Atormac
briv
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 2769  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (2,307 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 »  Neuroimaging Pat...
 » Pathogenesis
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed1152    
    Printed10    
    Emailed0    
    PDF Downloaded39    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
REVIEW ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 260-271

Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review


1 Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
2 Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, Uttar Pradesh, India

Date of Submission11-Oct-2020
Date of Acceptance18-Jan-2021
Date of Web Publication24-Apr-2021

Correspondence Address:
Dr. Ravindra K Garg
Department of Neurology, King George Medical University, Lucknow - 226 003, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.314531

Rights and Permissions

 » Abstract 


Background: A variety of neuroimaging abnormalities in COVID-19 have been described. Objectives: In this article, we reviewed the varied neuroimaging patterns in patients with COVID-19-associated neurological complications. Methods: We searched PubMed, Google Scholar, Scopus and preprint databases (medRxiv and bioRxiv). The search terms we used were “COVID -19 and encephalitis, encephalopathy, neuroimaging or neuroradiology” and “SARS-CoV-2 and encephalitis, encephalopathy, neuroimaging or neuroradiology”. Results: Neuroimaging abnormalities are common in old age and patients with comorbidities. Neuroimaging abnormalities are largely vascular in origin. COVID-19-associated coagulopathy results in large vessel occlusion and cerebral venous thrombosis. COVID-19-associated intracerebral hemorrhage resembles anticoagulant associated intracerebral hemorrhage. On neuroimaging, hypoxic-ischemic damage along with hyperimmune reaction against the SARS-COV-2 virus manifests as small vessel disease. Small vessel disease appears as diffuse leukoencephalopathy and widespread microbleeds, and subcortical white matter hyperintensities. Occasionally, gray matter hyperintensity, similar to those observed seen in autoimmune encephalitis, has been noted. In many cases, white matter lesions similar to that in acute disseminated encephalomyelitis have been described. Acute disseminated encephalomyelitis in COVID-19 seems to be a parainfectious event and autoimmune in origin. Many cases of acute necrotizing encephalitis resulting in extensive damage to thalamus and brain stem have been described; cytokine storm has been considered a pathogenic mechanism behind this. None of the neuroimaging abnormalities can provide a clue to the possible pathogenic mechanism. Conclusions: Periventricular white-matter MR hyperintensity, microbleeds, arterial and venous infarcts, and hemorrhages are apparently distinctive neuroimaging abnormalities in patients with COVID-19.


Keywords: Acute disseminated encephalomyelitis, encephalitis, encephalopathy, leukoencephalopathy, SARS-COV-2
Key Message: A variety of neuroimaging abnormalities in COVID-19 have been described. Neuroimaging abnormalities are often vascular in origin. None of the neuroimaging abnormality is specific for COVID-19. Hypoxic-ischemic encephalopathy, on neuroimaging, manifests as diffuse leukoencephalopathy, widespread microbleeds and subcortical white matter hyperintensities.


How to cite this article:
Garg RK, Paliwal VK, Malhotra HS, Sharma PK. Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review. Neurol India 2021;69:260-71

How to cite this URL:
Garg RK, Paliwal VK, Malhotra HS, Sharma PK. Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review. Neurol India [serial online] 2021 [cited 2021 May 9];69:260-71. Available from: https://www.neurologyindia.com/text.asp?2021/69/2/260/314531




COVID-19 is caused by a novel coronavirus named severe acute respiratory syndrome corona virus-2 (SARS-COV-2). The SARS-COV-2 virus is a positive-stranded RNA virus that belongs to the family Coronaviridae. World Health Organization reports that, currently, there are more than 36.7 million confirmed COVID-19 cases world-wide. So far, across the world, 1064838 COVID-19 related deaths have been reported. COVID-19 pandemic is active in 235 countries.[1] Approximately 20% of COVID-19 patients have severe disease and 5% of them eventually become critically ill. A critical illness is characterized by dysfunction of multiple body organs including, respiratory functions, neurological dysfunction, cardiac dysfunction, shock, renal failure, liver damage, and metabolic derangements. The mortality is higher in older age groups and in those with comorbidities.[2]

Increasing number of reports are now demonstrating neuroimaging abnormalities in COVID-19-associated encephalopathy/encephalitis.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24] [Table 1] and [Table 2] In this article, we have reviewed the neuroimaging pattern, diagnostic utility, and possible pathogenic mechanisms of COVID-19-associated neuroimaging abnormalities.
Table 1: Neuroimaging findings in COVID-19 (data from cohort studies)

