Intravenous tpa has been a mainstay of acute stroke

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1 J Neurosurg 115: , 2011 Aggressive intervention to treat a young woman with intracranial hemorrhage following unsuccessful intravenous thrombolysis for left middle cerebral artery occlusion Case report Kyle M. Fargen, M.D., M.P.H., 1 Brian L. Hoh, M.D., 1 Gregory L. Fautheree, M.D., 1 Walter R. Morgan, M.D., 2 Gregory J. Velat, M.D., 1 Michael F. Waters, M.D., Ph.D., 2 and J Mocco, M.D., M.S. 1 Departments of 1 Neurosurgery and 2 Neurology and Neurosciences, University of Florida, College of Medicine, Gainesville, Florida Stroke patients whose condition does not improve after intravenous administration of tissue plasminogen activator (tpa) may be candidates for endovascular intervention. Patients with new intracerebral hemorrhage noted during such interventions pose a difficult challenge to neurointerventionists and are often sequestered as treatment failures and deemed inappropriate for intraarterial recanalization efforts. The authors present a case in which aggressive intervention was performed despite evidence of contrast extravasation on preintervention angiography. This 37-yearold woman presented with an occlusion of the M 1 segment of the left middle cerebral artery and a National Institutes of Health Stroke Scale score of 24. She received intravenous tpa without improvement. Angiography revealed M 1 thrombus as well as active contrast extravasation without arterial displacement. Thromboaspiration was performed in light of her known hemorrhage with excellent recanalization. Immediate postprocedure imaging demonstrated a large insular hematoma and emergent craniectomy and hematoma evacuation were performed. At 4 months follow-up, the patient was living at home, was ambulating, and had excellent comprehension with mild expressive aphasia. There is little peer-reviewed data in the literature to aid in the decision-making process when contrast extravasation is recognized at the time of preinterevention angiography. Continuation of mechanical endovascular stroke intervention, in light of active contrast extravasation, may be warranted in young patients with major deficits and absence of arterial displacement or delayed global filling. Further thrombolytics are not advised. In select stroke patients, continuation of a planned attempt at mechanical recanalization without the further use of thrombolytics may be warranted in light of known intracerebral hemorrhage. (DOI: / JNS101514) Key Words intracranial hemorrhage Penumbra stroke recanalization thrombectomy vascular disorders Intravenous tpa has been a mainstay of acute stroke therapy since 1995 when the NINDS and the European Cooperative Acute Stroke Study (ECASS) trials demonstrated improved outcomes in those receiving IV tpa therapy compared with placebo. 6,14 However, IV tpa therapy was associated with a 6.4% risk of symptomatic intracerebral hemorrhage in the NINDS trial, a 3.4-fold increase in odds compared with placebo. 14 The risks of intracerebral hemorrhage with IV thrombolysis have been consistently demonstrated in more recent studies, 2,5,7,9,16,18 suggesting a risk of symptomatic intracerebral hemorrhage to be approximately 5% 10%. Stroke patients who do not show improvement after IV tpa administration may be candidates for intraarterial Abbreviations used in this paper: IV = intravenous; MCA = middle cerebral artery; NIHSS = National Institutes of Health Stroke Scale; NINDS = National Institute of Neurological Disorders and Stroke; TIMI = Thrombolysis in Myocardial Infarction; tpa = tissue plasminogen activator. thrombolysis or thrombectomy. Although the superiority of endovascular stroke therapies over IV tpa alone has not been demonstrated in any randomized trials to date, numerous prospective trials have suggested improved results with different endovascular interventions for stroke including intraarterial administration of thrombolytic agents, 4,8 mechanical thrombectomy, 3,15,17 and stent placement. 1,10 12 Patients with new intracerebral hemorrhage prior to intraarterial acute stroke intervention pose a difficult challenge to neurointerventionists and are often sequestered as treatment failures and deemed inappropriate for intraarterial recanalization efforts. We present the case of a female patient who received IV tpa therapy for an acute occlusion of the M 1 segment of the left MCA and was found to have active contrast extravasation prior to thrombectomy. She underwent an aggressive course of intraarterial recanalization therapy followed by clot evacuation. Additionally, we discuss factors to be considered when deciding to continue with, or abort, treatment in this setting. 359

