Surg Neurol 1992;38:353-8
353
Selective and Superselective Infusion of Urokinase for Embolic Stroke Masayuki Ezura, M.D. and Shigeki Kagawa, M.D. Department of Neurosurgery, Shirakawa Kosei Hospital, Shirakawa, Japan
Ezura M, Kagawa S. Selective and superselective infusion of urokinase for embolic stroke. Surg Neurol 1992;38:353-8.
Intraarterial administration of urokinase using Tracker microcatheter was performed in 11 patients with acute cerebral infarction caused by embolic occlusion of the internal carotid or the middle cerebral artery. Recanalization was observed in seven cases (64%) following the fibrinolytic therapy, and the time until recanalization from the start of the treatment was on the average 2.8 hours. Recanalization was seen in five out of six cases that received superselective infusion of urokinase, while it was seen in two out of five cases that received selective infusion. This study suggests that superselective infusion of urokinase is an excellent therapeutic method for embolic occlusion of the cerebral artery. KEYWORDS: Fibrinolytic therapy; Recanalization; Urokinase; Embolic stroke; Tracker microcatheter
The treatment of acute embolic stroke is controversial at present. This report discusses the clinical findings resulting from intravascular application of a fibrinolytic agent intended to restore circulation easily and reliably in 11 cases of acute embolic stroke.
Materials and Methods This study consisted of 11 cases of major cerebral artery occlusion within 24 hours of onset of cerebral infarction treated in our department between October 1988 and January 1990. The criteria for a differential diagnosis of embolic stroke from cerebral thrombosis were sudden onset, and electrocardiographic findings of atrial fibrillation and multiple premature contractions of the heart. Table 1 summarizes the individual cases. The median age was 66 years. All of the cases were administered brain protective agent within 30 minutes of admission. We have always chosen the so-called Sendai Cocktail [12] (10 mL/kg 20% mannitol, 10 mg/kg vitamin E, and
Address reprint requests to: Masayuki Ezura, M.D., Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980, Japan. Received January 13, 1992; accepted March 24, 1992.
© 1992 by ElsevierSciencePublishing Co., Inc.
10 mg/kg phenytoin) as brain protective agent, because we have believed it to be the most effective combination of drugs at the present time in protecting the brain from the cerebral ischemia. After excluding hemorrhagic cerebrovascular diseases on computed tomographic (CT) scans, transfemoral cerebral angiography was performed in all cases, and it confirmed the occlusion of the major cerebral arteries. The occlusion sites were the terminal portion of the internal carotid artery (two cases), the origin of the middle cerebral artery (two cases), and the distal portion of the middle cerebral artery (seven cases). Collateral circulation was divided into three groups: (1) rich ( 1 0 0 % - 7 0 % ) , (2) moderate ( 7 0 % - 4 0 % ) , and (3) poor ( 4 0 % - 0 % ) , according to the collaterally distributed area ratio in lateral view of the cerebral angiograms. The following cerebral fibrinolysis procedure was performed in all cases diagnosed as embolic stroke. A Tracker-18 microcatheter (Target Therapeutics, Los Angeles, CA) with a 2.7 french (F) tip diameter was selectively introduced as close to the vascular occlusion site as possible via a 5.0-6.0 F catheter. In some cases, the catheter could be introduced not immediately in front of the embolus but to the proximal portion from the final branching of the occluded vessel. Twenty-four thousand units of urokinase were then administered over 10 minutes, after which digital subtraction angiography (DSA) was used to check for recanalization. In the cases DSA revealed no satisfactory recanalization, 240,000 (or occasionally 60,000) units of urokinase were added, and then DSA was again performed. This procedure was repeated until recanalization was achieved or the maximum urokinase dosage of 1,440,000 units was administered. In the cases in which repeated DSA did not reveal any sign of recanalization, we abandoned further fibrinolysis before the total dosage of urokinase reached 1,440,000 units because of fear of increasing the hemorrhagic tendency. Recanalization was classified into five stages: (1) complete (100%), (2) almost complete ( 1 0 0 % - 7 0 % ) , (3) half ( 7 0 % - 4 0 % ) , (4) partial ( 4 0 % - 0 % ) , and (5) none (0%), according to the avascular area ratios in lateral view of cerebral angiograms before and after the procedure. 0090-3019/92/$5.00
JO
60
62 78 75
3
4 5 6 7 8 9 10 11
M M M M F M F F
M
It rt It rt It rt rt rt
M, M2 M, C, M, C, M, M,
It M,
It M,
It M,
Location
C,, C, portion
Rich Moderate Poor Moderace Poor Poor Moderate Poor
Rich
Moderate Rich
of internal
No No No No No Yes Yes Yes
No
No No
LDA on CT
Findings before therapy
Collateral circulation
Abbreviations: CT, computed tomography; SSI, superselective infusion; UK, urokinase.