Click here to view
Table 2: Spectrum of neuroimaging pattern in COVID-19

Click here to view


Neurological complications

Analysis of TriNetX database comprising of data of 40,469 COVID-19 patients noted that 9086 (22.5%) patients had some kind of neuropsychiatric complications. The frequently encountered neurological complications were headache, sleep disorders, encephalopathy, myalgia, pain, loss of taste and smell, cerebrovascular disease, dizziness, extrapyramidal and movement disorders, seizures, polyneuropathy, and radiculopathy and plexopathy.[25] Mao and colleagues, in a retrospective study from China, noted neurological complications in 36.4% (78/214) of indoor patients with laboratory-confirmed COVID-19. Among severe central nervous system complications, altered consciousness was noted in 16 (7.5%) patients. Stroke was the next serious complication noted in 6 (2.8%) patients. Five patients had ischemic stroke and one had intracerebral hemorrhage. Patients with stroke had severe COVID-19.[26] Of note, neurological complications are generally more common in older age groups and patients with pre-existing comorbidities.[27]

Search strategy for Neuroimaging patterns in COVID-19

For this review, we searched all publications regarding neuroimaging aspects of COVID-19-associated encephalitis and encephalopathy. We searched PubMed, Google Scholar, Scopus, preprint databases (medRxiv and bioRxiv). We reviewed all kinds of published articles including case reports, case series, cohort studies, and review articles. The search terms used were “COVID -19 and encephalitis, encephalopathy, neuroimaging or neuroradiology” and “SARS-CoV-2 and encephalitis, encephalopathy, neuroimaging or neuroradiology”. Relevant full-text articles from journals' websites were reviewed. We analyzed the neuroimaging characteristics of COVID-19-associated neurological complications. The last search was performed on September 27, 2020.


 » Neuroimaging Patterns in COVID-19 Top


Large vessel occlusion

Many reports have described cases of large cerebral vessel occlusion in COVID-19 patients. For example, in a retrospective study, conducted in 56 hospitals of China and enrolled 917 confirmed COVID-19 patients, revealed neurological complications in 32 (3.5%) patients. Altered consciousness (n = 25) and stroke (n = 10) were the most frequent neurological complications. The majority had either infarct in the region of a large cerebral vessel territory or the water-shed region.[27],[28] Similar observations were recorded in a large study that included data from Europe and America. The study focussed on large cerebral vessel occlusions. In this study 88 (1.3%) patients with acute ischemic strokes were included, 66 patients had a large cerebral vessel occlusion. In majority, the middle cerebral artery and internal carotid artery were occluded.[29] Oxley described 5 young patients of COVID-19-associated ischemic strokes; in 4 patients, infarcts were in the territory of the middle cerebral artery and internal carotid artery. In one patient, posterior cerebral circulation was involved.[30]

Infrequently, infarcts in multiple brain territory has been described.[31] Guillan and colleagues described a 67-year-old COVID-19 affected man, who presented with altered mental status and acute cortical vision loss. MRI brain noted infarcts in the territories of the middle cerebral artery, the left posterior cerebral artery, and the right superior cerebellar artery.[32] Large vessel occlusion strokes in patients with COVID-19 is associated with severe disease, multivessel involvement and enhanced mortality than patients without COVID-19.[33]

Cerebral venous thrombosis

Neuroimaging in patients with cerebral venous thrombosis demonstrates brain infarction, edema, or hemorrhage and the thrombosed sinus. Cerebral infarct does not correspond to any arterial territory and has hemorrhagic components. Lately, many reports have described cerebral venous thrombosis in COVID-19. In COVID-19 patients, both superficial and deep cerebral venous systems are likely to be affected. In COVID-19-associated cerebral venous thrombosis, multiple superficial venous sinuses (superior sagittal sinus, lateral sinus, and sigmoid sinus) are typically involved, however, thrombosis of the superior sagittal sinus involvement is the more frequent.[34],[35]

Thrombosis affecting the deep venous system (straight sinus, internal cerebral veins, vein of Galen, the vein of Rosenthal) can present with unusual neuroimaging findings. Chougar and colleagues described COVID-19 patients who had deep cerebral vein thrombosis with hemorrhagic venous infarction with several unusual imaging features. There was a large necrotic infarction in right thalamus and basal ganglion extending up to the right cerebral peduncle and the pons. There were hemorrhagic changes in the lateral ventricle too.[36]

