MRI scans revealed that 57.9% of severe SARS-CoV-2 infected patients had recent brain lesions! The study findings provide further evidence that SAR-CoV-2 affects the brain and causes brain lesions and also generates various neurological manifestations.
ccording to the study abstract, “The increased frequency of neurological manifestations, including central nervous system (CNS) manifestations, in patients with COVID-19 is consistent with the virus’s neurotropic nature. In most patients, brain magnetic resonance imaging (MRI) is a sensitive imaging modality in the diagnosis of viral encephalitides in the brain.”
The study team’s objectives were to determine the frequency of brain lesion patterns on brain MRI in SARS-CoV-2 pneumonia patients who developed focal and non-focal neurological manifestations. In addition, the stud was to compare the impact of the Glasgow Coma Scale (GCS) as an index of deteriorating cerebral function on positive brain MRIs in both neurological manifestations.
This retrospective study included an examination of SARS-CoV-2 pneumonia patients with real-time reverse transcription polymerase chain reaction (RT-PCR) confirmation, admitted with clinicoradiologic evidence of COVID-19 pneumonia, and who were candidates for brain MRI due to neurological manifestations suggesting brain involvement.
Brain imaging was acquired on a 3.0 T MRI system (Skyra; Siemens, Erlangen, Germany) with a 20-channel receive head coil.
Brain MRI revealed lesions in 38 (82.6%) of the total 46 patients for analysis and was negative in the remaining eight (17.4%) of all finally enclosed patients with RT-PCR confirmed SARS-CoV-2 pneumonia. Twenty-nine (63%) patients had focal neurological manifestations, while the remaining 17 (37%) patients had non-focal neurological manifestations. The patients had a highly significant difference (p = 0.0006) in GCS, but no significant difference (p = 0.4) in the number of comorbidities they had.
In all, about 29 patients had focal neurological manifestations. The other 17 patients had non-focal neurological manifestations. The most significant lesions came from territorial infarcts or cerebral hemorrhaging.
The SARS-CoV-2-Brain study findings indicated that Brain MRI is a feasible and important imaging modality in patients with SARS-CoV-2 pneumonia who develop neurological manifestations suggestive of brain involvement, particularly in patients with non-focal manifestations and a decline in GCS.
The study findings were published in the peer reviewed journal: Scientific Reports.
All patients selected, with RT-PCR proved SARS-CoV-2 pneumonia, to be enclosed in our retrospective analysis, had neurological manifestations that may suggest brain involvement, and thence, subjected to brain MRI (Fig. 1). Desforges et al.8 stated that the increased frequency of neurological manifestations in patients with corona viral disease, including CNS manifestations, is concordant with the neurotropic nature of such virus.
MRI revealed brain lesions in 38/46 (82.6%) of RT-PCR proved SARS-CoV-2 pneumonia patients, presented with neurological manifestations suggestive of CNS involvement and finally enclosed in this retrospective study. Recent brain lesions were shown in 22/38 (57.9%) of patients with brain MRI findings and 22/46 (47.8%) of enclosed patients.
Even though, significant lesions represented only 17/46 (37%), most of them were recent territorial infarcts (8/46; 17.4%; Fig. 5) and cerebral hemorrhage (5/46; 10.9%). In the meta-analysis, by Nepal et al.9, ischemic stroke and intracerebral hemorrhage were among the CNS affection that uncommonly presented in SARS-CoV-2 infection.
Acute cerebrovascular diseases with infarcts were reported in overall 6/214 patients with COVID-19 infection (2.8%); among them, 5/88 with severe (5.7%) versus 1/126 with non-severe (0.8%) COVID-19 infection4. Also, upon retrospective cohort analysis, Merkler et al.10 found a relatively increased frequency of acute ischemic stroke in emergency and hospital amitted-COVID-19 patients (31/1916; 1.6%), compared to their corresponding ones with influenza (3/1486; 0.2%).
In our study, the recent (acute and subacute) infarcts were found in eight patients (17.4%). Seven of those patients were presented with focal neurological manifestations and one only with impaired sensorium without localization. The relatively raised incidence of recent territorial infarcts, in our retrospective analysis, is due to the refined selection criteria of RT-PCR confirmed COVID-19 patients; as being admitted with clinicoradiologic evidence of pneumonia and presented with neurological manifestations suggesting CNS involvement and necessitating cross-sectional brain imaging.
Moreover, this study comprised both acute and subacute (recent) brain infarcts on MRIs, not only the acute ones, as reported in the meta-analysis. An Italian multicenter retrospective observational study reported 34/108 (31.5%) patients with ischemic strokes of hospitalized COVID-19 patients with acute neurological symptoms11.
Almost near this latter frequency, Helmes et al.3 reported cerebral ischemic stroke, on MRI, in 3/13 patients (23%), among 58 observational consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to RT-PCR proved-COVID-19.
Nevertheless, Radmanesh et al.5 reported acute or subacute infarcts in 13 out of 242 RT-PCR proved SARS-CoV-2 patients (5.4%), who underwent brain cross-sectional imaging, as they had neurological manifestations suggestive of brain involvement. Again, the refined selection in our study, in addition to the age and gender heterogeneity among the patients enclosed in the comparative retrospective studies, are still the contributing factors for the relatively higher frequency of recent territorial infarcts in our patients.