2 K. M. Fargen et al. Case Report History and Presentation. This 37-year-old woman with a medical history significant only for migraine headaches presented to Shands Teaching Hospital at the University of Florida after developing right-sided weakness associated with a migraine headache. She began having her usual migraine headache symptoms at 11:00 a.m. and took a dose of sumatriptan 2 hours after symptom onset. One hour later, she was found unresponsive with her eyes deviated to the left and without spontaneous movements of the right hemibody. Upon arrival to the hospital, initial evaluation demonstrated a dense aphasia with right hemiparesis and pathological reflexes, consistent with an NIHSS score of 24. She was subsequently intubated due to a Glasgow Coma Scale score of 7. She underwent CT angiography of the head and neck; the study demonstrated no overt evidence of intracranial hemorrhage on noncontrast imaging, but a small area of hyperdensity thought by the neuroradiologist to represent calcification was visualized in the left putamen (Fig. 1 left). The CT angiography (Fig. 1 right) demonstrated poor filling of the proximal left MCA. A CT perfusion study showed deficits in the left MCA territory, with reduced cerebral blood flow but preserved cerebral blood volume. The patient received weight-based IV tpa therapy per national stroke guidelines roughly 1 hour after being found unresponsive, but demonstrated no neurological improvement 30 minutes after IV tpa administration. Endovascular Treatment. The patient was taken emergently to the angiography suite where she underwent right femoral catheterization and subsequent cerebral angiography demonstrating occlusion at the proximal M 1 segment secondary to thrombus with TIMI Grade 1 flow distally (Fig. 2A). Active extravasation of dye was noted immediately in the area of the left insula indicating hemorrhage (Fig. 2B). At this point it was decided to continue with mechanical thrombectomy to recanalize the occluded M 1 segment, despite knowledge of her known intracranial hemorrhage, in an attempt to salvage her neurological function. No further thrombolytics or anticoagulants were administered. A Penumbra 054 reperfusion catheter was introduced over a Penumbra 032 reperfusion catheter and thrombectomy was performed. Postaspiration angiography demonstrated excellent recanalization of the left MCA. Unfortunately, continued contrast extravasation was noted. However, no shift of the major intracerebral arteries was seen (Fig. 2C). Following her mechanical recanalization, she was taken emergently to the CT scanner where imaging demonstrated a 6 3 cm left insular intracranial hemorrhage (Fig. 3). Hematoma Evacuation and Postoperative Course. The patient was taken directly from the CT scanner to the operating suite where she underwent emergent left frontotemporal craniectomy with hematoma evacuation (Fig. 4 left). She was monitored in the neurosurgical intensive care unit for the following week and was extubated. Physical examination at that time demonstrated improved understanding and an ability to follow commands but a significant expressive aphasia and right hemiplegia. She Fig. 1. Left: Noncontrast CT scan obtained on admission demonstrating a small area of hyperdensity near the left putamen (arrow) that was suspected to represent basal ganglia calcification. Right: A CT angiogram demonstrating evidence of left proximal MCA thrombus (arrow). Note the asymmetry of the distal M 1 segments. was discharged to inpatient rehabilitation on postoperative Day 10 and then to home with home healthcare 6 weeks later. The patient was evaluated in clinic 3 months after her craniectomy, at which time her NIHSS score was 12. She underwent uncomplicated cranioplasty and at 4 months follow-up (Fig. 4 right) her modified Rankin Scale score was 3. She was living at home with excellent comprehension and a mild expressive aphasia and was ambulating well with a cane. Discussion The risk of intracranial hemorrhage after the administration of IV thrombolytic agents for acute stroke is well documented. 2,5 7,9,14,16,18 Patients whose neurological condition does not improve after IV therapy may be candidates for endovascular stroke intervention, which includes intraarterial thrombolysis, mechanical thrombectomy, angioplasty, and/or stent placement. In those patients being considered for intraarterial acute stroke intervention, the presence of intracerebral hemorrhage is considered a contraindication for further intervention. In addition, contrast extravasation frequently occurs as a result of intraarterial acute stroke intervention, which likewise poses a difficult challenge to neurointerventionists decision making. Whether hemorrhaging occurs before or during intervention, there is little peer-reviewed data in the literature to aid in the decision-making process when contrast extravasation is recognized at the time of angiography. While pursuing recanalization without the use of intraarterial thrombolytics may allow for vessel recanalization and improvements in perfusion of distal brain tissue, recanalization may potentially increase the rate of bleeding and increase the risk of brain tissue damage from the expanding hematoma. On the other hand, aborting the procedure and halting all further attempts at recanalization may doom the patient to the significant morbidity associated with a major territory stroke or to death. In the presented case, the patient was a young woman 360