Cavalcanti and co-workers described neuroimaging in 3 patients with COVID-19-associated cerebral venous thrombosis. One patient had thrombosis in both the superficial and deep cerebral venous systems. Another patient had thrombosis of the straight sinus, the vein of Galen, and internal cerebral veins. In the third patient, venography demonstrated thrombosis of the deep medullary veins. These patients either had hemorrhagic infarcts and/or hydrocephalus. All patients clinically had acute encephalopathy. In two patients, chest imaging revealed characteristic ground-glass lung abnormalities.[34]

Intracerebral hemorrhage

COVID-19-associated intracerebral hemorrhage on neuroimaging resembles anticoagulant associated intracerebral hemorrhage. COVID-19-associated intracerebral hemorrhage are frequently a lobar in location. These hemorrhages are often multiple, irregular in shape, and may have intraventricular extension.[37],[38],[39] The fluid-blood levels within the intracranial hematoma, akin to that seen in anticoagulant-associated hematoma, is a characteristic finding of COVID-19 intracranial hemorrhage [Figure 1].[40],[41]
Figure 1: X-ray chest shows patchy reticular and nodular lung shadows, with basal, peripheral and bilateral distribution. (Left) Non-contrast axial computed tomography of the brain showsan irregular (heterogeneous) left gangliocapsular hemorrhage. (Right)

Click here to view


In COVID-19, heparin therapy can precipitate massive multifocal intraparenchymal hemorrhage with intraventricular extension and can lead to rapid deterioration and death.[38] In a retrospective study of 33 COVID-19 patients with neuroimaging-documented intracerebral hemorrhage, five catastrophic large hemorrhages with herniation were observed while in others hemorrhages were small.[42] Ghani and colleagues described three cases of intracranial hemorrhage in critically ill patients because of anticoagulation therapy.[43]

Nicholson and co-workers described the neuroimaging pattern in 4 patients with encephalopathy. MRI demonstrated varied picture like subcortical or cortical petechial multiple hemorrhages, subarachnoid bleed, parenchymal hematoma with fluid level, and intraventricular hemorrhage. Susceptibility-weighted imaging showed much more extensive abnormality consistent with thrombotic microangiopathy. All 4 patients had markedly elevated D-dimer levels.[44] In a retrospective cohort study, authors noted that anticoagulation use was associated with a five-fold increased risk of intracerebral hemorrhage and COVID-19-associated intracerebral hemorrhage , in turn, was associated with increased mortality.[45]

Neuropathological examination of the brain corroborated the frequent cerebrovascular complications in COVID-19. In an autopsy study, the most notable finding was widespread microthrombi and acute infarction. Acute parenchymal micro-hemorrhages, especially within the necrotic infarct were noted. Hemorrhagic transformation of infarct indicated vessel damage and reperfusion injury.[46]

Small vessel disease

Cerebral small vessel disease refers to involvement of vessels of small caliber, including smaller arteries, arterioles, capillaries, and small veins. Small vessel disease is, otherwise, common in aging adults. Small subcortical infarcts, lacunar infarcts, cerebral microbleeds, cortical microinfarcts, and white matter hyperintensity of presumed vascular origin represent the major neuroimaging markers of small vessel disease [Figure 2].[47]
Figure 2: Axial sections of MRI (Brain) show an unremarkable T1W image (a) while T2W (b) and FLAIR (c) depict multiple subcortical hyperintensities especially at the ventricular angles. Of note is the presence of multiple cortical microhemorrhages seen in susceptibility weighted angiography sequence (d)

Click here to view


Coolen and co-workers performed an MRI evaluation in 19 critically ill patients of COVID-19 immediately after death (within 24 hours). MRI abnormalities were observed in 4 patients. Brain MRI abnormalities were consistent with cerebral small vessel disease. Abnormalities were diffuse microbleeds and macrobleeds, and marked deep white matter changes. In one patient imaging abnormality was consistent with posterior reversible encephalopathy syndrome.[48]

Leukoencephalopathy

Hyperintense T2/FLAIR white matter abnormalities a common neuroimaging abnormality in COVID-19-associated encephalopathy. These white matter hyperintensities generally indicate cerebral microangiopathy. Damage to the deep perforating cerebral vessels is held responsible for white matter abnormalities of the brain. The deep perforating cerebral vessels lack anastomotic system, hence white matter becomes vulnerable to cerebral ischemia.[49]