66 56 64 66
JO
M
69
1
2
M
Sex
Age (yr)
6 24 6.5 3 4.5 2.5 2 10.5 10 8
8
UK
7.5 6 4 12 11.5 10
9
Recanalizarion
Onset to (h)
carotid artery; F, female; LDA, low-density
4 22 5.5 1 2.5 2 1 10 8 6
6.5
Admission
1. Suntnuvy of Clinical Features and Results in 11 Patients
No.
Table
SSI SI SI SSI SI SSI SSI SSI SSI SI SI
Selectivity
Findings
of middle
Almost complete None None Almost complete None Almost complete Partial None Complete Half Partial
infarction
infusion;
Excellent Excellent Excellent Poor Poor Poor Poor Poor Poor Poor
Good
Outcome
artery; rt, right; SI, selective
No No No No Yes No No Yes No Yes
Yes
Hemorragic
after therapy
cerebral
Degree of recanalization
area; It, left; M, male; M,, M, portion
42 30 54 96 42 24 144 96 102 48 96
Dose of UK (X IO4 units)
Fibrinolytic Therapy for Embolic Stroke
Serial DSA was performed by way of intravenous injection to check for recanalization or reocclusion in the second postoperative week. During the second postoperative month, the outcome was classified into five degrees of success: (1) excellent (normal), (2) good (able to function in society), (3) fair (restricted to home), (4) poor (restricted to home and requiring assistance), and (5) death.
Results Recanalization was observed in 7 of the 11 cases (Table 1). In these seven cases, the time from the start of urokinase infusion to recanalization was 2.8 -+ 2.6 hours (mean -+ SE). The time from onset to recanalization varied from 4 hours to 12 hours. In six of these cases, the occlusion site had shifted toward peripheral branching, and complete recanalization was observed in only one case. Computed tomography (CT) scans demonstrated postoperative hemorrhagic infarction in four cases, but there was no associated deterioration in their condition. The catheter could be introduced immediately in front of the embolus (superselective infusion) in six cases. In the remaining five cases, the catheter could be introduced not immediately in front of the embolus but to the proximal portion from the final branching of the occluded vessel (selective infusion). The reasons for selective infusion were: (1) the site of occlusion was just distal to the branching portion, and (2) the catheterized vessel was very tortuous, and we could not introduce the catheter immediately in front of the embolus. Some degree of recanalization was observed in five of the six superselective infusion cases, with four cases demonstrating half recanalization or better. In contrast, only one case each of half and partial reocanalization were observed among the five selective infusion cases. The achievement of some degree of recanalization (5/6 : 2/5) and half recanalization or better (4/6 : 1/5) were both significantly higher in superselective infusion (p < 0.05). The outcome 2 months after the procedures was good in four cases (36%); seven cases (64%) had a poor outcome, and there were no deaths.
