Advertisement

Coronavirus Positive Patients Presenting with Stroke-Like Symptoms

      Key Words

      Several studies from Wuhan, China have reported neurological manifestations in patients who tested positive for coronavirus disease 2019 (COVID-19). One study reported 214 COVID-19 positive patients, out of which 41.1% had severe infection. 5.7% of patients with severe infection had acute cerebrovascular disease.
      • Mao Ling
      • Jin Huijuan
      • Wang Mengdie
      • et al.
      Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China.
      Another study looked at 221 COVID-19 positive patients, out of which 5% had ischemic infarcts and 0.5% had cerebral hemorrhage.
      • Li Y
      • Li M
      • Wang M
      • et al.
      Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study.
      A recent study from Mount Sinai Hospital in New York reported five cases of cerebral infarcts due to large vessel occlusion in patients who tested positive for COVID-19. Several mechanisms such as vascular endothelium dysfunction and pro-inflammatory responses which can accelerate atherosclerosis and enhance coagulopathy have been proposed as potential causes for ischemic infarcts.
      • Oxley TJ
      • Mocco J
      • Majidi S
      • et al.
      Large-vessel stroke as a presenting feature of covid-19 in the young.
      Studies seem to demonstrate a relationship between COVID-19 and stroke, however further investigation is needed. This paper presents a series of patients who presented with stroke and other neurological disorders to our stroke center in Philadelphia and were found to be COVID-19 positive. The goal is to identify risk factors and potential mechanisms of stroke etiologies for this subset of patients. We reviewed various stroke patterns, lab values, and risk factors in this subset.

