The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2016 Ó 2016 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter http://dx.doi.org/10.1016/j.jemermed.2016.06.016 Selected Topics: Neurological Emergencies ISCHEMIC STROKE AFTER WASP STING Ashish Kulhari, MD, Ashley Rogers, MD, Han Wang, MD, Vishakhadatta Mathur Kumaraswamy, MD, Wei Xiong, MD, and Michael DeGeorgia, MD Department of Neurology, University Hospitals Case Medical Center, Cleveland, Ohio Corresponding Address: Michael DeGeorgia, MD, Director, Neurocritical Care Center, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106 , Abstract—Background: Despite the common occurrence of hymenopteran stings worldwide, primary neurologic manifestations including stroke are rare. We report a case of a healthy male who developed a right middle cerebral artery (MCA) territory ischemic stroke after getting stung by a wasp. Case Report: A 44-year-old man with hypertension presented to the hospital with sudden-onset left hemiparesis, left facial weakness, and dysarthria after being stung by a wasp. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain revealed a right MCA territory infarct and a lack of flow in the distal right internal carotid artery and MCA. He was treated with intravenous tissue plasminogen activator. A computed tomography angiography scan of the brain performed 24 hours later revealed multiple regions of vasoconstriction in the territory of the bilateral MCA. Evaluations for causes of stroke, including echocardiography and telemetry, were not revealing. Immunologic testing showed significantly elevated levels of serum wasp immunoglobulin E. Therapy with aspirin and atorvastatin was started. At discharge, the patient had a mild left facial droop but normal strength in his left arm and leg. Why Should an Emergency Physician Be Aware of This?: Emergency physicians encounter large numbers of hymenopteran sting cases each year. These patients typically present with local reactions, such as itching, pain, and erythema. Systemic manifestations, such as anaphylaxis causing severe hypotension and bronchospasm, are less common but deadly. Neurologic complications, such as ischemic stroke, are extremely rare. This manuscript highlights the pathophysiology and management of stroke after a hymenopteran sting. There are no guidelines for the management of stroke after a hymenopteran sting, and therefore we intend to provide some guidance to physicians for treating stroke after a hymenopteran sting. Ó 2016 Elsevier Inc. All rights reserved. , Keywords—ischemic; stroke; wasp INTRODUCTION Hymenopterans—the ‘‘membrane-winged’’ insects that include ants, sawflies, bees, and wasps—cause nearly 100 million stings worldwide every year (1). Local reactions, such as itching, edema, pain, and erythema, are common. Systemic manifestations, such as urticaria, flushing, vomiting, diarrhea, and anaphylaxis causing severe hypotension and bronchospasm, are less common but deadly. Neurologic complications, such as ischemic stroke, are extremely rare; 13 cases of ischemic stroke after a bee or wasp sting have been published (Table 1). Previous case reports show that the timing of stroke ranges from <1 an hour to 24 hours after the sting. In most of these reported cases, the patient received multiple stings. There are no specific risk factors for stroke after bee or wasp stings, but all patients typically experience localized or systemic reactions before the stroke (2–14). Reprints are not available from the authors. RECEIVED: 26 February 2016; FINAL SUBMISSION RECEIVED: 4 May 2016; ACCEPTED: 4 June 2016 1 Author Age/Sex Sting Type and Location Onset of Deficits 2 Table 1. Case Reports of Ischemic Stroke after Bee/Wasp Sting Clinical Findings MRI/CT Findings Headache, right hemiplegia, seizure, and coma Right hemiplegia and global aphasia Dysarthria and left hemiparesis within few hours; quadriparesis and obtundation after 24 days NR; necropsy showed left hemorrhagic cortical infarct Left MCA infarct with left ICA occlusion Three small infarcts in right MCA territory; 24 days later, diffuse bilateral ischemic white matter lesions in left parietal and insula Left occipital infarct 36/M Wasp: multiple; neck, face, and arms <1 hour Riggs et al (3) 38/M 2 days Riggs et al (4) 52/M Wasp: multiple; face and neck Wasp: single; location not recorded Crawley and Schon (5) 30/F Wasp: single; left arm <1 hour Vision loss Bhat et al (6) 35/M Bee: multiple; all over body <1 day Sciffman et al (7) 57/F Honey bee: multiple; neck, face and arm 2 days Taurin et al (8) Temizoz et al (9) 36/M Wasp: location NR 14 days 60/M Bee: multiple; head face and limbs 2 hours