Retrospective analysis of neurological outcome after intra-arterial thrombolysis in basilar artery occlusion

Ischemia

Retrospective Analysis of Neurological Outcome After Intra-Arterial Thrombolysis in Basilar Artery Occlusion Yasuyuki Ezaki, M.D.,* Keisuke Tsutsumi, M.D.,† Masanari Onizuka, M.D.,‡ Junichi Kawakubo, M.D.,* Nobuhiro Yagi, M.D.,* Akira Shibayama, M.D.,* Tamotsu Toba, M.D.,§ Hiroaki Koga, M.D.,‡ and Hisaya Miyazaki, M.D.* *Department of Neurosurgery, Sankokai Miyazaki Hospital, †Department of Neurosurgery, Nagasaki Rosai Hospital, ‡Department of Neurosurgery, National Nagasaki Medical Center, ¶Koga Neurosurgery Clinic, Nagasaki City, Japan; §Department of Neurosurgery, Kitakyushu City Yahata Hospital, Fukuoka, Japan

Ezaki Y, Tsutsumi K, Onizuka M, Kawakubo J, Yagi N, Shibayama A, Toba T, Koga H, Miyazaki H. Retrospective analysis of neurological outcome after intra-arterial thrombolysis in basilar artery occlusion. Surg Neurol 2003;60:423–30. BACKGROUND

Basilar artery occlusion usually has a very poor outcome and is associated with a high mortality rate. Local intraarterial thrombolysis may improve the clinical outcome and reduce mortality in the treatment of acute basilar artery occlusion. We evaluated the possible variables affecting recanalization and clinical outcome in patients with basilar artery occlusions undergoing thrombolytic therapy. METHODS

We analyzed retrospectively the clinical course and outcome of a series of 26 patients between 1998 and 2001. All patients who were examined within 24 hours after onset of symptoms underwent emergency cerebral angiography and subsequent intra-arterial thrombolysis. Three patients additionally received percutaneous transluminal angioplasty of underlying stenosis at the site of thrombosis. RESULTS

Outcome was good in 9 patients (34.6%) and poor in 17 (65.4%). Recanalization could be achieved in 24 patients (92.3%) and was not affected by age, sex, site of occlusion, etiology, thrombolytic drugs, or time interval. Good outcome was associated with younger age, good initial clinical condition, and no evidence of brain stem infarction. There was no association between the interval (greater or less than 6 hours) from the onset of symptoms until the end of thrombolysis and survival.

Address reprint requests to: Yasuyuki Ezaki, Department of Neurosurgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki City, 852-8501, Japan. Received October 7, 2002; accepted March 26, 2003. © 2003 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010 –1710

CONCLUSIONS

We confirm that intra-arterial thrombolysis reduces mortality in basilar artery occlusion. Young patients (⬍75 years) without any infarct in brain stem before the start of treatment seem to be the ideal candidates for thrombolysis. Basilar artery thrombosis could and should be reopened, even late (after 6 hours) after symptom onset. © 2003 Elsevier Inc. All rights reserved. KEY WORDS

Cerebral infarction, basilar artery, thrombolysis.

cute basilar artery occlusion is a catastrophic neurologic event. Recent advances in interventional techniques and the development of instruments have led to the creation of new therapeutic approaches for acute cerebral artery thrombosis. Institutions that perform local intraarterial thrombolysis (LIT) for the treatment of acute cerebral artery thrombosis have been increasing in number. Despite the lacks of data demonstrating clinical benefits, many physicians consider that LIT should be positively applied, but even with advances in thrombolytic techniques, basilar artery occlusion remains a frequently fatal disease [2,4,6,13,20,23]. Zeumer et al reported the first LIT cases for basilar artery occlusion in 1983 [28]. Some authors have recently reported success in treating vertebrobasilar artery thrombosis with LIT [2,4,8,16,18,19,21–24,27]. However, there is no clearcut strategy regarding the optimal management of vertebrobasilar occlusion. In this study, we investigated the indications and prognoses of LIT in pa-

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tients with acute basilar artery occlusion encountered during the last four years.

