We hereby present our experience stemmed from this current retrospective observational study, which has been conducted at Jaber Al-Ahmad Hospital. Neuro-radiologic observations were analyzed and reported in a cohort of patients, consecutively hospitalized at our institute, with positive coronavirus 2019 disease.
In this study, we had reviewed the intracranial neuro-radiological findings in patients systemically infected with COVID-19; this is the best of our knowledge and systematic review describing neuroimaging results in patients with COVID-19 infection.
In our study, we observed that COVID-19 male patients had more neurological complications 48/74 (64.86%); our result were near in line with Chougar et al. [8]. Males were more affected 48/73 (65.8%).
At our institution, COVID-19 ill elderly patients above 60 years old with various risk factors were more vulnerable to cerebro-vascular disease were 42 patients 56.8% this result agreed with Sanaz Katala et al. [1].
Many studies had suggested that coronaviruses have neuro-invasive properties, although in the absence of respiratory symptoms. During COVID-19 outbreak, several new reported cases suggested the association between coronavirus and neurological symptoms. Our study found those mild symptoms such as headache; myalgia and anosmia were among the most mutual neurological manifestations associated with SARS-CoV-2 infection, Munhoz et al., [9]. study supported our observations.
The most frequent neurological manifestations in included patients were impaired consciousness not explained by therapy 41/74 (55.4%); Chougar et al. [8] studied impaired consciousness representing 39/73 (53.4%).
The majority of the included patients with imaging findings of acute/subacute infarct had focal neurological deficits on clinical examination. Similarly, patients with acute hemorrhage had either focal neurologic deficits or a history of syncopal attack; this observation was as Mao et al. [10].
Acute respiratory distress syndrome and hypoxemia that can be seen in COVID-19 patients can affect mental status. While alteration in mental status warrants clinical neurological examination, failure of clinical examination to detect a focal neurologic deficit or no history of syncope or fall, the neurological imaging may not be particularly revealing, an observation that is concordant with prior studies of brain imaging in acute altered mental status [11].
Many studies believed that hyperimmune response due to cytokine storms may explain these neurologic manifestations, while the others had proposed direct invasion by virus of human brain cells by hematogenous, transcribrial or neuronal dissemination retrograde routs. In addition, the neurotropism of SARS-CoV-2 might mediate by angiotensin-converting enzyme 2 receptors (ACE2) that were expressed by brain capillary endothelial cells. Rupture of cerebral endothelium leads to irreversible brain damage that contributed in pathophysiology of SARS-CoV-2 neurologic manifestations [12].
Diversified neurological clinical manifestations were described in COVID-19 patients. The data were different on this study. Available associated neurological findings were infarction, hemorrhage (in different sites), PRES, cerebral edema, leuko-encephalopathic WM abnormalities, microhemorrhage, vascular thrombosis and acute necrotizing encephalopathy.
Neuro-imaging modalities such as CT and MRI had revealed many findings in the context of different clinical scenarios. 35.1% of our patients during the same time frame of the study testing positive for SARS-CoV-2 were admitted and hospitalized with normal or unrelated COVID-19 neurological findings, while in Sanaz Katala et al. [1] study they found 40% of their COVID-19 infectious patients had displayed normal results.
While our other COVID-19 patients had demonstrated imaging abnormalities in different areas of the brain, including ischemic stroke 54.06%, hemorrhage 25.69% and other neurological abnormalities, Sanaz Katala et al. [1] found that the most common neuroradiologic abnormality were both ischemic and hemorrhagic cerebrovascular events were seen among 27% COVID-19 patients. Other many studies were found the ischemic and hemorrhagic cerebro-vascular manifestation lower percentage than our results as in Munhoz et al. [9] found 2.8–5.7%, Mao [10] and Asadi-Pooya et al. [6] both reported that ischemic or hemorrhagic CVD account for 5–5.7% of neurologic manifestations associated with COVID-19.
The stroke pathogenesis in COVID-19 may be from the impairment of coagulation or endothelial functions. Coagulopathy may be related to the thrombophilic effects of systemic inflammation; the presence of lupus anti-coagulant and anti-phospholipid antibodies has also been reported. [13,14,15].
