Delayed treatment for a case of acute ischaemic stroke using mechanical embolectomy the L5 Merci Retriever

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1 Case Study Australian Institute of Radiography The Radiographer 2009; 56 (2): Delayed treatment for a case of acute ischaemic stroke using mechanical embolectomy the L5 Merci Retriever J Velkovic 1,2, S McEwan 1, A Coulthard 1,2 1 Department of Medical Imaging, Level 3 Ned Hanlon Building, Royal Brisbane and Women s Hospital, Brisbane, Queensland, Australia. 2 The University of Queensland, Brisbane, Queensland, Australia. Correspondence john_velkovic@health.qld.gov.au Abstract Endovascular therapies for acute ischaemic stroke represent important alternatives or adjuncts to thrombolysis. A middle-aged male suffered a Thrombolysis in Myocardial Infarction (TIMI) Grade 0 distal left middle cerebral artery (LMCA) occlusion resulting in right hemiparesis and dysphasia. Intravenous thrombolysis was contraindicated due to pre-existing anticoagulant therapy and associated risk of intracranial haemorrhage. The patient underwent rescue mechanical embolectomy with an L5 Merci Retriever, with adjuvant local intra-arterial (IA) thrombolysis. Successful TIMI Grade 3 restoration of LMCA blood flow occurred within eight hours of ictus. Aphasia resolved within 24 hours, whilst other motor and speech symptoms gradually improved over 6 months, allowing the patient to resume work and independent living. Mechanical embolectomy appears to be a safe and effective alternative in cases of delayed presentation, or where intravenous thrombolysis is contraindicated. Combined mechanical embolectomy and adjuvant IA thrombolysis, instituted within eight hours of ictus in an anticoagulated patient, achieved favourable clinical outcome (modified Rankin Score of 2) without major thromboembolic or haemorrhagic complications. Keywords: acute ischaemic stroke, delayed treatment, mechanical embolectomy, Merci Retriever. Introduction Stroke is a leading cause of mortality and permanent disability, and more than 85% are of ischaemic aetiology. 1 Outcomes following stroke have slowly improved as public awareness and management strategies continually evolve, yet time constraints of current therapies limit such treatment to fewer than 10% of potential candidates. 1 Acute ischaemic stroke therapy was revolutionised by the introduction of intravenous (IV) tissue plasminogen activator (tpa) to recanalise thrombus-occluded cerebral vessels. Due to blood-brain barrier degradation in prolonged cerebral ischaemia, 2 treatment must be initiated within three hours of ictus to minimise the risk of haemorrhage into infarcted brain tissue. 3 For patients presenting after the three-hour threshold, or where contraindications to IV thrombolysis exist 2 (for example, pre-existing anticoagulant therapy), mechanical embolectomy and/or intra-arterial (IA) thrombolysis offer viable therapeutic alternatives without excess risk of mortality or intracranial haemorrhage. 2,4 7 Endovascular stroke therapies possess inherent advantages, 6 including ability to precisely locate and evaluate angiographically the presence of occlusive clots and treatment effect, achieve higher effective local concentration of thrombolytics at the clot site, and opportunity for combining therapeutic techniques. Unfortunately, endovascular treatment is time-consuming, resource intensive, limited to specialised centres, and may involve procedural complications (vessel dissection/perforation, vasospasm, thromboembolism). 6 Mechanical clot retrieval can achieve vessel recanalisation in up to 100% of patients, 8 compared to conservative management (24.1%), or intravenous (46.2%) or intra-arterial (63.2%) thrombolysis. 5 Figure 1: The L5 Merci Retriever (Courtesy Concentric Medical). The L5 Merci Retriever (Concentric Medical, Mountain View, CA, USA) is a mechanical clot retrieval (embolectomy) platform, constructed from a flexible core wire of nitinol (shape memory metal alloy) and a series of polymeric filaments attached at the tip (Figure 1). 4 Platinum tip markers allow the device to be