Subjects and Methods Between 1998 and 2001 we performed intra-arterial thrombolysis in 26 patients with angiographically confirmed basilar artery occlusion. All patients who were examined within 24 hours after onset of symptoms underwent emergency cerebral angiography and subsequent LIT. Informed consent for the angiographic and thrombolytic procedures was obtained from each patient or their nearest relative. There were no strict time limits for inclusion based on symptom duration in cases of basilar artery occlusion. The timing of referral for treatment varied widely in this group of patients. Onset of symptoms was defined as the last time the patients felt normal or were at neurologic baseline. The duration of symptoms was defined as the number of hours from the onset of symptoms until the end of thrombolysis. The criterion for application of LIT was detection of basilar artery occlusion corresponding to neurologic manifestation by digital subtraction angiography without intracranial hemorrhage and fresh infarction on computed tomography (CT). We elected to treat these patients aggressively because of their continued neurologic decline and the overall poor prognosis associated with basilar artery occlusion. The procedure was performed with the patients under mild sedation to allow for continuous neurologic monitoring. A femoral artery sheath was inserted; initially a diagnostic angiogram was obtained. Once the diagnosis of basilar thrombosis was confirmed, systemic anticoagulation was begun with IV heparin. Heparin anticoagulation was maintained after the procedure in the intensive care unit, except for patients with hemorrhage. After a guiding catheter was placed in the vertebral artery, a microcatheter was advanced under road-mapping guidance to the proximal aspect of the basilar artery thrombus. Fibrinolytic agents were then infused into the proximal aspect of the thrombus, combined with the mechanical destruction of the clot by the guide wire. We believe that mechanical destruction of the clot is important to deliver the drug to the distal part of the clot and accelerate the thrombolysis. LIT was performed using urokinase (UK), recombinant tissue plasminogen activator (tPA), or prourokinase (ProUK). Three patients additionally received percutaneous transluminal angioplasty (PTA) of an underlying stenosis at the site of thrombosis. Infusion was continued either until the

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vessel was recanalized or until the maximal dose of the fibrinolytic agent (urokinase, 960.000IU; t-PA, 9.000.000IU; ProUK, 4.500IU). On the basis of angiogram findings, the site of the basilar occlusion was classified in accordance with the criteria of Archer and Horenstein [1]: (1) caudal, from the confluence of the vertebral arteries to the origin of the anterior inferior cerebellar artery; (2) midbasilar, from the origin of the anterior inferior cerebellar artery to the origin of the superior cerebellar arteries; and (3) oral, the top of the basilar artery. Recanalization was assessed by repeated angiography after treatment without delay and scored as “complete,” “partial,” or “no recanalization” according to perfusion criteria established by the thrombolysis in Myocardial Infarction Study Group (TIMI) [25]. The application of these criteria to cerebral vessels has been reported previously [9]. “No recanalization” (TIMI Grade 0 or 1) was defined as minimal or no perfusion with no opacification of the distal vessels. “Partial recanalization” (TIMI Grade 2) was defined as an obstruction that resulted in a delayed opacification of the distal vessels. “Complete recanalization” (TIMI Grade 3) was defined as unimpeded perfusion of the distal vasculature, regardless of whether a residual stenosis or a focal flow gap was present. The criteria for classifying occlusions as either cardioembolic or atherothrombotic were based on the results of angiographic study and on clinical features. An infarct lesion was observed by imaging on the day following LIT in all patients. Patterns of infarction on magnetic resonance imaging (MRI) after LIT were divided into three types: Type A, infarction in the brain stem; Type B, infarction in the thalamus only; and Type C, infarction in the cerebellar hemisphere only. Clinical assessment was performed at admission by Glasgow Coma Scale (GCS) and after 3 months using the Glasgow Outcome Scale (GOS). Good recovery (GR) and moderately disabled (MD) were defined as “good,” and severely disabled (SD), vegetative survival (VS), and dead (D) as “poor” outcomes. The statistical association of clinical and neuroradiological baseline characteristics with recanalization and clinical outcome was tested by the ␹2 test or Fisher’s exact test and Mann-Whitney test for unpaired groups; p ⬍ 0.05 was considered significant.