Although high incidence of deep vein thrombosis and elevated D-dimer levels in COVID-19 patients was reported, Tang et al., [16] did not find evidence of cerebral venous thrombosis in their cohort; we disagreed with their observation as we found two patients with vascular thrombosis, one left transverse sinus thrombosis and another had left internal carotid artery thrombosis.
Parenchymal hematomas and hemorrhage were found in 19 (25.69%) patients, most (n = 14) of whom had hemorrhages attributed to anticoagulation, a finding that highlights the risks of initiating anticoagulant therapy in response to the prothrombotic features of patients with COVID-19.
Microhemorrhages were found in 3 patients (4.05%), demonstrating innumerable variable size multiple scattered minute discrete foci of abnormal blooming signal that seen in both cerebral deep white matter without involvement of corpus callosum; our results were not in keeping with another recent observational study describing 4 patients with COVID-19 with microhemorrhage in the corpus callosum [17].
Blood spread to the CNS is proposed to be due to viral related to ACE2 receptors in the endothelial capillary, resulting in damaging to its lining. This could lead to increase the blood–brain barrier permeability and loss of hemostatic regulation, leading to cerebral edema [18].
In our result, this mechanism could explain PRES cases, as has been recently seen in 2 other cases of PRES with COVID-19 (19). However, each of our 3 patients with PRES also had the typical risk factors of chronic renal disease and elevated blood pressure.
Three of included patients (4.05%) had microhemorrhage; Lin et al. [18], 3/51 (5.8%) had patients with a microhemorrhage pattern compatible with critical illness-associated microbleeds.
In our results, three patients (4.05%) had only leuko-encepalopathic WM abnormalities, and also three patients (4.05%) had only microhemorrhage and we did not find combination of these both findings in our study. Radmanesh et al. found that four patients (14.8%) had only leukoencephalopathy, one patient (3.7%) had only microhemorrhages, and six patients had a combination of both [17].
In our study the leuko-encephalopathic WM abnormalities were presenting as abnormal high signal intensities on T2WI and FLAIR images were predominantly depicted at the periventricular and deep subcortical white matter. In contrary, Radmanesh et al. showed predilection for the corpus callosum and juxta-cortical WM [17].
We also found that two of our patients with COVID-19 had evidence of cerebral edema, similar to those shown in a recent case report of a patient with fulminant cerebral edema [19, 20].
In our study we found two patients with acute necrotizing encephalopathy without hemorrhage, the lesions appeared as bilateral thalamic, bilateral occipital subcortical, bilateral temporal cortical and subcortical T2 and FLAIR hyperintense SI.Bilateral thalami damage is often a distinctive feature in ANE [21]. Hemorrhage in thalamic lesions is an additional MRI features suggestive of ANE, but may be missing, without ruling out the diagnosis [22].
Wong et al. [22] observed that the absence of hemorrhage in ANE seems to be with better outcome, while in our study the included patients died (p value 0.506).
Respiratory virus-induced neuro-immunopathology due to a dysregulation of host immune response has been described, in particular for ANE; this can be induced by the cytokinic storm secondary to viral infections [23].
Neurotoxicity triggered by immune response to COVID-19, associated with IgG targeting a neuronal antigen found in fiber tracts, is suspected here. These antibodies may invade an autoantigen through molecular mimic to the virus. Destruction of the cells produces releasing large amounts of autoantigens; also this may stimulate self-reactive cells and lead to self-reactive antibodies. After COVID-19 infection, the inflammatory storm could contribute the production of IgG and interrupt the blood–brain barrier, thus causing an ANE [22].
The study had its limitations, primarily, as with all retrospective studies; it was subject to systematic review confounders. MR examinations were exclusively conducted in critically ill patients, hence the natural existence of indication bias.
The lack of control group undermined the specificity of findings to COVID-19 and limited our drawn conclusions. The lack of histologic and pathologic assessment was also considered one of our main study limitations.
Some of our patients with mild neurological symptoms didn’t undergo to imaging due to regulatory constraints imposed during the COVID-19 pandemic, and on the contrary, other patients with more obvious neurologic impairment may have been too unstable to undergo imaging.
Finally, our study was not comprehensive to a few potential areas of interest. For example, intracranial vasculitis could be a rational finding of infection, but, due to absence of MR angiography with contrast in our cohort, we were unable to assess the prevalence of intracranial vasculitis.
