Neurological Research A Journal of Progress in Neurosurgery, Neurology and Neurosciences
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism Yasushi Okada, Seizo Sadoshima, Yoshisuke Saku, Takanari Kitazono, Katsumi Irie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya & Masatoshi Fujishima To cite this article: Yasushi Okada, Seizo Sadoshima, Yoshisuke Saku, Takanari Kitazono, Katsumi Irie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya & Masatoshi Fujishima (1992) Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism, Neurological Research, 14:2, 167-170, DOI: 10.1080/01616412.1992.11740042 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740042
Published online: 23 Jul 2016.
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Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 04 August 2017, At: 18:42
Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism Yasushi Okada, Seizo Sadoshima*, Yoshisuke Saku, Takanari Kitazono, Katsumi lrie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya and Masatoshi Fujishima*
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
Departments of Cerebrovascular Disease and Neuroradiology, St. Mary's Hospital, Kurume 830, and the Second Department of Internal Medicine*, Faculty of Medicine, Kyushu University, Fukuoka 812, japan
Keywords: Thrombosis; plasminogen activator tissue-type; brain embolism; haemorrhagic transformation; brain haemorrhage
INTRODUCTION Haemorrhagic transformation (HT) is considered to be the most undesirable complication after thrombolytic therapy for acute ischaemic stroke. Recent intra-arterial thrombolytic1 - 3 and the current intravenous tissue plasminogen activator studies4 - 6 suggest, however, that haemorrhagic infarction and parenchymatous haemorrhages are not so extensive. In this study, we treated acute ischaemic stroke patients with recombinant tissue plasminogen activator (rt-PA ), and examined the beneficial effects of thrombolysis and the influence of HT on their clinical outcome.
SUBJECTS AND METHODS We studied 26 patients (14 males and 12 females, mean 66 12 years) with acute brain embolism who were admitted to St. Mary's Hospital from May 1, 1989 through October 30, 1990. The criteria for their entry were (1) abrupt onset of symptoms in the territory of the internal carotid artery, (2) atrial fibrillation or other heart diseases, ( 3) age < 80 years, (4) admission < 6 hours from stroke onset. We performed cerebral angiography in 15 of 26 patients to confirm the occlusion of the vessels and initiated rt-PA thrombolytic therapy within 6 hours after obtaining informed consent from the patients' families. For the other 11 patients in the same initial conditions, they were conventionally treated either because we could not get informed consent or we were unable to perform cerebral angiography for some practical reason. We estimated their severity of neurological deficits by means of the Hemispheric Stroke Scale7 at admission, 24 hours, 3, 7, 14 and 30 days. The neurological state at 30 days was classified into five groups; excellent, 0- 5 points; good, 6- 20 points; moderate, 21-60 points; poor, 61-100 points; and deceased.
±
Address for correspondence: Yasushi Okada, MD, Department of Cerebrovascular Disease, St. Mary's Hospital, 422 TsubukuHonmachi, Kuru me 830, Japan. Accepted for publication December
1991.
©
1992 Forefront Publishing Group 0161- 6412/ 92 / 020167-04
Serial computed tomography (CT) was also done at admission, 24 hours, 3, 7, 14, and at 30 days. The size of the infarcted lesion was expressed as the maximum hypodense area/ipsilateral hemisphere x 100% on day 3 and was classified as either small ( 30% )8 . HT was evaluated at every CT examination and was subdivided into 4 types according to the pattern or degree of hyperdensity; (1) petechial haemorrhage, with spotty and scattered hyperdense areas, usually along the cortical margin of the ischaemic lesion, (2) diffuse haemorrhage, (3) small haematoma, with a homogeneous hyperdense area < 3 em in diameter in the ischaemic area, and (4 ) massive haematoma > 3 em in diameter, accompanied by prominent mass effect8 . Soon after the neurological and CT examinations, we performed conventional cerebral angiography both before and immediately after thrombolytic therapy. Fifteen, 20 or 30 MU of rt-PA (SM9527 by Sumitomo Pharmacy Co. Ltd, Osaka, Japan) was administered intravenously for 10 patients and intra-arterially for 5 patients for 1 h. We defined the disappearance of the embolic occlusion as complete re-opening, and existence of some stenotic or occlusive lesions with sufficient restoration of anterograde blood flow as partial re-opening. In 7 cases with either mild neurological deficits or a small infarct on CT, anticoagulant therapy (heparin 10,000 U I day) was started from at least 4 days after the onset of stroke. We compared the characteristics of HT concerning cumulative incidence, timing of occurrence and the subtypes between the patients treated with thrombolytic therapy (thrombolytic group ) and those treated with conventional therapy (conventional group). Furthermore, we focused on the clinical significance of HT recognized at 24 h after thrombolysis because such early HT is rare in natural history and is possible to have potential effects on the clinical outcome after thrombolytic therapy.