Results There were 19 males and 7 females ranging in age from 45 to 84 years (mean: 67.2 years). Tops of the basilar artery occlusions were detected in 2 pa-

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1

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Characteristics of Patients with and without Recanalization

RECANALIZATION (N ⴝ 24)

Sex Male Female Age (y) 75ⱕ 75⬎ Site of occlusion Caudal Midbasilar Top Etiology cardioembolic atherosclerotic (unknown) Time to therapy, h 6ⱕ 6⬎ Fibrinolytic agents t-PA UK Pro-UK

NO RECANALIZATION (N ⴝ 2)

COMPLETE

PARTIAL

P

6 3 65.3 1 8

12 3 68.1 4 11

.6349a

6 2 1

7 7 1

.4855b

1 1 0

2 3 (4)

9 5 (1)

.6027a

1 1 (0)

3 6

9 6

.4003a

1 1

4 4 1

1 13 1

.0671c

0 2 0

.2240c .6146a

1 1 68 1 1

Time to therapy: time period from symptom onset to end of thrombolysis; t-PA: recombinant tissue plasminogen activator; UK: urokinase; Pro-UK: prourokinase. a Fisher’s exact test, b␹2 test, cMann-Whitney test.

tients. Ten patients had midbasilar occlusions, and 14 presented with caudal-type occlusions. LIT was achieved within 3 to 11 hours from the last clinical neurologic progression. RECANALIZATION The occluded vessel was recanalized successfully in 24 patients (92.3%; complete in 9 [34.6%]; partial in 15 [57.7%]). Recanalization was not achieved in two (7.7%). Table 1 compares the characteristics of patients with and without recanalization. As recanalization was not achieved in only two patients, no significant difference was apparent between the recanalization and no recanalization groups. The statistical difference between the complete and partial recanalization groups was, thus, analyzed. Of 20 patients younger than 75 years old, complete recanalization was achieved in eight (40%); partial recanalization was achieved in 11 (55%); and recanalization was not obtained in one (5%). Of six patients aged 75 years or older, complete recanalization was achieved in one (16.7%); partial recanalization was achieved in four (66.7%); and recanalization was not obtained in one (16.7%), showing that recanalization was partial in many cases. Thirteen patients (50%) were treated within 6 hours. There was no association between recanalization

and early treatment within 6 hours from symptom onset. With regard to thrombolytic drugs, recanalization was achieved in all five patients treated with t-PA, but there was no significant difference in the recanalization rate because of different thrombolytic drugs. Recanalization was not affected by sex, site of occlusion, or etiology. PROGNOSIS Outcome was good for 9 patients (34.6%) and poor for 17 (65.4%). In detail, GOS after 3 months was GR in 7 (26.9%), MD in 2 (7.7%), SD in 6 (23.1%), VS in 4 (15.4%), and D in 7 (26.9%). Table 2 shows the clinical and angiographic variables potentially affecting outcome. Age was significantly higher in the poor prognosis group (mean age: 60.0 and 70.9 years old in the good and poor prognosis groups respectively, p ⬍ 0.005), and the prognosis was poor in all patients aged 75 years or older. Initial neurologic status was a reliable predictor of outcome. All 5 patients with GCS scores over 10 at the time of treatment had good outcomes. In contrast, only 4 (19%) of 21 patients with GCS scores under 10 had a good outcome. The prognosis was not significantly correlated with sex, site of occlusion, etiology, time to therapy, or type of thrombolytic drugs. The prognosis was good in 4

426 Surg Neurol 2003;60:423–30

2

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Clinical and Radiological Variables Associated with Outcome

OUTCOME GROUP

Sex Male Female Age (y) 75ⱕ 75⬎ Pretreatment GCS 10⬍ 10ⱖ Site of occlusion Caudal Midbasilar Top Etiology Cardioembolic Atherosclerotic (Unknown) Time to therapy, h 6ⱕ 6⬎ Fibrinolytic agents t-PA UK Pro-UK recanalization Complete Partial no MRI (post LIT) Type A Type B, C

GOOD (N ⴝ 9)

POOR (N ⴝ 17)

8 1 60.0 0 9

11 6 70.9 6 11

.3574a

5 4

0 17

.0019a

4 4 1

10 6 1

.7546b

4 4 (1)

8 5 (4)

.6731a

P

.0081c .0634a

hemorrhages occurred in that group. Bleeding complications occurred in 7.7% of patients, with death ensuing in 3.8%. There were 17 Type A patients in whom the subsequent infarction included the brain stem. The prognoses were MD in 1, SD in 5, VS in 4, and D in 7. There was one Type B patient in whom the subsequent infarction was localized in the thalamus, and the prognosis was GR. Eight patients were Type C, having infarctions localized in the cerebellar hemisphere, and the prognoses were GR in 6, MD in 1, and SD in 1. The prognoses were poor in all Type A patients excluding one, while the prognosis was good in all Type B and C patients excluding 1 who developed rethrombosis. Infarctions including the brain stem that developed after LIT were significantly associated with poor outcomes.

