Central Annals of Vascular Medicine & Research

Case Report *Corresponding author Anish Desai, Department of Pulmonary and Critical Care Medicine, Winthrop University Hospital, 222 A Case of Paradoxical Cerebral Station Plaza North, Suite 400, Mineola 11501, NY, USA; Tel: 001-516-663-2004; E-mail: Submitted: 31 December 2014 and Ischemic Accepted: 02 February 2015 Published: 04 February 2015 after Local Thrombolysis for Copyright © 2015 Desai et al. Deep OPEN ACCESS Anish Desai1*, Alexander Fe2, Girish B. Nair3 and Michael S. Keywords Niederman4 • DVT • Local thrombolysis 1 Department of Pulmonary and Critical Care Medicine, Winthrop University Hospital, USA • PFO 2 Department of Internal Medicine, Winthrop University Hospital, USA • Stroke 3Department of Pulmonary and Critical Care Medicine, Winthrop University Hospital, USA 4Department of Medicine, Winthrop University Hospital, USA

Abstract Case: A 68-year-old woman presented to our emergency room with subjective fevers, non-productive cough and severe pain in the right lower extremity. Of note, she had sustained a right patellar fracture 6 weeks earlier, treated with a brace. Physical examination showed right lower extremity swelling. Subsequently, she was diagnosed with extensive right deep (DVT). Local thrombolysis of the DVT was achieved by injecting tissue plasminogen activator (tpa) followed by mechanical aspiration. Immediately post procedure; the patient experienced an acute deterioration in her mental status with left hemiparesis. CT angiography of the head confirmed a right middle cerebral (MCA) ischemic stroke. Successful reperfusion was achieved by performing an emergent embolectomy in the M1 branch of the MCA. A bubble contrast transthoracic echocardiogram showed a patent foramen ovale (PFO). The patient’s neurological symptoms gradually improved and at 6 month follow up she had no focal neurological deficits. Discussion: We describe the first case of an embolic stroke complicating catheter directed thrombolysis (CDT) for DVT in patient with elevated pulmonary arterial pressure as a result of acute pulmonary emboli. Currently there are no guidelines mandating routine checks for PFOs prior to performing CDT. This case illustrates the need for high clinical vigilance for PFO in patients being evaluated for CDT and provides a unique insight into a rare complication.

ABBREVIATIONS treatment with anticoagulation, around 40-50% of patients develop post thrombotic syndrome (PTS), especially following VTE: Venous Thrombo Embolism; DVT: Deep Venous a proximal deep venous thrombosis (DVT) [2]. PTS usually Thrombosis; CDT: Catheter Directed Thrombolysis; tpa: tissue happens due to damage to the venous valves, which in turn leads plasminogen activator; PTS: Post Thrombotic Syndrome; PFO: to impedance in cephalad venous drainage. This can cause leg Patent Foramen Ovale; TOAST: Trial of Org 10172 in Acute Stroke Treatment; CT: Computed Tomographic; MCA: Middle Cerebral swelling, edema, heaviness, skin discoloration and in its most Artery; PE: ; IVC: Inferior Vena Cava; TIA: severe form, can cause chronic skin ulceration [3]. It has been Transient Ischemic Attack shown that by wearing elastic stockings, the incidence of PTS can be reduced by 50% [2], but even with this recommended INTRODUCTION Venous thrombo-embolism (VTE) is the third leading cause the incidence of PTS even further, studies have been performed treatment, one in five patients will still develop PTS. To reduce of cardiovascular mortality, after coronary artery disease and to evaluate the role of catheter directed thrombolysis (CDT). stroke [1]. The mainstay of treatment is anticoagulation, as it Several trials and small case series [4,5] have shown that CDT helps prevent formation of new clot, while allowing clot lysis by can reduce the incidence of PTS even further, but may result in the body’s own endogenous mechanisms. Even after adequate increased bleeding events, length of stayand blood transfusions.

Cite this article: Desai A, Fe A, Nair GB, Niederman MS (2015) A Case of Paradoxical Cerebral Embolism and Ischemic Stroke after Local Thrombolysis for . Ann Vasc Med Res 2(1): 1013. Desai et al. (2015) Email: Central