RESULTS HTs on CT were demonstrated in a total of 12 patients (80%) of the thrombolytic group and in 6 (55% ) of
Neurological Research, 1992, Volume 14, Suppl
167
Thrombolytic therapy in acute brain embolism: Y. Okada et al.
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
the conventiona l group during 1 month. Of these, HTs recognized at 24 h were observed significantly more in the thrombolytic group (8/15, 53%, small haematoma, 6; massive haematoma , 1; and petechial haemorrhage, 1) than in the conventiona l group (1 /11, 9%, small haematoma, 1) (p < 0.01, Figure 1, Table 1). All other 9HTs were of the petechial type, of which one developed at day 3, six at day 7, and two at day 14.
Initial HSS did not differ between the thrombotic group (66 16, mean SO) and the conventiona l group (62 ± 15). Six patients (40%) of the thrombolytiC group, including four with HT, showed a favourable clinical improvemen t at 24 h, while none of the conventiona l group recovered within 24 h. The reduction of HSS during 24 h after onset was significantly higher in the thrombolyti c group (14 25) than in the
±
±
±
Figure 1: CT scan at 24 h after stroke onset of eight patients (cases 1-8) in the thrombolytic group showing a haemorrhagic transformation in the infarcted lesion. Haemorrhagic transformation seemed to affect the clinical worsening of only one patient with a massive haematoma (case 8)
Table 1:
Haemorrhagic transformation , reopening of occluded vessels, size of infarcted lesions and neurological outcome of patients treated with thrombolytic therapy
Patient
1 2 3 4 5 6 7
8 9
10 11 12 13 14 15
Doses of rt-PA(MU)
20 20 20 30 15 30 30 30 30 30 30 20 20
3o 20
Re-opening of occluded vessels partial partial none none partial none none none none none none none complete complete none
0; the day haemorrhagic transformation appeared.
168 Neurological Research, 1992, Volume 14, Suppl
Haemorrhagic transformation small haematoma (1) petechial (1) small haematoma (1) small haematoma (1) small haematoma (1) small haematoma (1) small haematoma (1) (1) massive petechial (3) (7) petechial petechial (7) petechial (7) none none none
Size of infarcted lesions small small small small medium large large large large large medium large small small large
Neurological outcome excellent good good good fair poor dead poor poor poor good poor excellent excellent dead
Thrombolytic therapy in acute brain embolism: Y. Okada et al.
±
conventional group ( -7 14). Although four (27%) of the thrombotic group and four (36%) of the conventional group developed clinical deterioration at 24 h, HT per se seemed to affect only one patient with a massive haematoma in their clinical course. The other cases were considered to have deteriorated due to large infarcts with brain oedema. The neurological state at 1 month was somewhat better in the thrombolytic group (excellent, 3; good, 4; fair, 1; poor, 5; and dead, 2) than that in the conventional group (0, 1, 0, 7, 3, respectively) although mean HSS at 1 month was not statistically significant (43 37 vs. 60 31 ). Two patients in the thrombolytic group had complete recanalization of the occluded arteries and excellent outcome, and did not show any HT throughout their clinical course. In patients with HT at 24 h (cases 1-8) and the remaining patients (cases 9-15) in the thrombolytic group, there were no significant differences in mean doses of rt-PA (24 MU vs. 26 MU), frequency in the re-opening of occluded vessels (38% vs. 29% ), the size of infarcted lesions (31% vs. 36% ), and the neurological outcomes.
