Benefits of intravenous thrombolysis in acute ischemic stroke related to extra cranial internal carotid dissection. Dream or reality?

Research

Benefits of intravenous thrombolysis in acute ischemicstroke related to extra cranial internal carotid dissection.Dream or reality?

Blanca Fuentes�1, Jaime Masjuan2, Marıa Alonso de Lecinana2, Patricia Simal3, Jose Egido3,

Fernando Dıaz-Otero4, Antonio Gil-Nunez4, Patricia Martınez-Sanchez1,

Exuperio Dıez-Tejedor1, and Madrid Stroke Network

Background Small clinical series have reported the safety of

intravenous thrombolysis in ischemic stroke related to extra-

cranial internal carotid dissection. However, no studies speci-

fically analyzing the effects on stroke outcome are available.

Aims Our goal was to evaluate whether patients with is-

chemic stroke related to extracranial internal carotid dissec-

tion obtain any benefit from intravenous thrombolysis.

Methods Multicenter, prospective and observational study

conducted in four university hospitals from the Madrid Stroke

Network. Consecutive ischemic stroke patients who received

intravenous thrombolysis were included, as well as patients

with extracranial internal carotid dissection regardless of

intravenous thrombolysis treatment. Stroke severity (NIHSS)

and three-month outcome (modified Rankin Scale) were

compared between the following groups: (1) intravenous

thrombolysis-treated patients with ischemic stroke related

to extracranial internal carotid dissection vs. other causes of

stroke; (2) intravenous thrombolysis-treated extracranial in-

ternal carotid dissection patients vs. nonintravenous throm-

bolysis treated. Outcome was rated at three-months using the

modified Rankin Scale. A good outcome was defined as a

modified Rankin Scale score r2.

Results A total of 625 intravenous thrombolysis-treated pa-

tients were included; 16 (2.56%) had extracranial internal

carotid dissection. Besides, 27 patients with extracranial

internal carotid dissection and ischemic stroke who did not

receive intravenous thrombolysis were also included. As

compared with other etiologies, patients with extracranial

internal carotid dissection were younger, had similar stroke

severity and showed less improvement in their NIHSS score at

Day 7 (1.38; (95% CI �3.77 to 6.54) vs. 6.81; (95% CI �5.99 to

7.63) P 5 0.004), but without differences in good outcomes at

three-months (43.8% vs. 58.2%; NS). Extracranial internal

carotid dissection intravenous thrombolysis-treated patients

had more severe strokes at admission than those who were

nonintravenous thrombolysis treated (median NIHSS: 15 vs. 7;

P 5 0.031). Intravenous thrombolysis was safe in extracranial

internal carotid dissection with no symptomatic hemorrhagic

events; however, without differences in good outcome com-

pared with the natural course of extracranial internal carotid

dissection (nonintravenous thrombolysis treated) after ad-

justment for stroke severity (46.7% vs. 64.3%; NS).

Conclusions As compared with otheretiologies, stroke due to

extracranial internal carotid dissection seems to obtain similar

benefits from intravenous thrombolysis in outcome at three-

months. Although intravenous thrombolysis is safe in stroke

attributable to extracranial internal carotid dissection, no

differences in outcome were found when comparing intrave-

nous thrombolysis treated with nonintravenous thromboly-

sis-treated patients, even after adjustment for stroke severity.

Key words: cervical artery dissection, intravenous thrombo-

lysis, outcome, stroke

Introduction

Cervical artery dissection is a common cause of ischemic

stroke (IS) in young people but is a rare cause of stroke overall.DOI: 10.1111/j.1747-4949.2011.00637.x

Conflict of interest: None declared.

Funding: B. Fuentes was provided with a grant by the Instituto de Salud

Carlos III (Carlos III Health Institute) and the Agencia Laın Entralgo –

Comunidad de Madrid (I3SNS) (Lain Entralgo Agency – Community of

Madrid).

Correspondence: Dr Blanca Fuentes�, Stroke Unit, Department of

Neurology, University Hospital La Paz, IdiPAZ, Paseo de la Castellana,

261, 28046 Madrid, Spain.

