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DOI: 10.1055/s-0043-1768060
Neuroimaging Spectrum in COVID-19 Infection: A Single-Center Experience
Abstract
Background and Purpose The ongoing coronavirus disease 2019 (COVID-19) pandemic is a multisystemic disease and involvement of the nervous system is well established. The neurological and neuroimaging features of the disease have been extensively evaluated. Our study aimed to elucidate the neuroradiological findings in COVID-19 infected patients admitted to our institute during the first and second waves of the pandemic in India.
Methods This was a single-center retrospective study of all COVID-19 positive patients who underwent neuroimaging between March 2020 and May 2021. The presenting neurological complaints, the imaging findings in computed tomography (CT) imaging, and/or magnetic resonance imaging (MRI) were recorded. They recorded the findings in the subheadings of ischemic stroke, hemorrhagic stroke, parainfectious demyelination, acute encephalitis syndrome, and changes of global hypoxic changes. Patients with age-related, chronic, and incidental findings were excluded.
Results The study comprised of 180 COVID-19 positive patients who underwent neuroimaging. CT scan was performed for 169 patients, MRI for 28, and a combination of both CT and MRI was performed for 17 patients. Seventy percent of patients were males, and median age was 61.5 years (interquartile range: 48.25–70.75). Out of the 180 patients, 66 patients had nonspecific findings that could not be attributed to COVID-19 infection. In the remaining 114 patients, 77 (42.7%) had ischemic findings, while 22 (12.2%) had hemorrhagic stroke. Hypoxic ischemic changes were noted in five patients. The rest of the patients had a spectrum of changes including, cerebellitis (3), tumefactive demyelination (1), COVID-19-associated encephalitis (1), hemorrhagic acute demyelinating encephalomyelitis (1), transverse myelitis (1), cytotoxic lesions of corpus callosum (1), Guillain-Barre syndrome (1), and COVID-19-associated microhemorrhages (1).
Conclusion Neurological manifestations of COVID-19 infection are not uncommon, and our understanding of this topic is expanding. A complex interplay of neurotropism and direct central nervous system invasion, immune activation and cytokine storm, vasculitis, and parainfectious processes are implicated in the pathophysiology. While the most common imaging finding was ischemic stroke, followed by hemorrhagic stroke, a diverse range of parainfectious findings was also noted in our study.
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Introduction
The World Health Organization classified coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus, as a pandemic on March 11, 2020.[1] What started as a respiratory infection was later discovered to be a multisystem disease with an affinity for the nervous system as well. As the pandemic evolved, it became clear that neurological symptoms were common and ranged from mild symptoms like anosmia, dysgeusia, and headache to severe central nervous system symptoms like seizures, focal neurological deficit, and acute altered mental status.[2] [3]
The current literature suggests that direct viral invasion and hyperimmune related reactions are the two main pathophysiological factors associated with neurological manifestation. The direct viral invasion of the neurons and cerebral vessel endothelium through the hematological, transcribrial, and neuronal retrograde dissemination pathways is thought to be responsible for anosmia, encephalitis, and vasculitis, whereas the immune hyperactivation and cytokine storm are responsible for the hypercoagulable state responsible for thromboembolic and hemorrhagic syndromes.[4] [5] Further, a delayed immune response is also linked to Guillain-Barre syndrome and acute demyelinating encephalomyelitis (ADEM) like manifestation.[5] [6]
This study analyzes the spectrum of neuroimaging findings during the first and second waves of COVID-19 infection admitted at out facility.
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Materials and Methods
After approval from the institutional ethics committee, a retrospective review of neurological imaging of patients with the reverse transcription-polymerase chain reaction (RT-PCR positive) and/or COVID-19 Reporting and Data System category-5 on high-resolution computed tomography of thorax was performed. The study comprised of patients from both the first and second waves of COVID-19 pandemic who were scanned between March 2020 and May 2021. Available computed tomography (CT) and/or magnetic resonance imaging (MRI) data were systematically recorded and analyzed. COVID-19 suspect cases who turned out to be RT-PCR negative and whose chest findings did not corroborate with a diagnosis of COVID-19 were excluded from the study.