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
±
±
DISCUSSION The present study showed that thrombolytic therapy using rt-PA increased the incidence of HT in acute embolic stroke, especially parenchymatous small haematoma within 24 hours, compared with conventional therapy. However, the neurological outcomes of the patients with HT were not necessarily unfavourable, and four of them (33%) demonstrated early clinical improvement. Interestingly, half of the patients with HT recognized at 24 h after thrombolytic therapy had either good or excellent outcomes. Bruckmann et a/. 9 also reported a successful case with a small putamina! HT after effective thrombolytic therapy. These results indicate that early HT immediately after thrombolytic therapy may occur with the restoration of blood flow to severe ischaemic area where brain tissue or blood brain barrier has been dama~ed; even within a few hours after ischaemic insult1 . HT was more closely related with the severity of the neurological deficits and was independent on rt-PA treatment when it was given within 90 min 4 or 3 hours 11 from the onset of brain ischaemia. Our study is also impressive in that patients with complete recanalization and excellent outcomes did not reveal any haemorrhage during the course of treatment. · The incidence of HT in the present study is excessively higher than in previous studies. HT was seen in 5-4~% ~f the non-anticoag_ulated Batients with brain embolism 1n the1r natural h1storyB· 2 - 15 . Mon et a/. 3 reported that 19% of patients with middle cerebral artery occlusion revealed HT within 24 hours after urokinase fibrinolytic therapy. In recent ongoing studies using intravenous rt-PA within 90 min 4 and 8 h5 , HT occurred in 6 of 74 (8%) within 24 h and in 31 of 71 (44%) up to 14 days, respectively. The reason why HT was developed at such a high rate in the present study is unclear. We did not use any other thrombolytic agents. One possibility is that we identified very mild and small hyperdense lesion as HT, together with frequent examinations at early stage using high resolution CT.
HT per se seemed to have little influence on the clinical course of the patients with thrombolytic therapy except for the development of massive haematoma. Parenchymatous haematoma with clinical deterioration similarly occurred in 3 of 74 (4.1%) and 4 of 71 (5.4%) in recent ongoing rt-PA studies 4•5 . We thus believe that those with significant HT should undergo early recanalization of the occluded arteries after severe ischaemia of large area. Thus, these patients must be excluded from inclusion by means of some clinical and neuroradiological assessments. Although we have not randomized the control, our study suggests that thrombolytic therapy with 15-30 MU rt-PA < 6 h for acute brain embolism seems to be promising even with the significant increase in the incidence of HT. HT after thrombolytic therapy may not be hazardous as previously considered and further study should therefore continue to evaluate for potential benefits.
CONCLUSIONS Haemorrhagic transformation occurred more frequently in patients with thrombolytic therapy than in those with conventional therapy. Haematoma recognized at 24 h CT was significantly more in the former, although the neurological outcomes of these patients were not affected by the haemorrhagic transformation per se except for patients with massive haematoma. Thrombolytic therapy with recombinant tissue plasminogen activator therefore seems to be safe and promising when it is carefully performed at the very early stage of stroke.
