key: cord-0924617-xq53xosf
authors: Iqbal, Yousaf; Haddad, Peter M; Latoo, Javed; Alhatou, Mohammed Ibrahim; Alabdulla, Majid
title: Ischaemic stroke as the presenting feature of COVID-19: a series of three cases from Qatar
date: 2021-03-08
journal: Oxf Med Case Reports
DOI: 10.1093/omcr/omab006
sha: 135df796780ad8df1d180b5659c1a301328ff235
doc_id: 924617
cord_uid: xq53xosf

Most cases of stroke associated with coronavirus disease 2019 (COVID-19) occur during the course of a characteristic COVID-19 respiratory illness. We report three patients where the presenting feature of COVID-19 was stroke. Two patients had no respiratory symptoms throughout their clinical course. In each case, COVID-19 was confirmed by a reverse transcription polymerase chain reaction (RT-PCR) test and the diagnosis of ischaemic stroke by brain imaging. The patients were relatively young (40, 45 and 50 years). None had a prior history of cerebrovascular events. Stroke risk factors were absent in one, limited to overweight and smoking in another but more prominent in the third patient. Two patients had large vessel occlusion and elevated D-dimer levels. Multiple infarcts were seen in two patients. Clinicians should consider the possibility of COVID-19 in patients presenting with stroke and conversely consider investigating for stroke if a patient with COVID-19, even if mildly ill, develops acute neurological symptoms.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It typically presents with respiratory symptoms, but many systems can be involved [1] . A retrospective analysis of hospital patients in Wuhan, China conducted early in the pandemic showed a wide range of neurological complications including central and peripheral nervous system manifestations and skeletal muscular injury [2] . Since then, neurological and neuropsychiatric features, including stroke, have been increasingly recognized [3] . A study from New York reported that 0.9% of hospitalized patients with COVID-19 suffered a radiologically proven ischaemic stroke [4] . An earlier study from China reported a higher incidence of stroke (4.6%) [5] . In the New York study, the median age of the stroke patients was 62.5 years and the median time between onset of first COVID-19 symptoms and stroke was 10 days [4] .

We report three cases seen in Qatar where stroke was the presenting feature of COVID-19. All three patients were taken by ambulance to the Emergency Department of a major hospital, with a tertiary stroke centre, in Doha, the capital of Qatar. The time between the onset of neurological symptoms and arrival at hospital was no more than a few hours. In all cases COVID-19 was diagnosed by a reverse transcription polymerase chain reaction (RT-PCR) test and stroke was confirmed by brain imaging. Clinical features are summarized in Table 1 and below. One patient was diagnosed with diabetes and hypertension during his admission (case 3). Risk factors for stroke were absent in another (case 2) and limited to smoking and overweight in the third (case 1). All three patients had normal echocardiograms and electrocardiograms (ECGs) showed no significant abnormalities. All received comprehensive care from the multidisciplinary stroke team. None received thrombolysis or thrombectomy. All three patients had neuropsychiatric features and two received input from the psychiatric consultation-liaison team (Table 1) .

A 45-year-old man presented with a sudden onset of generalized tonic-clonic seizures, dysarthria, right-sided facial weakness, weakness of the left side of the body and confusion. He had a recent COVID-19 exposure. On admission, a COVID-19 PRC test was positive. Computer tomography (CT) brain showed a right posterior cerebral artery (PCA) territory infarct. CT angiogram showed occluded P2 segment of right PCA and absent nonopacified intracranial right vertebral artery. Subsequent magnetic resonance imaging (MRI) confirmed the right-sided PCA infarct but showed additional right pontine paramedian, left cerebellar, right superior cerebellar artery (SCA) and left-sided middle cerebral artery (MCA) territory acute infarcts (see Fig. 1 ). He required intubation and treatment for COVID-19 and aspiration pneumonia. Subsequently he experienced a prolonged period of delirium. His clinical course was marked by multiple generalized tonic-clonic seizures that required treatment with levetiracetam.

A 50-year-old man was admitted following sudden onset of left-sided weakness, confusion and agitation. He had decreased level of consciousness, left hemianopia, left upper and lower limb weakness and sensory loss. CT showed a right MCA territory acute infarct (see Fig. 2 ), right proximal internal carotid artery (ICA) severe stenosis and severe stenosis/occlusion of M2 branches of right MCA. He had no respiratory symptoms, but chest X-ray showed bilateral apical pulmonary ground glass opacities. He tested positive for COVID-19 (PRC test). He developed a pulmonary embolism 3 weeks post-admission. MRI brain performed on Day 54 confirmed the right MCA distribution stroke with subacute extension. His clinical course was complicated by delirium.

