The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–3, 2017 Ó 2017 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter http://dx.doi.org/10.1016/j.jemermed.2017.01.025 Clinical Communications: Adult THE USE OF TISSUE PLASMINOGEN ACTIVATOR IN THE TREATMENT OF WALLENBERG SYNDROME CAUSED BY VERTEBRAL ARTERY DISSECTION Alexis Salerno, MD,* Bradford V. Cotter, MD,* and Michael E. Winters, MD† *Emergency Medical Services, University of Maryland Medical Center, Baltimore, Maryland and †Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland Corresponding Address: Michael E. Winters, MD, Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street, 6th Floor, Suite 200, Baltimore, MD 21201 , Abstract—Background: Acute cerebrovascular accident (CVA) is a devastating cause of patient morbidity and mortality. Up to 10% of acute CVAs in young patients are caused by dissection of the vertebral or carotid artery. Wallenberg syndrome results from a CVA in the vertebral or posterior inferior artery of the cerebellum and manifests as various degrees of cerebellar dysfunction. The administration of a thrombolytic medication has been recommended in the treatment of patients with stroke caused by cervical artery dissection. Surprisingly, there is scant literature on the use of this medication in the treatment of this condition. Case Report: We describe a 42-year-old man with the sudden onset of headache, left-sided neck pain, vomiting, nystagmus, and ataxia 1 h after completing a weightlifting routine. Computed tomography angiography revealed a grade IV left vertebral artery injury with a dissection flap extending distally and resulting in complete occlusion. Subsequent magnetic resonance imaging and angiography demonstrated acute left cerebellar and lateral medullary infarcts, consistent with Wallenberg syndrome. The patient was treated with tissue plasminogen activator, which failed to resolve his symptoms. Why Should an Emergency Physician Be Aware of This?: Emergency physicians frequently manage patients with acute CVAs. For select patients, the administration of tissue plasminogen activator can improve outcomes. However, the risk of major hemorrhage with this medication is significant. Cervical artery dissection is an important cause of acute stroke in young patients and is often missed on initial presentation. It is imperative for the emergency physician to consider acute cervical artery dissection as a cause of stroke and to be knowledgeable regarding the efficacy of thrombolytic medications for this condition. Ó 2017 Elsevier Inc. All rights reserved. , Keywords—ischemic stroke; vertebral artery dissection; Wallenberg syndrome INTRODUCTION Approximately 10% of strokes occur in patients <50 years of age (1). A common cause of stroke in younger people is vertebral artery dissection (VAD; 2). Given the low incidence of this condition, there is little guidance for the emergency department (ED) management of its acute manifestation. When the stroke occurs in the vertebral or posterior cerebellar artery of the brain stem, the resulting constellation of neurologic signs and symptoms is known as Wallenberg syndrome. It can include deficits in balance, gait, and coordination as well as hoarseness, hiccups, nystagmus, and dysphagia. Some patients have crossed signs and symptoms in relation to the location of the lesion, e.g., ipsilateral facial numbness and weakness or loss of pain and temperature sensation and contralateral arm/leg numbness or weakness (3). Thrombolytic therapy is often considered, but evidence is limited Reprints are not available from the authors. RECEIVED: 3 November 2016; FINAL SUBMISSION RECEIVED: 8 January 2017; ACCEPTED: 22 January 2017 1 2 A. Salerno et al. regarding its use for dissection-related ischemic stroke (DRIS) resulting from VAD (4). In this case report, we describe our management of a young man with acute cerebellar stroke caused by VAD. CASE REPORT A 42-year-old man was transported to the ED after acute onset of left-sided neck pain and headache, vertigo, vomiting, and ataxia. These symptoms developed 1 h after a lunchtime workout and 30 min before his ED presentation. His history was significant for hypertension, hyperlipidemia, and a right internal carotid artery pseudoaneurysm that was managed medically after a vehicle crash 7 years earlier. His current medications included lisinopril, lovastatin, and escitalopram. He was a current smoker and had a paternal family history of stroke. The patient was in moderate distress, diaphoretic, and anxious. His vital signs were blood pressure, 143/64 mm Hg; heart rate, 65 beats/min; respiratory rate, 15 breaths/ min; and pulse oximetry reading of 100% on room air. Neurologic examination was significant for leftward rotatory nystagmus, miosis/ptosis of the left eye, decreased sensation and strength along the left face, and dysmetria and positive pronator drift of the left arm. Ataxia made him unable to walk. His National Institutes of Health Stroke Scale score was 5. A computed tomography (CT) scan of his head revealed no evidence of hemorrhage. CT angiography revealed a grade IV left vertebral artery injury with a dissection flap extending distally and resulting in complete occlusion. Flow was diminished in the left posterior inferior cerebellar artery territory (Figures 1 and 2). After Figure 2. Computed tomography angiography of the head and neck (coronal view), demonstrating loss