E-mail: [email protected] Centre, Department of Neurology, Neurosciences Research,

IdiPAZ Health Research Institute, University Hospital La Paz, Madrid

Autonoma University, Madrid, Spain2Stroke Unit, Department of Neurology, University Hospital Ramon y

Cajal, IRYCIS Health Research Institute, Alcala de Henares University,

Madrid, Spain3Stroke Unit, Department of Neurology, University Hospital Clınico San

Carlos, Madrid Complutense University, Madrid, Spain4Stroke Unit, Department of Neurology, University Hospital Gregorio

Maranon, Madrid Complutense University, Madrid, Spain

& 2011 The Authors.International Journal of Stroke & 2011 World Stroke Organization Vol 7, January 2012, 7–13 7

mailto:[email protected]

Its management remains uncertain and most studies have been

focused on antiplatelet drugs or anticoagulation (1, 2). In-

travenous thrombolysis (IVT) is the current standard therapy

for acute IS patients and cervical artery dissection is not an

exclusion criteria. Some theoretical safety concerns have been

expressed regarding this therapy: axial or longitudinal exten-

sion of the vessel wall hematoma; dislocation of intraluminal

thrombus with subsequent arterial embolism; vessel leakage

causing subarachnoid hemorrhage in those cases with intra-

cranial extension of the dissection, and pseudoaneurism

formation (3). Small clinical series have reported the safety

of IVT in acute IS related to extracranial internal carotid

dissection (eICAD) (3–5). However, few studies specifically

analyzing the possible beneficial effects on stroke outcome are

available. A systematic review and meta-analysis only identi-

fied four small, retrospective and uncontrolled studies provid-

ing insufficient data on the efficacy of thrombolysis (2). More

recently, data from a large multicenter Swiss Stroke Data Bank

showed that IVT-treated patients with cervical artery dissec-

tions did not recover as well as IVT-treated patients with other

causes of stroke (6). However to date, there are no studies

comparing the outcome of IVT-treated eICAD patients with a

control group of eICAD patients not receiving IVT (those

following the natural course of this disease).

Aims

Our goal was to evaluate whether patients with acute IS related

to eICAD obtain the same benefit from IVT as patients with

other causes of stroke, and also to assess whether they achieve a

better outcome than eICAD patients not treated with IVT.

Methods

Study design

Multicenter observational analysis with prospective inclusion

of all consecutive IVT-treated, acute IS patients at four stroke

units sharing a common extrahospital stroke code and in-

hospital stroke care protocols, from January 2003 to December

2008. Consecutive patients with IS related to eICAD within the

same time period who were not treated with IVT were also

prospectively included. Diagnosis of eICAD was carried out on

the basis of T1-weighted axial cervical MRI scans with the fat-

saturation technique (7), angiographic studies with MR

angiography (MRA) (8), CT angiography (CTA) (9) or selec-

tive catheter angiography of craniocervical vessels. The diag-

nostic studies were performed during hospitalization and after

treatment in the IVT group. Patients with eICAD but without

brain infarction (i.e. with symptoms of transient ischemic

attack (TIA), headache, cervicalgia or Horner’s syndrome)

were excluded.

Treatment

Patients who fulfilled the SITS-MOST criteria for thromboly-

tic therapy received IV-tPA in a standard 0�9 mg/kg dose (10%

bolus, 90% continuous infusion for one-hour) within three-

hours of stroke onset.

Clinical assessment

Stroke onset was defined, as the last time the patient was

known to be without neurological deficit. Neurological ex-

amination and cranial computed tomography (CT) scans were

performed on admission in order to establish the stroke

subtype and indication for treatment. Intracranial arterial

status was based on the results of transcranial doppler con-

ducted before IVT and another evaluation within the first 24 h

after IVT. Transcranial doppler evaluation was not a study

procedure and it was performed according to each physician

criteria, but the register was open to include this additional

information. Stroke severity was assessed at baseline according

to the National Institutes of Health Stroke Scale (NIHSS)

score, at two- and 24 h after treatment and at Day 7. All

evaluations were done by NIHSS-certified neurologists; cov-

ariables included age, gender, stroke risk factors, stroke

etiology, as well as blood glucose and systolic arterial blood

pressure at admission. Previous antithrombotic treatments

(antiplatelet agents or anticoagulants) were recorded. Time

from stroke onset to IVT was recorded. Significant neurologi-

cal improvement was defined as a decrease of at least four

points from baseline NIHSS score or complete recovery at 24 h

or at least eight points or complete recovery at Day 7.

