Download Outcome of Acute Stroke Patients Without Visible Occlusion on Early

Outcome of Acute Stroke Patients Without Visible Occlusion
on Early Arteriography
Marcel Arnold, MD; Krassen Nedeltchev, MD; Caspar Brekenfeld, MD; Urs Fischer, MD;
Luca Remonda, MD; Gerhard Schroth, MD; Heinrich Mattle, MD
Downloaded from http://stroke.ahajournals.org/ by guest on August 11, 2017
Background—The aim of this study was to determine the clinical and radiological outcome of acute stroke patients who
had no vessel occlusion on arteriography and to define predictors of clinical outcome.
Methods—We analyzed clinical and radiological data of stroke patients whose arteriography performed within 6 hours of
symptom onset did not visualize any vessel occlusion.
Results—Twenty-eight of 283 consecutive patients (10%) who underwent arteriography with the intention to perform
intraarterial thrombolysis did not show any arterial occlusion. Their median baseline National Institutes of Health
Stroke Scale (NIHSS) score was 7. Time from symptom onset to arteriography ranged from 115 to 315 minutes;
on average, it was 226 minutes. Presumed stroke cause was cardiac embolism in 11 patients (39%), small artery
disease in 6 (21%), coronary angiography in 1 (4%), and undetermined in 10 patients (36%). After 3 months,
modified Rankin Scale score (mRS) was ⱕ2 in 21 patients (75%), indicating a favorable outcome. Six patients
(21%) had a poor outcome (mRS 3 or 4) and 1 patient (4%) had a myocardial infarction and died. Twenty-seven
patients had follow-up brain imaging. It was normal in 5, showed a lacunar lesion in 8, a striatocapsular infarct
in 2, a small or medium-sized anterior circulation infarct in 6, multiple small anterior circulation infarcts in 2, and
multiple posterior circulation infarcts in 4. No predictors of clinical outcome were identified.
Conclusions—Most acute stroke patients with normal early arteriography show infarcts on brain imaging; however,
clinical outcome is usually favorable. (Stroke. 2004;35:1135-1140.)
Key Words: stroke 䡲 outcome 䡲 thrombolysis
A
subgroup analysis of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke
Trial showed that patients with all stroke subtypes derived
a clinical benefit from thrombolytic treatment.1 Even in
patients who were classified as having small vessel disease
according to the Trial of Org 10172 in Acute Treatment
(TOAST) criteria, thrombolysis improved the outcome.
However, the demonstration of an arterial occlusion was
not mandatory in NINDS. Therefore, the question whether
acute stroke patients without arterial occlusion should be
treated with thrombolysis has not been resolved yet.2,3 The
answer depends mainly on the spontaneous course of such
patients. For this reason, we analyzed our acute stroke
patients who underwent arteriography with the intention to
perform intraarterial thrombolysis (IAT) but who did not
show any occluded vessel and therefore were not treated.
The aim was to determine their clinical and radiological
outcome and to identify predictors of clinical outcome.
underwent cerebral arteriography immediately after clinical evaluation and computerized tomography (CT) or magnetic resonance
imaging (MRI). The indications for IAT have been published
previously.4 Eventually, 191 patients with occlusions of intracranial
vessels correlating to the clinical signs underwent IAT. In 92 (33%)
patients, IAT was not performed for the following reasons: occlusion
of small branches only of the middle cerebral artery (MCA) or the
posterior cerebral artery (n⫽7 or n⫽1, respectively); extracranial
carotid artery occlusion or high-grade stenosis (n⫽49) or vertebral
artery occlusion and contralateral vertebral hypoplasia (n⫽5) preventing access to the occluded intracranial artery; aortic dissection
(n⫽2); and no visualization of any occlusion of an intracranial artery
(n⫽28). Data of the latter 28 patients without intracranial vessel
occlusion were analyzed and are the subject of this study. The
neurological status was assessed after admission using the NIHSS
score by a neurologist.5 The clinical stroke subtypes were categorized according to the Oxfordshire Community Stroke Project
(OCSP) classification.6 All patients immediately underwent CT or
MR scans after neurological evaluation to exclude intracerebral
hemorrhage. Early parenchymal CT signs of ischemia were defined
according to the criteria by von Kummer et al.7 Arteriography was
performed by transfemoral approach. All patients received a 4-vessel
diagnostic arteriography to assess the complete vessel status and
collateral circulation if present. Either a control CT (n⫽3) or control
MRI (n⫽26) scan was performed 1 or 2 days after arteriography. CT
or MRI lesions were classified similar to the criteria published by
Subjects and Methods
From January 1998 to December 2002, 283 patients with acute
cerebral ischemia met our institutional criteria for IAT and therefore
Received November 11, 2003; final revision received January 7, 2004; accepted January 23, 2004.
