- Email: [email protected]
Intracerebral hemorrhage after thrombolytic therapy managed with ventricular drainage
898
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
2. Kosary IZ, Braham J, Shaked I, et al. Cervical syringomyelia associated with occipital meningioma. Neurology 1969;19: 1127–30. 3. Williams B, Timperley WR. Three cases of communication syringomyelia secondary to midbrain gliomas. J Neurol Neurosurg Psychiatry 1977;40:80–8. 4. Arunkumar MJ, Korah I, Chandy MJ. Dynamic CSF flow study in the pathophysiology of syringomyelia associated with arachnoid cysts of the posterior fossa. Br J Neurosurg 1998;12:33–6. 5. Welch K, Shillito J, Strand R, et al. Chiari I malformations – an acquired disorder? J Neurosurg 1981;55:604–9.
6. Jain R, Sawlani V, Phadke R, et al. Retrocerebellar arachnoid cyst with syringomyelia: a case report. Neurol India 2000;48:81–3. 7. Arunkumar MJ, Haran RP, Chandy MJ. Spontaneous fluctuation in the size of a midline posterior fossa arachnoid cyst. Br J Neurosurg 1999;13:326–8. 8. Tokime T, Okamoto S, Yamagata S, et al. Syringomyelia associated with a posterior fossa cyst. Illustration of two cases. J Neurosurg 1997;86:907. 9. Balagura S, Kuo DC. Spontaneous retraction of cerebellar tonsils after surgery for Arnold-Chiari malformation and posterior fossa cyst. Surg Neurol 1988;29:137–40.
doi:10.1016/j.jocn.2006.06.009
Intracerebral hemorrhage after thrombolytic therapy managed with ventricular drainage Darweesh Al-Khawaja b
a,*
, Guy D. Eslick b, Stephen J. Fuller b, Kevin Seex
a
a Department of Neurosurgery, Nepean Hospital, Penrith, New South Wales, Australia Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia
Received 2 January 2006; accepted 4 June 2006
Abstract Intracerebral hemorrhage (ICH) after thrombolytic treatment for acute myocardial infarction (AMI) is a serious complication causing significant morbidity and mortality. Drainage of the haematoma by craniotomy is associated with poor outcome. We present a patient who received tissue plasminogen activator (t-PA) for acute myocardial infarction; he subsequently developed an ICH with ventricular system extension. The patient was managed by insertion of an external ventricular drain. The hemorrhage was successfully evacuated by insertion of the external ventricular drain. This was unexpected as ICH are usually viscous and difficult to aspirate in the acute phase. This suggests that ICHs following thrombolytic therapy remain liquid for up to 10 h. External ventricular drains can be used in the management of patients with ICH complicating thrombolytic therapy for management of acute myocardial infarction or ischemic stroke. This reduces the need for craniotomy and associated morbidity and mortality. 2006 Elsevier Ltd. All rights reserved. Keywords: Acute intracerebral hemorrhage; External ventricular drain; Tissue plasminogen activator; Thrombolytic therapy
1. Introduction
2. Case report
Thrombolytic therapy has emerged as an important risk factor for intracerebral hemorrhage (ICH) and is a serious complication of treatment for acute myocardial infarction, pulmonary embolism, and stroke.1 The incidence of ICH after thrombolytic treatment for acute myocardial infarction is as high as 2% and the mortality rate approaches 50%.2 It is known that the risk of ICH increases with age,3 low body weight,4 hypertension and use of alteplase (recombinant tissue plasminogen activator) rather than streptokinase.4
A 50-year-old man presented to the emergency department with a 40-minute history of acute retrosternal chest pain on exertion. His risk factors for ischemic heart disease were obesity, type 2 diabetes mellitus and hypertension. He was a non-smoker and there was no previous family history of ischemic heart disease. On examination, he was normotensive and he had bilateral inspiratory crepitations, although the chest X-ray did not show evidence of pulmonary edema. The electrocardiogram (ECG) was consistent with an acute myocardial infarction with greater than 1 mm ST elevation in the anterior and inferior leads. In addition, the echocardiogram showed left ventricular wall hypertrophy and diastolic dysfunction. He was treated with oxygen, aspirin, sublingual nitrate and
* Corresponding author. Present address: Department of Neurosurgery, St. Vincent’s Hospital, Darlinghurst, Sydney, New South Wales 2000, Australia. Tel.: +61 2 83821111. E-mail address: [email protected] (D. Al-Khawaja).