A posttreatment CT scan was performed after 24 h (range

22–36 h) or, in case of neurological deterioration, in order to

assess hemorrhagic complications. Symptomatic intracerebral

hemorrhage was defined as local or remote parenchymal

hemorrhage type 2 combined with a neurological deteriora-

tion of four or more points on the NIHSS from baseline, or

from the lowest NIHSS value between baseline and 24 h, or

leading to death. Cerebral edema was defined as per the SITS-

MOST protocol (10). Functional outcome was rated using the

modified Rankin scale (mRS) after 90 days. We defined a good

outcome as a mRS score r2. Further analyses across the

distribution of mRS scores were also developed. Serial mon-

itoring of the dissected internal carotid artery patency was

conducted based on each physician’s criteria. Those data were

also included in the study data bank.

Statistical analysis

Analyses were performed using SPSS 12.0 software (SPSS Inc.,

Chicago, IL, USA). Three-month outcomes (mRS) were

compared: (1) IVT-treated patients with IS related to eICAD

vs. tPA-treated patients with other causes of stroke; (2) tPA-

treated vs. non-tPA-treated eICAD patients. Comparisons

were made using w2-tests for categorical variables and the

& 2011 The Authors.International Journal of Stroke & 2011 World Stroke Organization Vol 7, January 2012, 7–138

Research B. Fuentes et al.

Mann–Whitney U-test for continuous measures, as appropri-

ate. Univariate and multivariate adjusted forward stepwise

logistic regression models were constructed to adjust for the

effect of stroke severity on admission. Significance was tested

by the likelihood ratio. To compare neurological outcomes at

different time-points among the three groups of study, mixed

regression models were constructed using SAS Enterprise Guide

3.0.2.446 software (SAS Institute Inc., Cary, North Carolina,

USA).

Results

Six hundred and twenty-five patients treated with IVT were

included; 16 (2�56%) had eICAD. Besides, 27 patients with

eICAD and IS who did not receive IVTwere also included in the

study. The main reasons for not receiving IVTwere: time from

stroke onset, i.e. more than three-hours (18 patients), stroke

on awakening (three patients), minor stroke (three patients),

progressive stroke (two patients) and neuroimaging evidence

of an established cerebral infarction in the cranial CT at

admission (one patient). In two patients (one tPA treated),

an endovascular procedure was conducted with stent implan-

tation in the dissected carotid artery. One patient with no

evidence of connective tissue disease had two episodes of

cerebral infarction due to spontaneous eICAD (the first in

2006 affecting left internal carotid and the second in 2008

affecting the right internal carotid). These two episodes have

been included separately in the analysis. The most commonly

used diagnostic procedures for eICAD diagnosis were MRA

(21 patients), followed by CTA (nine patients) and selective

catheter angiography of craniocervical vessels (13 patients).

IVT-treated patients

Table 1 shows baseline and demographic data including risk

factors, stroke etiology, presence of concomitant diseases,

antithrombotic treatments at stroke onset and degree of neu-

rological severity of the 625 IVT-treated patients. Patients with

eICAD were younger and had a significantly lower frequency of

arterial hypertension and atrial fibrillation and higher rates of

prior TIA than patients with no diagnosis of eICAD.

Stroke severity was similar in both groups of patients

(median baseline NIHSS 15�5 eICAD vs. 13�0 non-eICAD;

P 5 0�989). However, IVT-treated patients with eICAD had a

significantly higher frequency of cerebral edema (62�5% vs.

37�9%; P 5 0�000) than patients without eICAD, with no

differences in the proportions of symptomatic hemorrhagic

transformation (0% vs. 4�6%; P 5 0�474) or any hemorrhagic

transformation (21�3% vs. 25%; P 5 0�459).