Representative Case Report Case 4 A 62-year-old male became unable to express his intentions in words at 8:00 A.M. on November 14, 1989, and was admitted to our department at 12:00 P.M. the same day. H e had undergone resection of the small intestine in 1981 following occlusion of the superior mesenteric artery. Postoperatively he demonstrated ventricular pre-
Surg Neurol 1992;38:353-8
355
mature contractions and transient atrial fibrillation, and a diagnosis of idiopathic hypertrophic cardiomyopathy was made. Initial examination showed mild motor aphasia and mild right paresis. The pulse was irregular, and an electrocardiogram revealed ventricular premature contractions. A CT scan demonstrated no abnormalities. A diagnosis of acute cerebral infarction was made, and administration of the Sendai Cocktail was begun. Immediate cerebral angiography demonstrated occlusion of the left middle cerebral artery. In addition, leptomeningeal anastomoses through the anterior cerebral artery were well developed as collaterals (Figure 1). A Tracker microcatheter was then inserted at the origin of the left M1 portion via the angiographic catheter. After 960,000 units ofurokinase had been injected, recanalization was observed in the left M 1 portion (Figure 2). H e returned home without neurological abnormalities on November 22.
Discussion There is still no established procedure for the restoration of circulation in acute cerebral infarction. We have treated this disorder aggressively believing that improvement is possible through restored circulation in acute cerebral infarction. However, as surgical procedures for restoring circulation such as external-intracranial arterial bypass surgery and thromboembolectomy require general anesthesia, they are complex. In addition, multiple emboli in the peripheral cerebral arteries cannot be treated surgically, and there are other restrictions including age and complications. Urokinase has been administered intraarterially via an angiographic catheter [1,5-7], but the results have not been uniform. However, recent advances in intravascular surgery now allow the superselective introduction of catheters into the peripheral portions of cerebral arteries. As this technique may allow restoration of circulation more easily and reliably, intravascular fibrinolysis has been attempted especially in cases of embolic stroke [ 2 - 4 , 8 - 1 0 ] . In this study, we performed intravascular fibrinolysis in acute embolic stroke. The success rate of recanalization in this study was 64%, which is roughly the same reported in previous studies [2,3,8,10]. The achievement of some degree of recanalization (5/6 : 2/5) and half recanalization or better (4/6 : 1/5) were both significantly higher in superselective infusions. Probably in selective infusion the injected urokinase is carried away by open arterial branches preventing the concentration from rising at the occlusion site. Therefore, we hope that catheters can be improved to allow introduction as close as possible to the site of vascular occlusion.
356
Surg Neurol 1992;38:353-8
Ezura and Kagawa
Figure 1. Left internal carotid angiograms of case 4, anteroposterior views (left) and lateral views (right), immediately beforefibrin~'[ytic therapy. Early phase-b-~pper) revealsocclusionof left middle cerebra~artery(M C--~ at its origin. Late phase (lower) reveals well-developed collateral vessels, which ar-7-~pplied by left anterior cerebral artery via leptomeningeal anastomosis.
Patients with a good outcome all had middle cerebral artery occlusions without any low density area on the initial CT scan (see Table 1). Statistical analysis demonstrates that they had more favorable collateral circulation than patients with a poor outcome had (p ~ 0.05; Table 2). These findings indicate that some kinds o f cerebral blood flow study are required to determine which patients have to receive local fibrinolysis. N o other significant differences were observed between the groups o f good and poor outcomes. The two cases with good outcomes in which recanalization was not confirmed angiographically immediately after fibrinolytic therapy suggest that although therapeutic effects were not observed directly, the method accelerated spontaneous recanalization.
Yoshimoto [ 11] reported that surgery requires 6.1 + 0.3 hours between administration o f the brain-protecting agent and recanalization. In contrast, this fibrinolyric procedure required only 2.8 + 2.6 hours, a significantly shorter time (p ~ 0.01). Damaged nerve cells are believed to gradually lose reversibility even during the time circulation restoration surgery required. Local fibrinolysis therefore, is, an excellent therapeutic method for restoring circulation in a short time. Further studies on the concentration and rate o f fibrinolytic agent administration are necessary, especially for cases in which fibrinolysis is difficult, such as extended embolus or thrombosis. The possibility o f mechanical destruction of embolus by a guide wire or catheter should also be investigated. I m p r o v e m e n t o f
Fibrinolytic T h e r a p y for Embolic Stroke
Surg N e u r o l 1992;38:353-8
,aaaD
Figure 2. Left internal carotid angiograms of case 4, anteroposterior vt'ew
(left) and lateral view (right), immediately after fibrinolytic therapy. Recanalization of the left MCA is demonstrated.
