Since the pandemic hit, researchers have been uncovering ways COVID-19 impacts other parts of the body, besides the lungs.
Now, for the first time, a visual correlation has been found between the severity of the disease in the lungs using CT scans and the severity of effects on patient’s brains, using MRI scans. This research is published in the American Journal of Neuroradiology.
It will be presented at the 59th annual meeting of the American Society of Neuroradiology (ASNR) and has also been selected as a semifinalist for that organization’s Cornelius Dyke Award.
The results show that by looking at lung CT scans of patients diagnosed with COVID-19, physicians may be able to predict just how badly they’ll experience other neurological problems that could show up on brain MRIs, helping improve patient outcomes and identify symptoms for earlier treatment.
CT imaging can detect illness in the lungs better than an MRI, another medical imaging technique.
However, MRI can detect many problems in the brain, particularly in COVID-19 patients, that cannot be detected on CT images.
“We’ve seen patients with COVID-19 experience stroke, brain bleeds and other disorders affecting the brain,” says lead author Abdelkader Mahammedi, MD, assistant professor of radiology at the University of Cincinnati and a UC Health neuroradiologist.
“So, we’re finding, through patient experiences, that neurological symptoms are correlating to those with more severe respiratory disease; however, little information has been available on identifying potential associations between imaging abnormalities in the brain and lungs in COVID-19 patients.
“Imaging serves as proof for physicians, confirming how an illness is forming and with what severity and helps in making final decisions about a patient’s care.”
In this study, which was conducted not only at UC, but also at large institutions in Spain, Italy and Brazil, researchers reviewed electronic medical records and images of hospitalized COVID-19 patients from March 3 to June 25, 2020. Patients who were diagnosed with COVID-19, experienced neurological issues and who had both lung and brain images available were included.
Of 135 COVID-19 patients with abnormal CT lung scans and neurological symptoms, 49, or 36%, were also found to develop abnormal brain scans and were more likely to experience stroke symptoms.
Mahammedi says this study will help physicians classify patients, based on the severity of disease found on their CT scans, into groups more likely to develop brain imaging abnormalities. He adds that this correlation could be important for implementing therapies, particularly in stroke prevention, to improve outcomes in patients with COVID-19.
“These results are important because they further show that severe lung disease from COVID-19 could mean serious brain complications, and we have the imaging to help prove it,” says Mahammedi, who is also a member of the UC Gardner Neuroscience Institute.
“Future larger studies are needed to help us understand the tie better, but for now, we hope these results can be used to help predict care and ensure that patients have the best outcomes.”
In this mini-review, we aim to summarize some of the most common imaging findings seen in patients with COVID-19. However, it is important to bear in mind that the exact relationship with SARS-CoV-2 has not yet been fully established. Indeed, while COVID-19 associated neurological features offer a possible causal or synergetic relationship between cerebral events and SARS-CoV-2 infection, coincidental events (rather than casual association) might explain some of these imaging results. In fact, due to high prevalence of the COVID-19 in communities, co-incidence of the infection with other diseases is an expected and highly likely phenomenon.
In our prior review on 20 studies consisting of 90 patients with neuro-COVID-19 symptoms (among 116 patients with coronavirus family infection) , 37 (41 %) patients had normal imaging studies (brain CT or MRI). Amongst those who displayed abnormal neuroimaging findings (59 %), vascular thrombosis, cortical signal abnormalities, hemorrhage, hemorrhagic posterior reversible encephalopathy syndrome (PRES), acute hemorrhagic necrotizing encephalopathy (ANE), meningitis/encephalitis, and acute disseminated encephalomyelitis (ADEM) were the most common reported abnormalities .
Similarly, in a recent observational study  on 73 patients who presented with neurological symptoms, 41.1 % demonstrated normal brain MRI. The remainder 58.9 % had various neuroimaging abnormalities, including acute ischemic infarcts (23.3 %), cerebral venous thrombosis (1.4 %), multiple microhemorrhages (11.3 %), perfusion abnormalities (47.7 %), multifocal white matter lesions (5.5 %), basal ganglia lesions (5.5 %), meningeal enhancement (4.8 %), central pontine myelinolysis (4.1 %), hypoxia-induced lesions (4.1 %), restricted diffusion foci within the corpus callosum consistent with cytotoxic lesions of the corpus callosum (CLOCC, 4.1 %), PRES (2.7 %), and neuritis (2.7 %).
The authors have also found that two imaging patterns of multifocal white matter lesions and basal ganglia abnormities (observed primarily in ICU patients with a more severe illness) were related more explicitly to SARS-CoV-2 infection itself rather than the disease complications.
In another multicenter observational study by Kermer et al. on 37 patients , the most frequent white matter abnormalities were described in three distinct patterns: signal abnormalities in the medial temporal lobe (43 %), non-confluent multifocal white matter hyperintense lesions on FLAIR and diffusion associated with hemorrhages (30 %), and white matter microhemorrhages (24 %).
They stated medial temporal lobe signal abnormalities were similar to those found in viral or autoimmune encephalitis, whereby patterns 2 and 3 presented microhemorrhages. They also found that the presence of hemorrhage would worsen the prognosis in these patients.