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
899
Fig. 1. Pre-operative CT scan showing the intracerebral hematomal extending to the ventricles, with midline shift.
Fig. 2. Post-operative CT scan showing the reduction of the size of the hematoma after insertion of the ventricular drain.
morphine. He had no contraindications to thrombolytic therapy. Six minutes after presentation and 46 minutes after onset of chest pain, he was given intravenous Metalyse (TNK-t-PA) (Bochringer Ingelheim International GmbH, Germany) and a bolus injection of heparin followed by heparin infusion. Three hours after thrombolytic therapy he developed a dense left hemiplegia. The heparin infusion was ceased and reversed with protamine sulfate. A head CT scan (Fig. 1) showed a large left parietal ICH, with extension into the ventricular system, causing hydrocephalus. The hematoma measured 6 · 4 · 4 cm (volume = 96 cm3). The patient’s level of consciousness deteriorated acutely. His Glasgow Coma Scale score (GCS) dropped to 3/15. He was intubated and ventilated. A full blood count showed hemoglobin: 118 g/L (135–180 g/L). White cell count and platelet count were normal. His INR was 1.1. He was given 8 units of platelets, 4 units of fresh frozen plasma (FFP) and 10 units of cryoprecipitate. An external ventricular drain (EVD) was inserted 10 h after the thrombolysis procedure and started draining 15 mL/h. Over the next 6 h his level of consciousness improved. He started localizing to pain (GCS 8). A repeat CT scan 24 h after EVD insertion (Fig. 2) showed significant resolution of the ICH and intraventricular hemorrhage. The size of the hematoma had reduced to 3 · 2 · 2 cm (volume = 12 cm3).
The patient was extubated after 5 days. Three weeks later he was transferred to the rehabilitation unit. Two months after the insertion of the EVD he had normal speech with mild residual right hemiparesis, and he was able to walk.
3. Discussion Six plasminogen activators have been approved by the Federal Drug Administration (FDA) in the US for use in the treatment of major thrombotic disease. These agents facilitate thrombolysis and restore blood flow to reduce ischemic tissue damage following thrombosis. Each of the six agents differs in its specific mechanism of action upon plasminogen and newer agents such as Metalyse (TNKt-PA) have enhanced fibrinolytic specificity and rate of lysis (t-PA has a higher risk of inducing intracranial hemorrhage than other thrombolytic agents). The use of these drugs is likely to increase, thus we expect to see more complications associated with these agents. One of the major side effects of thrombolytic therapy is ICH, which still occurs despite dose adjustment of thrombolytic drugs and the introduction of new neuroimaging techniques5 to avoid inappropriate use of thrombolytic agents in acute stroke. This is of great clinical
900
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
importance because more than 50% of patients die or are left with a significant neurological deficit. There are several prospective, randomized, controlled studies comparing the surgical and medical management of ICH.6–12 Surgical interventions include craniotomy, craniectomy, stereotactic needle aspiration, and stereotactically guided endoscopic aspiration. Recently, Fernandes et al.13 performed a meta-analysis that included most of these randomized studies, which showed a non-significant reduction in the chances of death and dependence after surgery. Based strictly on the results of these studies, surgery may be most beneficial when reserved for patients with subcortical ICH who are less than 60 years old, with a hematoma volume more than 10 cm3, without a profoundly impaired level of consciousness at presentation. The Surgical Treatment for Intracerebral Hemorrhage (STICH) study9 aimed to determine if early surgery would be of value in ICH and if so, which patients would benefit. The study concluded that among patients with spontaneous supratentorial ICH in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment. The results of this study have been challenged.1 Currently, there are no guidelines for management of ICH following thrombolytic therapy. Because of the significant co-morbidities, most patients are treated conservatively. Our patient developed an ICH with ventricular extension as a complication of