Discussion ⬎.9999

a

5 4

8 9

2 7 0

3 12 2

.5586c

5 4 0

4 11 2

.0795c

1 8

16 1

⬍.0001a

GCS: Glasgow coma scale; Time to therapy: time period from symptom onset to end of thrombolysis; t-PA: recombinant tissue plasminogen activator; UK: urokinase; Pro-UK: prourokinase; MRI: magnetic resonance imaging; LIT: local intra-arterial thrombolysis. a Fisher’s exact test, b␹2 test, cMann-Whitney test.

(44.4%) of 9 patients in whom recanalization was complete, while the prognosis was good in 4 (26.7%) of 15 patients in whom recanalization was partial. Because the number of cases of nonrecanalization was small in this study, the correlation between the presence or absence of recanalization and prognosis could not be clarified. The mortality rate was 20.8% (5/24) in cases of recanalization but 100% for the 2 patients in whom recanalization was not obtained. The degree of recanalization was slightly correlated with neurologic outcome. Two patients had pontine hemorrhage after successful intra-arterial recanalization with urokinase (420.000 and 480.000 IU). Both of these patients were treated within 6 hours of symptom onset. Thirteen patients were treated after 6 hours, and no

Basilar artery occlusion usually has a very poor outcome and is associated with a high mortality rate [2,4,6,13,20,23]. Becker et al reported that all of three patients in whom vertebrobasilar artery occlusion was not recanalized died [2]. Because the prognosis is poor in many patients with vertebrobasilar occlusion treated only with conservative therapy, many reports advocate the use of LIT [2,4,6,13,16,18,19,21–24,27]. The first large-scale observation in 43 patients with basilar artery occlusions and LIT was described by Hacke et al in 1988 [14]. They reported that recanalization significantly improved clinical outcome and survival in basilar artery occlusion. In their series, all patients without recanalization died, while 14 of 19 patients displaying recanalization survived. As factors related to the prognosis, initial clinical condition, etiology, time after the onset, age, location and length of occlusion on angiography, presence or absence of recanalization, and degree of collateral circulation have been reported [2,4,5– 8,12,13,16,17,21– 23,26,27]. In this study, age, initial clinical condition, and infarction appearing after LIT were significantly associated with outcome. Although the difference was not significant, the prognosis tended to be better in cases of good recanalization. Recanalization was not achieved in 2 patients, and their prognoses were the worst, suggesting that as cases resulting in complete recanalization increase, the overall prognosis will improve. However, a high percentage of patients with successful, angiographically verified recanalization died. One reason for this negative outcome in patients with successful recanalization might be fragmentation of the clot

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and transportation into more distal vessels supplying the PCA territory, the brain stem, and the thalamus. Recanalization is a necessary but not sufficient criterion for good outcome after thrombolysis. There are patients who seem to benefit from LIT and those who do not. The ability to distinguish between these subpopulations before initiation of thrombolytic therapy is important. Our data are still a small population from a statistical point of view. Studies with large series of patients are needed to investigate the feasibility of randomized controlled trials. The clinical diagnosis of basilar artery thrombosis can be difficult and definitive diagnoses are often delayed, in part because basilar thrombosis is relatively rare, and the initial evaluating physician may not make the correct diagnosis from the sometimes vague presenting symptoms. Fatal hemorrhage is also a serious therapeutic complication [2,8]. To limit hemorrhage transformation of infarctions, it has become fairly standard practice in the anterior circulation to restrict LIT to the first 6 hours of symptoms. However, many reports describe that the time window of therapeutic basilar artery occlusion is longer than that of anterior circulation [2,6,16,21,23]. In our cases, 2 patients had pontine hemorrhage after successful intra-arterial recanalization with UK (420.000 and 480.000 IU). Both of these patients were treated within 6 hours of symptom onset. Thirteen patients who were treated after 6 hours had no hemorrhagic infarction. Bleeding complications occurred in 7.7% of patients, with death ensuing in 3.8%. The risk of hemorrhagic infarction accompanying the thrombolytic therapy was not significantly higher, and hemorrhagic complications were not associated with clinical deterioration in the previous results [4,23,24]. Extending this time limit may have proved beneficial to some patients and did not increase the risk of hemorrhagic transformation at least in this small series. It is possible that the brain stem is tolerant to longer periods of ischemia than is the cerebral cortex. Preserved collateral flow may lead to a prolonged therapeutic window. In our series, the time to therapy from the last neurologic deterioration did not seem to correlate with the ability to achieve recanalization or with the overall outcome. These results stress the need for thrombolytic therapy even in patients with delayed arrival because of the poor prognosis associated with conservatively treated cases. The site and length of occlusion and collateral status have been shown to have an important impact on prognosis [2,4 – 6,10,16,21,23]. In several studies, tops of basilar occlusions were associated