REFERENCES
2
3
4
5
6
7
8
9
10
del Zoppo Gj, Ferbert A, Otis S, Bruck mann H, Hacke W , Zyroff j, Harker LA, Zeumer H. Local intra arterial fibrinolytic therapy in acute carotid territory stroke. Stroke 1988; 19: 307-313 Hacke W , Zeumer H, Ferbert A, Bruckmanri H, del Zoppo Gj. Intra arterial thrombolytic therapy improves outcome in patients with acute vertebra-basilar occlusive diseases. Stroke 1988; 19: 1216-1222 Mori E, Tabuchi M, Yoshida T, Yamadori A. lntracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 1988; 19: 802-812 Brott T, Haley C, Levy D, Barsan W, Sheppard G, Broderick j, Reed R, Marler j. Safety and potential efficacy of tissue plasminogen activator (t-PA) for stroke (abstract). Stroke 1990; 21 : 181 del Zoppo Gj. The rt-PA Acute Stroke Study Group: an open multicenter trial of recombinant tissue plasminogen activator in acute stroke; a progress report. Stroke 1990; 21 (suppl IV): IV174-IV175 Yamaguchi T, Hayakawa T, Kikuchi H, Abe T. Thrombolytic therapy in embolic and thrombotic cerebral infarction; a cooperative study. In : Hacke W, del Zoppo G), Hirschberg M, eds. Thrombolytic Therapy in Acute Ischemic Stroke. Berlin : Springer-Verlag, 1991 ; pp 168-173 Adams Rj, Meador Kj, Sethi KD, Grotta jC, Thomson DS. Graded neurologic scale for use in acute hemispheric stroke treatment protocols. Stroke 1987; 18: 665-669 Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, Sadoshima S, Fujishima M, Omae T. Haemorrhagic transformation in cerebral embolism. Stroke 1989; 20: 598-603 Bruckmann H, Ferbert A. Putamina! hemorrhage after recanalization of an embolic MCA occlusion treated with tissue plasminogen activator. Neuroradiology 1989; 31 : 95- 97 Okada Y, Sadoshima S, Nakane H, Utsunomiya H, Fujishima
Neurological Research,
1~92,
Volume 14, Suppl
169
Thrombolytic therapy in acute brain embolism: Y. Okada et al. M. Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism. Stroke 1992;
11
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
12
23: 20-23 del Zoppo G), Copeland BR, Anderchek K, Hacke W, Koziol JA. Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction. Stroke 1990; 21 : 596-601 Fisher M, Zito )L, Siva A, de Girolami U. Hemorrhagic infarction:
170
Neurological Research, 1992, Volume 14, Suppl
13
14
a clinical and 0 study (abstract). Stroke 1984; 15: 192 Hornig CR, Dorndorf W, Agnoli AL. Hemorrhagic cerebral infarction-a prospective study. Stroke 1986; 17: 179-185 Lodder ). CT-detected hemorrhagic infarction; relation with the size of the infarct, and the presence of midline shift. Acta
Neurol Scand 1984; 70: 329-335 15
Weisberg LA. Nonseptic cardiogenic cerebral embolic stroke; clinical-0 correlations. Neurology 1985; 35: 896-899
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism Yasushi Okada, Seizo Sadoshima, Yoshisuke Saku, Takanari Kitazono, Katsumi Irie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya & Masatoshi Fujishima To cite this article: Yasushi Okada, Seizo Sadoshima, Yoshisuke Saku, Takanari Kitazono, Katsumi Irie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya & Masatoshi Fujishima (1992) Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism, Neurological Research, 14:2, 167-170, DOI: 10.1080/01616412.1992.11740042 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740042
Published online: 23 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 04 August 2017, At: 18:42
Influence of haemorrhagic transformation on the outcome of thrombolytic therapy for patients with acute brain embolism Yasushi Okada, Seizo Sadoshima*, Yoshisuke Saku, Takanari Kitazono, Katsumi lrie, Tetsuzo Ogasawara, Hidetsuna Utsunomiya and Masatoshi Fujishima*
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
Departments of Cerebrovascular Disease and Neuroradiology, St. Mary's Hospital, Kurume 830, and the Second Department of Internal Medicine*, Faculty of Medicine, Kyushu University, Fukuoka 812, japan
Keywords: Thrombosis; plasminogen activator tissue-type; brain embolism; haemorrhagic transformation; brain haemorrhage
INTRODUCTION Haemorrhagic transformation (HT) is considered to be the most undesirable complication after thrombolytic therapy for acute ischaemic stroke. Recent intra-arterial thrombolytic1 - 3 and the current intravenous tissue plasminogen activator studies4 - 6 suggest, however, that haemorrhagic infarction and parenchymatous haemorrhages are not so extensive. In this study, we treated acute ischaemic stroke patients with recombinant tissue plasminogen activator (rt-PA ), and examined the beneficial effects of thrombolysis and the influence of HT on their clinical outcome.