t-PA treatment for acute anterior MI. The haematoma showed reduction in size of more than 80% less than 24 h after insertion of an external ventricular drain. Despite reversal of heparin with protamine sulfate and infusion of platelets, FFP and cryoprecipitate, the intracerebral clot remained liquid and was able to be drained by an EVD. Therefore, treatment of patients with ICH following thrombolytic therapy may be possible with placement of an EVD by burr hole under local anesthetic. This treatment is relatively simple, could significantly change outcome and reduces the morbidity and mortality associated with craniotomy. Important points that should be considered in treatment of patients with ICH are: Difficulty in reversing the anticoagulant effect of thrombolytic agents; Invasive procedures after thrombolytic therapy, even after a delay of 12 h, and sometimes 24 h, result in bleeding complications, and require blood transfusion;14 Fibrinogen levels after thrombolytic therapy remain low for 24 h,15,16 (because normal fibrinogen concentrations are not achieved until full repletion by hepatic synthesis of fibrinogen, a process which may require 24–36 h). In summary, our case highlights that the ICH formed as a complication of thrombolytic treatment remains fluid for at least 10 h. Previously, craniotomy and drainage of the hematoma would have been considered the definitive neudoi:10.1016/j.jocn.2006.06.008
rosurgical procedure. Patients with acute myocardial infarction are at high anesthetic risk and would not generally be considered suitable for a craniotomy, particularly after thrombolytic therapy. However, a burr hole aspiration or external ventricular drainage can be done quickly under local anesthetic with dramatic improvement in outcome. Our patient shows that drainage of an ICH with EVD following thrombolytic treatment can be performed safely and effectively with a good clinical outcome. References 1. Nakano T, Ohkuma H. Surgery versus conservative treatment for intracerebral hemorrhage – is there an end to the long controversy? Lancet 2005;365:361–2. 2. Maggioni AP, Franzosi MG, Santoro E, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. N Eng J Med 1992;327:1–6. 3. Anderson JL, Karagounis L, Allen A, et al. Older age and elevated blood pressure are risk factors for intracerebral hemorrhage after thrombolysis. Am J Cardiol 1991;68:166–70. 4. Simoons ML, Maggioni AP, Knatterud G, et al. Individual risk assessment for intracranial haemorrhage during thrombolytic therapy. Lancet 1993;342:1523–8. 5. The TIMI Investigators. Hemorrhagic events during therapy with recombinant tissue plasminogen activator, heparin, aspirin for acute myocardial infarction. Am Coll Physicians 1991;115:256–65. 6. Auer LM, Deinsberger W, Niederkorn K, et al. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study. J Neurosurg 1989;70:530–5. 7. Batjer HH, Reisch JS, Allen BC, et al. Failure of surgery to improve outcome in hypertensive putaminal hemorrhage: a prospective randomized trial. Arch Neurol 1990;47:1103–6. 8. Chen X, Yang H, Czherig Z. A prospective randomized trial of surgical and conservative treatment of hypertensive intracranial hemorrhage. Acta Academiae Medicinae Shanghai 1992;19:237–40. 9. Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for intracerebral hemorrhage (STICH): A single-center, randomized clinical trial. Neurology 1998;51:1359–63. 10. Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke 1999;30:1833–9. 11. Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous intracerebral hemorrhage. J Neurosurg 1989;70:755–8. 12. Tan SH, Ng PY, Yeo TT, et al. Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management. Surg Neurol 2001;56:287–93. 13. Fernandes HM, Gregson B, Siddique S, et al. Surgery in intracerebral hemorrhage: the uncertainty continues. Stroke 2000;31: 2511–6. 14. TIMI Research Group. Immediate vs. delayed catheterization and angioplasty following thrombolytic therapy for acute MI: TIMI IIA results. JAMA 1988;260:2849–58. 15. Stump DC, Califf RM, Topol EJ, et al. Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator: Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group. Circulation 1989;80:1222–30. 16. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute Phase II myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) Trial. N Eng J Med 1989;320:618–26.