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with the most favorable outcome. Top of basilar occlusions generally show preservation of flow into the cerebellar arteries; the arteries penetrating the brainstem; and the posterior cerebellar artery, which can be supplied by the anterior circulation via the posterior communicating artery. In addition, distal basilar thrombosis tended to be embolic, while middle and proximal basilar thrombosis tended to be the result of thrombosis on atherosclerotic lesions. Thrombolysis of an embolus lodged in a normal artery is more favorable than that of a thrombus formed at a site of atherosclerosis. In contrast to other observations, the small number of patients in our series precludes a definite conclusion that the recanalization rate and the prognosis are not significantly correlated with the sites of occlusion. Recanalization was achieved in all patients treated with t-PA but owing to the small number of patients treated with t-PA and pro-UK, the fibrinolytic agent used in this series had no statistically significant effect on recanalization or outcome. The type of thrombolytic medication that should be used in patients with basilar artery thrombosis is still under discussion. In contrast, additional treatment with PTA for patients in whom a severe stenosis remained because of focal atherosclerotic narrowing and treatment with direct PTA from the beginning of therapy to shorten the duration of therapy has achieved good results in some cases [3,18,19,24]. We successfully performed PTA on the basilar artery in 3 patients with severe atherosclerotic lesions underlying the site of thrombosis, and the artery continued to remain patent after the procedures. It was used effectively in 3 patients in our series. Complete resolution of the thrombus is not always achievable, but if the stenosis portion is left untreated, the basilar artery will most likely reocclude. Therefore, PTA was performed and felt to be an important part of the therapy. However, angioplasty of intracranial vertebrobasilar arteries is reported infrequently because of the potential lifethreatening risks of vessel rupture, thromboembolic occlusion, and brain stem infarction because of damage to the small perforating arteries [8,18,19]. The selection of the balloon size and appropriate pressures to inflate the balloon have not yet been established. The development of a microballoon catheter suitable for PTA of intracranial vessels is expected and the role of PTA in this region may increase. The prognosis was poor in patients aged 75 years or older regardless of whether or not the occlusion was recanalized, and this was consistent with studies reporting that outcomes were poor in elderly

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patients [4,16,26]. The reduction of cerebral recoverability because of aging may be generally involved in this poor outcome. Recanalization was incomplete in all but one of the elderly patients, suggesting that only partial recanalization was achieved due to difficulty in accessing the lesion because of severe atherosclerosis. If these differences in the degree of reperfusion are involved in addition to cerebral fragility in elderly patients, technical improvement and selection of a drug aimed at complete recanalization may improve the prognosis. Our patients with GCS of ⱕ10 at admission had a worse prognosis than patients with a score of ⬎10. In contrast to previous studies [2,23], a correlation between severity of stroke and outcome was observed in our series and some other reports [10,13]. However, in a few patients, thrombolysis provided a satisfactory functional outcome even after initial coma. Therefore, severe neurologic deficit may not be appropriate as a single exclusion criterion. It may be necessary for optimized patient selection to combine neurologic deficits with other predictive variables. However, we would not consider thrombolytic therapy for comatose patients who are mechanically ventilated and have lost many brainstem reflexes. When LIT is performed for anterior circulation ischemia, it is important to maintain the residual blood flow in the ischemic region. The site and length of occlusion in the angiogram and the degree of collateral circulation were used as a method of indirect evaluation of blood flow in the brain stem in some reports [6], but precise evaluation of blood flow in the brain stem is still difficult. Although there are a still few institutions in which MRI [diffusion-weighted image (DWI) or perfusion image] and single photon emission tomography (SPECT) are always available, clinical examination and CT scan data also cannot adequately assess the extent of ischemia in posterior-circulation stroke at the very early stage [20]. It is thus necessary to plan positive therapy in consideration of the specific conditions of each ischemic lesion that is very likely to become serious if treated with conservative therapy alone. A prolonged time to presentation should not exclude the potential for therapy if neurologic deterioration is continuing while eloquent neurologic function remains. In this study, we established relatively mild criteria for application based on the above circumstances, considering that each institution experienced only a small number of cases and performed positive intravascular therapy. The use of perfusion imaging and the development of SPECT