At Day 7, fewer patients in the group of IVT-treated eICAD

showed significant neurological improvement (28�6% vs.

51�1%; 0�081). In addition, mean improvement in NIHSS

from baseline to Day 7 was significantly lower in eICAD

patients (1�38; (95% CI �3�77 to 6�54) vs. 6�81; (95% CI

�5�99 to 7�63) P 5 0�004). Figure 1 shows the temporal

evolution in NIHSS scores, comparing patients who received

IVT according to eICAD diagnosis.

A total of 604 (96�6%) patients were followed up at three-

months. Seventy-nine (13�1%) patients in the non-eICAD

Table 1 Baseline characteristics of IVT-treated patients according to eICAD diagnosis

No eICAD

n 5 609

eICAD

n 5 16 P

Age, mean7SD (years) 67�0713�6 49�3713�5 0�000

Male gender, n (%) 326 (53�7%) 8 (50�4%) 0�482

Time from stroke onset to hospital admission, mean7SD (minutes) 74�1738�4 86�5730�2 0�216

Time from stroke onset to IVT 137�8734�7 137�5728�5 0�970

Medical history, n (%)

Arterial hypertension 369 (60�9%) 3 (18�8%) 0�001

Diabetes mellitus 109 (18%) 2 (12�5%) 0�434

Hypercholesterolemia 196 (32�5%) 4 (25%) 0�369

Atrial fibrillation 116 (19�1%) 0 (0%) 0�035

Heart failure 43 (7�1%) 1 (6�3%) 0�686

Cigarette smoking 155 (25�6%) 6 (37�5%) 0�211

Prior CI 55 (9�1%) 0 (0%) 0�224

Prior TIA 38 (6�3%) 4 (25%) 0�019

Prior antiplatelet treatment 193 (31�8%) 1 (6�3%) 0�020

Prior anticoagulant drugs 19 (3�1%) 0 (0%) 0�605

Admission variables

Plasma glucose on admission (mg/dl), mean7SD 128�7741�9 129�7759�8 0�929

Systolic blood pressure on admission (mmHg), mean7SD 147�4721�5 135�3718�2 0�038

Stroke severity – median NIHSS (p25, p75) 14 (9, 18) 15 (11, 16) 0�989

eICAD, extracranial internal carotid dissection; IVT, intravenous thrombolysis; TIA, transient ischemic attack.


B. Fuentes et al. Research

group were dead at three-months and 0 (0%) in the eICAD. No

significant differences in the proportion of patients with good

outcome were found between patients with eICAD compared

with non-eICAD (43�8% vs. 58�2%; P 5 0�185) (Fig. 2).

eICAD patients

A significant delay in time from stroke onset to hospital arrival

was found in the group of eICAD patients who did not receive

IVT (average 21 vs. two-hours). Table 2 summarizes the

baseline characteristics of eICAD patients. As expected, pa-

tients with eICAD had a low frequency of common vascular

risk factors, and no significant differences were found when

comparing the two groups according to IVT treatment.

IVT-treated patients with eICAD had more severe strokes

on admission than the patients who received no treatment

(median NIHSS: 15 vs. 7; P 5 0�031).

IVT-treated patients with eICAD had a significantly higher

frequency of cerebral edema (62�5% vs. 18�5%; P 5 0�006). The

unadjusted OR for developing cerebral edema associated with

IVT treatment in eICAD patients was 10 (95% CI 2�19–45�6;

P 5 0�003). However, it did not remain an independent risk

factor for cerebral edema after adjustment for stroke severity

on admission (OR 5�71; 95% CI 0�97–33�47; P 5 0�053).

A nonsignificant trend towards a higher frequency of any

hemorrhagic transformation was found in IVT-treated eICAD

patients (25% vs. 7�4%; P 5 0�125). No patient with eICAD

had a symptomatic hemorrhagic transformation, indepen-

dently of treatment group.