Clinical and Imaging Data
Clinical and demographic data, including age and sex, coexisting comorbidities, mean duration of onset of symptoms, clinical presentation, inflammatory markers, and outcome, were collected. CT head was performed on Siemens SOMATOM Definition Flash Dual Source Dual Energy 128 × 2 slices CT scanner and Siemens SOMATOM Definition Drive Dual Source Dual Energy 128 × 2 slice CT scanner. In addition, CT angiography was performed in patients who had an acute focal neurological deficit or a nonhypertensive pattern of hemorrhage on plain CT head. MRI was performed on a 3T scanner (GE Discovery MR750w) and included axial T1-weighted imaging (T1WI), axial T2WI, three-dimensional fluid-attenuated inversion recovery, diffusion, and susceptibility-weighted images. Whenever indicated, post-contrast T1WIs, MR Angiogram, and MR venogram were obtained.
The MRI and CT studies were evaluated by two experienced radiologists in consensus (PG & ST with experience of 11 and 8 years, respectively). The imaging features were recorded in the subheadings of ischemic stroke, hemorrhagic stroke, parainfectious demyelination, acute encephalitis syndrome, and changes of global hypoxic changes. Patients with age-related changes and incidental findings, which were not related to ongoing COVID-19 infection were excluded with consensus.
Large vessel occlusion was defined as occlusion of the internal carotid artery, the M1 and M2 segments of middle cerebral artery, the P1 and P2 segment of posterior cerebral artery, the basilar trunk, the intracranial vertebral artery, and the posterior cerebral artery.[7] The small vessel occlusion included infarcts secondary to occlusion of perforating vessels, deep penetrating branches of cerebral vessels from the circle of willis.[8]
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Statistical Analysis
Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp, Armonk, IBM Corp, United States). Qualitative variables like age, gender, comorbidities, clinical symptoms, and imaging features were described by frequency and percentages.
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Result
A total of (5821) COVID-19-positive patients were admitted between May 2020 and May 2021 out of which 180 patients underwent imaging for neurological symptoms. CT scan was performed for 169 patients, MRI for 28 and a combination of both CT and MRI was performed for 17 patients. CT brain was the most used investigation modality, and MRI was reserved for cases where the clinical condition was not explained by the CT images. The median age was 61.5 years (interquartile range: 48.25–70.75). Male patients comprised 70% (126) and females 30% (54) of the study cohort. The most frequent complaint was of a focal neurological deficit (40%), presenting with weakness of either side of the body with or without aphasia and cranial nerve deficits. The next most common presentation was with altered sensorium (37.8%) followed by headache (16.2%). Other complaints were generalized weakness (3.8%), seizures (2.7%), giddiness, and vertigo (3.9%).
Of these 180 patients, who underwent neuroimaging with either CT and/or MRI brain 66 (36.6%) patients had findings not related to COVID-19 infection ([Fig. 1]). Most of these were recorded as normal study, age-related atrophic changes, or changes not related to the co-existing COVID-19 infection. Among the 114 patients with acute or subacute findings on CT/MRI of neuroaxis, features of acute or subacute ischemic stroke were the most common and were recorded in 77 patients (42.7%; 77 out of 180). On further subclassification, 52 of these 77 patients (67.5%) had large vessel occlusions, 19 (24.6%) had small vessel occlusions, and 6 (7.8%) patients had watershed infarcts. A unique feature reported in 11 patients (14.2%) was the presence of a free-floating thrombus (FFT) in the major neck arteries, predominantly involving the common carotid bifurcation. Of these 11 patients, 10 had major vessel occlusion and only one patient had small vessel occlusion.
Hemorrhagic stroke was reported in 22 patients (12.2%), with 11 cases of parenchymal hemorrhage, 6 cases of aneurysmal hemorrhage, 2 patients with nonaneurysmal subarachnoid hemorrhage, 2 cases of cerebral venous sinus thrombosis, and 1 case of subdural hemorrhage. Of the parenchymal hemorrhages, two cases were secondary to anticoagulation use. The majority of intraparenchymal hemorrhages occurred in the gangliocapsular (5 cases) and thalamic regions (3 cases).
