key: cord-0058142-6710x3sy authors: Barletta, Antonino; Colleoni, Maria Luisa; Quilici, Luca; Gallizioli, Gabriele; Gerevini, Simonetta title: Vascular Manifestations in COVID 19 date: 2021-03-18 journal: Neuroimaging of Covid-19 DOI: 10.1007/978-3-030-67521-9_3 sha: 0ef583271b92f1e3ae00281383f52ae1bba11190 doc_id: 58142 cord_uid: 6710x3sy Neurological symptoms described in COVID-19 infected patients (hypo-ageusia, anosmia, confusion, seizures, etc.) are often associated to presence of stroke and/or brain hemorrhages that sometimes can occur together. As COVID-19 has spread around the world, evidence has grown for an association with cerebrovascular disease. The association between COVID-19 and cerebrovascular complications were reported in an early retrospective case series from Wuhan [1], Italy [2, 3], and Netherlands [4] and extensively reported in Chap. 10.1007/978-3-030-67521-9_2. Neurological symptoms described in COVID-19 infected patients (hypo-ageusia, anosmia, confusion, seizures, etc.) are often associated to presence of stroke and/or brain hemorrhages that sometimes can occur together. As COVID-19 has spread around the world, evidence has grown for an association with cerebrovascular disease. The association between COVID-19 and cerebrovascular complications were reported in an early retrospective case series from Wuhan [1] , Italy [2, 3] , and Netherlands [4] and extensively reported in Chap. 2. The reported incidence of cerebrovascular disease in patients testing positive for SARS-CoV-2 ranges from 1% to 6%, potentially equating to large numbers of individuals as the pandemic progresses in some countries [5, 6] , and multiple regions with high COVID-19 prevalence have reported stable or increased incidence of large vessel stroke and increased incidence of cryptogenic stroke (patients with no found typical cause of stroke). Moreover the mean patient age in several thrombectomy case series of COVID-19 is younger than the typical population having this procedure [7] [8] [9] , and case-control analysis of acute stroke protocol imaging from late March to early April, 2020, across a large New York City health system showed that, after adjusting for age, sex, and vascular risk factors, SAS-CoV-2 positivity was independently associated with stroke. Some hypotheses have been postulated to explain cerebrovascular involvement in this infection. The ACE1-Angiotensin II system is more active in the elderly males and this might explain why increasing mortality and cerebrovascular complications are observed more often in these patients [10, 11] . Early indicators suggest that another process linked with these cerebrovascular complications is the onset of a sepsis-induced coagulopathy (SIC), precursor of disseminated intravascular coagulation (DIC), due to an uncontrolled cytokine release [12] . Endothelial damage and thrombogenic-hemorrhagic processes are compounded by SARS-COV2 neurotropic and neuro invasive ability [13] , demonstrated on other strains of human coronavirus in the past [14] . The alteration of coagulability resulted confirmed by the effectiveness of anticoagulant therapy with heparin or rTPA [15] . Lower levels of lymphocytes, platelet count, and higher blood urea nitrogen were also found in patients with CNS symptoms. No laboratory differences were found between patients with stroke or cerebral hemorrhage. From an imaging point of view, no peculiar aspects, helpful to discriminate cerebrovascular complications of COVID-19 from classical stroke clinical presentation, were reported at the moment. Therefore, for this reason arterial and venous imaging evaluation is essential for COVID-19 patients with acute cerebrovascular events, keeping in mind that data supporting an association between COVID-19 and stroke in young populations without typical vascular risk factors, at times with only mild respiratory symptoms, are increasing. Numerous studies in the literature have investigated the correlation between stroke and cardiovascular and inflammatory events during COVID-19 infection. Cardiac involvement with acute cardiac injury, arrhythmias and heart failure in COVID-19 patients has been described [16] [17] [18] . A metaanalysis of six studies observed cardiac injury in 8.0% patients, mostly occurring in patients who were sicker and in the ICU [19] . The hypothesized mechanisms, including an acute inflammatory response and plaque destabilization, could potentially lead to a