Dysarthria, vertigo, tinnitus, and bilateral cerebellar signs Left homonymous hemianopia and nausea and vomiting Nystagmus and nausea and vomiting Left hemiplegia and dysarthria Dechyapirom et al (10) 64/M 16 hours Left hemiplegia and facial nerve palsy Rajendiran et al (11) 25/M Bee: multiple; face, neck, chest, and arms Bee: multiple; head and neck 1 day Left arm weakness and blurry vision Viswanathan et al (12) 59/M 2.5 hours Bilir et al (13) 35/M Dysarthria, left hemiplegia, left facial weakness, and left gaze palsy Right hemiparesis Left MCA infarct Wani et al (14) 40/M Left hemiplegia, left gaze preference, and obtundation Bilateral thalami and left parieto-occipital infarct Bee: multiple; face, neck, scalp, and anterior aspect of chest Bee: multiple; NR Wasp: multiple; face, head, and neck A few hours, with worsening 24 days later 6 hours 1 day Recovery Antihistamines, cortisone, and phenobarbital NR Died Epinephrine, methylprednisolone, and diphenhydramine NR Epinephrine, hydrocortisone, and chlorpheniramine Dexamethasone, antihistamines, and mannitol Antihistamines and antiemetics Full recovery Left dorsal medulla infarct Bilateral frontal lobe infarcts, right temporoparietal and bilateral centrum semiovale infarct Right MCA territory infarct Methyl-prednisolone Improved Epinephrine, pheniramine, hydrocortisone, chlorpheniramine, and aspirin Promethazine, methylprednisolone, and t-PA Mild left-sided hemiparesis Right frontoparietooccipital infarct with hemorrhagic transformation Right MCA territory infarct Antihistamines and antiemetics Full recovery Antihistamines, hydrocortisone, aspirin, atorvastatin, and heparin Adrenaline, methylprednisolone, and ranitidine Chlorpheniramine and hydrocortisone Left strength 4+/5 and resolution of facial palsy Bilateral cerebellar hemorrhagic infarct Right occipital infarct NR Died Left homonymous hemianopia Recovered Residual right hemiparesis Vegetative state (Continued ) A. Kulhari et al. Day (2) Treatment CT = computed tomography; F = female; ICA = internal carotid artery; M = male; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; NR = not reported; t-PA = tissue plasminogen activator. t-PA, aspirin and atorvastatin Multiple right MCA territory infarcts, MRA no signal in distal right ICA and MCA Left hemiplegia and mild dysarthria 1 hour Wasp: single; leg 44/M Current case Treatment MRI/CT Findings Clinical Findings Onset of Deficits Sting Type and Location Age/Sex Author Table 1. Continued Mild left face droop 3 Recovery 2: CASE REPORT A 44-year-old right-handed white man with a history of mild hypertension was working outside when a wasp stung him on his leg. He acutely developed a diffuse rash and urticaria but had no cardiorespiratory symptoms. Approximately 1 hour late, he developed left hemiplegia, a left facial droop, and dysarthria and was taken to the emergency department (ED) by ambulance. By the time he reached the ED, his symptoms were starting to improve. On examination, he had left hemiparesis (Medical Research Council score of 4+/5), mild left facial weakness (upper motor neuron pattern), and mild dysarthria with a calculated National Institutes of Health Stroke Scale score of 4. Initial vital signs revealed hypertension that was probably caused by cerebral autoregulation in response to ischemia. His blood pressure was 146/116 mm Hg, his heart rate was 85 beats/min, his respiratory rate was 20 breaths/min, and his oxygen saturation was 100% on room air. Routine laboratory examinations were normal. His electrocardiogram revealed a normal sinus rhythm. A noncontrast computed topography (CT) scan of his head was normal. A magnetic resonance imaging (MRI) scan of the brain, however, showed multiple areas of diffusion restriction in the territory of the right MCA involving both cortical and deep structures (Figure 1). An intracranial magnetic resonance angiography (MRA) scan revealed a lack of signal in the distal right internal carotid artery (ICA) and MCA that was suggestive of either an occlusion from a thrombus or a critical stenosis (Figure 2). An extracranial MRA scan was normal. He was still within 4.5 hours after the onset of symptoms and was therefore treated with intravenous tissue plasminogen activator (t-PA). Because of his low National Institutes of Health Stroke Scale score, endovascular intervention was not pursued. He was treated with intravenous steroids and histamine antagonists for systemic allergic response. A computed tomography angiography scan of the head performed 24 hours later showed multiple regions of vasoconstriction in the bilateral proximal MCA arteries (Figure 3). After the results of the CTA