From Departments of Neurology (M.A., K.N., U.F., H.M.) and Neuroradiology (C.B., L.R., G.S.), University of Bern, Bern, Switzerland.
Correspondence to Dr Heinrich Mattle, Department of Neurology, University of Berne, Freiburgstrasse, Inselspital, CH-3010 Berne, Switzerland.
E-mail [email protected]
© 2004 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000125862.55804.29
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May 2004
TABLE 1.
Baseline Data and Clinical and Radiological Outcome of Each Patient
Age (y),
Sex
Initial
NIHSS
Symptom
Onset to
Arteriogram
(min)
1
62, F
7
170
LACS
2
59, M
6
120
LACS
3
73, M
10
120
4
40, F
5
5
73, M
5
6
49, M
5
7
45, M
14
240
POCS
CE
Lacunar paramedian thalamus infarct
2
8
75, M
8
310
PACS
UD
Medium-sized cortical anterior circulation infarct
(posterior MCA territory)
6
9
18, M
6
115
POCS
CE
Normal MRI
0
10
55, M
8
150
PACS
UD
Small cortical anterior circulation infarct (anterior MCA territory)
3
11
49, M
10
255
LACS
SAD
Lacunar paramedian pons infarct
3
12
66, M
6
285
PACS
CE
No follow-up CT or MRI
1
13
68, M
5
280
PACS
CE
Small anterior circulation infarct (anterior MCA territory)
1
14
64, M
4
315
LACS
SAD
Lacunar paramedian pons infarct
2
15
81, M
16
290
PACS
UD
Normal CT
0
16
77, M
5
315
PACS
UD
Lacunar infarct medial thalamus
1
17
64, M
6
130
POCS
CE
Multiple posterior circulation infarcts (bilateral paramedian
thalamus infarcts)
1
18
53, F
25
120
POCS
CE
Multiple posterior circulation infarcts (bilateral paramedian
thalamus and bilateral midbrain infarcts)
1
19
62, M
13
230
PACS
UD
Striatocapsular infarct
4
20
50, F
5
210
LACS
SAD
Normal MRI
1
21
63, M
5
120
POCS
CE
Multiple posterior circulation infarcts (bilateral cerebellar
infarcts, right anterior thalamus infarct, and right midbrain
infarct)
3
22
42
7
255
PACS
UD
Small cortical anterior circulation infarct (posterior MCA
territory)
1
23
50, M
9
280
PACS
UD
Striatocapsular infarct
3
24
38, F
8
240
PACS
UD
Normal MRI
0
25
62, M
8
250
PACS
CE
Lacunar basal ganglia infarct
2
26
45, M
10
266
PACS
CE
Small cortical anterior circulation infarct (anterior MCA territory)
2
27
82, F
6
210
PACS
UD
Small cortical anterior circulation infarct (anterior MCA territory)
1
28
59, M
8
315
PACS
CE
Multiple small cortical anterior circulation infarcts (ACA and
MCA territory)
1
Patient
Type of Infarction
on CT/MRI
1 or 2 Days After Stroke
mRS 3 Months
After Stroke
SAD
Lacunar basal ganglia infarct
2
SAD
Lacunar infarct lateral thalamus
1
POCS
Iatrogenic
Multiple posterior circulation infarcts (bilateral midbrain
and right thalamus infarct)
3
240
PACS
UD
Normal MRI
0
250
LACS
CE
Multiple small anterior circulation infarcts (cortical
and subcortical MCA territory)
2
240
LACS
SAD
Lacunar basal ganglia infarct
2
Clinical
Subtype
Stroke
Cause
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NIHSS indicates National Institutes of Health Stroke Scale; mRS, modified Rankin Scale score, LACS, lacunar syndrome; PACS, partial anterior circulation syndrome;
POCS, posterior circulation syndrome; SAD, small artery disease; CE, cardioembolic; UD, undetermined cause; P, difference between subgroups by Mann–Whitney
test or Fisher exact test; NS, not significant.