A paradoxical embolism occurs when venous clot passes through an intracardiac defect with a right-to-left shunt and is propagated into the arterial circulation. In general, paradoxical embolism is relatively rare, consisting of less than 2% of all arterial emboli [6,7]. Paradoxical embolism is most commonly defect, pulmonary arteriovenous malformations, and ventricular septaldue to defect an identified [8]. Most patent frequently, foramen paradoxical ovale (PFO), emboli atrial travel septal to the extremities, the brain, and less likely the coronary, renal, or splenic [8]. a paradoxical embolism resulting in ‘ischemic’ cerebro-vascular accidentHere, post we present CDT. the first reported case of a patient developing CASE PRESENTATION A 68-year-old woman presented to our emergency room with subjective fevers, dyspnea, and right leg swelling and non-productive cough of several days’ duration. Of note, she had sustained a right patellar fracture 6 weeks earlier that was Figure 1 Axial T1 weighted image demonstrating right cerebral territory infarction. history and was not takingany prescription medications. There wastreated no familywith a historybrace. Sheof thromboembolic had no other significant disease. Vitalpast signsmedical on admission were unremarkable. Physical examination showed DISCUSSION right lower extremity swelling extending up to the groin. Venous Catheter directed thrombolysis is a novel technique which Dopplerultrasound revealeddeep venous thrombosis extending permits delivery of thrombolytic locally with minimal systemic from the right common femoral vein to the proximal popliteal side effects. The catheter is introduced into the affected vein vein. Subsequently, a computed tomographic (CT) angiogram and advanced into the area of thrombosis. Thrombolytic scan of the chest showed bilateral pulmonary emboli in segmental be injected or mechanical techniques may be used tocause clot branches supplying right upper lobe, lingula and both lower lysis and aspiration, thereby requiring a much lower dose than lobes. Heparin drip was started and due to the extensive DVT, needed for systemic thrombolysis. CDT can be used in patients it was decided by the treating team to administer localized with contraindication to anticoagulation and can reduce the treatment to help reduce the clot burden. CDT with9mg of t-PA incidence of PTS. The main complications of CDT for DVT are was performed in the right common femoral vein, followed by local and distant bleeding complications, infection and local mechanical aspiration using the AngioJet system. Follow up failure with occlusion or of the vessel [5,9]. Large trials venography showed a small amount of residual in the evaluating the role of CDT [5,9] have not reported cerebro- central portion of the right femoral vein with establishment of vascular accidents, although we do not know if these patients had an associated pulmonary embolism. Three intra-cerebral bleeds were observed in a Cochrane review evaluating utility flowAbout distally. 2 minutes after administering t-PA, the patient experienced an acute deterioration in her mental status with of thrombolysis in DVT [10]. In 2 cases, streptokinase was left hemiparesis. Rapid sequence intubation was performed and administered, while in the third case - t-PA was the culprit and in the patient underwent immediate CT angiogram of her brain, all these cases thrombolysis was administered systemically via a which revealed a right middle cerebral artery (MCA) embolic peripheral vein. stroke. This was followed by magnetic resonance imaging of the We found three other cases that are somewhat related to our presented case but secondary to systemic anticoagulation for PE. territory. Successful reperfusion was achieved by performing an One case report described a patient who underwent thrombolysis brain (Figure 1) which confirmed the stroke in right cerebral emergent embolectomy in the M1 branch of the MCA along with with 40 mg alteplase for massive PE and subsequently developed administration of intra-arterial t-PA.Intravenous thrombolysis an absent left femoral pulse from paradoxical embolism to the left was contraindicated as the patient had received t-PA moments femoral artery [11]. Second case report described a patient who earlier. A 2-D echocardiogram showed elevatedright ventricular underwent thrombolysis with urokinase for PE and subsequently systolic pressure to 38 mmHg.This was followed by a bubble study developed ischemic stroke from paradoxical embolism to the right internal carotid artery [12]. Third case underwent thrombolysis by a trans-esophageal echocardiogram, that was otherwise not of a PE and subsequently developed a fatal stroke [13]. consistentwhich revealed with any a patent cardio foramen embolic ovalesource. (PFO), An inferior later confirmedvena cava A patent foramen ovale may occur in up to 27.3% of the setting of an acute ischemic stroke. She was subsequently started general population [14] and it increases the risk of recurrent onfilter heparin was inserted and warfarin as anticoagulation and was discharged was not deemed home safe after in twothe stroke [15]. Independent risk factors for development of weeks. Over the course of six months, she made good neurological paradoxical embolism in patients who develop cryptogenic recovery with no residual weakness. stroke include: a history of DVT or PE, migraine, recent prolonged