Other imaging findings associated with COVID-19 infection in this study cohort included cerebellitis (3 patients), tumefactive demyelination (1 patient), COVID-19-associated encephalitis (1 patient), hemorrhagic ADEM (1 patient), COVID-19-associated transverse myelitis (1 patient), COVID-19-associated cytotoxic lesion of the corpus callosum (1 patient), Guillain-Barre syndrome (1 patient), and COVID-19-associated microhemorrhages (1 patient). These patients represent changes secondary to direct viral invasion, parainfectious, or postinfectious conditions. Further, hypoxic ischemic changes were reported in 5 patients on imaging.
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Discussion
The COVID-19 infection is caused by a single-stranded, positive-sensed RNA virus (SARS-CoV-2) with multisystem involvement. Although mild-to-moderate pulmonary manifestations are the most frequent presentation, about one-third of patients have neurological manifestations[9] [10] and 14 to 17% of admitted patients will require neuroimaging.[11] [12] The involvement of both the central and peripheral nervous system is well established in patients with COVID-19 infection, and this apparent neurotropism could be attributed to the widespread expression of angiotensin receptor enzyme-2 in the endothelial cells, glial cells, and astrocytes in the nervous system.[13] This expression is enhanced in coexisting comorbidities like diabetes and hypertension.[14] Other implicated mechanisms of neuro invasion are invasion of olfactory epithelium, the Trojan horse mechanism of leucocyte invasion, and subsequently bypassing the blood–brain barrier and trans-synaptic spread via the nerve terminals of the vagus nerve.[5]
In addition to direct central nervous system (CNS) invasion, other mechanisms of neurological involvement include parainfectious effects with immune hyperactivation and cytokine storm, delayed postinfectious immune response, complications arising from prolonged hospitalization, and drug-related effects.[15]
Ischemic stroke was the most common neuroimaging feature in our cohort of admitted patients with COVID-19, accounting for 42.7% of cases, of which more than two-thirds were large-vessel occlusion with territorial infarction and the rest were secondary to small vessel occlusion or watershed infarcts. Thus, a larger proportion of patients had large vessel occlusion. This contrasts with noninfected population where the incidence of large vessel usually ranges between 24 and 35% stroke ([Fig. 2]).[16] [17] In addition, 14% of the patients had FFT in major arteries, which accounted for one-fifth of the overall large vessel occlusion stroke load. This is a considerable rise from the average incidence of FFT in stroke patients, which is 1.53% ([Fig. 3]). A proinflammatory environment with cytokine storm, endothelial dysfunction, and activation of the coagulation cascade promoting a hypercoagulable state is responsible for the increased incidence of stroke in COVID-19 infection.[18] [19] [20]
Hemorrhagic stroke was reported in 22 patients in our cohort (12.2%) of cases. Half of these were parenchymal hemorrhage, of which two cases were secondary to anticoagulation use. Subarachnoid hemorrhage was reported in eight cases, of which six were aneurysmal rupture and two were nonaneurysmal subarachnoid hemorrhage ([Fig. 4]). The increased turnover and instability of arterial collagen are postulated to be related to an increased risk of aneurysmal rupture and subarachnoid hemorrhage. This mechanism is mediated by modulation of matrix metalloproteinase 2 enzyme expressed on the arterial basement membrane by the virus. Another mechanism is the vascular injury induced by the cytokine storm and elevated levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha.[21] [22] On the other hand, nonaneurysmal subarachnoid hemorrhage is linked to microthrombosis with secondary hemorrhage, coagulation dysfunction such as disseminated intravascular coagulation, and cytokine storm induced endothelitis.[23] [24] Though the causal relation of subarachnoid and intraparenchymal hemorrhage with COVID-19 infection is not established, we did find increased severity and mortality in our patient cohort. Cerebral venous sinus thrombosis was reported in only two patients (1.11%) in our cohort; thus, it was a rare association with COVID-19 infection ([Fig. 5]).