357
!
catheters, including their plasticity, torque and friction, and more effective fibrinolytic agents are also needed. We thank Dr. Takashi Yoshimoto, director of the Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, and Dr. Akira Takahashi, director of the Division of Intravascular Neurosurgery, Kohnan Hospital, for valuable advice on this report.
T a b l e 2. Comparison of good and poor outcome groups Outcome
Age (yr; median) Interval for Onset to UK (h; median) Dose of UK ( × 104 units; mean -+ SE) LDA on initial CT LDA( - ) LDA( + ) Occlusion site MCA ICA Collateral flow rich moderate/poor
Good
Poor
Statistical difference
66.5 7.3
66 4.5
NS ~ NS a
55.5 +0.8
78.9 +--0.6
NS b
4 0
4 3
NS'
4 0
5 2
NS c
3 1
0 7
p < 0.0Y
Abbreviations:MCA, middle cerebral artery; ICA, internal carotid artery. ~Welch rank-sum test. bWelch t test. ~Chi-square test.
References 1. Araki O, Matsunaga M, Kobayashi S, Yamaguchi K, Shingu T, Fujita Y. Regional continuous intraarterial infusion of urokinase in the acute stage of the cervical and intracranial major artery occlusion--particularly on a case of successful improvement after therapeutic recanalization (in Japanese). Neurol Surg 1985;13:465-71. 2. Del Zoppo GJ, Ferbert A, Otis S, BrO.ckmann H, Hacke W, Zyroff J, Harker LA, Zeumer H. Local intraarterial fibrinolytic therapy in acute carotid territory stroke: a pilot study. Stroke 1988;19:307-13. 3. Del Zoppo GJ, Zeumer H, Harker LA. Thrombolytic therapy in stroke: possibilities and hazards. Stroke 1986;17:595-607. 4. Jungreis CA, Wechsler LR, Horton JA. Intracranial thrombolysis via a catheter embedded in the clot. Stroke 1989;20:1578-80. 5. Miyakawa T, Sakuragawa N. The cerebral vessels and thrombosis (in Japanese). Rinsho Ketsueki 1984;25:1018-26. 6. Mori E, Tabuchi M, Yoshida T, Yamadori A. Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 1988;19:802-12.
358
Surg N e u r o l 1992;38:353-8
7. Satoh K, Iwano K, Ueda S, Matsumoto K. Intraarterial urokinase infusion therapy for the acute intracranial major artery occlusion. Neurol Surg 1988;16:67-72. 8. Takahashi A, Suzuki J. Intravascular neurosurgery and treatment of abnormalities in the central nervous system. In: Suzuki J, ed. Advances in surgery for cerebral stroke. Tokyo, Springer-Verlag, 1988:89-94. 9. Zeumer H, Hiindgen R, Ferbert A, Ringelstein EB. Local intraarterial fibrinolytic therapy in inaccessible internal carotid occlusion. Neuroradiology 1984;26:315-17.
Ezur~ and Kagawa
10. Zeumer H. Vascular recanalizing techniques in interventional neuroradiology. J Neurol 1985 ;231:287-94. 11. YoshimotoT. Surgical treatment ofcerebralischemiain the acute stage (in Japanese). In: Takakura K, ed. Treatment of ischemic and occlusive cerebrovascular diseases. Tokyo: Gendai Iryosha, 1989:61-67. 12. Yoshimoto T, Ogawa A, Suzuki J. Acute stage revascularization under the administration of a new cerebral protective agent, "Sendai Cocktail," In: Suzuki J, ed. Advances in surgery for cerebral stroke. Tokyo, Springer-Verlag, 1988:559-62.