This prior debate can also be extrapolated to the higher relative percentage frequency of recent intracerebral hemorrhage in our study (5/46; 10.9%; Fig. 6) than that of acute intracerebral hemorrhage 11/242 (4.5%) patients reported by Radmanesh et al.5
Actually, four patients were among five patients presented with severe SARS-CoV-2 pneumonia, who experienced cardiac arrest, and their brain MRI showed a picture of global hypoxic-ischemic encephalopathy (Table 2). They represented 4/46 patients with SARS-CoV-2 pneumonia (8.7%) and 4/38 of them with positive brain MRI (10.5%).
A retrospective study from China reviewed 274 patients of COVID-19, of which 24 (8.8%) developed hypoxic encephalopathy, which progressed to death in 23 (95.8%) and recovery in 1 (4.2%)12. As in our series, the global hypoxic-ischemic encephalopathy diagnoses, on MRI, in the series of Chen et al.12 were likely due to arrest-induced hypoxemia, rather than direct relation to SARS-CoV-2 pathogenesis.
Among 242 proved COVID-19 patients, with neurological manifestations necessitating cross-sectional imaging, one patient had imaging findings of widespread anoxic brain injury following a large acute supra-and infratentorial hemorrhage5. In comatose cardiac arrest survivors (non-COVID-19 patients), the MR abnormalities were diffuse and extensive, involving the cortex, thalamus, and the cerebellum in patients who never awakened, meanwhile, the patients who awakened had normal or localized findings on MR images13.
Moreover, the leptomeninges in 28 patients, subjected to contrast-enhanced brain MRI among our selected patients, did not show contrast enhancement; two of them were of the post-arrest subgroup (group C) as shown in Table 3. However, Helmes et al.3 reported leptomeningeal enhancement in 8/13 patients, among their 58 observational series out of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to RT-PCR proved COVID-19.
Yet, only one (12.5%) of those eight patients, who presented with clinical neurologic features, had diffuse bi-frontal slowing of electroencephalogram (EEG) waves, consistent with encephalopathy and cerebrospinal fluid (CSF) RT-PCR for SARS-CoV-2 was negative in 7/7 (100%) of them3.
Similarly, brain MRI was normal in two patients reports from USA and Italy, whose EEG revealed diffuse slowing consistent with encephalopathy14. Nevertheless, some researchers detected the nucleic acid in the cerebrospinal fluid of some patients and the brain tissue on autopsy of patients with other kinds of SARS-CoVs15.
The positive brain MRI in this study on confirmed patients of COVID-19 (SARS-CoV-2) pneumonia was relatively higher in the group A patients than those of group B; and as a logic finding was the relatively lower frequency of the MRI-revealed chronic brain lesions in-group A patients, as they presented with focal neurological manifestations (Table 1).
Nevertheless, the percentage frequency of the recent and significant recent lesions on brain MRI were apparently almost equal in the two groups (Table 1). Interestingly also, there was no significant difference in the mean number of comorbidities between the two groups. The latter finding may indicate the predisposition of recent lesions by such factors. Actually, as stated before, four patients with brain MRI showed a picture of global hypoxic-ischemic encephalopathy were in-group B patients (Table 2).
In addition, the MRI of two patients, with impaired sensorium without clinical localization, revealed recent cerebral infarct and recent cerebral hemorrhage, respectively. All such patients are responsible for the statistically highly significant lower GCS in-group B patients (Table 1), which showed relatively lesser negative brain MRIs than group A patients. In another term, relatively higher negative brain MRI were among the patients presented with focal neurological manifestations or relatively higher GCS (Table 1).
Nonspecific subcortical changes, suggestive of white matter microangiopathy, were found in five patients, on brain MRI, in our series (Table 3). Such lesions were the most common abnormal findings noted in 134/242 patients with SARS-CoV-2 presented with neurological manifestations in another series5. They found the lesions, to be as much as expected for age, in 108 (44.6%) patients; and more than expected for age in 26 patients (1%).
In our series, two patients, below 50 years of age and presented with non-focal neurological manifestations, out of those aforementioned five patients, had such microangiopathic lesions as lone finding on brain MRI. Interestingly, they had laboratory evidence of prior viral infections, via serum IgG level assay and one of them got MERS-CoV infection (Table 3).
Recombination of corona viruses, indicative of super infection with new corona virus is possible in the same patient, has been postulated16. The remaining three patients, who were above 50 years old and presented with focal neurological manifestations, had microangiopathic lesions, associated with lacunar infarcts on brain MRI. Nevertheless, all the five patients presented with the focal subcortical microangiopathic lesions on brain MRI in our series had full GCS (Table 3).
Despite the fact that the current study’s strength is that it demonstrated the feasibility of brain MRI in SARS-CoV-2 pneumonia patients with newly developed neurological manifestations indicating brain involvement. However, because it is retrospective, has a small number of non-randomized patients (particularly group C), and there is no available baseline brain MRI study prior to SARS-CoV-2 infection, the current study may not accurately estimate the timing of some brain lesions and patterns on MRI. The age, gender, and comorbidity heterogeneity may limit the strong link between SARS-CoV-2 and cerebrovascular disease.
In conclusion, brain MRI is a feasible and important imaging modality in selected patients with SARS-CoV-2 pneumonia on developing neurological manifestations, suggestive of brain involvement, particularly in patients with non-focal manifestations and decline in GCS.