The study cohort includes three patients presenting with cerebellitis (2 pediatric cases and 1 adult), manifested with obstructive hydrocephalus, and altered sensorium during active COVID-19 infection and needed ventricular drainage ([Fig. 6]). There are isolated case reports of COVID-19-associated cerebellitis in both adult and pediatric populations and it is proposed to be secondary to direct viral neurotropism or immune mediated injury.[25] [26] We report one case of encephalitis associated with COVID-19, who presented with seizure, encephalopathy, and left hemiparesis ([Fig. 7]). COVID-19-associated meningitis and encephalitis are uncommon with an incidence of 0.03 to 0.1%.[27] We also report COVID-19-associated acute transverse myelitis and paraspinal myosotis. It is rare and represents parainfectious and postinfectious process.[28] Paraspinal myositis is proposed to be secondary to direct muscular viral infection with SARS-CoV-2 or parainfectious inflammatory process ([Fig. 8]).[29]
We report one case each of tumefactive demyelination and hemorrhagic acute demyelinating encephalomyelitis ([Figs. 9] and [10]). Both patients presented with acute onset encephalopathy in the background of ongoing COVID-19 infection. Only one case of tumefactive demyelination associated with COVID-19 infection has been published in the literature.[30] An increased incidence of ADEM has been reported in COVID-19 pandemic. A systematic review of COVID-19-associated ADEM revealed a longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, and more predilection of periventricular white matter and splenium of the corpus callosum on imaging.[31]
COVID-19-associated cytotoxic lesions of the corpus callosum was reported in one patient. MRI revealed diffusion restriction in the splenium and posterior part of the body of corpus callosum, in bilateral corona radiata, and posterior limb of internal capsules ([Fig. 11]). Although it is typically described in children, our patient was an adult. Hyperinflammatory response and cytokine storm with selective vulnerability of the corpus callosum splenium to cytokinopathy are thought to be the cause.[32] [33]
Cerebral microhemorrhages are a well-documented entity in critically ill patients with COVID-19 infection.[34] These microbleeds are predominantly subcortical and callosal in distribution. They are proposed to be secondary to severe hypoxia (akin to high altitude cerebral edema/ acute respiratory distress syndrome), consumption of coagulopathy, or COVID-19 induced endotheliitis. We could demonstrate this finding in only one patient, mostly because MRI data was available in limited cases ([Fig. 12]). Our cohort also included a case of COVID-19-associated Guillain-Barre syndrome, showing enhancement of the cauda equina nerve roots.
Apart from the direct CNS invasion, hypoxia-related changes are also described in the CNS owing to respiratory involvement and impaired gas exchange at the alveoli-capillary level. Features of hypoxic ischemic insult were reported in five patients, with all of them having a fatal outcome.
The study has several limitations. First, CT scans were the most used imaging modality in most patients, with only a few cases undergoing MRI. This is particularly true for cases during the first wave and early part of the second wave. MRI was reserved for COVID-19 cases with clinical dilemma or with the highest clinical urgency. Second, the study includes the hospitalized patient with positive RT-PCR, hence postinfectious COVID-19-associated condition occurring during the convalescent phase could not be included. Third, this study had inherent limitations related to its retrospective nature.
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Conclusion
As the COVID-19 epidemic has evolved, our understanding of the neurological presentation and neuroimaging findings linked with this illness has grown. We offer a view of neuroimaging characteristics for a tertiary care hospital in India, where ischemic and hemorrhagic stroke are the most common manifestations, as reported globally.
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Conflict of Interest
None declared.