cardioembolic stroke. The relationship between inflammation and stroke is complex because the inflammation could precede, causing it, the stroke, or follow it [20, 21] . The interaction between inflammatory cells within the vascular wall and conventional risk factors alters the dynamics of atherosclerosis. This has a potential to acutely worsen in the presence of systemic inflammation and effect the coagulation cascade [22, 23] . In reference to risk factors the literature data suggest age and comorbidities like hypertension, diabetes and cardiovascular disease to be associated with higher mortality in COVID-19 [18, 24, 25] . In particular a report of patients with COVID-19 and stroke emphasizes coexistence of history of smoking (38.5%), alcohol intake (15.4%), and increased blood pressure (≥130/80 mmHg) (53.8%) [26] . Moreover, patients with stroke were more likely to have other underlying disorders, includ-ing hypertension (69.2% vs. 22.1%, p < 0.001) and diabetes mellitus (46.2% vs. 12.0%, p < 0.01) [28] . A report from the Chinese Center for Disease Control and Prevention describes a significantly higher mortality rate in patients with hypertension, diabetes and CVD (6%, 7.3% and 10.5%, respectively, versus an overall rate of 2.5%) among 44,672 COVID-19 cases. Some more details about cardiac involvement will be summarized in Chap. 6 (Other possible location of Cov-19 infection). From an interventional neuroradiological point of view, the treatment of stroke does not differ based on the presence or absence of COVID-19 infection. However, stroke management can be challenging as it involves the need to harmonize the "time is brain" concept and the safe and effective management of the potential spreading source of the virus. The triage processes during needs to ascertain whether the patient is a COVID suspect and delineate pathways for timely treatment and minimum exposure to health care personnel. The organization and management of the out-ofhospital territorial emergency must consider both the number of confirmed infections and the organizational capacity of structures not ready to manage stroke. Similarly, the hospital organization will have to consider adequate logistical and structural changes. Guidelines to manage patients with acute stroke during COVID-19 have been published [27, 28] , giving more and more importance to the concept of "protected stroke code." As discussed above, one of the supposed pathogenetic mechanisms in COVID viral infection is coagulopathy induced by a proinflammatory state. This aspect should be considered when dealing with hemorrhagic manifestations of stroke. Discussions regarding anticoagulation for COVID-19 patients have been intensifying as evidence of hypercoagulability in this population continues to accumulate. Recent literature findings can be helpful in this regard. In a cohort of 755 patients diagnosed with positive COVID-19 and with neuroimaging, 4.4% had ICH [29] . The majority of these patients received therapeutic anticoagulation, most commonly UFH. The most frequent indication for starting anticoagulation was elevated D-dimer levels, reflecting what is indicated by the literature data. In our center, from March to May 2020, we evaluated a cohort of 205 COVID+ patients. All underwent at least one brain CT. Forty-five underwent a brain CT angiography and 50 a brain MRI (50% of these on 3 T Magnet). Forty percent (79/205) of the brain CTs showed pathological changes; in particular among these 33% showed lobar infarcts, 37% lacunar infarct, and 35% hemorrhagic stroke. On MRI we registered a recurrent pattern of ischemic and/or haemorrhagic lesions in 50% of patients. Case 6: ex-post re-interpretation: the lack of complete clinical information due to the peculiar moment of the pandemic, the execution of the first CT scan not in the proper acute phase of the neurological symptoms made difficult the correct definition and classification of this case. As a matter of fact, the actual revision of imaging opens a differential diagnostic issue versus PRES or PRES like classification. We consider this case here as a "vascular" case because it has been classified and treated as vascular; furthermore, we are conscious of possible different interpretations such as PRES like lesion. Case 7 F, 77 years old. Right hemiparesis. Fever and dyspnea of mild onset rapidly progressing are associated (Fig. 3.24 ). pneumonia. 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