SUBJECTS AND METHODS We studied 26 patients (14 males and 12 females, mean 66 12 years) with acute brain embolism who were admitted to St. Mary's Hospital from May 1, 1989 through October 30, 1990. The criteria for their entry were (1) abrupt onset of symptoms in the territory of the internal carotid artery, (2) atrial fibrillation or other heart diseases, ( 3) age < 80 years, (4) admission < 6 hours from stroke onset. We performed cerebral angiography in 15 of 26 patients to confirm the occlusion of the vessels and initiated rt-PA thrombolytic therapy within 6 hours after obtaining informed consent from the patients' families. For the other 11 patients in the same initial conditions, they were conventionally treated either because we could not get informed consent or we were unable to perform cerebral angiography for some practical reason. We estimated their severity of neurological deficits by means of the Hemispheric Stroke Scale7 at admission, 24 hours, 3, 7, 14 and 30 days. The neurological state at 30 days was classified into five groups; excellent, 0- 5 points; good, 6- 20 points; moderate, 21-60 points; poor, 61-100 points; and deceased.
±
Address for correspondence: Yasushi Okada, MD, Department of Cerebrovascular Disease, St. Mary's Hospital, 422 TsubukuHonmachi, Kuru me 830, Japan. Accepted for publication December
1991.
©
1992 Forefront Publishing Group 0161- 6412/ 92 / 020167-04
Serial computed tomography (CT) was also done at admission, 24 hours, 3, 7, 14, and at 30 days. The size of the infarcted lesion was expressed as the maximum hypodense area/ipsilateral hemisphere x 100% on day 3 and was classified as either small ( 30% )8 . HT was evaluated at every CT examination and was subdivided into 4 types according to the pattern or degree of hyperdensity; (1) petechial haemorrhage, with spotty and scattered hyperdense areas, usually along the cortical margin of the ischaemic lesion, (2) diffuse haemorrhage, (3) small haematoma, with a homogeneous hyperdense area < 3 em in diameter in the ischaemic area, and (4 ) massive haematoma > 3 em in diameter, accompanied by prominent mass effect8 . Soon after the neurological and CT examinations, we performed conventional cerebral angiography both before and immediately after thrombolytic therapy. Fifteen, 20 or 30 MU of rt-PA (SM9527 by Sumitomo Pharmacy Co. Ltd, Osaka, Japan) was administered intravenously for 10 patients and intra-arterially for 5 patients for 1 h. We defined the disappearance of the embolic occlusion as complete re-opening, and existence of some stenotic or occlusive lesions with sufficient restoration of anterograde blood flow as partial re-opening. In 7 cases with either mild neurological deficits or a small infarct on CT, anticoagulant therapy (heparin 10,000 U I day) was started from at least 4 days after the onset of stroke. We compared the characteristics of HT concerning cumulative incidence, timing of occurrence and the subtypes between the patients treated with thrombolytic therapy (thrombolytic group ) and those treated with conventional therapy (conventional group). Furthermore, we focused on the clinical significance of HT recognized at 24 h after thrombolysis because such early HT is rare in natural history and is possible to have potential effects on the clinical outcome after thrombolytic therapy.
RESULTS HTs on CT were demonstrated in a total of 12 patients (80%) of the thrombolytic group and in 6 (55% ) of
Neurological Research, 1992, Volume 14, Suppl
167
Thrombolytic therapy in acute brain embolism: Y. Okada et al.
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
the conventiona l group during 1 month. Of these, HTs recognized at 24 h were observed significantly more in the thrombolytic group (8/15, 53%, small haematoma, 6; massive haematoma , 1; and petechial haemorrhage, 1) than in the conventiona l group (1 /11, 9%, small haematoma, 1) (p < 0.01, Figure 1, Table 1). All other 9HTs were of the petechial type, of which one developed at day 3, six at day 7, and two at day 14.
Initial HSS did not differ between the thrombotic group (66 16, mean SO) and the conventiona l group (62 ± 15). Six patients (40%) of the thrombolytiC group, including four with HT, showed a favourable clinical improvemen t at 24 h, while none of the conventiona l group recovered within 24 h. The reduction of HSS during 24 h after onset was significantly higher in the thrombolyti c group (14 25) than in the
±
±
±
Figure 1: CT scan at 24 h after stroke onset of eight patients (cases 1-8) in the thrombolytic group showing a haemorrhagic transformation in the infarcted lesion. Haemorrhagic transformation seemed to affect the clinical worsening of only one patient with a massive haematoma (case 8)
Table 1:
Haemorrhagic transformation , reopening of occluded vessels, size of infarcted lesions and neurological outcome of patients treated with thrombolytic therapy
Patient
1 2 3 4 5 6 7
8 9
10 11 12 13 14 15
Doses of rt-PA(MU)
20 20 20 30 15 30 30 30 30 30 30 20 20
3o 20
Re-opening of occluded vessels partial partial none none partial none none none none none none none complete complete none
0; the day haemorrhagic transformation appeared.