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References
- 1 World Health Organization Director-General's Opening Remarks at the Media Briefing on COVID-19–11 March 2020. Accessed March 22, 2023 at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—211-march-2020
- 2 Amanat M, Rezaei N, Roozbeh M. et al. Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study. BMC Neurol 2021; 21 (01) 116
- 3 Panda S, Jain S, Sharma S, Tiwari S. Neurological manifestations in COVID-19. Chemistry World. [RSC Books, Preprint]. 19 February 2021 (accessed: 2 June 2021). Accessed March 22, 2023 at: https://www.chemistryworld.com/the-coronavirus-pandemic-and-the-future/neurological-manifestations-in-covid-19/4013172
- 4 Zhou Z, Kang H, Li S, Zhao X. Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol 2020; 267 (08) 2179-2184
- 5 Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA Neurol 2020; 77 (08) 1018-1027
- 6 Bratosiewicz-Wąsik J. Neuro-COVID-19: an insidious virus in action. Neurol Neurochir Pol 2022; 56 (01) 48-60
- 7 Rennert RC, Wali AR, Steinberg JA. et al. Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke. Neurosurgery 2019; 85 (Suppl. 01) S4-S8
- 8 Wardlaw JM, Smith EE, Biessels GJ. et al; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12 (08) 822-838
- 9 World Health Organization. Neurology and COVID-19: scientific brief, 29 September 2021. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Neurology-2021.1
- 10 Misra S, Kolappa K, Prasad M. et al. Frequency of neurologic manifestations in COVID-19: a systematic review and meta-analysis. Neurology 2021; 97 (23) e2269-e2281
- 11 Jain R, Young M, Dogra S. et al. COVID-19 related neuroimaging findings: a signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. J Neurol Sci 2020; 414: 116923
- 12 Yoon BC, Buch K, Lang M. et al. Clinical and neuroimaging correlation in patients with COVID-19. Am J Neuroradiol 2020; 41 (10) 1791-1796
- 13 Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 2020; 9 (01) 45
- 14 Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. Lancet Respir Med 2020; 8 (04) e21
- 15 Moonis G, Filippi CG, Kirsch CFE. et al. The spectrum of neuroimaging findings on CT and MRI in adults with COVID-19. Am J Roentgenol 2021; 217 (04) 959-974
- 16 Dozois A, Hampton L, Kingston CW. et al. PLUMBER study (prevalence of large vessel occlusion strokes in Mecklenburg County emergency response). Stroke 2017; 48 (12) 3397-3399
- 17 Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front Neurol 2017; 8: 651
- 18 Panda S, Tiwari S, Pamnani J. et al. Large vessel occlusions by free floating thrombi in strokes during the COVID-19 pandemic- a single center observational study. Neurol India 2022; 70 (02) 623-632
- 19 Kihira S, Schefflein J, Mahmoudi K. et al. Association of coronavirus disease (COVID-19) with large vessel occlusion strokes: a case-control study. Am J Roentgenol 2021; 216 (01) 150-156
- 20 Fridman S, Lownie SP, Mandzia J. Diagnosis and management of carotid free-floating thrombus: a systematic literature review. Int J Stroke 2019; 14 (03) 247-256
- 21 Cezar-Junior AB, Faquini IV, Silva JLJ. et al. Subarachnoid hemorrhage and COVID-19: association or coincidence?. Medicine (Baltimore) 2020; 99 (51) e23862
- 22 Muhammad S, Petridis A, Cornelius JF, Hänggi D. Letter to editor: Severe brain haemorrhage and concomitant COVID-19 Infection: A neurovascular complication of COVID-19. Brain, behavior, and immunity. 2020 Jul;87:150.
