Stroke Snapshot: Intracranial Vasculopathy in COVID-19

Acute ischemic stroke is a potentially life-threatening neurologic manifestation of infection with the SARS-CoV-2 virus that causes COVID-19.^1,2 The pathophysiology of unusual COVID-19–related cerebrovascular insults is presumed to be related to multiple factors, including a systemic hyperinflammatory and hypercoagulable state.³ Cerebral ischemic events have been described in COVID-19, often in patients under age 50, and sometimes without identifiable cerebrovascular risk factors. Some also present with evidence of large vessel occlusion (LVO).⁴ We demonstrate a unique and atypical case of acute ischemic stroke secondary to focal vasculopathy without evidence of hypercoagulability in a young patient with COVID-19, requiring mechanical thrombectomy and emergent intracranial stenting. We also review the currently available literature on COVID-19–related neurovascular events.

COVID-19 and Cerebrovascular Disease

COVID-19 increasingly has been reported as a potential culprit in cerebrovascular events, including acute ischemic stroke, intracranial hemorrhage and cerebral venous sinus thrombosis.^3,5,6 The mechanism of these neurovascular events is likely multifactorial, and can be affected by the severity of COVID-19, disruption of the blood-brain barrier (BBB), and subsequent development of hypercoagulability secondary to a neuroinflammatory response with immune-mediated thrombosis, cytokine storm, and changes to angiotensin-converting enzyme 2 (ACE-2) receptor function.^1,7,8 The relevance of possible direct neurovascular damage is not well understood.

In a single-center study of 214 people with COVID-19 who were hospitalized in Wuhan, China, acute cerebrovascular disease was observed in 5.7% of those with severe disease and 0.8% of those with mild-to-moderate illness.¹ In another single-center retrospective study of 519 people with COVID-19, the incidence of acute ischemic stroke was 3.21% with higher rates of LVO compared to people with strokes who did not have COVID-19 (63.1% vs 23.6%, P=.006).⁵ Additionally, a study assessing COVID-19–related acute ischemic stroke found 21.6% of individuals presenting with acute ischemic stroke and COVID-19 had LVO.⁹ A systematic review of 4,466 people with COVID-19 suggested a 1.2% (range 0.9%-2.7%) pooled incidence of acute ischemic stroke, with a 40.9% prevalence of LVO in these individuals.⁶

Elevated D-dimer levels have been observed in people of all ages with COVID-19 and have been associated with more severe illness and increased risk of thrombotic events, including acute ischemic stroke.¹⁰ In a New York–based study, 32 people with COVID-19–related acute ischemic stroke were found to have a median D-dimer level of 3,913 ng/mL (range 2,549–1,000,000).¹¹ Elevated levels of interleukin-6 and C-reactive protein secondary to cytokine storm have also been associated with increased risk of myocardial and cerebral ischemic events.¹² Treatment of these conditions may include a variety of medications, including steroids, antivirals, anticoagulants, and antiplatelet therapies. Interestingly, in the case presented here, there was no laboratory evidence of hypercoagulability or other abnormalities.

Although LVO has been frequently observed in COVID-19–related ischemic stroke, other presentations have also been noted, including hemorrhagic stroke, CNS vasculitis, and small vessel disease.^13,14 Focal intracranial vasculopathy, however, remains a rarely observed phenomenon. Other viral infections have been implicated in cases of intracranial vasculopathy, most frequently associated with varicella zoster virus (VZV), cytomegalovirus (CMV), and HIV.¹⁵

There have been 2 atypical reports of children with focal central nervous system arteriopathy with resultant ischemic strokes due to COVID-19.^16,17 The first, age 12 years, had new-onset seizures and an acute subcortical left middle cerebral artery territory infarction. MRI demonstrated focal vasculopathy of the proximal M1 segment. The second case was age 13 years with headaches and fluctuating right-sided weakness, who was found to have left middle cerebral artery territory infarcts in the frontal and parietal lobes. Corresponding MRI vessel wall imaging was consistent with focal vasculitis of the left M1 segment. Neither child was considered a candidate for acute endovascular treatment.

We describe acute treatment of an atypical focal intracranial lesion related to COVID-19–related acute ischemic stroke. Treatment utilized mechanical thrombectomy and emergent intracranial stenting, the latter of which is not routinely used for LVO treatment, although it has been previously described as a potential rescue therapy for refractory atherosclerotic lesions.¹⁸ Intracranial stenting is not favored for treatment of other types of progressive vasculopathies or inflammatory vasculitis. In the case described, there was no evidence of associated hypercoagulability, underlying atherosclerotic disease, severe inflammatory response, small vessel disease, or diffuse vasculitis that have been described in association with COVID-19. Considering the successful and timely treatment, CD achieved a good functional neurologic outcome, and has remained symptom free since.

Summary

COVID-19–related neurovascular events have been well described, mostly due to underlying hypercoagulable state, systemic inflammation, or diffuse vasculitic process, potentially requiring steroid, antiviral, and anticoagulation therapies. We highlight here another rare but possible COVID-19–related entity of focal intracranial vasculopathy without other underlying abnormalities in an otherwise previously healthy person in their early third decade. We demonstrate successful treatment with an aggressive endovascular approach involving intracranial stenting. An excellent clinical outcome was achieved, and such treatment could be considered for select individuals with refractory focal vasculopathy in the setting of COVID-19.