168 Neurological Research, 1992, Volume 14, Suppl
Haemorrhagic transformation small haematoma (1) petechial (1) small haematoma (1) small haematoma (1) small haematoma (1) small haematoma (1) small haematoma (1) (1) massive petechial (3) (7) petechial petechial (7) petechial (7) none none none
Size of infarcted lesions small small small small medium large large large large large medium large small small large
Neurological outcome excellent good good good fair poor dead poor poor poor good poor excellent excellent dead
Thrombolytic therapy in acute brain embolism: Y. Okada et al.
±
conventional group ( -7 14). Although four (27%) of the thrombotic group and four (36%) of the conventional group developed clinical deterioration at 24 h, HT per se seemed to affect only one patient with a massive haematoma in their clinical course. The other cases were considered to have deteriorated due to large infarcts with brain oedema. The neurological state at 1 month was somewhat better in the thrombolytic group (excellent, 3; good, 4; fair, 1; poor, 5; and dead, 2) than that in the conventional group (0, 1, 0, 7, 3, respectively) although mean HSS at 1 month was not statistically significant (43 37 vs. 60 31 ). Two patients in the thrombolytic group had complete recanalization of the occluded arteries and excellent outcome, and did not show any HT throughout their clinical course. In patients with HT at 24 h (cases 1-8) and the remaining patients (cases 9-15) in the thrombolytic group, there were no significant differences in mean doses of rt-PA (24 MU vs. 26 MU), frequency in the re-opening of occluded vessels (38% vs. 29% ), the size of infarcted lesions (31% vs. 36% ), and the neurological outcomes.
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
±
±
DISCUSSION The present study showed that thrombolytic therapy using rt-PA increased the incidence of HT in acute embolic stroke, especially parenchymatous small haematoma within 24 hours, compared with conventional therapy. However, the neurological outcomes of the patients with HT were not necessarily unfavourable, and four of them (33%) demonstrated early clinical improvement. Interestingly, half of the patients with HT recognized at 24 h after thrombolytic therapy had either good or excellent outcomes. Bruckmann et a/. 9 also reported a successful case with a small putamina! HT after effective thrombolytic therapy. These results indicate that early HT immediately after thrombolytic therapy may occur with the restoration of blood flow to severe ischaemic area where brain tissue or blood brain barrier has been dama~ed; even within a few hours after ischaemic insult1 . HT was more closely related with the severity of the neurological deficits and was independent on rt-PA treatment when it was given within 90 min 4 or 3 hours 11 from the onset of brain ischaemia. Our study is also impressive in that patients with complete recanalization and excellent outcomes did not reveal any haemorrhage during the course of treatment. · The incidence of HT in the present study is excessively higher than in previous studies. HT was seen in 5-4~% ~f the non-anticoag_ulated Batients with brain embolism 1n the1r natural h1storyB· 2 - 15 . Mon et a/. 3 reported that 19% of patients with middle cerebral artery occlusion revealed HT within 24 hours after urokinase fibrinolytic therapy. In recent ongoing studies using intravenous rt-PA within 90 min 4 and 8 h5 , HT occurred in 6 of 74 (8%) within 24 h and in 31 of 71 (44%) up to 14 days, respectively. The reason why HT was developed at such a high rate in the present study is unclear. We did not use any other thrombolytic agents. One possibility is that we identified very mild and small hyperdense lesion as HT, together with frequent examinations at early stage using high resolution CT.