Ann Vasc Med Res 2(1): 1013 (2015) 2/3 Desai et al. (2015) Email: Central travel, sleep apnea, waking up with a transient ischemic attack 3. Kearon C. Natural history of venous thromboembolism. Circulation. (TIA) or stroke, and Valsalva maneuver prior to the event [16]. 2003; 107: I22-30. Paradoxical embolism is extremely rare after thrombolysis. 4. Bashir R, Zack CJ, Zhao H, Comerota AJ, Bove AA. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein Box -1 The criteria for diagnosis of paradoxical embolism are the thrombosis. JAMA Intern Med. 2014; 174: 1494-1501. following [7] 1. Embolism in arterial system that is not originated from the left 5. Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, et al. heart or from the arterial system itself. Long-term outcome after additional catheter-directed thrombolysis 2. Abnormal communication between the arterial and venous versus standard treatment for acute iliofemoral deep vein thrombosis systems as evidenced by imaging tests. (the CaVenTstudy): a randomised controlled trial. Lancet. 2012; 379: 3. Presence of venous thrombosis or embolism in the form of DVT or 31-8 pulmonary embolism (PE). 4. Increased right-sided pressure which contributes right to left 6. Mirarchi FL, Hecker J, Kramer CM. Pulmonary embolism complicated shunting be it transient or longstanding. by patent foramen ovale and paradoxical embolization. J Emerg Med. 5. Demonstration of a thrombus trapped in a PFO (straddling 2000; 19: 27-30. 7. Guo S, Roberts I, Missri J. Paradoxical embolism, deep vein thrombosis, paradoxical embolism. pulmonary embolism in a patient with patent foramen ovale: a case thrombus) is extremely rare but highly specific for diagnosing report. J Med Case Reports. 2007; 1: 104 8. Loscalzo J. Paradoxical embolism: clinical presentation, diagnostic ischemic stroke as a result of CDT for a pelvic DVT. We postulate strategies, and therapeutic options. Am Heart J. 1986; 112: 141-145. thatAs upon far as localized we know, CDT, this smaller is the thrombi first reported that were case broken of an 9. Baekgaard N, Broholm R, Just S, Jørgensen M, Jensen LP. Long-term off migrated through the PFO into the left atrium aided by the results using catheter-directed thrombolysis in 103 lower limbs with increased right-sided pressures, as a result of the coexisting acute iliofemoral venous thrombosis. Eur J Vasc Endovasc Surg. 2010; pulmonary emboli. This brings up the question of whether or 39: 112-117. not, clinicians should routinely check for the presence of a PFO 10. Watson L, Broderick C, Armon MP. Thrombolysis for acutedeep vein prior to thrombolysis of either a DVT or PE, or whether CDT for thrombosis. Cochrane Database Syst Rev. 2014; 23; 1: CD002783. DVT should be pursued in the presence of a PFO. We believe that, despite the rarity of developing a paradoxical embolism, it is 11. Liu YF, Bayliss M. Paradoxical embolism: a rare complication of thrombolysis. BMJ Case Rep. 2009; 2009. worthwhile to do screening echocardiography prior to pursuing CDT in hemodynamically stable patient given the multitude of 12. Carlsson J, Miketic S, Kuhn A, Brune S, Tebbe U. [Paradoxical cerebral complications associated with an ischemic stroke. pulmonary embolism]. Dtsch Med Wochenschr. 1994; 119: 222-226. embolism during fibrinolysis therapy in deep vein thrombosis and CONCLUSION 13. Bracey TS, Langrish C, Darby M, Soar J. Cerebral infarction following As experience and use of CDT increases, there is likely to be thrombolysis for massive pulmonary embolism. Resuscitation. 2006; an increased incidence of similar cases of paradoxical embolism. 68: 135-137. This case illustrates the need for high clinical vigilance for a PFO 14. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent and provides unique insight into an exceedingly rare complication resulting from a fairly common procedure. 965 normal hearts. Mayo Clin Proc. 1984; 59: 17-20. foramen ovale during the first 10 decades of life: an autopsy study of 15. Handke M, Harloff A, Olschewski M, Hetzel A, Geibel A. Patent foramen REFERENCES ovale and cryptogenic stroke in older patients. N Engl J Med. 2007; 1. Goldhaber S. Epidemiology of Pulmonary Embolism and Deep Vein 357: 2262-2268. Thrombosis, Haemostasis and Thrombosis. 3rd ed. New York, NY. 16. Ozdemir AO, Tamayo A, Munoz C, Dias B, Spence JD. Cryptogenic stroke 1994; 1327-1333. and patent foramen ovale: clinical clues to paradoxical embolism. J 2. Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E, Neurol Sci. 2008; 275: 121-127. et al. Below-knee elastic compression stockings to prevent the post- thrombotic syndrome: a randomized, controlled trial. Ann Intern Med. 2004; 141: 249-256.

Cite this article Desai A, Fe A, Nair GB, Niederman MS (2015) A Case of Paradoxical Cerebral Embolism and Ischemic Stroke after Local Thrombolysis for Deep Vein Thrombosis. Ann Vasc Med Res 2(1): 1013.

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