3 Aggressive endovascular stroke intervention after hemorrhage Fig. 2. Anteroposterior left internal carotid artery injection angiograms. A: Initial run demonstrating an irregular proximal M 1 segment with thrombus and poor distal MCA filling. B: Contrast extravasation is seen in the left insular region (arrow) on late-phase image. C: Postthrombectomy angiogram demonstrating excellent recanalization. Note that the ipsilateral anterior cerebral artery is not displaced. who had no evidence of neurological improvement after initial IV tpa administration. Of note, she did have a small area of hyperdensity on the admission head CT that was reviewed by members of the neurological and neuroradiological departments and was thought to represent basal ganglia calcification. Based on this interpretation, no contraindication to IV tpa therapy was present and therefore IV tpa was administered by the treating neurologist. In retrospect, this imaging abnormality likely represented a small amount of intracranial blood products and may have represented the origin of the intracerebral hemorrhage. At the time of the first angiographic run, a small amount of contrast extravasation was seen in the left insular region as well as a proximal M 1 thrombosis with TIMI Grade 1 flow distally. Based on the patient s young age, the lack of major vessel displacement (indicating limited mass effect) or filling delays to suggest elevated intracranial pressure, and the involvement of the dominant hemisphere with a high degree of deficits on admission, it was decided to pursue further recanalization attempts to salvage the MCA territory. Thromboaspiration was performed and an excellent angiographic result was obtained, once again demonstrating no major vascular displacement. The head CT scan performed immediately following the procedure demonstrated a large insular hematoma, and surgical evacuation was performed. Hemicraniectomy alone was considered, but given the active bleeding visualized on angiography it was thought best to pursue aggressive hematoma evacuation to provide the opportunity for hemostasis, if required. The patient has made dramatic improvements and has returned to a quality of life that is well within both her and her family s desired threshold for recovery; she does, however, have persistent left-hemisphere deficits. It is unclear if these deficits are residua from her initial stroke or represent Fig. 3. Noncontrast head CT scan obtained following thrombectomy demonstrating a large insular hematoma. Note that the hyperdensity is due to both blood products and extravasated contrast dye. 361

4 K. M. Fargen et al. decision of continuing with endovascular recanalization attempts, with the potential benefit of salvaging distal brain tissue from acute ischemia, must be weighed against the risk of further brain injury from hematoma expansion. In some patients, continuation of a planned attempt at mechanical recanalization without further use of thrombolytic agents may be warranted in light of known intracranial hemorrhage. Fig. 4. Noncontrast head CT. Left: Scan obtained following hematoma evacuation and hemicraniectomy. Right: Scan obtained following uncomplicated cranioplasty. deficits due to further insults incurred from the hemorrhage and subsequent hematoma evacuation. Continuation of endovascular intervention to restore perfusion may be warranted in certain stroke patients with active extravasation of contrast at the time of intervention. For instance, a young patient with a devastating, dominant-hemisphere MCA stroke and an NIHSS score greater than 20 at admission may provide impetus for further treatment given the degree of deficit that will occur if therapy is aborted. Acute endovascular stroke intervention has previously shown promise in young patients (18 35 years of age), 13 suggesting that younger patients may be an ideal population for more aggressive intervention in such a scenario. In addition, the absence of 1) displacement of large arteries, and 2) evidence of delayed global filling may indicate limited mass effect or intracranial pressure elevations from the enlarging hematoma. Conversely, patients with brisk extravasation or with displacement of major arterial vessels are likely poor candidates for further intervention, and cessation of intervention should be considered. In those cases in which further attempts are made at recanalization with known extravasation, any further administration of thrombolytic agents is likely to lead to devastating hemorrhage and is