Mead et al8 as follows: (1) large cortical MCA infarct (more than half
of the MCA territory); (2) medium-sized or small anterior circulation
infarct (less than half or the MCA territory or any of the ACA territory);
(3) large (⬎1.5 cm) subcortical infarct (striatocapsular); (4) lacunar
(⬍1.5 cm) anterior circulation infarct; (5) lacunar (⬍1.5 cm) posterior
circulation infarct; and (6) nonlacunar posterior circulation infarct.
Stroke cause was determined using additional investigations as
necessary and classified according to the TOAST criteria.9 Outcome
was assessed 3 months after the ictus by clinical examination using
the modified Rankin scale (mRS).10 The mRS scale scores of 0 to 2
were defined as “favorable” and mRS scores of 3 to 5 as “poor”
outcome. Death corresponds to a mRS score of 6. For the analysis of
predictors of clinical outcome, we considered variables that may
influence clinical outcome and dichotomized patients into 2 groups
(patients with favorable outcome [mRS ⱕ2] versus patients with
poor outcome or death [mRS 3 to 6]).
Statistical analysis was performed with SPSS 10 statistical software (SPSS Inc). Comparisons of clinical and radiological charac-
Arnold et al
teristics and outcome were performed using Fisher exact test.
Two-sided P⬍0.05 were considered significant.
Results
Demographic, Clinical, and Radiological Data
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Twenty-eight patients (21 men, 7 women) with a mean age of
58⫾12 (range 18 to 82) years who did not show any vessel
occlusion on early arteriography were identified. The median
baseline NIHSS on admission was 7 and ranged from 4 to 25.
Clinical neurological examinations indicated a lacunar syndrome in 7 patients (25%), a partial anterior circulation
syndrome in 15 (54%), and a posterior circulation syndrome
in 6 patients (21%). No total anterior circulation syndrome
was observed. The mean time from symptom onset to
arteriography was 226 minutes (range 115 to 325 minutes).
All but 1 admission CT was normal. Only 1 patient (4%)
showed early parenchymal CT signs of ischemia, and other
abnormalities such as hyperdense artery signs were not
observed. Presumed stroke cause was cardiac embolism in 11
patients (39%), small artery disease in 6 (21%), iatrogenic
after coronary angiography in 1 (4%), and undetermined in 10
patients (36%).
Radiological Outcome
On follow-up brain imaging, 8 patients (29%) showed a
lacunar lesion, 2 (7%) had a striatocapsular infarct, 6
(21%) had a small- or medium-sized anterior circulation
infarct, 2 (7%) had multiple anterior circulation infarcts,
and 4 (14%) had multiple posterior circulation infarcts. In
5 patients (18%), follow-up MRI (n⫽4) or CT (n⫽1) did
not reveal any ischemic lesion. One patient (4%) with
rapid resolution of his clinical deficits had clinical but no
imaging follow-up. Baseline data and clinical and radiological outcome of each patient are summarized in Table 1.
Acute Stroke with Normal Early Arteriography
TABLE 2.