- 23 Ghosh R, Roy D, Ray A. et al. Non-aneurysmal subarachnoid hemorrhage in COVID-19: a case report and review of literature. Med Res Arch 2022; 10 (01) 2673
- 24 Harrogate S, Mortimer A, Burrows L, Fiddes B, Thomas I, Rice CM. Non-aneurysmal subarachnoid haemorrhage in COVID-19. Neuroradiology 2021; 63 (01) 149-152
- 25 Fadakar N, Ghaemmaghami S, Masoompour SM. et al. A first case of acute cerebellitis associated with coronavirus disease (COVID-19): a case report and literature review. Cerebellum 2020; 19 (06) 911-914
- 26 Moreno-Escobar MC, Feizi P, Podury S. et al. Acute cerebellitis following SARS-CoV-2 infection: a case report and review of the literature. J Med Virol 2021; 93 (12) 6818-6821
- 27 Favas TT, Dev P, Chaurasia RN. et al. Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions. Neurol Sci 2020; 41 (12) 3437-3470
- 28 Román GC, Gracia F, Torres A, Palacios A, Gracia K, Harris D. Acute transverse myelitis (ATM): clinical review of 43 patients with COVID-19-associated ATM and 3 post-vaccination ATM serious adverse events with the ChAdOx1 nCoV-19 vaccine (AZD1222). Front Immunol 2021; 12: 653786
- 29 Mehan WA, Yoon BC, Lang M, Li MD, Rincon S, Buch K. Paraspinal myositis in patients with COVID-19 infection. Am J Neuroradiol 2020; 41 (10) 1949-1952
- 30 Kelley B, Mixis B, Beinlich B, Chagharvand S, Allen S. Tumefactive acute disseminated encephalomyelitis after recent COVID-19 infection. Case Rep Neurol 2021
- 31 Wang Y, Wang Y, Huo L, Li Q, Chen J, Wang H. SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature. J Neurol 2022; 269 (03) 1071-1092
- 32 Edjlali M, Le Gal A, Louvet M. et al; Garches COVID-19 Collaborative Group. Teaching NeuroImages: cytotoxic lesions of the corpus callosum in encephalopathic patients with COVID-19. Neurology 2020; 95 (22) 1021-1022
- 33 Moreau A, Ego A, Vandergheynst F. et al. Cytotoxic lesions of the corpus callosum (CLOCCs) associated with SARS-CoV-2 infection. J Neurol 2021; 268 (05) 1592-1594
- 34 Agarwal S, Jain R, Dogra S. et al. Cerebral microbleeds and leukoencephalopathy in critically ill patients with COVID-19. Stroke 2020; 51 (09) 2649-2655
Address for correspondence
Publication History
Article published online:
28 April 2023
© 2023. Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 World Health Organization Director-General's Opening Remarks at the Media Briefing on COVID-19–11 March 2020. Accessed March 22, 2023 at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—211-march-2020
- 2 Amanat M, Rezaei N, Roozbeh M. et al. Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study. BMC Neurol 2021; 21 (01) 116
- 3 Panda S, Jain S, Sharma S, Tiwari S. Neurological manifestations in COVID-19. Chemistry World. [RSC Books, Preprint]. 19 February 2021 (accessed: 2 June 2021). Accessed March 22, 2023 at: https://www.chemistryworld.com/the-coronavirus-pandemic-and-the-future/neurological-manifestations-in-covid-19/4013172
- 4 Zhou Z, Kang H, Li S, Zhao X. Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol 2020; 267 (08) 2179-2184
- 5 Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA Neurol 2020; 77 (08) 1018-1027
- 6 Bratosiewicz-Wąsik J. Neuro-COVID-19: an insidious virus in action. Neurol Neurochir Pol 2022; 56 (01) 48-60
- 7 Rennert RC, Wali AR, Steinberg JA. et al. Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke. Neurosurgery 2019; 85 (Suppl. 01) S4-S8
- 8 Wardlaw JM, Smith EE, Biessels GJ. et al; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12 (08) 822-838
- 9 World Health Organization. Neurology and COVID-19: scientific brief, 29 September 2021. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Neurology-2021.1
- 10 Misra S, Kolappa K, Prasad M. et al. Frequency of neurologic manifestations in COVID-19: a systematic review and meta-analysis. Neurology 2021; 97 (23) e2269-e2281