2 28 The Radiographer J Velkovic, S McEwan, A Coulthard Table 1: Definition of mrs, TIMI and GCS. Scale Definition Modified Rankin Score (MRS) 0 No symptoms 1 No significant disability. Able to carry out all usual activities 2 Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities 3 Moderate disability. Requires some help, but able to walk unassisted 4 Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted 5 Severe disability. Requires constant nursing care and attention, bedridden, incontinent 6 Dead Thrombolysis in Myocardial Infarction (TIHI) 0 Absence of any antegrade flow beyond a coronary occlusion 1 Faint antegrade coronary flow beyond the occlusion, with incomplete filling of the distal coronary bed 2 Delayed/sluggish antegrade flow with complete filling of the distal territory 3 Normal flow which fills the distal coronary bed completely Glasgow Coma Score (GCS) Eye opening 1 No eye opening 2 Eye opening in response to painful stimulus 3 Eye opening to speech 4 Eyes opening spontaneously Best verbal response 1 No verbal response 2 Incomprehensible sounds. (Moaning but no words.) 3 Inappropriate words. (Random or exclamatory articulated speech, but no conversational exchange) 4 Confused. (The patient responds to questions coherently but there is some disorientation and confusion.) 5 Oriented. (Patient responds coherently and appropriately to questions such as the patient s name and age, where they are and why, the year, month, etc.) Best motor response 1 No motor response 2 Extension to pain (adduction of arm, internal rotation of shoulder, pronation of forearm, extension of wrist, decerebrate response) 3 Abnormal flexion to pain (adduction of arm, internal rotation of shoulder, pronation of forearm, flexion of wrist, decorticate response) 4 Flexion/Withdrawal to pain (pulls part of body away when painful stimulus applied) 5 Localises to pain. (Purposeful movements towards painful stimuli) 6 Obeys commands. (Patient does as commanded) visualised fluoroscopically. The L5 Series is the second generation of Merci Retrievers, which saw addition of the polymeric filaments to increase surface area to improve engagement with clot. Prior to deployment, the device is navigated across an occluding clot within a microcatheter under digital subtraction angiography (DSA) guidance. As the Merci Retriever is unsheathed from the microcatheter, it forms into non-tapering helical loops complete with incorporated filaments which trap and remove blood clot. 9 The Merci Retriever was evaluated in the Mechanical Embolus Removal in Cerebral Ischaemia (MERCI) and MultiMERCI trials, and found initially to be safe and effective in patients ineligible for or failing IV thrombolysis, or in conjunction with IA thrombolysis. 4,7,10 Additionally, these trials found that higher recanalisation rates resulted in lower mortality and improved clinical outcomes, and that recanalisation rates achieved with the Merci Retriever improved with adjuvant use of IA thromboysis. 7 Numerous clinical variables utilised in this study allowing meaningful comparison of clinical and angiographic findings and treatment effect observed in stroke patients are presented in Table 1. The modified Rankin Score (mrs) is a widely-used, simple overall assessment of neurological function following various forms of brain injury (0 is normal, higher mrs equates to

3 Delayed treatment for a case of acute ischaemic stroke using mechanical embolectomy the L5 Merci Retriever The Radiographer 29 Figure 3a: Non-subtracted left carotid artery angiogram demonstrating LMCA occlusion (arrow). Figure 2: Initial non-contrast cranial CT demonstrates loss of grey-white matter differentiation and hypodensity (region within oval). The same region within the right hemisphere has an intact grey-white matter interface (arrows). Figure 3b: Left carotid artery DSA demonstrating LMCA occlusion (arrow). Figure 3c: Vasospasm of internal carotid artery (arrow).

4 30 The Radiographer J Velkovic, S McEwan, A Coulthard Figure 4b: Merci Retriever (arrowhead) deployed distal to the occluding clot (arrow). Figure 4a: Microcatheter navigated beyond location of clot (arrow), demonstrating patent distal LMCA vascular bed. Figure 4c: Merci Retriever is retracted back towards the carotid bifurcation, engaging the clot. Figure 4d: TIMI 3 flow re-established after clot removal (arrow). New-onset LACA occlusion (arrowhead).