353
Selective and Superselective Infusion of Urokinase for Embolic Stroke Masayuki Ezura, M.D. and Shigeki Kagawa, M.D. Department of Neurosurgery, Shirakawa Kosei Hospital, Shirakawa, Japan
Ezura M, Kagawa S. Selective and superselective infusion of urokinase for embolic stroke. Surg Neurol 1992;38:353-8.
Intraarterial administration of urokinase using Tracker microcatheter was performed in 11 patients with acute cerebral infarction caused by embolic occlusion of the internal carotid or the middle cerebral artery. Recanalization was observed in seven cases (64%) following the fibrinolytic therapy, and the time until recanalization from the start of the treatment was on the average 2.8 hours. Recanalization was seen in five out of six cases that received superselective infusion of urokinase, while it was seen in two out of five cases that received selective infusion. This study suggests that superselective infusion of urokinase is an excellent therapeutic method for embolic occlusion of the cerebral artery. KEYWORDS: Fibrinolytic therapy; Recanalization; Urokinase; Embolic stroke; Tracker microcatheter
The treatment of acute embolic stroke is controversial at present. This report discusses the clinical findings resulting from intravascular application of a fibrinolytic agent intended to restore circulation easily and reliably in 11 cases of acute embolic stroke.
Materials and Methods This study consisted of 11 cases of major cerebral artery occlusion within 24 hours of onset of cerebral infarction treated in our department between October 1988 and January 1990. The criteria for a differential diagnosis of embolic stroke from cerebral thrombosis were sudden onset, and electrocardiographic findings of atrial fibrillation and multiple premature contractions of the heart. Table 1 summarizes the individual cases. The median age was 66 years. All of the cases were administered brain protective agent within 30 minutes of admission. We have always chosen the so-called Sendai Cocktail [12] (10 mL/kg 20% mannitol, 10 mg/kg vitamin E, and
Address reprint requests to: Masayuki Ezura, M.D., Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980, Japan. Received January 13, 1992; accepted March 24, 1992.
© 1992 by ElsevierSciencePublishing Co., Inc.
10 mg/kg phenytoin) as brain protective agent, because we have believed it to be the most effective combination of drugs at the present time in protecting the brain from the cerebral ischemia. After excluding hemorrhagic cerebrovascular diseases on computed tomographic (CT) scans, transfemoral cerebral angiography was performed in all cases, and it confirmed the occlusion of the major cerebral arteries. The occlusion sites were the terminal portion of the internal carotid artery (two cases), the origin of the middle cerebral artery (two cases), and the distal portion of the middle cerebral artery (seven cases). Collateral circulation was divided into three groups: (1) rich ( 1 0 0 % - 7 0 % ) , (2) moderate ( 7 0 % - 4 0 % ) , and (3) poor ( 4 0 % - 0 % ) , according to the collaterally distributed area ratio in lateral view of the cerebral angiograms. The following cerebral fibrinolysis procedure was performed in all cases diagnosed as embolic stroke. A Tracker-18 microcatheter (Target Therapeutics, Los Angeles, CA) with a 2.7 french (F) tip diameter was selectively introduced as close to the vascular occlusion site as possible via a 5.0-6.0 F catheter. In some cases, the catheter could be introduced not immediately in front of the embolus but to the proximal portion from the final branching of the occluded vessel. Twenty-four thousand units of urokinase were then administered over 10 minutes, after which digital subtraction angiography (DSA) was used to check for recanalization. In the cases DSA revealed no satisfactory recanalization, 240,000 (or occasionally 60,000) units of urokinase were added, and then DSA was again performed. This procedure was repeated until recanalization was achieved or the maximum urokinase dosage of 1,440,000 units was administered. In the cases in which repeated DSA did not reveal any sign of recanalization, we abandoned further fibrinolysis before the total dosage of urokinase reached 1,440,000 units because of fear of increasing the hemorrhagic tendency. Recanalization was classified into five stages: (1) complete (100%), (2) almost complete ( 1 0 0 % - 7 0 % ) , (3) half ( 7 0 % - 4 0 % ) , (4) partial ( 4 0 % - 0 % ) , and (5) none (0%), according to the avascular area ratios in lateral view of cerebral angiograms before and after the procedure. 0090-3019/92/$5.00
JO
60
62 78 75
3
4 5 6 7 8 9 10 11
M M M M F M F F
M
It rt It rt It rt rt rt
M, M2 M, C, M, C, M, M,
It M,
It M,
It M,
Location
C,, C, portion
Rich Moderate Poor Moderace Poor Poor Moderate Poor
Rich
Moderate Rich
of internal
No No No No No Yes Yes Yes
No
No No
LDA on CT
Findings before therapy
Collateral circulation
Abbreviations: CT, computed tomography; SSI, superselective infusion; UK, urokinase.