- 11 Jain R, Young M, Dogra S. et al. COVID-19 related neuroimaging findings: a signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. J Neurol Sci 2020; 414: 116923
- 12 Yoon BC, Buch K, Lang M. et al. Clinical and neuroimaging correlation in patients with COVID-19. Am J Neuroradiol 2020; 41 (10) 1791-1796
- 13 Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 2020; 9 (01) 45
- 14 Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. Lancet Respir Med 2020; 8 (04) e21
- 15 Moonis G, Filippi CG, Kirsch CFE. et al. The spectrum of neuroimaging findings on CT and MRI in adults with COVID-19. Am J Roentgenol 2021; 217 (04) 959-974
- 16 Dozois A, Hampton L, Kingston CW. et al. PLUMBER study (prevalence of large vessel occlusion strokes in Mecklenburg County emergency response). Stroke 2017; 48 (12) 3397-3399
- 17 Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front Neurol 2017; 8: 651
- 18 Panda S, Tiwari S, Pamnani J. et al. Large vessel occlusions by free floating thrombi in strokes during the COVID-19 pandemic- a single center observational study. Neurol India 2022; 70 (02) 623-632
- 19 Kihira S, Schefflein J, Mahmoudi K. et al. Association of coronavirus disease (COVID-19) with large vessel occlusion strokes: a case-control study. Am J Roentgenol 2021; 216 (01) 150-156
- 20 Fridman S, Lownie SP, Mandzia J. Diagnosis and management of carotid free-floating thrombus: a systematic literature review. Int J Stroke 2019; 14 (03) 247-256
- 21 Cezar-Junior AB, Faquini IV, Silva JLJ. et al. Subarachnoid hemorrhage and COVID-19: association or coincidence?. Medicine (Baltimore) 2020; 99 (51) e23862
- 22 Muhammad S, Petridis A, Cornelius JF, Hänggi D. Letter to editor: Severe brain haemorrhage and concomitant COVID-19 Infection: A neurovascular complication of COVID-19. Brain, behavior, and immunity. 2020 Jul;87:150.
- 23 Ghosh R, Roy D, Ray A. et al. Non-aneurysmal subarachnoid hemorrhage in COVID-19: a case report and review of literature. Med Res Arch 2022; 10 (01) 2673
- 24 Harrogate S, Mortimer A, Burrows L, Fiddes B, Thomas I, Rice CM. Non-aneurysmal subarachnoid haemorrhage in COVID-19. Neuroradiology 2021; 63 (01) 149-152
- 25 Fadakar N, Ghaemmaghami S, Masoompour SM. et al. A first case of acute cerebellitis associated with coronavirus disease (COVID-19): a case report and literature review. Cerebellum 2020; 19 (06) 911-914
- 26 Moreno-Escobar MC, Feizi P, Podury S. et al. Acute cerebellitis following SARS-CoV-2 infection: a case report and review of the literature. J Med Virol 2021; 93 (12) 6818-6821
- 27 Favas TT, Dev P, Chaurasia RN. et al. Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions. Neurol Sci 2020; 41 (12) 3437-3470
- 28 Román GC, Gracia F, Torres A, Palacios A, Gracia K, Harris D. Acute transverse myelitis (ATM): clinical review of 43 patients with COVID-19-associated ATM and 3 post-vaccination ATM serious adverse events with the ChAdOx1 nCoV-19 vaccine (AZD1222). Front Immunol 2021; 12: 653786
- 29 Mehan WA, Yoon BC, Lang M, Li MD, Rincon S, Buch K. Paraspinal myositis in patients with COVID-19 infection. Am J Neuroradiol 2020; 41 (10) 1949-1952
- 30 Kelley B, Mixis B, Beinlich B, Chagharvand S, Allen S. Tumefactive acute disseminated encephalomyelitis after recent COVID-19 infection. Case Rep Neurol 2021
- 31 Wang Y, Wang Y, Huo L, Li Q, Chen J, Wang H. SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature. J Neurol 2022; 269 (03) 1071-1092
- 32 Edjlali M, Le Gal A, Louvet M. et al; Garches COVID-19 Collaborative Group. Teaching NeuroImages: cytotoxic lesions of the corpus callosum in encephalopathic patients with COVID-19. Neurology 2020; 95 (22) 1021-1022
- 33 Moreau A, Ego A, Vandergheynst F. et al. Cytotoxic lesions of the corpus callosum (CLOCCs) associated with SARS-CoV-2 infection. J Neurol 2021; 268 (05) 1592-1594
- 34 Agarwal S, Jain R, Dogra S. et al. Cerebral microbleeds and leukoencephalopathy in critically ill patients with COVID-19. Stroke 2020; 51 (09) 2649-2655