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
2. Kosary IZ, Braham J, Shaked I, et al. Cervical syringomyelia associated with occipital meningioma. Neurology 1969;19: 1127–30. 3. Williams B, Timperley WR. Three cases of communication syringomyelia secondary to midbrain gliomas. J Neurol Neurosurg Psychiatry 1977;40:80–8. 4. Arunkumar MJ, Korah I, Chandy MJ. Dynamic CSF flow study in the pathophysiology of syringomyelia associated with arachnoid cysts of the posterior fossa. Br J Neurosurg 1998;12:33–6. 5. Welch K, Shillito J, Strand R, et al. Chiari I malformations – an acquired disorder? J Neurosurg 1981;55:604–9.
6. Jain R, Sawlani V, Phadke R, et al. Retrocerebellar arachnoid cyst with syringomyelia: a case report. Neurol India 2000;48:81–3. 7. Arunkumar MJ, Haran RP, Chandy MJ. Spontaneous fluctuation in the size of a midline posterior fossa arachnoid cyst. Br J Neurosurg 1999;13:326–8. 8. Tokime T, Okamoto S, Yamagata S, et al. Syringomyelia associated with a posterior fossa cyst. Illustration of two cases. J Neurosurg 1997;86:907. 9. Balagura S, Kuo DC. Spontaneous retraction of cerebellar tonsils after surgery for Arnold-Chiari malformation and posterior fossa cyst. Surg Neurol 1988;29:137–40.
doi:10.1016/j.jocn.2006.06.009
Intracerebral hemorrhage after thrombolytic therapy managed with ventricular drainage Darweesh Al-Khawaja b
a,*
, Guy D. Eslick b, Stephen J. Fuller b, Kevin Seex
a
a Department of Neurosurgery, Nepean Hospital, Penrith, New South Wales, Australia Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia
Received 2 January 2006; accepted 4 June 2006
Abstract Intracerebral hemorrhage (ICH) after thrombolytic treatment for acute myocardial infarction (AMI) is a serious complication causing significant morbidity and mortality. Drainage of the haematoma by craniotomy is associated with poor outcome. We present a patient who received tissue plasminogen activator (t-PA) for acute myocardial infarction; he subsequently developed an ICH with ventricular system extension. The patient was managed by insertion of an external ventricular drain. The hemorrhage was successfully evacuated by insertion of the external ventricular drain. This was unexpected as ICH are usually viscous and difficult to aspirate in the acute phase. This suggests that ICHs following thrombolytic therapy remain liquid for up to 10 h. External ventricular drains can be used in the management of patients with ICH complicating thrombolytic therapy for management of acute myocardial infarction or ischemic stroke. This reduces the need for craniotomy and associated morbidity and mortality. 2006 Elsevier Ltd. All rights reserved. Keywords: Acute intracerebral hemorrhage; External ventricular drain; Tissue plasminogen activator; Thrombolytic therapy
1. Introduction
2. Case report
Thrombolytic therapy has emerged as an important risk factor for intracerebral hemorrhage (ICH) and is a serious complication of treatment for acute myocardial infarction, pulmonary embolism, and stroke.1 The incidence of ICH after thrombolytic treatment for acute myocardial infarction is as high as 2% and the mortality rate approaches 50%.2 It is known that the risk of ICH increases with age,3 low body weight,4 hypertension and use of alteplase (recombinant tissue plasminogen activator) rather than streptokinase.4
A 50-year-old man presented to the emergency department with a 40-minute history of acute retrosternal chest pain on exertion. His risk factors for ischemic heart disease were obesity, type 2 diabetes mellitus and hypertension. He was a non-smoker and there was no previous family history of ischemic heart disease. On examination, he was normotensive and he had bilateral inspiratory crepitations, although the chest X-ray did not show evidence of pulmonary edema. The electrocardiogram (ECG) was consistent with an acute myocardial infarction with greater than 1 mm ST elevation in the anterior and inferior leads. In addition, the echocardiogram showed left ventricular wall hypertrophy and diastolic dysfunction. He was treated with oxygen, aspirin, sublingual nitrate and
* Corresponding author. Present address: Department of Neurosurgery, St. Vincent’s Hospital, Darlinghurst, Sydney, New South Wales 2000, Australia. Tel.: +61 2 83821111. E-mail address: [email protected] (D. Al-Khawaja).
