key: cord-0972738-j4x4w30v authors: Diaz-Segarra, Nicole; Edmond, Arline; Kunac, Anastasia; Yonclas, Peter title: COVID-19 Ischemic Strokes as an Emerging Rehabilitation Population: A Case Series date: 2020-07-15 journal: Am J Phys Med Rehabil DOI: 10.1097/phm.0000000000001532 sha: 98c929892fee60f0f02a537312bc6a9646aed95c doc_id: 972738 cord_uid: j4x4w30v There is emerging literature that coronavirus disease of 2019 (COVID-19) infections result in an increased incidence of thrombosis secondary to a prothrombotic state. Initial studies reported ischemic strokes primarily occurring in the critically ill COVID-19 population. However, there have been reports of ischemic strokes as the presenting symptom in young non-critically ill COVID-19 patients without significant risk factors. Further characterization of the COVID-19 stroke population is needed. We present four cases of COVID-19 ischemic strokes occurring in patients 37 to 68 years of age with varying COVID-19 infection severities, premorbid risk factors, clinical presentations (e.g. focal and non-focal), and vascular distributions. These cases highlight the heterogeneity of COVID-19 ischemic strokes. The duration of the COVID-19 related prothrombotic state is unknown and it is unclear if patients are at risk for recurrent strokes. With more COVID-19 patients recovering and being discharged to rehabilitation, physiatric awareness of this prothrombotic state and increased incidence of ischemic strokes is essential. Due to the variable presentation of COVID-19 ischemic strokes, clinicians can consider neuroimaging as part of the evaluation in COVID-19 patients with either acute focal or non-focal neurologic symptoms. Additional studies are needed to clarify prothrombotic state duration, determine prognosis for recovery, and establish the physiatrist’s role in long term disease management. The coronavirus disease of 2019 (COVID-19) is an illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has resulted in 7,273,958 cases and 413,372 deaths worldwide as of June 11 th , 2020. 1 Commonly encountered symptoms include cough, fever, myalgia, and fatigue. More severe infections can lead to pneumonia, acute respiratory distress syndrome (ARDS), and multi-system organ failure. 2 Recent studies have reported an increased incidence of thrombosis associated with COVID-19 infections. [2] [3] [4] It is currently unknown if this prothrombotic state is due to the virus itself, a cytokine storm with resulting systemic inflammatory response, or endovascular dysfunction. 3 The most common thrombotic complication is pulmonary embolism, accounting for 87% of thrombotic events. 4 However, there have been increasing reports of ischemic strokes occurring with COVID-19 infections that may be part of the hypercoagulable spectrum of this disease. 2, [4] [5] [6] [7] [8] [9] Infection with severe acute respiratory syndrome (SARS), a closely related coronavirus, has been associated with large vessel ischemic strokes in 2.4% of cases. 10 Initial studies showed that neurologic symptoms were a feature of COVID-19 infections, with ischemic strokes reported in 3-5% of hospitalized patients, primarily occurring in the critically ill. 2, 8 However, there have been increasing reports of COVID-19 ischemic strokes as the presenting symptom in young noncritically ill patients without significant risk factors. [5] [6] [7] 9 Further characterization of COVID-19 ischemic stroke patients is needed to elucidate pathophysiology, identify risk factors, and develop management strategies. We present four patients who developed acute ischemic strokes during the course of their COVID-19 infection ( Table 1 ). The first case was a 54-year-old male with undiagnosed hypertension who Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. presented with dysarthria, hemiparesis, and decreased level of consciousness, found to have sustained basilar and right superior cerebellar artery infarctions ( Figure 1A ). The second case was a 37-year-old male with undiagnosed type 2 diabetes who presented with aphasia, hemiparesis, and hemi-sensory loss, found to have a left middle cerebral artery infarction ( Figure 1B ). The third case was a 65-year-old male with undiagnosed type 2 diabetes who presented after a motor vehicle accident with altered mental status and respiratory distress, subsequently requiring intubation due to