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Covid-19 Cases

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

Published April 28, 2020
N Engl J Med 2020;382: e60
DOI: 10.1056/NEJMc2009787
To rapidly communicate information on the global clinical effort against Covid-19, the Journal has initiated a series of case reports that offer important teaching points or novel findings. The case reports should be viewed as observations rather than as recommendations for evaluation or treatment. In the interest of timeliness, these reports are evaluated by in-house editors, with peer review reserved for key points as needed.
We report five cases of large-vessel stroke in patients younger than 50 years of age who presented to our health system in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all five patients.
Cough, headache, and chills lasting 1 week developed in a previously healthy 33-year-old woman (Patient 1) (Table 1). She then had progressive dysarthria with both numbness and weakness in the left arm and left leg over a period of 28 hours. She delayed seeking emergency care because of fear of Covid-19. When she presented to the hospital, the score on the National Institutes of Health Stroke Scale (NIHSS) was 19 (scores range from 0 to 42, with higher numbers indicating greater stroke severity), and computed tomography (CT) and CT angiography showed a partial infarction of the right middle cerebral artery with a partially occlusive thrombus in the right carotid artery at the cervical bifurcation. Patchy ground-glass opacities in bilateral lung apices were seen on CT angiography, and testing to detect SARS-CoV-2 was positive. Antiplatelet therapy was initiated; it was subsequently switched to anticoagulation therapy. Stroke workup with echocardiography and magnetic resonance imaging of the head and neck did not reveal the source of the thrombus. Repeat CT angiography on hospital day 10 showed complete resolution of the thrombus, and the patient was discharged to a rehabilitation facility.
Table 1
Variable Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Age — yr 33 37 39 44 49
Sex Female Male Male Male Male
Medical history and risk factors for stroke None None Hyperlipidemia, hypertension Undiagnosed diabetes Mild stroke, diabetes
Medications None None None None Aspirin (81 mg),
atorvastatin (80 mg)
NIHSS score          
On admission 19 13 16 23 13
At 24 hr 17 11 4 19 11
At last follow-up 13
(on day 14)
5
(on day 10)
NA; intubated and sedated, with multiorgan failure 19
(on day 12)
7
(on day 4)
Outcome status Discharged to
rehabilitation facility
Discharged home Intensive care unit Stroke unit Discharged to
rehabilitation facility
Time to presentation — hr 28 16 8 2 8
Signs and symptoms of stroke Hemiplegia on left side, facial droop, gaze preference, homonymous hemianopia, dysarthria, sensory deficit Reduced level of consciousness, dysphasia, hemiplegia on right side, dysarthria, sensory deficit Reduced level of consciousness, gaze preference to the right, left homonymous hemianopia, hemiplegia on left side, ataxia Reduced level of consciousness, global dysphasia, hemiplegia on right side, gaze preference Reduced level of consciousness, hemiplegia on left side, dysarthria, facial weakness
Vascular territory Right internal carotid artery Left middle cerebral artery Right posterior cerebral artery Left middle cerebral artery Right middle cerebral artery
Imaging for diagnosis CT, CTA, CTP, MRI CT, CTA, MRI CT, CTA, CTP, MRI CT, CTA, MRI CT, CTA, CTP
Treatment for stroke Apixaban (5 mg twice daily) Clot retrieval, apixaban (5 mg twice daily) Clot retrieval, aspirin (81 mg daily) Intravenous t-PA, clot retrieval, hemicraniectomy, aspirin (81 mg daily) Clot retrieval, stent, aspirin (325 mg daily), clopidogrel (75 mg daily)
Covid-19 symptoms Cough, headache, chills No symptoms; recently exposed to family member with PCR-positive Covid-19 None Lethargy Fever, cough, lethargy
White-cell count — per mm3 7800 9900 5500 9000 4900
Platelet count — per mm3 427,000 299,000 135,000 372,000 255,000
Prothrombin time — sec 13.3 13.4 14.4 12.8 15.2
Activated partial-thromboplastin time — sec 25.0 42.7 27.7 26.9 37.0
Fibrinogen — mg/dl 501 370 739 443 531
d-dimer — ng/ml 460 52 2230 13,800 1750
Ferritin — ng/ml 7 136 1564 987 596
Clinical Characteristics of Five Young Patients Presenting with Large-Vessel Stroke.*
*
Reference ranges are as follows: platelet count, 150,000 to 450,000 per cubic millimeter; prothrombin time, 12.3 to 14.9 seconds; activated partial-thromboplastin time, 25.4 to 34.9 seconds; fibrinogen, 175 to 450 mg per deciliter; d-dimer, 0 to 500 ng per milliliter; and ferritin, 30 to 400 ng per milliliter. CT denotes computed tomography, CTA CT angiography, CTP CT perfusion, MRI magnetic resonance imaging, NA not applicable, PCR polymerase chain reaction, and t-PA tissue plasminogen activator.
The patients were screened for smoking, hypertension, hyperlipidemia, diabetes, atrial fibrillation, congestive heart failure, illicit drug use, and neck trauma.
Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher numbers indicating more severe stroke.
Over a 2-week period from March 23 to April 7, 2020, a total of five patients (including the aforementioned patient) who were younger than 50 years of age presented with new-onset symptoms of large-vessel ischemic stroke. All five patients tested positive for Covid-19. By comparison, every 2 weeks over the previous 12 months, our service has treated, on average, 0.73 patients younger than 50 years of age with large-vessel stroke.
On admission of the five patients, the mean NIHSS score was 17, consistent with severe large-vessel stroke. One patient had a history of stroke. Other pertinent clinical characteristics are summarized in Table 1.
A retrospective study of data from the Covid-19 outbreak in Wuhan, China, showed that the incidence of stroke among hospitalized patients with Covid-19 was approximately 5%; the youngest patient in that series was 55 years of age.1 Moreover, large-vessel stroke was reported in association with the 2004 SARS-CoV-1 outbreak in Singapore.2 Coagulopathy and vascular endothelial dysfunction have been proposed as complications of Covid-19.3 The association between large-vessel stroke and Covid-19 in young patients requires further investigation.
Social distancing, isolation, and reluctance to present to the hospital may contribute to poor outcomes. Two patients in our series delayed calling an ambulance because they were concerned about going to a hospital during the pandemic.
Thomas J. Oxley, M.D.
J. Mocco, M.D.
Shahram Majidi, M.D.
Christopher P. Kellner, M.D. https://orcid.org/0000-0003-4604-8205
Hazem Shoirah, M.D.
I. Paul Singh, M.D.
Reade A. De Leacy, M.D.
Tomoyoshi Shigematsu, M.D. https://orcid.org/0000-0003-3463-0222
Travis R. Ladner, M.D.
Kurt A. Yaeger, M.D.
Maryna Skliut, M.D.
Jesse Weinberger, M.D.
Neha S. Dangayach, M.D.
Joshua B. Bederson, M.D.
Stanley Tuhrim, M.D.
Johanna T. Fifi, M.D.
Mount Sinai Health System, New York, NY [email protected]