Predictors of Clinical and Radiological Outcome
Characteristics
Mean age, y (SD)
After 3 months, mRS was ⱕ2 in 21 patients (75%), indicating
a favorable outcome. Six patients (21%) had a poor outcome
(mRS 3 or 4). One patient (4%) had a myocardial infarction
1 day after his stroke and died. Before myocardial infarction,
his NIHSS score was 8.
Predictors of Outcome
Age, sex, initial NIHSS score, clinical stroke syndrome, time
to arteriography, stroke cause, early signs of ischemia on
admission CT, and vascular risk factors failed to predict
clinical outcome (Table 2).
Discussion
The outcome of 28 acute stroke patients with normal early
arteriograms was favorable in 21 (75%). This is the main
message of our study. Nevertheless, the majority (78%)
has cerebral infarction according to brain imaging, and
death or significant disability occurs in one quarter of the
patients. Another small series of 10 patients without a
visible clot on arteriography that was performed within 4
hours of symptom onset gave similar results. Eight of 10
follow-up brain scans showed a new cerebral infarct.11
Four of these 10 patients (40%) were disabled (mRS⬎2)
Favorable Outcome,
(mRS 0 –2)
n⫽21 (%)
Poor Outcome or
Dead, mRS (3– 6)
n⫽7 (%)
P
Value
57 (8)
61 (8)
NS
Sex
Male
Female
14 (67)
7 (100)
7 (33)
NS
0 (0)
Diabetes
Yes
3 (75)
1 (25)
No
19 (76)
6 (24)
Yes
6 (75)
2 (25)
No
15 (75)
5 (25)
NS
Smoking
NS
Hypercholesterolemia
Yes
8 (80)
2 (20)
No
13 (72)
5 (28)
NS
Hypertension
Yes
7 (67)
2 (33)
No
14 (74)
5 (26)
NS
NIHSS score on admission
0–5
7 (88)
1 (12)
NS
6–10
11 (79)
3 (21)
NS
⬎10
3 (50)
3 (50)
NS
6
9
NS
NS
Median NIHSS score
Clinical subtype
LACS
6 (86)
1 (14)
PACS
11 (73)
4 (27)
TACS
0
0
POCS
4 (67)
2 (33)
Time to angiography (min)
Median
Clinical Outcome
1137
Mean (SD)
240
230
231 (52)
209 (68)
5 (83)
1 (17)
10 (91)
1 (9)
NS
CRAO cause
Small artery disease
Cardioembolic
Iatrogenic
0 (0)
1 (100)
Undetermined
6 (60)
4 (40)
Small artery disease
5 (83)
1 (17)
Yes
0 (0)
1 (17)
No
21 (100)
6 (83)
NS
Early CT signs
NS
NIHSS indicates National Institutes of Health Stroke Scale; mRS, modified
Rankin Scale score, LACS, lacunar syndrome; PACS, partial anterior circulation
syndrome; TACS, total anterior circulation syndrome; POCS, posterior circulation syndrome; P, difference between subgroups by Mann-Whitney test or
Fisher exact test; NS, not significant.
after 3 months. Good outcomes were also reported in 4 of
5 patients of another series who had been treated with IAT,
even without visible occlusion on arteriography.12
There may be 2 pathomechanisms leading to ischemic
stroke and disability in patients with normal arteriography.
First, occlusions of arterioles are not visualized on clinical
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May 2004
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arteriography. They may account for most of the lacunar
infarcts. Second, an occlusion of a larger vessel may cause
an ischemic stroke before it recanalizes spontaneously.
Such a mechanism may be operative when collaterals are
inadequate to preserve perfusion until recanalization
occurs.