of blood flow in the left vertebral artery (arrows). consultation with a neurologist, we administered intravenous tissue plasminogen activator (tPA). The patient was admitted to the neurocritical care unit. Magnetic resonance imaging and magnetic resonance angiography scans revealed acute left cerebellar and lateral medullary infarcts, consistent with Wallenberg syndrome. The hospital course was complicated by progressive cerebral edema and hydrocephalus requiring posterior decompression and placement of an intraventricular catheter. At a subacute rehabilitation facility, he continued to exhibit ataxia, visual disturbance, and hoarseness. DISCUSSION Figure 1. Computed tomography angiography of the head and neck (transverse view), demonstrating dissection of the left vertebral artery (arrow). Thrombolytic therapy is often administered to patients with acute manifestations of DRIS, based on the assumption that it is caused by thromboembolism from the site of vessel injury, even though significant concerns remain about its risks: intraluminal shear forces, expansion of the dissection flap, and bleeding (5–8). Tsivgoulis et al. undertook a prospective study of the treatment of DRIS, with the objective of evaluating the safety and outcome of intravenous thrombolysis (7). They identified 39 patients who experienced DRIS (four with VAD) and received thrombolysis. Complete recanalization of the previously occluded vessel was achieved in Vertebral Artery Dissection about half of them (21/39 [54%]). None had evidence of symptomatic intracranial hemorrhage, but four (10%) died. Favorable functional outcome and functional independence rates were 61% and 68%, respectively. In the same article, Tsivgoulis et al. reported the results of their meta-analysis of nine articles involving 234 patients with DRIS (7). Those treated with systemic tPA demonstrated symptomatic intracranial hemorrhage, mortality, and complete recanalization rates of 2%, 4%, and 45%, respectively. Favorable outcome was associated with lower initial National Institutes of Health Stroke Scale scores and posterior circulation lesions. Overall, these patients had a favorable functional outcome rate of 41% and a functional independence rate of 61%. Engelter et al. analyzed data from a multicenter database containing clinical information from patients with cervical artery dissection and ischemic stroke (9). The 68 patients who received tPA were significantly more likely to have severe stroke (National Institutes of Health Stroke Scale score of 16 vs. 3) and complete occlusion of the dissected vessel (66% vs. 40%) than the 548 who did not. The rate of favorable 3-month outcome was significantly higher in the group that did not receive tPA (85% vs. 54%). However, when controlled for stroke severity, the groups were not significantly different. With the exception of the Engelter et al. study, most studies lacked a comparison arm and sought to support the safety of intravenous thrombolysis for DRIS. Aside from the surrogate marker of recanalization rates, current literature has yet to produce any well-controlled functional outcome data on the efficacy of thrombolysis for DRIS (4). In addition, potential complications (e.g., dissection flap extension or new thromboembolic events) and the associated increase in morbidity would likely be unappreciated by current methodologies. Many patients who present with symptoms of DRIS do not qualify for thrombolytics. As discussed by our colleagues 5 years ago, these patients could benefit from anticoagulation with intravenous heparin (10). New evidence suggests that treatment with endovascular stenting might also be an option for stroke patients and may yield better outcomes if combined with intra-arterial thrombolysis (11). Because stenting often requires interventional radiology consultation, interdepartmental communication and collaboration are necessary. It remains unclear if this patient’s VAD was spontaneous or related to an underlying genetic predisposition. An evaluation for underlying collagen vascular disease or other causal disorders was not pursued by the inpatient team. 3 WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? Emergency physicians should know the symptoms of dissection-related ischemic stroke (i.e., vertigo, diplopia, and dysarthria) and should be knowledgeable about its treatment (10). Dissection of the vertebral artery is an important cause of stroke in patients <50 years of age. Because its symptoms are caused primarily by thromboembolism, tPA is used to treat select patients; however, comparative studies have not shown better outcomes for those who receive the thrombolytic. Other treatment options are showing promise, such as combining tPA administration with endovascular stenting. Acknowledgment—The manuscript was copyedited by Linda J. Kesselring, MS, ELS. REFERENCES 1. Mozaffarian D, Benjamin EJ, Go AS, et al. Executive summary: heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 2016;133:447–54. 2. Daou B, Hammer C, Chalouhi N, et al. Dissecting pseudoaneurysms: predictors of symptom occurrence, enlargement, clinical outcome, and treatment. J Neurosurg 2016;29:1–7. 3. Wallenberg’s syndrome information page. National Institute of Neurological Disorders and Stroke. Available at: https://www. ninds.nih.gov. Accessed January 3, 2017. 4. Jauch EC, Saver JL, Adams HP Jr, et al. 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