scan of the head, we considered that the distal right ICA cut-off seen on the MRA scan was caused by severe vasoconstriction of the proximal right MCA interrupting the laminar flow of blood. Evaluation for causes of stroke, including echocardiography, telemetry, and a lipid panel, were not revealing. Aspirin and atorvastatin were started for secondary stroke prevention. Immunologic testing revealed significantly elevated levels of serum wasp immunoglobulin E. At discharge, 2 days after admission, a mild left facial droop remained but he had normal strength in his left arm and leg. 4 A. Kulhari et al. Figure 1. Magnetic resonance imaging scan of the brain showing diffusion restriction in the territory of the right middle cerebral artery involving both the cortical and subcortical structures, which is suggestive of acute infarct. DISCUSSION The pathophysiology of wasp sting injury stems from both direct toxic effects from the wasp venom and severe allergic reactions (15–18). Allergic reactions are mainly caused by phospholipase, an enzyme in the venom (18). Vascular pathologies, such as ischemic stroke, are primarily manifestations of the toxic effects of venom. Wasp venom contains vasoactive peptides, such as thromboxane, leukotrienes, serotonin, and histamine, which cause vasoconstriction of cerebral vessels, leading to ischemic stroke (17). These vasoactive peptides are also prothrombotic and proinflammatory and can lead to thrombus formation (18). We believe that the mechanism of stroke in our patient was cerebral vasoconstriction caused by the vasoactive peptides. In addition, after wasp stings, patients can develop paroxysmal atrial fibrillation, which can cause cardioembolic cerebral infarcts (14). Finally, severe hypotension during anaphylaxis after a wasp sting can also contribute to ischemic stroke (14). In addition to stroke, other systemic complications, including cardiac dysrhythmias, myocardial infarction, acute tubular necrosis, renal failure, hemolysis, rhabdomyolysis, and disseminated intravascular coagulation can also occur (10). Management of bee or wasp stings starts with airway, breathing, and circulation stabilization. Antihistamines, steroids, and epinephrine are used to control the allergic response. There are no guidelines for the management of ischemic stroke after such stings because of the limited number of cases. Our patient was young with significant neurologic deficits, and we therefore treated him with Figure 2. Intracranial magnetic resonance angiography scan (arrows) showing the lack of signal in the distal right internal carotid and middle cerebral arteries, which is suggestive of a critical stenosis or occlusion. 2: 5 Figure 3. Computed tomography angiography scan of the head (arrows) showing multiple regions of vasoconstriction in the bilateral M1 segment of the middle cerebral artery. intravenous t-PA. He fortunately had a good outcome. Because these patients can develop severe cerebral vasoconstriction, their intravascular volumes and hemodynamic statuses should be closely monitored. We believe that aggressive blood pressure augmentation and fluid resuscitation is important in these patients, especially if the mechanism of stroke is cerebral vasoconstriction or anaphylaxis. We also believe that steroids and antihistamines play a pivotal role in preventing cerebral vasoconstriction by reducing the intravascular inflammation caused by the vasoactive peptides present in the wasp venom. Therefore, we think it is safe to treat these patients with intravenous steroids and antihistamines. flushing, vomiting, diarrhea, and anaphylaxis causing severe hypotension and bronchospasm, are less common but deadly. Neurologic complications, such as ischemic stroke after a wasp sting, are rare but may occur and can be caused by both allergic and toxic reactions to wasp venom. While there are no specific guidelines for the management of ischemic stroke in this setting, treatment with intravenous t-PA is reasonable if there are no contraindications. Because the pathophysiology also involves cerebral vasoconstriction, careful attention to intravascular volume and hemodynamic status is important. Steroids and antihistamines may also play a pivotal role in preventing cerebral vasoconstriction. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? REFERENCES Emergency physicians encounter large numbers of hymenopteran stings every year. These patients typically present with local reactions, such as itching, edema, pain, and erythema. Systemic manifestations, such as urticaria, 1. Sundaramoorthy K, Vishwanathan S, Arulneyam J. 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