artery, lack of extended
infarct signs on CT, and efficient leptomeningeal collaterals).
Although not part of published prospective randomized rtPA trials,
information about the status of the brain vessels would be helpful in
the selection of patients who may benefit the most. Our purpose was to
determine the feasibility of CT angiography (CTA) in patients with
acute hemispheric ischemia and to evaluate its relevance for
thrombolytic therapy. 
8) of acute
hemispheric ischemia. CTA findings were compared with
Doppler ultrasonography (US; n=22) and intra-arterial
digital subtraction angiography (DSA; n=7). Twenty patients received
thrombolytic therapy, the remaining patients received
intravenous heparin.
Key Words: angiography • computed tomography • ischemia, cerebral • stroke • thrombolytic therapy
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Several encouraging
studies have demonstrated the potential of thrombolytic
therapy to improve the clinical outcome in patients suffering from
acute cerebral ischemia.1 2 3 A particular
subgroup of patients with distinct characteristics may have potential
for greatest benefit; this subgroup is defined by a moderate or severe
persisting neurological deficit for less than 3 to 6
hours,1 3 4 5 6 an occlusion of the MCA because of
better recanalization rates compared with ICA
occlusions,7 8 9 an initial CT without
extended infarct signs as defined by Hacke et al in
1995,1 and efficient collateral
circulation.1 10 Until now, the initial
workup has been based mainly on clinical examination and CT. An
additional vascular evaluation (eg, conventional
intra-arterial DSA, US, or MRA) would be helpful to gather
information about the site of the occlusion and the extent of
collateral circulation. Furthermore, if spontaneous lysis of the
occluding thrombus has already taken place, administration of
thrombolytic agents may still do some harm.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We studied of 40 consecutive patients with clinical signs of
moderate or severe acute hemispheric ischemia (NIHSS score of
at least 8 without a tendency to improve) admitted to our emergency
room (Department of Neurology, University of Heidelberg) within 6 hours
of symptom onset. 8), moderate recovery (NIHSS score 4 to
7), and good to complete recovery (NIHSS score <4).
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
CTA was successfully completed in all patients without the
occurrence of any side effects. CTA reconstructions were of
diagnostic quality in all 40 patients. ICA occlusion was
diagnosed in 3, occlusion of the ICA bifurcation in 4, occlusion of the
MCA trunk (M1 segment; Figure 1
) in 22,
and occlusion of the distal MCA or a branch (M2 segment; Figure 2) in 5 patients. In 6 patients we did
not find vascular occlusions. Collateral circulation was graded as
"absent" in 6 patients, "moderate" in 5, and "good" in 29
cases.
View larger version (66K):
[in a new window]
Figure 1. M1 segment occlusion (see arrows) in 3-D
reconstruction and perfusion deficit (see arrows) due to lack of
collaterals in the source image.
View larger version (70K):
[in a new window]
Figure 2. M2 segment occlusion (see arrows) in 3-D
reconstruction with good collateral circulation displayed in the source
image. ). There
was a significant positive correlation (see Table 2) of the extent of collateral
circulation as estimated by CTA with the clinical outcome after
therapy. The correlation was stronger for patients who received
thrombolytic therapy compared with heparin-treated
patients.
View this table:
[in a new window]
Table 1. Outcome After Therapy Initiation Based on Clinical
and Diagnostic Findings
View this table:
[in a new window]
Table 2. Nonparametric Correlation (Spearman)
Between Extent of Leptomeningeal Collateral Circulation as Revealed by
CTA and Clinical Outcome After Therapy
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The quick initiation of thrombolytic therapy has
been shown to be a critical determinant of therapeutic success in
patients with acute hemispheric
ischemia.1 2 3 Therefore, a rapid,
reliable workup is required in these very sick patients. Physical
examination and CT to rule out hemorrhage are standards for
assessment of stroke patients in the emergency room.
Selected Abbreviations and Acronyms
CTA
=
CT angiography
DSA
=
digital subtraction angiography
ICA
=
internal carotid artery
LCBS
=
leptomeningeal collateral blood supply
MCA
=
middle cerebral artery
MRA
=
magnetic resonance angiography
NIHSS
=
National Institutes of Health Stroke Scale
3-D
=
three-dimensional
US
=
Doppler ultrasonography
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E,
von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH,
Hennerici M. Intravenous thrombolysis with
recombinant tissue plasminogen activator for
acute hemispheric stroke. JAMA. 1995;274:1017–1025.