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with a higher resolution for emergency cases are awaited. Although it is natural that the overall prognosis was poor in patients in whom occlusion resulted in brain stem infarction (Type A), this progression to brain stem infarction could be predicted if MRI including DWI was performed on admission in some patients [20]. Ischemic changes in the brain stem were excluded from the indications of LIT in consideration of the risk of postoperative hemorrhagic infarction in many reports [2,4,19,23], while the development of hemorrhagic infarction was not associated with clinical deterioration in other reports [24,27], and no consensus has been achieved. In the near future, when many institutions are able to perform MRI for emergency care during the acute phase, it will be necessary to accumulate information, including the investigation of each ischemic region, to determine whether cases with ischemic changes in the brain stem on DWI are included in the indication. The fact that DWI abnormalities may be potentially reversible must also be considered [11], as recently shown by Kidwell et al [15]. Acute DWI lesions probably contain not only irreversibly injured tissue but also parts of the penumbra. Rochemont et al [11] described that patients with only relatively small or no DWI lesions have a potentially favorable outcome if reperfusion is achieved rapidly with intra-arterial thrombolysis and small DWI lesions, even if located in the brainstem, do not exclude a favorable outcome. In their patients with successful reperfusion, the small, acute DWI brainstem lesion did not increase in size, and the patients showed good recovery. In conclusion, we confirm that intra-arterial thrombolysis may lead to a favorable clinical outcome in selected cases with basilar artery occlusion. The data show a trend toward a greater degree of recanalization in patients younger than 75 years old and treated with t-PA, but these trends were not significant. Age, initial clinical condition, and infarctions appearing after LIT were significantly associated with outcome. Young patients (⬍75 years) without brain stem infarcts before the start of thrombolysis seem to be the ideal candidates for LIT. Good results can be achieved if recanalization is performed even after 6 hours after symptoms onset. REFERENCES 1. Archer CR, Horenstein S. Basilar artery occlusion. Stroke 1977;8:383–90. 2. Becker KJ, Monsein LH, Ulatowski J, Mirski M, Williams M, Hanley DF. Intraarterial thrombolysis in vertebrobasilar occlusion. AJNR Am J Neuroradiol 1996; 17:255–62.

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3. Becker KJ, Crain BJ, Monsein LH, Pappalardo PA, Hanley DF. Arterial changes after thrombolysis and percutaneous transluminal angioplasty in vertebrobasilar thrombosis. AJNR Am J Neuroradiol 1997;18: 514 –8. 4. Brandt T, von Kummer R, Muller-Kuppers M, Hacke W. Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 1996;27:875–81. 5. Brandt T, Knauth M, Wildermuth S, et al. CT angiography and Doppler sonography for emergency assessment in acute basilar artery ischemia. Stroke 1999;30:606 –12. 6. Cross DT 3rd, Moran CJ, Akins PT, Angtuaco EE, Diringer MN. Relationship between clot location and outcome after basilar artery thrombolysis. AJNR Am J Neuroradiol 1997;18:1221–8. 7. Cross DT 3rd, Moran CJ, Akins PT, Angtuaco EE, Derdeyn CP, Diringer MN. Collateral circulation and outcome after basilar artery thrombolysis. AJNR Am J Neuroradiol 1998;19:1557–63. 8. Cross DT 3rd, Derdeyn CP, Moran CJ. Bleeding complications after basilar artery fibrinolysis with tissue plasminogen activator. AJNR Am J Neuroradiol 2001; 22:521–5. 9. del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in acute cerebral thromboembolism. Stroke 1998;29:4 –11. 10. Devuyst G, Bogousslavsky J, Meuli R, Moncayo J, de Freitas G, van Melle G. Stroke or transient ischemic attacks with basilar artery stenosis or occlusion: clinical patterns and outcome. Arch Neurol 2002;59:567– 73. 11. du Mesnil de Rochemont R, Neumann-Haefelin T, Berkefeld J, Sitzer M, Lanfermann H. Magnetic resonance imaging in basilar artery occlusion. Arch Neurol 2002;59:398 –402. 12. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA 1999;282: 2003–11. 13. Gonner F, Remonda L, Mattle H, et al. Local intraarterial thrombolysis in acute ischemic stroke. Stroke 1998;29:1894 –900. 14. Hacke W, Zeumer H, Ferbert A, Bruckmann H, del Zoppo GJ. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988;19:1216 –1222. 15. Kidwell CS, Saver JL, Mattiello J, et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol 2000;47:462–9. 16. Kuwayama N, Endo S, Kubo M, et al. Local Intraarterial Fibrinolysis for acute cerebral artery occlusion: Retrospective analysis of outcome and recanalization time. Surg Cereb Stroke (Jpn) 1999;27:85–90. 17. Levy EI, Scarrow AM, Kanal E, Rubin G, Yonas H, Kirby L. Reversible ischemia determined by xenonenhanced CT after 90 minutes of complete basilar artery occlusion. AJNR Am J Neuroradiol 1998;19: 1943–6.