The question arises whether it is justified to exclude
patients without occlusion on arteriography from
thrombolytic therapy. To date, the answer cannot be
derived from randomized trials or controlled studies. In the
present series, little may have been gained with
thrombolysis. The majority had a favorable clinical outcome without treatment. The question that remains is the
one of arteriolar occlusions, ie, whether such patients have
a salvageable penumbra. The answer cannot be given from
our angiography series, because neither CT nor any clinical findings was predictive of the outcome. The shortcoming of our study is that we did not perform systematically
perfusion CT or perfusion-weighted imaging (PWI) and
diffusion-weighted imaging (DWI) MRI before arteriography. These techniques might have been helpful to identify
potential candidates for thrombolysis despite normal arteriography. Schellinger et al evaluated DWI and PWI and
magnetic resonance angiography (MRA) within 6 hours of
stroke onset.13 Of 8 patients with normal intracranial
MRA, 4 had small lacunar, 2 basal ganglia, and 2 presumedly cardioembolic infarcts. A small PWI–DWI mismatch indicating salvageable tissue was observed in only 1
of the 8 patients. Based on pathophysiological considerations, the authors recommended no thrombolysis in patients without vessel occlusion and without PWI–DWI
mismatch. They would, however, reluctantly and carefully
perform thrombolysis in patients with PWI–DWI mismatch but no vessel occlusion. However, DWI-positive
patients may show imaging lesion reversal.14 Therefore,
these recommendations, which are based on pathophysiological considerations, have to be confirmed by randomized controlled trials.
In conclusion, acute stroke patients with normal arteriograms will mostly have a favorable spontaneous recovery.
The chances to prevent the few unfavorable outcomes in such
patients with thrombolysis may be small, because the ischemic damage is probably irreversibly set already at the time of
arteriography. This statement is based on pathophysiological
considerations. In the intravenous NINDS trial, a clinical
benefit was shown in all subgroups of patients, including
patients with small artery disease. However, vessel imaging
was not mandatory in the NINDS study. Hopefully, ongoing
clinical studies based on DWI and PWI or vessel imaging or
both (eg, EPITHET, DIAS, SaTIS, DEFUSE) will improve
patient selection and give the answer whether stroke patients
with normal vessel status will benefit from thrombolysis.15
Acknowledgments
We thank Dr Pietro Ballinari for statistical advice.
References
1. The NINDS t-PA Stroke Study Group. Generalized efficacy of t-PA for
acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial.
Stroke. 1997;28:2119 –2125.
2. Caplan LR, Mohr JP, Kistler JP, Koroshetz W. Should thrombolytic
therapy be the first-line treatment for acute ischemic stroke? Thrombolysis—not a panacea for ischemic stroke. N Engl J Med. 1997;337:
1309 –1310.
3. Caplan LR. Treatment of patients with stroke. Arch Neurol. 2002;59:
703–707.
4. Arnold M, Schroth G, Nedeltchev K, Loher T, Remonda L, Stepper F,
Sturzenegger M, Mattle HP. Intraarterial thrombolysis in 100 patients
with acute stroke due to middle cerebral artery occlusion. Stroke. 2002;
33:1828 –1833.
5. Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J,
Spilker J, Holleran R, Eberle R, Hertzberg V, Roorick M, Moomaw CJ,
Walker M. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864 – 870.
6. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification
and natural history of clinically identifiable subtypes of cerebral
infarction. Lancet. 1991;22:337:1521–1526.
7. von Kummer R, Allen KL, Holle R, Bozzao L, Bastianello S, Manelfe C,
Bluhmki E, Ringleb P, Meier DH, Hacke W. Acute stroke: usefulness of
early CT findings before thrombolytic therapy. Radiology. 1997;205:
327–333.
8. Mead GE, Lewis SC, Wardlaw JM, Dennis MS, Warlow CP. How well
does the Oxfordshire community stroke project classification predict the
site and size of the infarct on brain imaging? J Neurol Neurosurg
Psychiatry. 2000;68:558 –562.
9. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL,
Marsh EE III. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172
in Acute Stroke Treatment. Stroke. 1993;24:35– 41.
10. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients.
Stroke. 1988;19:604 – 607.
11. Derex L, Tomsick TA, Brott TG, Lewandowski CA, Frankel MR, Clark
W, Starkman S, Spilker J, Udsten GJ, Khoury J, Grotta JC, Broderick JP;
EMS Bridging Trial. Outcome of stroke patients without angiographically
revealed arterial occlusion within four hours of symptom onset. AJNR
Am J Neuroradiol. 2001;22:685– 690.