Notes

This case was published on April 28, 2020, at NEJM.org.
Disclosure forms provided by the authors are available with the full text of this case at NEJM.org.
We dedicate this case to our inspiring colleague Gary Sclar, M.D., a neurologist who died of Covid-19.

Supplementary Material

Disclosure Forms (nejmc2009787_disclosures.pdf)

References

1.
Li Y, Wang M, Zhou Y, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. March 13, 2020 (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550025) (preprint).
2.
Umapathi T, Kor AC, Venketasubramanian N, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004;251:1227-1231.
3.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-1062.

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New England Journal of Medicine
eLocator: e60

History

Published online: April 28, 2020
Published in issue: May 14, 2020

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Thomas J. Oxley, M.D., J. Mocco, M.D., Shahram Majidi, M.D., Christopher P. Kellner, M.D. https://orcid.org/0000-0003-4604-8205, Hazem Shoirah, M.D., I. Paul Singh, M.D., Reade A. De Leacy, M.D., Tomoyoshi Shigematsu, M.D. https://orcid.org/0000-0003-3463-0222, Travis R. Ladner, M.D., Kurt A. Yaeger, M.D., Maryna Skliut, M.D., Jesse Weinberger, M.D., Neha S. Dangayach, M.D., Joshua B. Bederson, M.D., Stanley Tuhrim, M.D., and Johanna T. Fifi, M.D.

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Mount Sinai Health System, New York, NY
[email protected]

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