66 56 64 66
JO
M
69
1
2
M
Sex
Age (yr)
6 24 6.5 3 4.5 2.5 2 10.5 10 8
8
UK
7.5 6 4 12 11.5 10
9
Recanalizarion
Onset to (h)
carotid artery; F, female; LDA, low-density
4 22 5.5 1 2.5 2 1 10 8 6
6.5
Admission
1. Suntnuvy of Clinical Features and Results in 11 Patients
No.
Table
SSI SI SI SSI SI SSI SSI SSI SSI SI SI
Selectivity
Findings
of middle
Almost complete None None Almost complete None Almost complete Partial None Complete Half Partial
infarction
infusion;
Excellent Excellent Excellent Poor Poor Poor Poor Poor Poor Poor
Good
Outcome
artery; rt, right; SI, selective
No No No No Yes No No Yes No Yes
Yes
Hemorragic
after therapy
cerebral
Degree of recanalization
area; It, left; M, male; M,, M, portion
42 30 54 96 42 24 144 96 102 48 96
Dose of UK (X IO4 units)
Fibrinolytic Therapy for Embolic Stroke
Serial DSA was performed by way of intravenous injection to check for recanalization or reocclusion in the second postoperative week. During the second postoperative month, the outcome was classified into five degrees of success: (1) excellent (normal), (2) good (able to function in society), (3) fair (restricted to home), (4) poor (restricted to home and requiring assistance), and (5) death.
Results Recanalization was observed in 7 of the 11 cases (Table 1). In these seven cases, the time from the start of urokinase infusion to recanalization was 2.8 -+ 2.6 hours (mean -+ SE). The time from onset to recanalization varied from 4 hours to 12 hours. In six of these cases, the occlusion site had shifted toward peripheral branching, and complete recanalization was observed in only one case. Computed tomography (CT) scans demonstrated postoperative hemorrhagic infarction in four cases, but there was no associated deterioration in their condition. The catheter could be introduced immediately in front of the embolus (superselective infusion) in six cases. In the remaining five cases, the catheter could be introduced not immediately in front of the embolus but to the proximal portion from the final branching of the occluded vessel (selective infusion). The reasons for selective infusion were: (1) the site of occlusion was just distal to the branching portion, and (2) the catheterized vessel was very tortuous, and we could not introduce the catheter immediately in front of the embolus. Some degree of recanalization was observed in five of the six superselective infusion cases, with four cases demonstrating half recanalization or better. In contrast, only one case each of half and partial reocanalization were observed among the five selective infusion cases. The achievement of some degree of recanalization (5/6 : 2/5) and half recanalization or better (4/6 : 1/5) were both significantly higher in superselective infusion (p < 0.05). The outcome 2 months after the procedures was good in four cases (36%); seven cases (64%) had a poor outcome, and there were no deaths.