Numerous publications have already ascertained the thrombo-inflammatory nature of SARS-Cov-2 infection [9,10]. The elevated production of coagulopathy factors such as fibrinogen, platelet, D-dimer, and inflammatory cytokines (interleukin-6), along with capillary endothelial damage, predispose patients to thromboembolic events, leading to stroke, thrombosis, and hemorrhage.
Therefore, it is not surprising that stroke-related imaging findings are among the most frequent abnormalities seen in patients with neuro-COVID symptoms. Findings such as territorial acute/subacute infarction, multiple ischemic foci, evidence of thrombus in large intra and extra-cranial vessels, cerebral venous thrombus complicated by hemorrhagic infarcts, and cortical/subcortical microhemorrhages have been reported frequently in various observational studies [6,11].
The precise pathophysiology of white matter microhemorrhages in COVID-19 patients remains unclear. It has been suggested that they might be related to diffuse endothelial dysfunction, secondary to the direct viral invasion of the endothelial cells (via ACE-2 receptors) and the subsequent endothelial inflammation.
Guillain-Barre syndrome (GBS)
GBS has been reported as a significant parainfectious peripheral neurological sequelae of SARS-CoV-2 infection, similar to other coronavirus strains. These patients generally have normal MRI studies of the central nervous system, although post-contrast enhancement in the cervical and lumbar nerve roots has been reported frequently . COVID-19 associated GBS mainly develops within a few days to weeks of established viral infection.
This temporal relationship reflects a post-infective immune-mediated process as the primarily responsible mechanism. In a review by Caress et al.  on 37 cases of GBS associated with COVID-19, the mean time interval between COVID-19 symptoms and GBS onset was 11 days.
Brain imaging had been performed in fewer than half of patients (14/37), which displayed cranial nerve abnormalities only in 28 % of them. Furthermore, spine imaging was obtained in 15 cases, with 40 % showing abnormal features, including root enhancement, radiculitis, leptomeningeal enhancement, and myelopathy.
MRI perfusion abnormalities are observed in a large number of individuals presenting with COVID-19 associated neurologic signs. These abnormalities might be related to hypoxic-ischemic events and seizures, or present as an isolated finding . In Helms et al. study, bilateral frontotemporal hypoperfusion, leptomeningeal enhancement, and stroke-related abnormalities were the most conspicuous neuroimaging findings in COVID-19 patients presenting with a severe illness .
Acute inflammatory/infectious CNS syndromes
A range of COVID-19 associated inflammatory features is identified on radiological exams, including post-infectious ADEM, acute hemorrhagic leukoencephalitis, myelitis, and autoimmune encephalitis. As mentioned earlier, virus-induced vasculopathy and coagulopathy, direct invasion of CNS, hyperinflammatory reactions and post-infective autoantibodies might partly explain these findings.
In terms of radiologic findings, unilateral FLAIR hyperintensity and/or diffusion restriction in the medial temporal lobe have been frequently reported in these patients, similar to changes with autoimmune limbic encephalitis . Similar imaging results have been featured in the concept of meningitis/encephalitis in a few case series [6,14].
PRES, multifocal white matter abnormalities, basal ganglia lesions, and leptomeningeal enhancement have also been named as relevant neuroimaging manifestations in COVID-19 [11,15]. Again the vasculitis-like phenomenon and inflammatory cascades, secondary to COVID-19-induced CNS damages, are the likely responsible mechanism for these findings .
COVID-19 in brain PET
Nuclear medicine operations are not routinely employed in COVID-19 patients . However, it is assumed that molecular imaging with FDG PET-CT is potentially able to add valuable data regarding the pathophysiological basis of the disease [18,19]. In this era, a few reports have described metabolic abnormalities in patients presenting with neuro-COVID-19 manifestations. In a case series by Delorme et al.  brain FDG PET-CT was performed in four COVID-19 patients with possible immune encephalitis.
PET displayed a consistent pattern of metabolic abnormalities in all patients: hypometabolism in the prefrontal or orbito-frontal cortices and hypermetabolism in the cerebellar vermis. None of these patients had specific MRI features nor significant cerebrospinal fluid (CSF) abnormalities. Regarding the PET-CT findings and the negative CSF SARS-CoV-2 PCR results, the authors suggested a parainfectious cytokine storm or immune-mediated process rather than a direct neuroinvasion mechanism.
Other case reports have issued similar findings. Grimaldi et al. , demonstrated diffuse cortical hypometabolism, associated with putaminal and cerebellum hypermetabolism in autoimmune encephalitis concomitant with SARS-CoV-2 infection. In another case study, anosmia of COVID-19 was evaluated using FDG PET-CT.
They found hypometabolism of the left orbitofrontal cortex in a COVID-19 patient, representing with persistent isolated anosmia . These findings, along with normal morphological data on MRI, might suggest reduced neuronal activity and functional alterations in neuro-COVID-19 patients. However, further studies (specifically using BOLD functional MRI) are still needed in this regard before we draw a definite conclusion.
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686796/
More information: A. Mahammedi et al, Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study, American Journal of Neuroradiology (2021). DOI: 10.3174/ajnr.A7072
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