5 Delayed treatment for a case of acute ischaemic stroke using mechanical embolectomy the L5 Merci Retriever The Radiographer 31 worse outcome). The Glasgow Coma Score (GCS), and National Institute of Heath Stroke Score (NIHSS) in particular for stroke, are alternative rating scales used to record neurological status and injury severity. Normally, GCS and NIHSS are 15 and 0 respectively. Decreased GCS and increased NIHSS each represent worsening neurological function. The NIHSS is a 42-point rating scale, and further detail may be obtained in Lyden, Brott and Tilley, et al. 11 Thrombolysis in Myocardial Infarction (TIMI) describes the extent of blood flow observed angiographically in occluded blood vessels, with increasing TIMI rating corresponding to improved blood flow and distal perfusion. International Normalised Ratio (INR) is a medical laboratory index describing the extent of anticoagulation achieved over baseline by medications such as warfarin. Patients with an abnormal heart rhythm (atrial fibrillation), blood clots (deep vein thrombosis, pulmonary embolism), or mechanical heart valves often require long-term anticoagulation to prevent thrombotic complications. INR is vital for titrating anticoagulant dose to ensure therapeutic and safe anticoagulation. INR is approximately 1.0 in healthy individuals, and on anticoagulant treatment ideally lies between 2.0 to 3.0 for atrial fibrillation/venous thrombosis and 2.5 to 3.5 for mechanical heart valves. This case report describes an episode of acute ischaemic stroke in a previously anticoagulated patient, subsequently treated with a Merci Retriever and adjunctive IA tpa, that resulted in favourable clinical outcome. The intention to use case information for publication was discussed with the patient, who provided valid informed consent to allow use of non-identifiable clinical records and medical imaging for this report. Case report A 55-year-old male with a history of aortic valve replacement (AVR), long-term warfarin therapy, and smoking, experienced sudden onset expressive aphasia and right hemiplegia at approximately 6.30 am. GCS was 11 and NIHSS was 6 upon presentation to the Emergency Department. Initial non-contrast cranial CT demonstrated no evidence of intracranial haemorrhage, but there was a subtle loss of grey-white matter differentiation in the left fronto-parietal region (Figure 2). The patient was reviewed by the hospital Stroke Team approximately four hours post-ictus. IV thrombolysis was contraindicated due to an elevated INR of 1.9 (subtherapeutic INR for an AVR), and the patient was referred for cerebral angiography and possible neuro-endovacular therapy. Digital subtraction angiography (DSA) of the intracranial vessels via right common femoral artery puncture was undertaken six hours post-ictus under general anaesthesia. This revealed a TIMI Grade 0 distal left middle cerebral artery (LMCA) occlusion (Figure 3a, 3b). An eight French (Fr) balloon guide catheter was navigated through the left internal carotid artery, inducing significant vasospasm in the process (Figure 3c). Glyceryl trinitrate (GTN), a drug capable of inducing vascular smooth muscle relaxation and vasodilation, was infused into the artery to resolve the vasospasm. A Merci microcatheter was navigated across the occluding clot, demonstrating TIMI Grade 3 blood flow distally (Figure 4a). Following 500 units of IV heparin, a Merci Retriever (L5 series) was navigated distal to the clot and an initial attempt made to retrieve it (Figure 4b, 4c). A small quantity of material was retrieved without observable flow improvement. Local IA microcatheter delivery of two milligrams of (tpa) was performed to lyse the clot, and the Merci Retriever re-deployed. A second pass of the Merci Retriever resulted in recovery of a small firm, thrombus.timi Grade 3 flow was observed in the Figure 5: Right carotid DSA demonstrating collateral filling of LACA (arrowheads). distal LMCA and its branches (Figure 4d). Unfortunately, a new occlusion was then observed in the proximal left anterior cerebral artery (LACA) on a repeat DSA (Figure 4d). This represented either a procedural thromboembolic event (clot formation on catheters/guidewires and subsequent embolisation), or embolisation of a fragment of the original thrombus as it was being removed. IA tpa was delivered via microcatheter to lyse the clot. A left femoral artery puncture was performed, and DSA of the right internal carotid artery demonstrated excellent collateral circulation through the anterior communicating arteries and filling of the left anterior cerebral artery (LACA) (Figure 5). Bilateral carotid DSA revealed TIMI Grade 3 patency of LACA, LMCA and no new clot formation. Femoral arterial access closure was achieved with Angio-Seal (St Jude Medical, MN, USA) (right groin) and Starclose (Abbot Vascular, CA, USA) (left groin) vascular closure devices. Histologic analysis of the retrieved clot revealed a high platelet content, with absence of tumour cells and cholesterol. The patient was transferred to the Intensive Care Unit (ICU) and extubated the following day. Aphasia resolved on the first day post-procedure, with residual expressive dysphasia. After three weeks, normal ambulation had returned and further speech improvement had occurred. The patient was discharged after four months; five weeks of which was spent in medical rehabilitation. Within two weeks of discharge, the patient had returned to parttime work and resumed driving. Onset of depression and episodes of short-term memory loss hampered further clinical improvement beyond mrs of 2. Imaging findings There was no evidence of intracranial haemorrhage on initial non-contrast cranial CT, but a loss of grey-white matter differentiation in the left fronto-parietal region was apparent (Figure 2). DSA revealed a distal LMCA occlusion, with patency of lateral lenticulostriate, anterior temporal and temporo-occipital arteries maintained (Figures 3a, 3b). Two attempts at mechanical embolectomy with a Merci Retriever were made (Figures 4b,

6 32 The Radiographer S McEwan, J Velkovic, A Coulthard Figure 6a: Post-embolectomy bilateral carotid DSA demonstrates region of contrast staining (arrowheads). Figure 6b: Post-procedure non-contrast CT, demonstrating extravasation of procedural contrast into brain parenchyma. Figure 6c: Diffusion-weighted imaging (DWI) demonstrates a hyperintense (brighter than surrounding tissue) zone of restricted diffusion in the left temporal, frontal and insular regions, suggestive of acute ischaemia. Ischaemia causes cellular membrane dysfunction and decreased water molecule motion. Figure 6d: Apparent diffusion coefficient (ADC) map demonstrates a zone of hypointensity (darker than surrounding tissue), representing decreased diffusion coefficient and corresponding to the DWI abnormality. This reinforces an ischaemic aetiology for the observed MRI abnormalities.