Figure 3 shows temporal trends of mean NIHSS in eICAD

patients according to IVT treatment. Nonsignificant differ-

ences were found in the rates of significant neurological

improvement at Day 7 (28�6% vs. 26�9%; P 5 0�596) as well

as in the mean improvement on NIHSS scores from baseline to

Day 7 (1�38 (95% CI �3�77 to 6�54) in IVT-treated vs. 3�11;

(95% CI �0�77 to 7�00)) in non-IVT-treated.

We obtained data regarding pretreatment intracranial arter-

ial status from seven of the 16 (43�7%) IVT-treated eICAD and

in all of them an intracranial vessel occlusion was found. The

post-IVT evaluation was conducted in 14 of the 16 (87�5%)

treated patients and we found that one of the patients with pre-

IVT intracranial occlusion achieved no recanalization and the

other six, showed vessel patency. In the eICAD non-IVT-

treated group we obtained transcranial doppler data within the

first 24 h from stroke onset only from four out of the 27

patients (14�8%) and none of them had an intracranial

occlusion.

A total of 40 (93%) eICAD patients were followed up at

three-months. Only seven (43�8%) of eICAD IVT-treated

patients had a good outcome (mRSr2) compared with 18

(75%) of the non-IVT treated, and the differences were

Fig. 1 Temporal evolution in NIHSS scores comparing patients who received

IVT treatment according to eICAD diagnosis. P 5 0�013 for comparison in

Day 7 NIHSS score between non-eICAD patients and IVT-treated eICAD.

No eICAD IVT-treated

eICAD IVT-treated

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

eICAD non IVT-treated

Fig. 2 Outcome at three-months according to scores on the modified Rankin Scale. Numbers indicate the percentage of patients in each score. P 5 0�007 for

comparison between patients without eICAD and IVT-treated eICAD.



statistically significant (P 5 0�048) (Table 3). However, logistic

regression analysis showed that IVT was not associated with

outcome at three-months after adjustment for stroke severity

on admission. In addition, an analysis excluding eICAD

patients with baseline NIHSS lower than six was conducted.

The analysis included data from 14 eICAD IVT-treated and 15

non-IVT-treated patients. Median NIHSS on admission was

similar between the two groups (15�5 vs. 13; P 5 0�799) and no

differences in good outcome at three-months were found

(46�7% in IVT treated vs. 64�3% in non-IVT; P 5 0�282).

A total of 40 (93%) eICAD patients had a carotid occlusion–

subocclusion in the neuroimaging studies conducted during

hospital admission; 15 (100%) in the IVT group and 25

(92�6%) in the non-IVT (P 5 0�408). Data on carotid neuroi-

maging studies at six-months of follow-up were available in 33

(76�7%) eICAD patients. Patients who were IVT treated

tended toward lower rates of complete vessel recanalization

than those who did not receive IVT (58�3% vs. 71�4%;

P 5 0�347).

Discussion

Although IVT seems to be safe in patients with IS due to

eICAD, concerns about its efficacy have recently been raised in

a large series comparing IVT-treated eICAD with IVT-treated

patients with other causes of stroke (6). Moreover, a higher

frequency of unfavourable outcome has been shown after IVT

in young patients with eICAD when compared with control

subjects matched by age and adjusted for stroke severity but

not treated with IVT (11). Our study is the first prospective and

multicenter study that compares stroke outcome in IVT-

treated patients with eICAD patients who did not receive

IVT. This study shows that mean neurological improvement

within the first seven-days in eICAD patients is low, regardless

of the administration or not of IVT. Although we found a lower

frequency of good outcomes at three-months in IVT-treated

eICAD patients (43�8% vs. 75%), no statistically significant

differences were found compared with non-IVT-treated

patients after adjustment for stroke severity. It has been

reported that the natural course of stroke after an eICAD is

associated with high rates of poor outcomes (60% of death or

Table 2 Baseline characteristics of eICAD patients according to IVT therapy

eICAD IVT-treated

n 5 16

eICAD non-IVT

n 5 27 P

Age, mean7SD (years) 49�3713�5 45710�6 0�254

Male gender, n (%) 8 (50%) 15 (55�6%) 0�485

Medical history, n (%)