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18. Nakano S, Yokogami K, Yamada R, Goya T, Wakisaka S. Acute thrombolytic therapy and subsequent angioplasty for atherosclerotic stenosis of the basilar artery: case report. Neurol Med Chir (Tokyo) 1995;35: 674 –7. 19. Nakayama T, Tanaka K, Kaneko M, Yokoyama T, Uemura K. Thrombolysis and angioplasty for acute occlusion of intracranial vertebrobasilar arteries. Report of three cases. J Neurosurg 1998;88:919 –22. 20. Nighoghossian N, Derex L, Turjman F, et al. Hyperacute diffusion-weighted MRI in basilar occlusion treated with intra-arterial t-PA. Cerebrovasc Dis 1999; 9:351–4. 21. Orlandi G, Moscato G, Padolecchia R, Sartucci F. Early thrombolysis in stroke due to basilar artery occlusion. Neurol Sci 2001;22:399 –402. 22. Otsuka Y, Waki R, Fukazawa S, Kimura K, Nakayama N, Shimizu K. Local intra-arterial thrombolysis for hyperacute cerebral embolism. Jpn J Stroke 2000;22: 525–9. 23. Sliwka U, Mull M, Stelzer A, Diehl R, Noth J. Long-term follow-up of patients after intraarterial thrombolytic therapy of acute vertebrobasilar artery occlusion. Cerebrovasc Dis 2001;12:214 –9. 24. Terada T, Yokote H, Tsuura M, et al. Tissue plasminogen activator thrombolysis and transluminal angioplasty in the treatment of basilar artery thrombosis: case report. Surg Neurol 1994;41:358 –61. 25. The TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med 1985;312:932–6. 26. Ueda T, Sakaki S, Kumon Y, Ohta S. Multivariable analysis of predictive factors related to outcome at 6 months after intra-arterial thrombolysis for acute ischemic stroke. Stroke 1999;30:2360 –5. 27. Wijdicks EF, Nichols DA, Thielen KR, et al. Intraarterial thrombolysis in acute basilar artery thromboembolism: the initial Mayo Clinic experience. Mayo Clin Proc 1997;72:1005–13. 28. Zeumer H, Hacke W, Ringelstein EB. Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease. AJNR 1983;4:401–4.

COMMENTARY

The authors report their experience in 26 patients with basilar artery occlusion treated by intra-arterial thrombolysis and in three cases additional balloon angioplasty. Fifty percent of patients were treated within 6 hours from symptom onset and 50% within 6 to 11 hours. Recanalization rate was 92%; complete recanalization rate was 35%. Hemorrhage rate was 7.7%. Good outcome (good recovery plus moderately disabled) at 3 months was observed in 34.6% cases, and poor outcome or death in 65.4%. As expected, better recovery was obtained in younger patients, with less severe stroke, no brainstem infarction, and in whom complete recanalization could be achieved. I found it interesting that in the 50% of patients treated after 6 hours from symptom onset, good outcome could still be achieved and no hemorrhage was observed. The natural his-