12. Schumacher M, Yin L, Klisch J, Hetzel A. Local intraarterial fibrinolysis
without arterial occlusion? Neuroradiology. 1999;41:530 –536.
13. Schellinger PD, Fiebach JB, Jansen O, Ringleb PA, Mohr A, Steiner T,
Heiland S, Schwab S, Pohlers O, Ryssel H, Orakcioglu B, Sartor K,
Hacke W. Stroke magnetic resonance imaging within 6 hours after onset
of hyperacute cerebral ischemia. Ann Neurol. 2001;49:460 – 469.
14. Kidwell CS, Alger JR, Saver JL. Beyond mismatch: evolving paradigms
in imaging the ischemic penumbra with multimodal magnetic resonance
imaging. Stroke. 2003;34:2729 –2735.
15. Major ongoing stroke trials. Stroke. 2003;34:e61– e72.
Arnold et al
Acute Stroke with Normal Early Arteriography
1139
Editorial Comment
Outcome of Acute Stroke Patients Without Visible Occlusion on
Early Arteriography
To treat, or not to treat: that is the question:
Whether ’tis nobler in the mind to suffer
The uncertainties rendered by open case series,
Or to take arms against a sea of troubles,
And by performing adequate trials end them?
—Modified from William Shakespeare’s Hamlet (III, i)
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At present, only intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) administered
within 3 hours after symptom onset is proven to be effective
for the treatment of acute stroke. Based on level I evidence
from the NINDS trial and several meta-analyses, rt-PA has
been approved in many countries around the world, including
the USA, Canada, Australia, and most of Europe. A recent
meta-analysis (Marler et al, Lancet 2004, in press) also
demonstrates a significant effect of rt-PA in the 3- to 4.5-hour
window, albeit that has not changed approval regulations.
National and international committees and guidelines name
IVT with rt-PA within the 3-hour time window as the
first-line treatment of choice. In specific, the European Stroke
Initiative (EUSI) states “intravenous rt-PA (0.9 mg/kg, maximum 90 mg), with 10% of the dose given as a bolus followed
by an infusion lasting 60 minutes, is the recommended
treatment within 3 hours of onset of ischemic stroke (level I)”
and “the benefit from the use of intravenous rt-PA for
acute ischemic stroke beyond 3 hours after onset of the
symptoms is smaller, but present up to 4.5 hours (level
I).”1 The American Stroke Association (ASA) guidelines
state: “intravenous rt-PA (0.9 mg/kg, maximum dose 90
mg) is strongly recommended for carefully selected patients who can be treated within 3 hours of onset of
ischemic stroke (grade A).”2
Intraarterial thrombolysis (IAT) has been tested in multiple
case series with multiple substances3 and only one randomized controlled trial positive for pro-urokinase within 3 to 6
hours (level I [ASA] to II [EUSI] because of relatively small
sample size) has been published so far,4 but has not sufficed
for FDA approval. The EUSI states: “intraarterial treatment
of acute MCA [middle cerebral artery] occlusion in a 6-hour
time window using pro-urokinase results in a significantly
improved outcome (level II)” and “acute basilar occlusion
may be treated with intraarterial therapy in selected centers in
an institutional protocol as experimental therapy or within a
multicenter clinical trial (level IV).”1 The ASA states: “IAT
is an option for treatment of selected patients with major
stroke of ⬍6-hour duration due to large vessel occlusions of
the middle cerebral artery (grade B)” and “importantly, the
availability of IAT should generally not preclude the administration of intravenous rt-PA in otherwise eligible patients.”2
It has been an endeavor of many groups to improve the
selection of patients for IVT as well as IAT, and to define
which patients to treat and which not to treat. Several case
series, open trials, or trials with historical controls used MRI
criteria, such as the PWI/DWI–mismatch, or arteriographic
criteria for IAT, such as presence and site of a vessel
occlusion.5,6 Larger phase II and III trials addressing these
problems are under way (eg, DIAS/DEDAS, DEFUSE, EPITHET).7 In the current issue of Stroke, Arnold et al8 present
a subgroup of their patients (N⫽28/283) who were arteriographically screened for IAT with urokinase (not prourokinase!) but not treated because of absence of a vessel
occlusion. The median baseline NIHSS score was 7, time
from symptom onset to arteriography ranged from 1 hour 55
minutes to 5 hours 15 minutes (mean: 3 hours 46 minutes).