Arterial hypertension 3 (18�8%) 3 (11�1%) 0�394

Diabetes mellitus 2 (12�5%) 1 (3�7%) 0�308

Hypercholesterolemia 4 (25%) 3 (11�1%) 0�220

Atrial fibrillation 0 (0%) 1 (3�7%) 0�628

Heart failure 1 (6�3%) 0 (0%) 0�372

Cigarette smoking 6 (37�5%) 7 (25�9%) 0�322

Prior CI 0 (0%) 2 (7�4%) 0�389

Prior ipsilateral TIA 4 (25%) 10 (37%) 0�320

Prior antiplatelet treatment 1 (6�3%) 3 (11�1%) 0�521

Prior oral anticoagulant drugs 0 (0%) 1 (3�7%) 0�628

Admission variables

Plasma glucose on admission (mg/dl), mean7SD 129�7759�8 123�4751�7 0�729

Systolic blood pressure on admission (mmHg), mean7SD 135�3718�2 142727�8 0�426

Stroke severity – median NIHSS (p25, p75) 15 (12, 16) 7 (3, 13) 0�031

eICAD, extracranial internal carotid dissection; IVT, intravenous thrombolysis; TIA, transient ischemic attack.

Fig. 3 Temporal evolution in NIHSS scores comparing eICAD patients with

and without IVT treatment. No significant differences between groups.



dependence) (12). In addition, in the larger series of IVT-

treated stroke attributable to cervical artery dissection, up to

64% had poor outcomes at three-months (6).

The main limitations of our study are the small number of

eICAD patients and the baseline differences between eICAD

IVT-treated and those eICAD patients who did not receive IVT,

mainly regarding stroke severity on admission, which could be

considered a bias against a favourable outcome for the IVT

cases. The lower stroke severity in eICAD patients who did not

receive IVT could be due to several reasons. Firstly, in the

majority of eICAD patients who were not IVT treated, the

main contraindication was time from stroke onset, i.e. more

than three-hours (18 patients) and it is well known that

patients with more severe strokes go to the hospital faster

than those with mild symptoms, who remain longer at home

waiting to recover spontaneously. Three patients were ex-

cluded for IVT due to minor stroke. Finally, only six eICAD

patients were excluded for stroke on awakening (three pa-

tients), progressive stroke (two patients) and neuroimaging

evidence of an established cerebral infarction in the cranial CT

at admission (one patient). As this was an observational study,

which registered all eICAD cases within a certain time period,

without excluding any patient on the basis of any pre-

established criteria, a selection bias should not applicable to

our study and this only reflects the current clinical manage-

ment of eICAD patients. Nevertheless, further analysis exclud-

ing patients with mild strokes (NIHSSo6) on the one hand,

and a logistic regression analysis adjusting for stroke severity

on the other, showed that the differences in outcome between

the two groups were not statistically significant, although a

trend toward a lower frequency of good outcomes was found in

the eICAD IVT-treated group. This is in agreement with a

recently published study that showed that unfavorable out-

come was more frequent in alteplase-treated patients with

eICAD as compared with age, gender and stroke severity

matched controls (11). Another limitation in our study is

the lack of a proper protocol-based study of the intracranial

arterial status in eICAD patients. Although this register was

open to include the results of transcranial doppler, the

investigators only provide data of 87�5% of IVT-treated eICAD

and 14�8% of non-IVT-treated eICAD patients. This fact could

limit the analysis of the beneficial effect of IVT in eICAD

patients as compared with nontreated, as it is possible that the

majority of IVT-treated patients had intracranial arterial

occlusion which is associated with poorer outcomes. It has

been reported that up to 30% of eICAD with ischemic events

had a intracranial artery stenosis or occlusion detectable by

transcranial color dupplex sonography (13), and up to 46%

eICAD patients in Engelter et al.’s study had intracranial

occlusions, but the prognostic significance of this finding

could not be analyzed due to the nonavailability of data on

vessel patency for non-eICAD patients (6). Nevertheless, no

data on the possible differences in the frequency of intracranial

artery occlusions between different degrees of stroke severity

are available.

