Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection

Abstract

The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.

Introduction

Recent reports reflect emerging evidence for the neurotropism of the novel SARS-CoV-2 virus; patients have been presenting with neurological symptoms with unusual clustering frequency and age-predilection including hypercoaguability leading to ischemic stroke, hemorrhagic leukoencephalopathy, and Guillain-Barre syndrome.¹

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical syndrome characterized by thunderclap headache and alternating intracranial vascular vasoconstriction and vasodilation on vessel imaging; ischemic stroke, convexity subarachnoid hemorrhage (cSAH), and intraparenchymal hemorrhage can also occur.² RCVS is usually triggered by medications, post-postpartum state, or sexual activity³ but has not been reported with COVID-19. Herein we describe RCVS and extracranial dissection with concomitant SARS-CoV-2 infection.

Case Report

A female nurse in her thirties with migraines presented with a few weeks of severe cough, and three days of severe thunderclap headache different than her usual migraines. Nasopharyngeal swab was positive for SARS-CoV-2 on RT-PCR assay. Non-contrast CT brain demonstrated bilateral high frontal cSAH (Fig 1 A). She had no typical triggers for RCVS on review of medications and social history. Coagulation parameters were normal, hCG was negative, and neurologic exam was nonfocal. Diagnostic cerebral angiogram (DSA) on admission revealed a left V2 segment vertebral artery dissection and no other abnormalities (Fig 1B) which was also seen on CT angiogram (Fig 1C). She was transferred to the COVID19 Intensive care unit and started on verapamil, levetiracetam, aspirin, and analgesics. DSA seven days after admission demonstrated bilateral mild to moderate anterior circulation vasospasm suggestive of RCVS (Fig. 2, Fig. 3 ). She was discharged home with verapamil and follow-up CT angiogram.

Fig. 1.

CT brain on admission demonstrates bilateral convexity subarachnoid hemorrhage (A); diagnostic cerebral angiogram on admission demonstrates a left vertebral artery dissection (B), also seen on CT angiogram (C).

Fig. 2.

Diagnostic cerebral angiogram at one week demonstrates bilateral diffuse vasoconstriction in the anterior circulation, as measured on angiographic images.

Fig. 3.

3-dimensional rotational imaging shows left anterior cerebral artery and middle cerebral artery vasospasm in the M3 segment.

Conclusion

RCVS is a common cause of cSAH in young women but is generally not associated with viral infection. In our patient, dissection was present on initial DSA, with multifocal vasoconstriction seen only on repeat DSA. In this case, she had been coughing for a week prior to the presentation, which likely precipitated the dissection, leading to subsequent RCVS and cSAH. Extracranial dissection associated with RCVS is uncommon but reported; dissection may lead to vasoactive substance release precipitating RCVS.⁴ cSAH in RCVS is likely due to dynamic vessel wall changes, with vasoconstriction followed by vasodilation leading to reperfusion injury and hemorrhage.² However, SARS-CoV-2 also may also induce vasoconstriction; spikes in blood pressure may lead to loss of cerebral autoregulation, which is the proposed mechanism of RCVS.⁵ In particular, SARS-CoV-2 downregulates the ACE2 receptor, which functions to reduce sympathetic tone, increases vasodilation, and exerts antihypertensive effects. SARS-CoV-2 leads to downregulation of ACE2, which can cause overactivation of the classic renin-angiotensin axis and lead to vasoconstriction.⁶

Limitations of our case include the lack of follow-up imaging at this time, as the patient presented early in her course and had vasoconstriction on last imaging, as well as the unclear relationship between SARS-CoV-2 infection, dissection, and RCVS. However, the patient's RCVS2 score⁷ was 10, with a score of >5 having a high specificity and sensitivity (99% and 90% respectively) for diagnosing RCVS. Overall, this single case report only suggests a possible association between RCVS and SARS-CoV-2 infection, and more cases with epidemiological data are needed to validate a causal relationship. This case also suggests the need to consider potential neurological symptoms of SARS-CoV-2 infection.