By Dr Inna Lutsenko, Specialist, Neurologist, Center for Distance Learning and Advanced Training, Kyrgyz State Medical Academy after I.K.Akhunbaev
twitter: @inna_lutsenko
We already know that the SARS-COV2 can be associated with increased risk of acute stroke, most often ischemic. And yet, what subtypes of ischemic stroke are more common in patients with COVID-19 infection? By answering this question, we may be able to take further steps towards the more targeted treatment of ischemic stroke in COVID-19 and improve prediction of outcomes, which is important for assessing the epidemiological situation.
According to several studies [1-2] large vessel occlusion (LVO) is prevalent. SARS-CoV-2 infection is linked to a prothrombotic state causing venous and arterial thromboembolism and elevated D-dimer levels [2]. This phenomenon of hypercoagulability is often associated with deranged lab values seen in both inflammatory conditions and consumptive coagulopathies [2,3].Katz et al. [1] in their observational study in the network of New York hospitals noted that 57% of their ischemic stroke patients had extracranial or intracranial large vessel occlusion. One of these patients, a 62-y-old woman, had bilateral MCA infarctions. Werring et al. also described a series of patients with multiple LVO [1].. Notably, a correlation between high levels of D-dimer and LVO appearance has been described. For example, Werring et al. reported very high D-dimer levels (>7000 μg/L), in several patients, which were substantially higher than the median level reported in patients with COVID-19 alone (900 μg/L) [1].
In addition to hypercoagulability, two other mechanisms have also been proposed including, vasculitis, and cardiomyopathy (Fig. 1) [4], and patients presenting with a variety of ischemic stroke subtypes have been reported (Fig 1).
Fig. 1. Potential mechanisms of ischemic stroke in patients with COVID-19.
LAA, large artery atherosclerosis; CE, cardiac embolism; SAO, small artery occlusion; Other, other uncommon causes of stroke; Undetermined, undetermined causes of stroke; DVT, deep venous thrombosis. It should be noted that in COVID-19, many large artery occlusions may not be due to atherosclerosis but to embolization [4].
CNS vasculitis due to COVID-19 was described as a rare cause of multiple ischemic strokes with normal coagulation panel in young patients [6]. The expression of the ACE2 receptor in neurons and cerebral endothelial cells indicates a higher level of invasiveness for the SARS-CoV-2 in comparison with other coronaviruses (SARS and Middle East Respiratory Syndrome). Varga et al.[6] have shown direct viral infection of the endothelial cell and diffuse endothelial inflammation. This endothelial dysfunction can lead to vasoconstriction and break of the blood-brain barrier with cerebral ischemia and inflammation. Neuroimaging findings suggested the possibility of injury to the small intracranial vasculature in the distribution of distal perforating arteries. The association of ischemic and hemorrhagic lesions to the “patchy/punctate” enhancement pattern is suggestive of vasculitis [5].
Septic-like coagulopathy additionally may lead to cerebral venous thrombosis (CVT), pulmonary embolism, and ultimately disseminated intravascular coagulation [7]. CVT in COVID-19 patients [1,7,8], in particular, can present with a broad variety of neurologic signs and symptoms. Besides coagulopathy due to COVId-19 in CVT patients other factors often took place, including oral contraceptives intake, dehydration and anemia [7,8]
In conclusion, several ischemic stroke subtypes are being described in COVID19 patients. To our best knowledge, large vessel occlusion caused by hypercoagulability and cerebral vasculitis is common. In addition, small arteries occlusion could also be seen especially among patients with hypertension and diabetes. Defining the most common etiological subtypes in these stroke patients does matter and initiating appropriate treatment, not only symptomatic but also more targeted therapy (i.e. intravenous thrombolysis, mechanical thrombectomy, anticoagulants, anti- inflammatory medications and even steroids) will likely help to increase the chances of timely recovery and reduce post-stroke disability.
References:
1. Werring D.J. et al. Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry Published Online First: 30 April 2020. doi: 10.1136/jnnp-2020-323586 https://jnnp.bmj.com/content/early/2020/04/30/jnnp-2020-323586
2. Jeffrey M. Katz, MD; Richard B. Libman, MD; Jason J. Wang , PhD; Pina Sanelli, MD; Christopher G. Filippi, MD; Michele Gribko , DNP; Steven V. Pacia, MD; Ruben I. Kuzniecky, MD; Souhel Najjar , MD; Salman Azhar, MDCerebrovascular Complications of COVID-19. https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.120.031265.
3. Han H, Yang L, Liu R, Liu F, Wu K, Li J, et al. Prominent changes in blood coagulation
of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;0(0).
4. J. David Spence, Gabriel R. de Freitas, L. Creed Pettigrew, Hakan Ay, David S. Liebeskind, Carlos S. Kase, Oscar H. Del Brutto, Graeme J. Hankey, Narayanaswamy Venketasubramanian. Mechanisms of Stroke in COVID-19. Cerebrovasc Dis. DOI: 10.1159/000509581
5. R. Hanafi, P.-A. Roger, B. Perin, G. Kuchcinski, N. Deleval, F. Dallery, D. Michel, L. Hacein-Bey, J.-P. Pruvo, O. Outteryck, and J.-M. Constans. COVID-19 Neurologic Complication with CNS Vasculitis-Like Pattern. AJNR Am J Neuroradiol 41:1384–87 Aug 2020 www.ajnr.org
6. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;6736:19–20.
7. D.D. Cavalcanti, E. Raz, M. Shapiro, S. Dehkharghani, S. Yaghi, K. Lillemoe, E. Nossek, J. Torres, R. Jain, H.A. Riina, A. Radmanesh, and P.K. Nelson. Cerebral Venous Thrombosis Associated with COVID-19. Cavalcanti Aug 2020 www.ajnr.org
8. David E. Klein D.O. , Richard Libman M.D. , Claudia Kirsch M.D., 19 in the Young, Journal of Stroke Cerebrovascular Diseases (2020), doi:https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104989