Representative Case Report Case 4 A 62-year-old male became unable to express his intentions in words at 8:00 A.M. on November 14, 1989, and was admitted to our department at 12:00 P.M. the same day. H e had undergone resection of the small intestine in 1981 following occlusion of the superior mesenteric artery. Postoperatively he demonstrated ventricular pre-
Surg Neurol 1992;38:353-8
355
mature contractions and transient atrial fibrillation, and a diagnosis of idiopathic hypertrophic cardiomyopathy was made. Initial examination showed mild motor aphasia and mild right paresis. The pulse was irregular, and an electrocardiogram revealed ventricular premature contractions. A CT scan demonstrated no abnormalities. A diagnosis of acute cerebral infarction was made, and administration of the Sendai Cocktail was begun. Immediate cerebral angiography demonstrated occlusion of the left middle cerebral artery. In addition, leptomeningeal anastomoses through the anterior cerebral artery were well developed as collaterals (Figure 1). A Tracker microcatheter was then inserted at the origin of the left M1 portion via the angiographic catheter. After 960,000 units ofurokinase had been injected, recanalization was observed in the left M 1 portion (Figure 2). H e returned home without neurological abnormalities on November 22.
Discussion There is still no established procedure for the restoration of circulation in acute cerebral infarction. We have treated this disorder aggressively believing that improvement is possible through restored circulation in acute cerebral infarction. However, as surgical procedures for restoring circulation such as external-intracranial arterial bypass surgery and thromboembolectomy require general anesthesia, they are complex. In addition, multiple emboli in the peripheral cerebral arteries cannot be treated surgically, and there are other restrictions including age and complications. Urokinase has been administered intraarterially via an angiographic catheter [1,5-7], but the results have not been uniform. However, recent advances in intravascular surgery now allow the superselective introduction of catheters into the peripheral portions of cerebral arteries. As this technique may allow restoration of circulation more easily and reliably, intravascular fibrinolysis has been attempted especially in cases of embolic stroke [ 2 - 4 , 8 - 1 0 ] . In this study, we performed intravascular fibrinolysis in acute embolic stroke. The success rate of recanalization in this study was 64%, which is roughly the same reported in previous studies [2,3,8,10]. The achievement of some degree of recanalization (5/6 : 2/5) and half recanalization or better (4/6 : 1/5) were both significantly higher in superselective infusions. Probably in selective infusion the injected urokinase is carried away by open arterial branches preventing the concentration from rising at the occlusion site. Therefore, we hope that catheters can be improved to allow introduction as close as possible to the site of vascular occlusion.
356
Surg Neurol 1992;38:353-8
Ezura and Kagawa
Figure 1. Left internal carotid angiograms of case 4, anteroposterior views (left) and lateral views (right), immediately beforefibrin~'[ytic therapy. Early phase-b-~pper) revealsocclusionof left middle cerebra~artery(M C--~ at its origin. Late phase (lower) reveals well-developed collateral vessels, which ar-7-~pplied by left anterior cerebral artery via leptomeningeal anastomosis.
Patients with a good outcome all had middle cerebral artery occlusions without any low density area on the initial CT scan (see Table 1). Statistical analysis demonstrates that they had more favorable collateral circulation than patients with a poor outcome had (p ~ 0.05; Table 2). These findings indicate that some kinds o f cerebral blood flow study are required to determine which patients have to receive local fibrinolysis. N o other significant differences were observed between the groups o f good and poor outcomes. The two cases with good outcomes in which recanalization was not confirmed angiographically immediately after fibrinolytic therapy suggest that although therapeutic effects were not observed directly, the method accelerated spontaneous recanalization.
Yoshimoto [ 11] reported that surgery requires 6.1 + 0.3 hours between administration o f the brain-protecting agent and recanalization. In contrast, this fibrinolyric procedure required only 2.8 + 2.6 hours, a significantly shorter time (p ~ 0.01). Damaged nerve cells are believed to gradually lose reversibility even during the time circulation restoration surgery required. Local fibrinolysis therefore, is, an excellent therapeutic method for restoring circulation in a short time. Further studies on the concentration and rate o f fibrinolytic agent administration are necessary, especially for cases in which fibrinolysis is difficult, such as extended embolus or thrombosis. The possibility o f mechanical destruction of embolus by a guide wire or catheter should also be investigated. I m p r o v e m e n t o f
Fibrinolytic T h e r a p y for Embolic Stroke
Surg N e u r o l 1992;38:353-8
,aaaD
Figure 2. Left internal carotid angiograms of case 4, anteroposterior vt'ew
(left) and lateral view (right), immediately after fibrinolytic therapy. Recanalization of the left MCA is demonstrated.