Our study also corroborates the safety of IVT in IS due to

eICAD, with no patients with symptomatic hemorrhagic

transformation. However, compared with eICAD control

patients, the IVT-treated eICAD patients had a significantly

higher frequency of cerebral edema (62�5% vs. 18�5%). This

complication was not assessed in previous published studies

on this topic, as all of them only focused on hemorrhagic

transformation as a surrogate marker of IVT safety. However,

one study that reviewed data from 33 patients reported that

five patients had an intracranial hypertension complication,

and two of them died (3). It is true that in our study, the effect

of IVT on the risk for cerebral oedema development was not

statistically significant after adjustment for stroke severity on

admission, but the small sample size may also explain the lack

of significant differences in the adjusted analysis. Thus, larger

series of eICAD IVT-treated patients should include the

analysis of cerebral oedema to rule out a possible deleterious

effect of IVT treatment.

Another point of interest is the high rate of carotid arterial

occlusion reported in IVT-treated patients with cervical ar-

teries dissections, which ranges from 52% (3) to 90% (6). This

fact, along with the observation that up to 83% of eICAD

patients not treated with IVT also had arterial occlusion (13)

has led to rejection of the hypothesis that IVT could cause

progression of intramural bleeding to complete closure of the

vessel. One limitation of many of the studies on this topic is

that, in the majority (including ours) arterial dissection was

Table 3 Unadjusted outcome in IVT-treated patients with IS due to eICAD compared with those not treated with IVT

eICAD IVT-treated

n 5 16

eICAD non-IVT

n 5 27 P value

Cerebral edema; n (%) 10 (62�5%) 5 (18�5%) 0�006

Any hemorrhagic transformation; n (%) 4 (25%) 2 (7�4%) 0�125

Symptomatic hemorrhagic transformation; n (%) 0 (0%) 0 (0%) –

Significant neurological improvement at Day 7�, n (%) 4 (28�6%) 7 (26�9%) 0�596

Good outcome at three-months (mRSr2); n (%) 7 (43�8%) 18 (75%) 0�048

Complete carotid recanalization at six-months; n (%)w 7 (58�3%) 15 (71�4%) 0�347

�Significant neurological improvement was defined as a decrease of at least at least eight points or complete recovery at Day 7 (data available in 40

patients). wData available for 33 patients at six-month follow-up.eICAD, extracranial internal carotid dissection; IVT, intravenous thrombolysis; IS, ischemic

stroke.



diagnosed after the administration of IVT, as the therapeutic

window is short and arterial dissection is not a contraindica-

tion for IVT. Thus, a delay in starting treatment in order to rule

out this disease has ethical concerns. It has been reported that

up to 69% of patients with stroke secondary to eICAD with

severe stenosis or occlusion at the acute phase of stroke achieve

complete recanalization or less than 50% stenosis at one-year

of follow-up (14). However, to our knowledge, none of the

previous studies reported the findings of serial studies of vessel

patency in eICAD IVT-treated patients. In this sense, we found

that IVT-treated eICAD patients had lower rates of complete

recanalization of the internal carotid artery at six-months than

non-IVT-treated eICAD patients. However, due to the small

sample size, we were not able to detect statistically significant

differences in this analysis.

In conclusion, as compared with other etiologies, patients

with stroke due to eICAD seem to obtain fewer benefits from

IVT in the acute phase of stroke, with fewer improvements in

neurological evaluations within the first seven-days, but with-

out significant differences in outcome at three-months.

Although IVTseems to be safe in stroke attributable to eICAD,

no differences in the outcome were found when comparing

IVT-treated patients with non-IVT-treated patients, even after

adjusting for stroke severity.

Acknowledgements

This work is part of the Spanish collaborative research network

RENEVAS (Instituto de Salud Carlos III, Ministerio de Ciencia

e Innovacion, RD06/0026/008, RD07/0026/2003 and co-

financed by FEDER). We thank Belen SanJose for her biosta-

tistical assistance and Andres Garcıa Pastor for his help in

including patients in the study.

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Benefits of intravenous thrombolysis in acute ischemic stroke related to extra cranial internal carotid dissection. Dream or reality?