      Results

      The patients in this case series presented to our center from April 2020 to June 2020. The total number of stroke codes called during this time period was 127. Out of the 127 stroke codes, 2 stroke codes were called on patients who were COVID-19 positive and have been reported in our series. Seven of the stroke patients in our series were direct transfers from another hospital. The remaining two patients presented to our emergency department with symptoms lasting more than twenty four hours and therefore no stroke code was called. Most of the patients in our series were transfers from surrounding hospitals and outside the window for tPA. The high rate of outside hospital transfers seen in our case series is most likely due to higher acuity of these patients who had medical complications secondary to COVID- 19 along with stroke.
      Seventeen patients presented with stroke-like symptoms and tested positive for COVID-19 upon arrival to our hospital (Table 1). Three patients were diagnosed as seizures, two patients had subarachnoid hemorrhage (SAH), and one patient had a venous infarct. Of the remaining eleven patients, ten patients had ischemic infarcts as seen on MRI and one patient had a central retinal artery occlusion (CRAO) secondary to occlusive thrombus in the right internal carotid artery. Out of the ten patients who had imaging-confirmed ischemic strokes, five were due to large vessel occlusion, four were presumed embolic strokes, and one was a subcortical lacunar infarct thought to be related to small vessel disease. Three of the stroke patients were found to have evidence of atherosclerotic disease as seen on CTA/MRA head/neck imaging. Out of the two patients with SAH, one of them was found to have a posterior communicating artery aneurysm.
      Table 1Clinical Characteristics of Covid Positive Patients who presented with Stroke-Like Symptoms
      PatientAgeSexMedical HistoryDiagnosisInitial NIHSSStroke PatternVascular Territory InvolvedIV-tPAThrombectomyAtherosclerosis in Stroke TerritoryAntithrombotic AgentCovid-19 SymptomsWBC (per mm3)Platelet (B/L)INRD-dimer (ng/ml)DispositionCause of Death
      155MHTNIschemic Stroke2EmbolicAnterior and Posterior CirculationNoNoNoAspirinSore throat, Fever, Cough, SOB5.73031.13.93Skilled Nursing FacilityN/A
      278FCAD s/p Stent, PAD, DM2Ischemic StrokeUnknownEmbolicAnterior and Posterior CirculationNoNoNoNone due to thrombocytopeniaSOB11.4691.37147DeathRespiratory Failure, DIC
      372MStroke, CHFIschemic Stroke12EmbolicLeft MCANoNoYesAspirinSOB12.71671.33486DeathRespiratory Failure, Septic Shock
      473MHTN, DM2Ischemic Stroke23Large Vessel Intracranial Occlusion (Right M1)Right MCANoNoYesAspirinSOB20.423812043DeathRespiratory Failure, Septic Shock
      562MHTN, DM2Ischemic StrokeUnknownLarge Vessel Intracranial Occlusion (Right M1)Right MCANoNoNoAspirinCough, SOB8.92121.1524Skilled Nursing FacilityN/A
      648MHLDIschemic Stroke23Large Vessel Intracranial Occlusion (Left M1)Left MCAYesYesNoAspirinNone7.22371.16383HomeN/A
      764FHTNIschemic Stroke4EmbolicPosterior and Anterior CirculationNoNoNoAspirinCough, SOB64571.1419HomeN/A
      851MCAD, HTNIschemic Stroke15Large Vessel Intracranial Occlusion (Right ICA)Right MCANoYesNoAspirin + ClopidogrelSOB5.82731.42476DeathRespiratory Failure, Septic Shock
      970FNoneIschemic StrokeUnknownLarge Vessel Intracranial Occlusion (Right M1, A1)Right MCA and ACANoYesNoNone due to risk of hemorrhagic conversionSOB, Fever104831.311559DeathRespiratory Failure, Septic Shock
      1059MHTN, SmokerIschemic Stroke1Large Vessel Extracranial Occlusion (Right ICA)Right Central Retinal ArteryNoNoNoRivaroxabanSore throat7.63271.3450HomeN/A
      1183FDM2, HTNIschemic Stroke8Small Vessel DiseasePosterior CirculationNoNoYesAspirin + ApixabanCough, SOB2.51331.2282Acute RehabilitationN/A
      1254MHTNVenous Infarction due to Cerebral Venous Sinus ThrombosisUnknownN/AN/AN/AN/AN/AN/ACough, SOB13.437215748DeathObstructive Hydrocephalus, ICP Crisis, Respiratory Failure
      1362FHTN, HLDSeizureN/AN/AN/AN/AN/AN/AN/ANone1331211075HomeN/A
      1450MHTN, HIV, CKD, StrokeSeizureN/AN/AN/AN/AN/AN/AN/ANone3.923115619DeathRespiratory Failure
      1562FStroke, SeizuresSeizureN/AN/AN/AN/AN/AN/AN/ANone12.93401.2706DeathRespiratory Failure
      1638FNoneSubarachoid HemorrhageN/APosterior Communicating Artery AneurysmN/AN/AN/AN/AN/ACough, SOBNot collected3961.1971HomeN/A
      1763MNoneSubarachoid HemorrhageN/AN/AN/AN/AN/AN/AN/ASOB, Fever6.61881408DeathRespiratory Failure, Septic Shock
      All patients in our series were admitted for further work up. At the end of the hospital stay, three of the stroke patients were discharged directly to home as they did not meet any rehabilitation needs. Three others required either skilled nursing or rehabilitation facilities.
      In the time period from April 2020 to June 2020, we had 15 deaths in our ischemic stroke patients. Out of this, 5 deaths (33 %) occurred in the stroke patients who were found to be COVID-19 positive.
      Fig 1
      Fig. 1A. Patient 1: Ischemic stroke, DWI sequence showing embolic stroke pattern in the anterior and posterior circulations. B. Patient 12: Venous infractions, FLAIR sequence of MRI brain showing bilateral hyper intensities. C. Patient 16 SAH, CT HEAD SHOWING SAH in the left ambient cistern, quadrigeminal plate cistern and bilateral parieto-occipital lobes. D. Patient 6: Large vessel ischemic infract, DWI sequence with diffusion restriction in the left MCA territory.