COVID-19 related ARDS. Initial neuroimaging showed no acute intracranial abnormalities. He was unresponsive when sedation was held on hospital day four and magnetic resonance imaging (MRI) showed bilateral multifocal subcortical infarctions ( Figure 1C ). The fourth case was a 68year-old female with a history of hypertension and diabetes with COVID-19 respiratory symptoms, who required intubation due to ARDS. She developed septic shock, multi-system organ failure, and decreased command following on hospital day eight, with MRI showing a right posterior cerebral artery infarction ( Figure 1D ). None of the patients had a history of smoking, illicit drug use, or alcohol abuse. All patients had elevated ferritin, fibrinogen, c-reactive protein (CRP), and d-dimer levels. Stroke treatment included mechanical thrombectomy, intravenous tissue plasminogen activator, and/or aspirin. Computed tomography angiography (CTA) of the head and neck showed no significant atherosclerosis, stenosis, or dissections. Cardiac telemetry showed either normal sinus rhythm or sinus tachycardia. Echocardiograms performed showed no vegetations or thrombi. Patient outcomes varied including death, discharge home, or discharge to rehabilitation. COVID-19 ischemic strokes are poorly understood with multiple proposed mechanisms for associated neurologic manifestations. Coronaviruses, including COVID-19, are thought to have Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. direct neuroinvasive properties resulting in symptoms including encephalopathy and seizures. 2, 10 However, the relationship between the development of ischemic strokes and the neuroinvasive properties is unclear. Recent literature suggests a prothrombotic state is the more likely mechanism. 7 Autopsy findings of COVID-19 patients showed pulmonary thrombotic microangiopathy on histological evaluation. 11 While brain tissue was not evaluated, a similar process of thrombi formation is possible within the cerebral vasculature. In addition, coagulation cascade and inflammatory marker abnormalities seen in COVID-19 patients, such as elevated CRP, ferritin, d-dimer and fibrinogen levels, reflect a prothrombotic state. 3 These findings, present in the aforementioned cases, may have contributed to the development of COVID-19 ischemic strokes. Interestingly, the prothrombin time (PT) can be paradoxically prolonged in COVID-19 patients, as seen in these four cases. 3 However, the association between the prolonged PT and the prothrombotic state is currently unclear. infarctions, seen in case one, were less frequently reported. 7, 9 In addition, there have been documented cases of multifocal strokes occurring in critically ill COVID-19 patients, as seen in case three. 9 Medical histories varied among the previously reported cases with all currently presented cases having either premorbid or undiagnosed medical conditions including diabetes or hypertension. [5] [6] [7] 10 Our cases detailed two non-critically ill patients less than 55 years of age who presented to the hospital due to stroke symptoms, compared to the two critically ill patients greater than 55 years of age who developed strokes during their hospitalization. The first and second cases had focal neurologic defects that were consistent with the involved vascular distributions. However, cases three and four experienced non-focal, encephalopathic manifestations that led to additional neuroimaging and subsequent stroke diagnosis. The current cases also highlight the wide age range of patients susceptible to COVID-19 ischemic strokes, consistent with the current literature. [5] [6] [7] 9 Conclusion With more recovering COVID-19 patients being transferred to post-acute care, physiatric knowledge of increased thrombotic risk in this population is essential. Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Fibrinogen, 145-490 mg/dL; D-dimer, 90-500 ng/ml FEU; Ferritin, 30-400 ng/ml; Lactate dehydrogenase, 120-250u/l; C-reactive protein, 0-5 mg/L. § Minimum and maximum laboratory values as ordered during the patient's hospital course. Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. World Health Organization. Coronavirus disease 2019 (COVID-19) siutation-report-143 Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young Coexistence of Covid-19 and Acute Ischemic Stroke Report of Four Cases COVID-19 presenting as stroke