not advised. The relevance of these considerations remains anecdotal as they have not been evaluated previously or corroborated elsewhere in the literature. The experience of this patient suggests that continued aggressive therapy in the face of active intracerebral hemorrhage may be a worthwhile endeavor, particularly in young patients with major deficits from ischemia but without evidence of mass effect or elevated intracranial pressure. It must be stated, however, that this patient may represent an outlier with an outcome that is not representative of most patients suffering a similar series of events. Further evaluation with larger case series is warranted before any definite conclusions can be supported. Conclusions Patients with active contrast extravasation seen on angiography prior to endovascular intervention for stroke pose a difficult challenge for neurointerventionists. The Disclosure The University of Florida receives an educational grant and consulting fees from Codman Neurovascular. Dr. Mocco serves on the Clinical Events Committee Adjudication Board for the Conscious-2 and Conscious-3 International Studies (Actelion, Inc). He is a consultant for Nfocus and Lazarus Effect and receives honoraria from Edge Therapeutics. Dr. Hoh receives honoraria from Codman Neurovascular and Actelion, Inc., as well as nonfinancial research support from Micrus Endovascular. Drs. Fargen, Waters, Fautheree, Morgan, and Velat have no disclosures to report. Author contributions to the study and manuscript preparation include the following. Conception and design: Mocco, Fargen. Acquisition of data: Mocco, Fargen, Fautheree, Velat. Analysis and interpretation of data: Mocco, Fargen. Drafting the article: Mocco, Fargen. Critically revising the article: Mocco, Fargen, Hoh, Morgan, Velat, Waters. Approved the final version of the paper on behalf of all authors: Mocco. Other: Morgan (patient care), Waters (clinical care of patient). References 1. Brekenfeld C, Schroth G, Mattle HP, Do DD, Remonda L, Mordasini P, et al: Stent placement in acute cerebral artery oc clusion: use of a self-expandable intracranial stent for acute stroke treatment. Stroke 40: , Clark WM, Albers GW, Madden KP, Hamilton S: The rtpa (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke 31: , Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS: Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. Stroke 38: , Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, et al: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 282: , Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-pa stroke trials. Lancet 363: , Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. JAMA 274: , Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al: Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 352: , IMS II Trial Investigators: The Interventional Management of Stroke (IMS) II Study. Stroke 38: , Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al: Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375: ,

5 Aggressive endovascular stroke intervention after hemorrhage 10. Levy EI, Ecker RD, Horowitz MB, Gupta R, Hanel RA, Sauvageau E, et al: Stent-assisted intracranial recanalization for acute stroke: early results. Neurosurgery 58: , Levy EI, Mehta R, Gupta R, Hanel RA, Chamczuk AJ, Fiorella D, et al: Self-expanding stents for recanalization of acute cerebrovascular occlusions. AJNR Am J Neuroradiol 28: , Levy EI, Siddiqui AH, Crumlish A, Snyder KV, Hauck EF, Fiorella DJ, et al: First Food and Drug Administration-approved prospective trial of primary intracranial stenting for acute stroke: SARIS (stent-assisted recanalization in acute ischemic stroke). Stroke 40: , Mocco J, Tawk RG, Jahromi BS, Samuelson RM, Siddiqui AH, Hopkins LN, et al: Endovascular intervention for acute thromboembolic stroke in young patients: an ideal population for aggressive intervention? Clinical article. J Neurosurg 110:30 34, The National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333: , Penumbra Pivotal Stroke Trial Investigators: The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke 40: , Sena ES, Briscoe CL, Howells DW, Donnan GA, Sandercock PA, Macleod MR: Factors affecting the apparent efficacy and safety of tissue plasminogen activator in thrombotic occlusion models of stroke: systematic review and meta-analysis. J Cereb Blood Flow Metab 30: , Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, et al: Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke 39: , Wardlaw JM, Murray V, Berge E, Del Zoppo GJ: Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev (4):CD000213, 2009 Manuscript submitted September 1, Accepted March 21, Please include this information when citing this paper: published online April 15, 2011; DOI: / JNS Address correspondence to: J Mocco, M.D., M.S., Department of Neurosurgery, University of Florida, Box , Gaines ville, Florida jmocco@neurosurgery.ufl.edu. 363