After 3 months, 21 patients (75%) were independent (modified Rankin Scale score [mRS] ⱕ 2). However, in 22 patients,
infarcts were seen at follow-up imaging. Although no predictors of clinical outcome were identified, the authors concluded that patients with normal early arteriography usually
will experience a favorable clinical outcome when not treated
and discourage thrombolysis in these patients.
From a pathophysiological point of view, it makes sense to
treat patients with thrombolytics who have proof of an
obliterating thrombus, and to withhold a potentially threatening therapy in patients without a therapeutical substrate.
There are only few data about the outcome of patients with
patent vessels on early arteriography,6 and, to my knowledge,
outcome data of the PROACT II patients screened with
arteriography but not randomized (N⫽294 142 of these
without or with incomplete vessel occlusion) have not been
published. Therefore, the observations of Arnold et al are
interesting, albeit not surprising. However, with the evidence
at hand, the authors should test their hypothesis in a controlled, maybe even randomized, small trial (IAT versus
saline in acute stroke patients 3 to 6 hours with thrombolysis
in myocardial infarction [TIMI] 2 and 3 flow). Although they
will unlikely detect a clinical difference because of small
numbers, this would preclude withholding IVT from eligible
patients and render a study with a higher evidence level.
Granted, this limitation has been discussed.
Nevertheless, it is disturbing that 25% of patients each
were either dependent/dead (median baseline NIHSSS of 9,
outcome mRS 3 to 6) or had remaining nonincapacitating
functional deficits (median baseline NIHSSS of 7, outcome
mRS 2). Eight of 28 patients underwent arteriography within
3 hours (20 underwent arteriography within 4.5 hours), 1 had
residual symptoms (mRS 2), and 3 were dependent or dead.
When assuming a 30-minute delay caused by arteriography,
10 of 28 patients could have received IVT ⬍3 hours and 24
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of 28 patients within 4.5 hours, with the latter not approved
but with sound level I evidence in favor of IVT with rt-PA.
Mild or improving stroke symptoms are the reason for
withholding IVT in one third of patients, and, again, one third
of these have a poor outcome.9 Also, even lacunar infarcts
without an arteriographic vessel occlusion may profit from
IVT.10 Furthermore, microcirculatory defects can be overlooked on arteriography. Although recanalization most likely is
an independent predictor of good outcome, tissue reperfusion
may be even more important in congruence with MI in cardiology. Approved therapies based on level I evidence and recommended by most expert panels and stroke societies should not be
discarded in favor of open noncontrolled studies.2
In conclusion:
By indirections find directions out. (Hamlet, II, i)
More matter with less art. (Hamlet, II, ii)
Or . . .
In keeping with the times, not open case series but imagingbased studies with at least a control to obtain a higher level of
evidence should be designed. Simple IVT with early reperfusion
may be more helpful than invasive angiography without IAT.
Peter D. Schellinger, MD
Neurologische Universitätsklinik
Heidelberg, Germany
References
1. The European Stroke Initiative Executive Committee and the EUSI
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Outcome of Acute Stroke Patients Without Visible Occlusion on Early Arteriography
Marcel Arnold, Krassen Nedeltchev, Caspar Brekenfeld, Urs Fischer, Luca Remonda, Gerhard
Schroth and Heinrich Mattle
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Stroke. 2004;35:1135-1138; originally published online April 8, 2004;
doi: 10.1161/01.STR.0000125862.55804.29
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