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P. Schramm, P. D. Schellinger, J. B. Fiebach, S. Heiland, O. Jansen, M. Knauth, W. Hacke, and K. Sartor Comparison of CT and CT Angiography Source Images With Diffusion-Weighted Imaging in Patients With Acute Stroke Within 6 Hours After Onset Stroke, October 1, 2002; 33(10): 2426 - 2432. [Abstract] [Full Text] [PDF]
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K. W. Muir Heterogeneity of Stroke Pathophysiology and Neuroprotective Clinical Trial Design Stroke, June 1, 2002; 33(6): 1545 - 1550. [Abstract] [Full Text] [PDF]
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M. A. Ezzeddine, M. H. Lev, C. T. McDonald, G. Rordorf, J. Oliveira-Filho, F. G. Aksoy, J. Farkas, A. Z. Segal, L. H. Schwamm, R. G. Gonzalez, et al. CT Angiography With Whole Brain Perfused Blood Volume Imaging: Added Clinical Value in the Assessment of Acute Stroke Stroke, April 1, 2002; 33(4): 959 - 966. [Abstract] [Full Text] [PDF]
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P. Verro, L. N. Tanenbaum, N. M. Borden, S. Sen, and N. Eshkar CT Angiography in Acute Ischemic Stroke: Preliminary Results Stroke, January 1, 2002; 33(1): 276 - 278. [Abstract] [Full Text] [PDF]
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M. M. Kilpatrick, H. Yonas, S. Goldstein, A. B. Kassam, J. M. Gebel Jr, L. R. Wechsler, C. A. Jungreis, and M. B. Fukui CT-Based Assessment of Acute Stroke: CT, CT Angiography, and Xenon-Enhanced CT Cerebral Blood Flow Stroke, November 1, 2001; 32(11): 2543 - 2549. [Abstract] [Full Text] [PDF]
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M. H. Lev, A. Z. Segal, J. Farkas, S. T. Hossain, C. Putman, G. J. Hunter, R. Budzik, G. J. Harris, F. S. Buonanno, M. A. Ezzeddine, et al. Utility of Perfusion-Weighted CT Imaging in Acute Middle Cerebral Artery Stroke Treated With Intra-Arterial Thrombolysis:: Prediction of Final Infarct Volume and Clinical Outcome Editorial Comment: Prediction of Final Infarct Volume and Clinical Outcome Stroke, September 1, 2001; 32(9): 2021 - 2028. [Abstract] [Full Text] [PDF]
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V. Keris, S. Rudnicka, V. Vorona, G. Enina, B. Tilgale, and J. Fricbergs Combined Intraarterial/Intravenous Thrombolysis for Acute Ischemic Stroke AJNR Am. J. Neuroradiol., February 1, 2001; 22(2): 352 - 358. [Abstract] [Full Text] [PDF]
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E. COMMITTEE OF THE ASITN Intraarterial Thrombolysis: Ready for Prime Time? AJNR Am. J. Neuroradiol., January 1, 2001; 22(1): 55 - 58. [Full Text] [PDF]
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 T. Brott and J. Bogousslavsky Treatment of Acute Ischemic Stroke N. Engl. J. Med., September 7, 2000; 343(10): 710 - 722. [Full Text] [PDF]
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T. E. Mayer, G. F. Hamann, J. Baranczyk, B. Rosengarten, E. Klotz, M. Wiesmann, U. Missler, G. Schulte-Altedorneburg, and H. J. Brueckmann Dynamic CT Perfusion Imaging of Acute Stroke AJNR Am. J. Neuroradiol., August 1, 2000; 21(8): 1441 - 1449. [Abstract] [Full Text]
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 J. Rother, L. Jonetz-Mentzel, A. Fiala, J. R. Reichenbach, M. Herzau, W. A. Kaiser, and C. Weiller Hemodynamic Assessment of Acute Stroke Using Dynamic Single-Slice Computed Tomographic Perfusion Imaging Arch Neurol, August 1, 2000; 57(8): 1161 - 1166. [Abstract] [Full Text] [PDF]
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G. Gahn, J. Gerber, S. Hallmeyer, G. Hahn, R. H. Ackerman, H. Reichmann, and R. von Kummer Contrast-Enhanced Transcranial Color-Coded Duplexsonography in Stroke Patients with Limited Bone Windows AJNR Am. J. Neuroradiol., March 1, 2000; 21(3): 509 - 514. [Abstract] [Full Text]
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R. T.F. Cheung, T. Brandt, W. Hacke, M. Knauth, and K. Sartor Noninvasive Vascular Assessment in Suspected Acute Basilar Artery Occlusion • Response Stroke, December 1, 1999; 30 (12): 2759 - 2768. [Full Text] [PDF]
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J. R. Reichenbach, J. Röther, L. Jonetz-Mentzel, M. Herzau, A. Fiala, C. Weiller, and W. A. Kaiser Acute Stroke Evaluated by Time-to-Peak Mapping during Initial and Early Follow-up Perfusion CT Studies AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1842 - 1850. [Abstract] [Full Text]
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A. V. Alexandrov, A. M. Demchuk, T. H. Wein, and J. C. Grotta Yield of Transcranial Doppler in Acute Cerebral Ischemia Stroke, August 1, 1999; 30(8): 1604 - 1609. [Abstract] [Full Text] [PDF]
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S. Nakano, S. Wildermuth, M. Knauth, K. Sartor, and W. Hacke Limitations of CT Angiography in Patient Selection for Thrombolytic Therapy • Response Stroke, May 1, 1999; 30(5): 1148 - 1149. [Full Text] [PDF]
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T. Brandt, M. Knauth, S. Wildermuth, R. Winter, R. von Kummer, K. Sartor, and W. Hacke CT Angiography and Doppler Sonography for Emergency Assessment in Acute Basilar Artery Ischemia Stroke, March 1, 1999; 30(3): 606 - 612. [Abstract] [Full Text] [PDF]
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