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
899
Fig. 1. Pre-operative CT scan showing the intracerebral hematomal extending to the ventricles, with midline shift.
Fig. 2. Post-operative CT scan showing the reduction of the size of the hematoma after insertion of the ventricular drain.
morphine. He had no contraindications to thrombolytic therapy. Six minutes after presentation and 46 minutes after onset of chest pain, he was given intravenous Metalyse (TNK-t-PA) (Bochringer Ingelheim International GmbH, Germany) and a bolus injection of heparin followed by heparin infusion. Three hours after thrombolytic therapy he developed a dense left hemiplegia. The heparin infusion was ceased and reversed with protamine sulfate. A head CT scan (Fig. 1) showed a large left parietal ICH, with extension into the ventricular system, causing hydrocephalus. The hematoma measured 6 · 4 · 4 cm (volume = 96 cm3). The patient’s level of consciousness deteriorated acutely. His Glasgow Coma Scale score (GCS) dropped to 3/15. He was intubated and ventilated. A full blood count showed hemoglobin: 118 g/L (135–180 g/L). White cell count and platelet count were normal. His INR was 1.1. He was given 8 units of platelets, 4 units of fresh frozen plasma (FFP) and 10 units of cryoprecipitate. An external ventricular drain (EVD) was inserted 10 h after the thrombolysis procedure and started draining 15 mL/h. Over the next 6 h his level of consciousness improved. He started localizing to pain (GCS 8). A repeat CT scan 24 h after EVD insertion (Fig. 2) showed significant resolution of the ICH and intraventricular hemorrhage. The size of the hematoma had reduced to 3 · 2 · 2 cm (volume = 12 cm3).
The patient was extubated after 5 days. Three weeks later he was transferred to the rehabilitation unit. Two months after the insertion of the EVD he had normal speech with mild residual right hemiparesis, and he was able to walk.
3. Discussion Six plasminogen activators have been approved by the Federal Drug Administration (FDA) in the US for use in the treatment of major thrombotic disease. These agents facilitate thrombolysis and restore blood flow to reduce ischemic tissue damage following thrombosis. Each of the six agents differs in its specific mechanism of action upon plasminogen and newer agents such as Metalyse (TNKt-PA) have enhanced fibrinolytic specificity and rate of lysis (t-PA has a higher risk of inducing intracranial hemorrhage than other thrombolytic agents). The use of these drugs is likely to increase, thus we expect to see more complications associated with these agents. One of the major side effects of thrombolytic therapy is ICH, which still occurs despite dose adjustment of thrombolytic drugs and the introduction of new neuroimaging techniques5 to avoid inappropriate use of thrombolytic agents in acute stroke. This is of great clinical
900
Case reports / Journal of Clinical Neuroscience 14 (2007) 898–900
importance because more than 50% of patients die or are left with a significant neurological deficit. There are several prospective, randomized, controlled studies comparing the surgical and medical management of ICH.6–12 Surgical interventions include craniotomy, craniectomy, stereotactic needle aspiration, and stereotactically guided endoscopic aspiration. Recently, Fernandes et al.13 performed a meta-analysis that included most of these randomized studies, which showed a non-significant reduction in the chances of death and dependence after surgery. Based strictly on the results of these studies, surgery may be most beneficial when reserved for patients with subcortical ICH who are less than 60 years old, with a hematoma volume more than 10 cm3, without a profoundly impaired level of consciousness at presentation. The Surgical Treatment for Intracerebral Hemorrhage (STICH) study9 aimed to determine if early surgery would be of value in ICH and if so, which patients would benefit. The study concluded that among patients with spontaneous supratentorial ICH in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment. The results of this study have been challenged.1 Currently, there are no guidelines for management of ICH following thrombolytic therapy. Because of the significant co-morbidities, most patients are treated conservatively. Our patient developed an ICH with ventricular extension as a complication