357
!
catheters, including their plasticity, torque and friction, and more effective fibrinolytic agents are also needed. We thank Dr. Takashi Yoshimoto, director of the Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, and Dr. Akira Takahashi, director of the Division of Intravascular Neurosurgery, Kohnan Hospital, for valuable advice on this report.
T a b l e 2. Comparison of good and poor outcome groups Outcome
Age (yr; median) Interval for Onset to UK (h; median) Dose of UK ( × 104 units; mean -+ SE) LDA on initial CT LDA( - ) LDA( + ) Occlusion site MCA ICA Collateral flow rich moderate/poor
Good
Poor
Statistical difference
66.5 7.3
66 4.5
NS ~ NS a
55.5 +0.8
78.9 +--0.6
NS b
4 0
4 3
NS'
4 0
5 2
NS c
3 1
0 7
p < 0.0Y
Abbreviations:MCA, middle cerebral artery; ICA, internal carotid artery. ~Welch rank-sum test. bWelch t test. ~Chi-square test.
References 1. Araki O, Matsunaga M, Kobayashi S, Yamaguchi K, Shingu T, Fujita Y. Regional continuous intraarterial infusion of urokinase in the acute stage of the cervical and intracranial major artery occlusion--particularly on a case of successful improvement after therapeutic recanalization (in Japanese). Neurol Surg 1985;13:465-71. 2. Del Zoppo GJ, Ferbert A, Otis S, BrO.ckmann H, Hacke W, Zyroff J, Harker LA, Zeumer H. Local intraarterial fibrinolytic therapy in acute carotid territory stroke: a pilot study. Stroke 1988;19:307-13. 3. Del Zoppo GJ, Zeumer H, Harker LA. Thrombolytic therapy in stroke: possibilities and hazards. Stroke 1986;17:595-607. 4. Jungreis CA, Wechsler LR, Horton JA. Intracranial thrombolysis via a catheter embedded in the clot. Stroke 1989;20:1578-80. 5. Miyakawa T, Sakuragawa N. The cerebral vessels and thrombosis (in Japanese). Rinsho Ketsueki 1984;25:1018-26. 6. Mori E, Tabuchi M, Yoshida T, Yamadori A. Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 1988;19:802-12.
358
Surg N e u r o l 1992;38:353-8
7. Satoh K, Iwano K, Ueda S, Matsumoto K. Intraarterial urokinase infusion therapy for the acute intracranial major artery occlusion. Neurol Surg 1988;16:67-72. 8. Takahashi A, Suzuki J. Intravascular neurosurgery and treatment of abnormalities in the central nervous system. In: Suzuki J, ed. Advances in surgery for cerebral stroke. Tokyo, Springer-Verlag, 1988:89-94. 9. Zeumer H, Hiindgen R, Ferbert A, Ringelstein EB. Local intraarterial fibrinolytic therapy in inaccessible internal carotid occlusion. Neuroradiology 1984;26:315-17.
Ezur~ and Kagawa
10. Zeumer H. Vascular recanalizing techniques in interventional neuroradiology. J Neurol 1985 ;231:287-94. 11. YoshimotoT. Surgical treatment ofcerebralischemiain the acute stage (in Japanese). In: Takakura K, ed. Treatment of ischemic and occlusive cerebrovascular diseases. Tokyo: Gendai Iryosha, 1989:61-67. 12. Yoshimoto T, Ogawa A, Suzuki J. Acute stage revascularization under the administration of a new cerebral protective agent, "Sendai Cocktail," In: Suzuki J, ed. Advances in surgery for cerebral stroke. Tokyo, Springer-Verlag, 1988:559-62.
