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.
Clinical Presentation and History
CD, in their early 20s, presented to the emergency department within a few hours after acute onset left hemiplegia involving face, arm, and leg and a National Institutes of Health Stroke Scale (NIHSS) score of 11. They tested positive for COVID-19 using polymerase chain reaction (PCR) testing of a nasopharyngeal swab sample. CD had mild obesity but no other significant medical history.
Neuroimaging
A noncontrast head CT revealed multifocal right middle cerebral artery territory acute-to-subacute-appearing ischemic infarcts with scattered areas of small petechial hemorrhage. CT angio-graphy revealed a right M1 segment occlusion, also confirmed on later angiography (Figure 1A and 1B). CD was not a candidate for intravenous thrombolysis, but the decision was made to pursue endovascular therapy owing to acute neurologic worsening.
Treatment
CD underwent 2 passes of mechanical thrombectomy with contact aspiration, which successfully recanalized the occluded right M1 segment (Figure 2A). Follow-up angiography within a few minutes, however, revealed restenosis (Figure 2B). Balloon angioplasty was temporarily successful at recanalization, but repeat angiography again showed critical restenosis of the M1 segment. After another round of angioplasty and restenosis, a decision was made to place a stent in the right M1 segment, resulting in successful persistent recanalization and no further restenosis (Figure 3A and 3B). There was no evidence of atypical clotting or clot burden during the procedure. CD had a loading dose of tirofiban at the time of stent placement, followed by loading doses of oral aspirin and clopidogrel immediately after the procedure. CD was transferred to the neurocritical care unit for further postoperative monitoring and management.
Follow-up Care
Extensive investigation for stroke etiology was unrevealing and the clinical workup included a normal blood chemistry profile, blood cell counts, fasting lipid profile, and hemoglobin A1c levels. A hypercoagulability workup was remarkable only for a mildly elevated D-dimer, which peaked at 1,170, and a mildly elevated homocysteine level (16.8 uM/L). CD had no evidence of atherosclerotic disease. Lower extremity Doppler ultrasound was negative for deep venous thrombosis, and there was no evidence of systemic arterial or venous hypercoagulability. An echocardiogram was negative for significant abnormalities or intracardiac shunt. After consultation with infectious disease colleagues, CD was treated with remdesivir and dexamethasone until discharge.
After 5 days, CD was discharged with an NIHSS score of 1 because of a mild left facial droop. They continued on dual antiplatelet therapy for 6 months and then continued antiplatelet monotherapy. At 6 months’ poststroke, CD had no significant objective residual deficits, although subjective mild left-sided weakness for a few weeks after hospitalization was reported. Transcranial Doppler ultrasound at 2 months and cerebral angiogram at 6 months showed full patency of the stent (Figure 3C).
Discussion
Acute ischemic stroke caused by focal intracranial vasculopathy in the setting of COVID-19 has been reported only in 2 pediatric cases, whereas hypercoagulability and diffuse vasculitis as possible etiologies have been seen more often. In this case COVID-19 presented as a focal intracranial vasculopathy in an otherwise healthy adult in their third decade of life and resulted in an acute ischemic stroke. Unconventional rescue stenting successfully treated this rare condition.
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.
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