of t-PA treatment for acute anterior MI. The haematoma showed reduction in size of more than 80% less than 24 h after insertion of an external ventricular drain. Despite reversal of heparin with protamine sulfate and infusion of platelets, FFP and cryoprecipitate, the intracerebral clot remained liquid and was able to be drained by an EVD. Therefore, treatment of patients with ICH following thrombolytic therapy may be possible with placement of an EVD by burr hole under local anesthetic. This treatment is relatively simple, could significantly change outcome and reduces the morbidity and mortality associated with craniotomy. Important points that should be considered in treatment of patients with ICH are: Difficulty in reversing the anticoagulant effect of thrombolytic agents; Invasive procedures after thrombolytic therapy, even after a delay of 12 h, and sometimes 24 h, result in bleeding complications, and require blood transfusion;14 Fibrinogen levels after thrombolytic therapy remain low for 24 h,15,16 (because normal fibrinogen concentrations are not achieved until full repletion by hepatic synthesis of fibrinogen, a process which may require 24–36 h). In summary, our case highlights that the ICH formed as a complication of thrombolytic treatment remains fluid for at least 10 h. Previously, craniotomy and drainage of the hematoma would have been considered the definitive neudoi:10.1016/j.jocn.2006.06.008
rosurgical procedure. Patients with acute myocardial infarction are at high anesthetic risk and would not generally be considered suitable for a craniotomy, particularly after thrombolytic therapy. However, a burr hole aspiration or external ventricular drainage can be done quickly under local anesthetic with dramatic improvement in outcome. Our patient shows that drainage of an ICH with EVD following thrombolytic treatment can be performed safely and effectively with a good clinical outcome. References 1. Nakano T, Ohkuma H. Surgery versus conservative treatment for intracerebral hemorrhage – is there an end to the long controversy? Lancet 2005;365:361–2. 2. Maggioni AP, Franzosi MG, Santoro E, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. N Eng J Med 1992;327:1–6. 3. Anderson JL, Karagounis L, Allen A, et al. Older age and elevated blood pressure are risk factors for intracerebral hemorrhage after thrombolysis. Am J Cardiol 1991;68:166–70. 4. Simoons ML, Maggioni AP, Knatterud G, et al. Individual risk assessment for intracranial haemorrhage during thrombolytic therapy. Lancet 1993;342:1523–8. 5. The TIMI Investigators. Hemorrhagic events during therapy with recombinant tissue plasminogen activator, heparin, aspirin for acute myocardial infarction. Am Coll Physicians 1991;115:256–65. 6. Auer LM, Deinsberger W, Niederkorn K, et al. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study. J Neurosurg 1989;70:530–5. 7. Batjer HH, Reisch JS, Allen BC, et al. Failure of surgery to improve outcome in hypertensive putaminal hemorrhage: a prospective randomized trial. Arch Neurol 1990;47:1103–6. 8. Chen X, Yang H, Czherig Z. A prospective randomized trial of surgical and conservative treatment of hypertensive intracranial hemorrhage. Acta Academiae Medicinae Shanghai 1992;19:237–40. 9. Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for intracerebral hemorrhage (STICH): A single-center, randomized clinical trial. Neurology 1998;51:1359–63. 10. Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke 1999;30:1833–9. 11. Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous intracerebral hemorrhage. J Neurosurg 1989;70:755–8. 12. Tan SH, Ng PY, Yeo TT, et al. Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management. Surg Neurol 2001;56:287–93. 13. Fernandes HM, Gregson B, Siddique S, et al. Surgery in intracerebral hemorrhage: the uncertainty continues. Stroke 2000;31: 2511–6. 14. TIMI Research Group. Immediate vs. delayed catheterization and angioplasty following thrombolytic therapy for acute MI: TIMI IIA results. JAMA 1988;260:2849–58. 15. Stump DC, Califf RM, Topol EJ, et al. Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator: Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group. Circulation 1989;80:1222–30. 16. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute Phase II myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) Trial. N Eng J Med 1989;320:618–26.