      Conclusion

      COVID-19 positive patients who presented with acute stroke-like symptoms were found to have a variety of neurologic diagnoses including seizures, cerebral venous sinus thrombosis, arterial ischemic stroke, and subarachnoid hemorrhage.
      Three patients presented with seizure. There have been several case studies of COVID-19 causing hyponatremia.
      • Lippi G
      • South AM
      • Henry BM
      Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19).
      Patient 13 was found to have hypovolemic hyponatremia with a sodium of 106 mmol/L. Several mechanisms have been proposed, one of them being that the virus binds to angiotensin-converting enzyme receptors.
      • Tee LY
      • Yap B
      • Sidhu GK
      • Goh KS
      • Rosario BH
      Atypical presentation of COVID-19 in an older adult: lethargy and vomiting from severe hypovolemic hyponatremia.
      This can lead to renal excretion of these electrolytes. We believe that the seizure was triggered by the low sodium levels. Patient 15 had a history of seizures and chronic infarcts, while patient 14 only had a history of chronic infarcts. We believe these patients presented in status epilepticus in the setting of COVID- 19 infections lowering their seizure thresholds and causing metabolic derangements.
      The majority of our stroke patients had either large vessel occlusion infarcts or scattered, multi-territorial infarcts, suggestive of a proximal embolic source. Workup of these patients did not identify any embolic source, however this could suggest an underlying pro-inflammatory condition related to COVID-19 infection causing accelerated atherosclerosis or a hypercoagulable state. These patients did also have traditional risk factors for stroke such as hypertension, dyslipidemia, and diabetes, however; making it difficult to determine a single mechanism of stroke in COVID-19 patients. Anterior circulation infarcts were more common than posterior circulation infarcts. There was no predilection to any particular age group in our cohort.
      As evident from Table 1, five patients with ischemic stroke died. The cause of death for the stroke patients was primarily due to COVID-19 related respiratory failure and septic shock rather than complications of stroke. A recent study revealed that D-dimer is commonly elevated in patients with COVID-19 and that it can be a marker for disease severity with a higher risk of mortality.
      • Yao Y.
      • Cao J.
      • Wang Q.
      • et al.
      D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study.
      In our study population, patients who died had significantly elevated D-dimers and a more complicated hospital course compared to survivors. Patient 12 was diagnosed with extensive cerebral venous sinus thrombosis which led to ICP crisis, respiratory failure, and ultimately, death. Interestingly, patient 6 in our series had an elevated D-dimer but a good outcome which may have been secondary to his age and treatment with both IV-tPA and mechanical thrombectomy. It is also worth mentioning that two patients with ischemic strokes and one patient with central retinal artery occlusion improved to a degree that allowed discharge directly to home rather than rehabilitation facility.
      Most of the stroke patients were placed on an antiplatelet agent; the role of anticoagulation in the management of this patient population requires further investigation.

      Declaration of Competing Interest

      None.

      Disclosures

      None.

      Funding

      None.

      References

        • Mao Ling
        • Jin Huijuan
        • Wang Mengdie
        • et al.
        Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China.
        JAMA Neurol. 2020; 77: 683-690
        • Li Y
        • Li M
        • Wang M
        • et al.
        Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study.
        Stroke Vasc Neurol. 2020; (svn-2020-000431)
        • Oxley TJ
        • Mocco J
        • Majidi S
        • et al.
        Large-vessel stroke as a presenting feature of covid-19 in the young.
        N Engl J Med. 2020; 382: 360
        • Yao Y.
        • Cao J.
        • Wang Q.
        • et al.
        D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study.
        J Intensiv Care. 2020; 8: 49
        • Lippi G
        • South AM
        • Henry BM
        Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19).
        Ann Clin Biochem. 2020; 57: 262-265
        • Tee LY
        • Yap B
        • Sidhu GK
        • Goh KS
        • Rosario BH
        Atypical presentation of COVID-19 in an older adult: lethargy and vomiting from severe hypovolemic hyponatremia.
        Geriatr. Gerontol. Int. 2020; 20: 839-840

      Linked Article

      • Response to Letter to the Editor
        Journal of Stroke and Cerebrovascular DiseasesVol. 30Issue 7
        • Preview
          This is in response to the question asked by the author of the manuscript entitled “Comments on Coronavirus Positive Patients Presenting with Stroke-Like Symptoms”.
        • Full-Text
        • PDF
      • Comments on coronavirus positive patients presenting with stroke-like symptoms
        Journal of Stroke and Cerebrovascular DiseasesVol. 30Issue 7
        • Preview
          We read with interest the short communication entitled “Coronavirus Positive Patients Presenting with Stroke-Like Symptoms”,1 it was a case series on stroke presentation over COVID-19 patients. We are particularly interested on patient 10, the one and only one central retinal artery occlusion (CRAO) case secondary to occlusive thrombus in the internal carotid artery (ICA), who was also highlighted by the authors. CRAO is a blinding ocular emergency, and a harbinger of ischemic cerebrovascular stroke.
        • Full-Text
        • PDF