Clinical Characteristics of COVID-19-Related Reversible Cerebral Vasoconstriction Syndrome: A Systematic Review of Case Series

Abstract

Background and Objectives: Although reversible cerebral vasoconstriction syndrome (RCVS) is a rare disease, the condition may occur with COVID-19 infection. We aimed to investigate the clinical characteristics of RCVS through a systematic review of case reports and case series that reported on COVID-19-related RCVS. Methods: A literature search was performed in PubMed (MEDLINE), SCOPUS, and Web of Science. The search was confined to articles published between 17 November 2019 and 14 August 2024. The search terms were ("COVID-19" OR "SARS CoV-2") AND ("RCVS" OR "Reversible cerebral vasoconstriction syndrome"). The search protocol was registered in PROSPERO (CRD42024491818). A total of twenty-four cases were included, nine case series consisting of nineteen cases and five cases from our hospital. Clinical characteristics were investigated, including risk factors, symptoms, brain and angiographic findings, treatment options, and prognoses. Results: The average age was 37.1 years, and females comprised 70.8% of the cohort. COVID-19 vaccination was administered in five cases. Vasoconstriction was most frequently noted in middle cerebral arteries (90.9%). Among the included patients, 12 (50.0%) experienced strokes as a complication of RCVS, and the mortality rate was 9.1%. Follow-up imaging findings were available for 14 of the 24 cases (58.3%). Among these, vasoconstriction was fully improved in 64.3%, partially improved in 28.6%, and aggravated in 7.1%. Conclusions: While the recovery rate of vasoconstriction on brain angiographic findings was not uncommon, our systematic review indicates a potential for a relatively poor neurological prognosis in COVID-19-related RCVS.

Keywords: COVID-19 infection; prognosis; reversible cerebral vasoconstriction syndrome; stroke.

Figure 1

The strategy for selecting articles. There were 19 cases extracted from 9 articles. We added 5 of our hospital’s cases to this and investigated a total of 24 cases. n = number of articles; c = cases.

Figure 2

Frequency of involved cerebral vascular segments. Rt = right and Lt = left. Color coding according to frequency is noted in the figure. The number (%) written next to each segment indicates the frequency and the ratio (Number_case/Number_{total number of involved segments}). The total number of cerebral vessels involvement sites in our patients as determined by radiology was 119.

Figure 3

Mechanism of COVID-19-related reversible cerebral vasoconstriction syndrome during COVID-19 infection; viral elements invade endothelial cells through angiotensin-converting enzyme receptor 2. This can damage endothelial cells, resulting in microvascular dysfunction. Additionally, the angiotensin-converting enzyme 2 receptor is down-regulated during the virus invasion process, causing hyperactivation of the classical renin-angiotensin system pathway. This can cause sympathetic hypertonia in the cerebral vascular wall and a loss of the self-regulatory function of the cerebral vascular system due to a surge in blood pressure. Hyperactivation of the classic renin-angiotensin system pathway can also cause systemic inflammation and water retention; these can lead to increased blood–brain barrier permeability and the breakdown of arterial collagen, ultimately resulting in arterial instability. ACE = angiotensin-converting enzyme; ROS = reactive oxygen species; NO = nitrous oxide; BBB = blood–brain barrier; MMP-9 = matrix metalloproteinase-9.

Figure 4

Diagnostic and management flowchart for RCVS in patients with COVID-19.