7 Delayed treatment for a case of acute ischaemic stroke using mechanical embolectomy the L5 Merci Retriever The Radiographer 33 4c), interspersed with IA microcatheter delivery of tpa to the thrombus site. Following successful TIMI Grade 3 flow restoration to the LMCA vascular bed, a new-onset TIMI 0 flow defect of the LACA was noted on DSA (Figure 4d). Following failed attempts at revascularisation with IA tpa, a right carotid DSA demonstrated excellent LACA flow via right anterior communicating branch collateral circulation (Figure 5), indicating a reduced risk of infarction to the left frontal lobe. Bilateral carotid DSA (Figure 6a) and non-contrast CT (Figure 6b) performed at the conclusion of the procedure demonstrated contrast staining of the left fronto-parietal region, suggesting reperfusion injury and breakdown of the blood-brain barrier. 2,12 Post-procedure cranial MRI revealed a region of reduced diffusion (hyperintense region on diffusion-weighted (DWI) MRI) (Figure 6c), which corresponded to the hypodense brain parenchyma identified in the initial cranial CT (Figure 2). Reduced diffusion (hyperintensity on DWI) is a feature of acute cerebral ischaemia visible from 30 minutes up to five days post-ictus, whereby water molecules accumulate intra-cellularly secondary to deranged cellular transport mechanisms and restricted mobility. 13 However, DWI abnormalities may also result from pressure, thermal or ionic gradients, so apparent diffusion coefficient (ADC) maps are generated to identify brain tissue that is truly infarcted. 13 ADC mapping in this case showed an area of hypointensity (Figure 6d) that coincided with the DWI abnormality, suggesting acute ischaemia. DWI and the ADC map identify regions of brain that will invariably become infarcted, 13 which has important management and prognostic complications. Carotid Doppler ultrasound was performed due to suspicion of carotid atheromatous disease, but failed to detect any significant abnormality. Summary Treatment of acute stroke depends on timely intervention. This patient was unsuited to thrombolytic treatment and demonstrated signs of a dense LMCA stroke at the time of mechanical intervention. Use of the mechanical clot retrieval device (Merci Retriever) allowed for a more favourable clinical outcome than would have otherwise been achieved. Acknowledgements The authors have no financial disclosures relevant to this study. References 1 Gandhi CD, Christiano LD, Prestigiacomo CJ. Endovascular management of acute ischemic stroke. Neurosurg Focus 2009; 26(3): E2. 2 Patel RAG, Collins TJ. Techniques for acute stroke intervention. J Interv Cardiol. 2009; 22 (1): The National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333 (24): Smith WS, for the Multi MI. Safety of mechanical thrombectomy and intravenous tissue plasminogen activator in acute ischemic stroke. Results of the multi mechanical embolus removal in cerebral ischemia (MERCI) trial, Part I. AJNR Am J Neuroradiol. 2006; 27 (6): Nogueira RG, Yoo AJ, Buonanno FS, et al. Endovascular approaches to acute stroke, Part 2: A Comprehensive review of studies and trials. AJNR Am J Neuroradiol 2009 April 22, 2009: ajnr.a Gralla J, Brekenfeld C, Arnold M, et al. Acute stroke: Present and future of catheter-based interventions. Herz 2008; 33 (7): Smith WS, Sung G, Saver J, et al. Mechanical thrombectomy for acute ischemic stroke: Final results of the multi MERCI Trial. Stroke 2008; 39 (4): Bose A, Henkes H, Alfke K, et al. The penumbra system: A mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol 2008; 29 (7): Nogueira RG, Schwamm LH, Hirsch JA. Endovascular approaches to acute stroke, Part 1: Drugs, devices, and data. AJNR Am J Neuroradiol 2009; 30 (4): Josephson SA, Saver JL, Smith WS; Merci and Multi Merci Investigators. Comparison of mechanical embolectomy and intra-arterial thrombolysis in acute ischemic stroke within the MCA: MERCI and Multi MERCI compared to PROACT II. Neurocrit Care 2009; 10 (1): Lyden PM, Brott TM, Tilley BP, et al. Improved reliability of the NIH stroke scale using video training. Stroke 1994; 25 (11): Nakano S, Iseda T, Yoneyama T, et al. Early CT signs in patients with acute middle cerebral artery occlusion: incidence of contrast staining and hemorrhagic transformations after intra-arterial reperfusion therapy. Clin Imaging 2006; 30 (4): Srinivasan A, Goyal M, Azri FA, et al. State-of-the-art imaging of acute stroke. Radiographics 2006; 26 (suppl_1): S75 95.