A 40-year-old man presented with a sudden onset facial dropping, slurred speech, left arm weakness, confusion and focal facial seizures. A week earlier, he had tested positive for COVID-19 but was asymptomatic other than having a mild fever. CT brain showed a hypodense lesion in the right frontal region suggestive of small acute infarct. MRI brain showed multiple small acute frontal strokes (see Fig. 3 ) with focal meningeal enhancement suggestive of an underlying vasculitis. Subsequent MRI showed another infarct in the posterior limb of the internal capsule. He was commenced on levetiracetam for focal seizures. At presentation he has was diagnosed with diabetes and hypertension which were brought under control with treatment. 

Receiving inpatient rehabilitation Full recovery. Discharged home 1 Other stroke risk factors refers to any of the following: atrial fibrillation, diabetes, hypertension, hyperlipidaemia or past history of stroke, transient ischaemic attack or myocardial infarction. 2 Case 1 and 2 received additional input from the consultation-liaison psychiatry team to assist with the management of delirium and behavioural disturbance. 3 For secondary stroke prevention. 4 To treat seizures. Figures 3A and 3B : FLAIR axial image. Two small right frontal subcortical T2 hyperintensities, one seen in A and the second in B.

Most cases of stroke associated with COVID-19 occur during the course of a characteristic COVID-19 respiratory illness [4] . The three cases we report are unusual in several regards. First, in all three cases the presenting feature that led to admission was stroke. Furthermore, prior to the onset of stroke symptoms, symptoms of COVID-19 were absent in two cases (case 1 and 2) and restricted to a mild fever in the remaining patient (case 3). Stroke has previously been reported to be the presenting feature of COVID-19 [6] . Second, two patients (case 2 and 3) had no respiratory symptoms throughout their clinical course. Third, the patients were relatively young being aged between 40 and 50 years. This partly reflects the demographics of Qatar; nearly 90% of the population are foreign workers and the median age of the population is 32 years [7] . Nevertheless, other countries are recognizing that younger patients with COVID-19 can suffer strokes [8, 9] . We cannot prove the strokes were causally linked to COVID-19 but the young age, the absent/limited risk factors for stroke in two cases (cases 1 and 2) and the close temporal association of stroke and a positive COVID-19 PCR test are highly suggestive. Potential mechanisms for ischemic strokes in COVID-19 patients include a hypercoagulable state, vasculitis and cardiomyopathy [10] . Hypercoagulability reflects elevated plasma prothrombotic factors including von Willebrand factor (vWF), factor VIII, Ddimer, fibrinogen and anionic phospholipids and increased inflammatory cytokines (cytokine storm) [11] . Data are conflicting regarding whether anti-phospholipid antibodies (aPLs) also play a role in COVID-19 coagulopathy [12, 13] . Case 1 and case 2 involved large vessel occlusion. This could reflect in situ thrombosis but embolization due to hypercoagulability state or from an intracardiac thrombus is more probable [10] . The elevated D-dimer level in these two patients is consistent with hypercoagulability and may reflect the effect of pro-inflammatory cytokines. Hypercoagulability may have implications for offering more aggressive anticoagulant treatment for ischaemic stroke but needs to be balanced against potential risk of bleeding. The brain imaging in case 3 suggested multiple acute infarcts secondary to vasculitis.

In summary, ischaemic stroke can be the presenting feature of COVID-19. This can occur in young otherwise healthy individuals and in the absence of COVID-19 respiratory symptoms. Consequently, the possibility of COVID-19 infection needs to be considered in patients who present with stroke. The corollary is that investigations for stroke need to be considered in patients with COVID-19 illness, even if mild, who develop acute neurological symptoms [9] . These recommendations apply to young as well as older patients.

COVID-19 diagnosis and management: a comprehensive review

Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UKwide surveillance study

SARS-CoV-2 and stroke in a New York healthcare system

Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study

COVID-19 presenting as stroke

Worldometer Qatar population

Outcomes and spectrum of major neurovascular events among COVID-19 patients: a 3-center experience

COVID-19 related stroke in young individuals

Mechanisms of stroke in COVID-19

Current overview on hypercoagulability in COVID-19

Presence of antiphospholipid antibodies in COVID-19: case series study

A reality check on Antiphospholipid antibodies in COVID-19-associated coagulopathy

We thank the patients/next of kin for consenting to their cases being reported.

Nil.

P.M.H. reports personal fees from Janssen, Lundbeck, Otsuka, NewBridge Pharmaceuticals and Sunovion, outside the submitted work. The other authors report no conflicts of interest.

Ethical approval to report these cases was obtained from the Medical Research Center at Hamad Medical Corporation (MRC-04-20-831).

Written informed consent was obtained from two patients and next of kin for the third patient who was unable to give consent.

Dr Yousaf Iqbal.

All authors have been involved in all stages of the preparation of this case report and they have all read and approved the final version of this report.