HT per se seemed to have little influence on the clinical course of the patients with thrombolytic therapy except for the development of massive haematoma. Parenchymatous haematoma with clinical deterioration similarly occurred in 3 of 74 (4.1%) and 4 of 71 (5.4%) in recent ongoing rt-PA studies 4•5 . We thus believe that those with significant HT should undergo early recanalization of the occluded arteries after severe ischaemia of large area. Thus, these patients must be excluded from inclusion by means of some clinical and neuroradiological assessments. Although we have not randomized the control, our study suggests that thrombolytic therapy with 15-30 MU rt-PA < 6 h for acute brain embolism seems to be promising even with the significant increase in the incidence of HT. HT after thrombolytic therapy may not be hazardous as previously considered and further study should therefore continue to evaluate for potential benefits.
CONCLUSIONS Haemorrhagic transformation occurred more frequently in patients with thrombolytic therapy than in those with conventional therapy. Haematoma recognized at 24 h CT was significantly more in the former, although the neurological outcomes of these patients were not affected by the haemorrhagic transformation per se except for patients with massive haematoma. Thrombolytic therapy with recombinant tissue plasminogen activator therefore seems to be safe and promising when it is carefully performed at the very early stage of stroke.
REFERENCES
2
3
4
5
6
7
8
9
10
del Zoppo Gj, Ferbert A, Otis S, Bruck mann H, Hacke W , Zyroff j, Harker LA, Zeumer H. Local intra arterial fibrinolytic therapy in acute carotid territory stroke. Stroke 1988; 19: 307-313 Hacke W , Zeumer H, Ferbert A, Bruckmanri H, del Zoppo Gj. Intra arterial thrombolytic therapy improves outcome in patients with acute vertebra-basilar occlusive diseases. Stroke 1988; 19: 1216-1222 Mori E, Tabuchi M, Yoshida T, Yamadori A. lntracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 1988; 19: 802-812 Brott T, Haley C, Levy D, Barsan W, Sheppard G, Broderick j, Reed R, Marler j. Safety and potential efficacy of tissue plasminogen activator (t-PA) for stroke (abstract). Stroke 1990; 21 : 181 del Zoppo Gj. The rt-PA Acute Stroke Study Group: an open multicenter trial of recombinant tissue plasminogen activator in acute stroke; a progress report. Stroke 1990; 21 (suppl IV): IV174-IV175 Yamaguchi T, Hayakawa T, Kikuchi H, Abe T. Thrombolytic therapy in embolic and thrombotic cerebral infarction; a cooperative study. In : Hacke W, del Zoppo G), Hirschberg M, eds. Thrombolytic Therapy in Acute Ischemic Stroke. Berlin : Springer-Verlag, 1991 ; pp 168-173 Adams Rj, Meador Kj, Sethi KD, Grotta jC, Thomson DS. Graded neurologic scale for use in acute hemispheric stroke treatment protocols. Stroke 1987; 18: 665-669 Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, Sadoshima S, Fujishima M, Omae T. Haemorrhagic transformation in cerebral embolism. Stroke 1989; 20: 598-603 Bruckmann H, Ferbert A. Putamina! hemorrhage after recanalization of an embolic MCA occlusion treated with tissue plasminogen activator. Neuroradiology 1989; 31 : 95- 97 Okada Y, Sadoshima S, Nakane H, Utsunomiya H, Fujishima
Neurological Research,
1~92,
Volume 14, Suppl
169
Thrombolytic therapy in acute brain embolism: Y. Okada et al. M. Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism. Stroke 1992;
11
Downloaded by [Australian Catholic University] at 18:42 04 August 2017
12
23: 20-23 del Zoppo G), Copeland BR, Anderchek K, Hacke W, Koziol JA. Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction. Stroke 1990; 21 : 596-601 Fisher M, Zito )L, Siva A, de Girolami U. Hemorrhagic infarction:
170
Neurological Research, 1992, Volume 14, Suppl
13
14
a clinical and 0 study (abstract). Stroke 1984; 15: 192 Hornig CR, Dorndorf W, Agnoli AL. Hemorrhagic cerebral infarction-a prospective study. Stroke 1986; 17: 179-185 Lodder ). CT-detected hemorrhagic infarction; relation with the size of the infarct, and the presence of midline shift. Acta
Neurol Scand 1984; 70: 329-335 15
Weisberg LA. Nonseptic cardiogenic cerebral embolic stroke; clinical-0 correlations. Neurology 1985; 35: 896-899
