**4.7 Stroke: musculoskeletal neurological findings**

Stroke is commonly defined as sudden neurological deficit as a result of infarction or hemorrhage in the central nervous system [56]. This is a traditional definition, which has been updated over time with the fact that the neurological symptoms need to last more than 24 hours or CT and MRI confirmed focal infarction or hemorrhage compatible with the symptoms [57]. The typical subdivision of stroke includes ischemic stroke (infarction of brain, retina, or spinal infarction) and hemorrhagic stroke (intracerebral or subarachnoid hemorrhage) [58]. The cause of ischemic stroke is thromboembolism from the small vessel, larger artery, or the heart [59]. Classification of the hemorrhagic stroke depends on the anatomical location, whereas the most common are supratentorial hemorrhages [60].

There are numerous studies that report acute stroke complicating COVID-19 [61, 62]. The reported incidence of acute stroke in COVID-19 varies from 0.4% to 8.1%, due to the different ethnic and geographical variations: Asia (3.1%), Europe (1.2%) and, North America (1.1%) [63]. The reported incidence of stroke in COVID-19 patients treated in the intensive care units (ICU) is 1–3% [64–68]. Given the extent of the COVID-19 pandemic, this reported incidence is very high. Hemorrhagic stroke has been described from 21.7% to 25.7% COVID-19 patients with stroke, while the rest were ischemic strokes [69].

It has been stated that male COVID-19 patients, the median age of 63 years, are more likely to experience a stroke than women, but it is also known that the majority of ICU COVID-19 patients are older men as well [67]. Other reported risk factors include hypertension, diabetes mellitus [66, 70]. Race/ethnicity is also an important risk factor and it was observed that the black race had shown the highest prevalence (47%) [71]. A severe type of COVID-19 infection was observed as one of the most important risk factors for stroke in these patients [72–76]. There is a causal relationship between COVID-19 and stroke since the infection itself is more likely to induce thrombotic vascular events [63].

Described mechanisms of stroke in COVID-19 patients are diverse and multifactorial, considering that COVID-19 could be a trigger to typical stroke mechanisms, or alternatively, there are specific pathophysiological mechanisms [63]. The mechanisms for ischemic stroke in COVID-19 include sepsis-induced coagulopathy, presence of antiphospholipid antibodies, and thromboembolism, which show activated coagulation pathway in patients with COVID-19 who ordinarily already have elevated D-dimer and fibrinogen [77–81]. It is well known that COVID-19 uses the ACE-2 receptor to enter the cells, which leads to increased sympathetic activity, loss of blood pressure auto-regulation, and subsequent cerebral hypoperfusion [82]. Cytokine storm has also been suggested as one of the mechanisms in stroke development in COVID-19, due to its impact on atherosclerosis and thrombosis [83]. Finally, hypoxemia in COVID-19 patients may cause cerebral hypoperfusion and increase the risk of ischemia, together with previously explained thromboembolic mechanisms [84, 85].

Hemorrhagic strokes are less prevalent than ischemic strokes, but it has been implicated that some mechanism which plays a role in ischemic stroke, could lead to intracerebral hemorrhage in COVID-19 [86]. The proposed mechanisms include viral damage of vessel wall, downregulation of RAS and hypertension, cytokine destruction of blood–brain barrier, consumption coagulopathy caused by COVID-19 and cerebral hypoxia which induces micro-hemorrhages and microbleeds [87, 88]. It has been reported that COVID-19 patients who develop stroke are distinctly susceptible to large vessel occlusion, multi-territorial involvement and engagement of else ways infrequently affected vessels such as pericallosal artery [66, 68, 89].

Neuroimaging of stroke in COVID-19 patients standardly includes CT, MRI, and CT angiography (CTA). Small vessel occlusion in acute ischemic stroke was reported in 9% of cases, while large vessel infarctions were seen in almost 65% of cases [67, 68, 71, 90]. More frequent were ischemic strokes in posterior circulation [91]. It has been demonstrated that CTA verified occlusion in anterior or medial cerebral arteries with the co-development of floating thrombi in aorta and carotid arteries in patients with high D-dimer values, which confirms the influence of hypercoagulable state [71, 92]. Apart from standardly seen ischemic lesions, a small number of the patients (two of them were children) with acute stroke had: vasculitis or wall enhancement on MRI in the arterial wall [93]. Imaging findings of the hemorrhagic stroke include extensive hemispheric hematomas or multiple hematomas [94–97]. Hemorrhages may develop in severely ill patients, especially due to the failure of multiple organs or as a transformation of ischemic stroke, aneurysm rupture, or thrombosis of central venous sinus [66, 97, 98]. Some authors report a possible correlation between COVID-19 and arterial dissection, seen in the carotid artery, cervical vertebral artery or in posterior inferior cerebellar artery [99, 100].

A very small samples of patients were presented with acute stroke confirmed on neuroimaging and PCR confirmed COVID-19 [101]. Described atypical neuroimaging findings are seen in small number of COVID-19 patients with stroke and consist of: brain perfusion abnormalities, leptomeningeal enhancement [eight patients], focal cortico-pial enhancement in one patient, posterior reversible encephalopathy syndrome, microbleeds or leuco-encephalopathy [66, 102, 103]. Atypical findings express latent thrombotic angiopathy, vascular disruption and impairment of vascular autoregulation of the brain which happens in COVID-19 patients with stroke [103, 104].

#### **5. Conclusions**

Even though the COVID-19 virus is primarily a respiratory infection, new reported cases of neurological involvement have been presented daily all over the *Neurological Involvement in COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.99309*

world [105]. In this chapter, we portrayed the neurological manifestations and possible pathophysiological mechanisms of SARS-CoV-2 on nervous system [105]. Given the extent of the COVID-19 pandemic, it is important to monitor COVID-19 patients for potential neurological complications to provide them with timely diagnostics and treatment.