Leukoencephalopathy is a term that refers to an extensive subcortical white-matter tract involvement. In COVID-19 subcortical white-matter is particularly vulnerable because hypoxic injury inflicts additional damage to the deep penetrating cerebral vessels.[21],[50],[51] In a series described by Radmanesh and co-workers, out of 11 patients that were evaluated, 10 had leukoencephalopathy. T2/FLAIR MRI hyperintense lesions were symmetric and confluent and involved bilateral deep and subcortical white matter. These lesions also demonstrated mild restricted diffusion. All 11 patients of this series were critically ill and were on mechanical ventilation [Figure 2].[18]

Histopathology of the brain of patients, who died of critical illness, demonstrated hypoxic damage of cerebrum and cerebellum. Loss of neurons was recorded in the cerebral cortex, hippocampus, and cerebellar Purkinje cell layer. However, there was no evidence of the presence of cerebral thrombi or vasculitis.[52] Damage to cerebral neurons possibly resulted in diffuse or focal cerebral leukoencephalopathy.

Microbleeds

White matter microbleeds are common neuroimaging abnormalities in patients with COVID-19-associated encephalopathy. White matter microbleeds are small, bilateral, symmetrically distributed, round foci of low signal intensity with the predominant location in juxta-cortical white matter and corpus callosum. White matter microbleeds are best visualized in magnetic resonance imaging gradient echo (GRE) or susceptibility-weighted angiography sequences. White matter microbleeds are considered indicative of cerebral microangiopathy [Table 1] and [Figure 2].[15],[39],[53]

The presence of extensive white matter microbleeds has also been demonstrated on autopsy. von Weyhern and colleagues performed autopsy in six patients, who died from severe COVID-19. In younger patients, autopsy revealed the presence of diffuse cerebral petechial hemorrhage. Besides, there were extensive involvement of brain, meninges, and brainstem as well.[54]

Acute necrotizing encephalitis

Acute necrotizing encephalopathy is unusual devastating complication described in many viral infections. Acute necrotizing encephalopathy has also been described in severe COVID-19. Characteristically, in acute necrotizing encephalopathy imaging shows symmetric, multifocal lesions with predominant bilateral thalamic and brainstem involvement. Other commonly involved structures are brain stem, cerebral white matter, and cerebellum. T2/FLAIR images reveal hyperintense lesions with hemorrhage. Postcontrast images may show a ring enhancement. Intense inflammatory reaction resulting in cytokine storm is held responsible for acute necrotizing encephalopathy in COVID-19.[55],[56] Histopathology of autopsied affected brain tissue may reveal the perivascular lymphocytic infiltration and neuronal necrosis.[57] Virhammar and colleagues, in a similar case, demonstrated SARS-CoV-2 viral RNA in CSF.[58]

Delamarre and colleagues in a recently published case report demonstrated that clinical syndrome and neuroimaging lesions of acute necrotizing encephalopathy showed significant improvement following methylprednisolone and intravenous immunoglobulin treatment.[59]

Acute disseminated encephalomyelitis

There are reports where a neuroimaging picture like acute disseminated encephalomyelitis (ADEM) has been described following the SARS-COV-2 infection. These patients clinically present with acute encephalopathy and imaging lesions are characterized by bilateral, asymmetrically distributed white matter T2/FLAIR hyperintensity. Patients of COVID-19-associated ADEM show improvement following methylprednisolone therapy [Figure 3].[60],[61]
Figure 3: T2W-axial section (a) of MRI (Brain) shows subcortical and periventricular hyperintensities (left > right) that do not show gadolinium-contrast (b) uptake. Involvement of the medullary pyramids (c, arrowheads) is evident on T2W sequence. Sagittal (d-f) and axial (g-i) sections of MRI (Spine) show involvement of the spinal cord (predominantly central and paracentral) extending from the lower medulla to C5 vertebral level (arrowhead, arrow) that is iso-hypointense on T1W (d and g), hyperintense on T2W (e and h) and gadolinium-contrast uptake essentially sparing the zone of involvement on T1-contrast (f and i) sequences

Click here to view


An autopsy study confirmed demyelinating changes in the brain, in a patient who died of COVID-19. The authors demonstrated hemorrhagic white matter demyelinating lesions throughout the brain. Histopathology revealed scattered clusters of macrophages, associated axonal injury, and a perivascular ADEM-like change in the subcortical white matter.[62]

Cortical gray matter hyperintensity

In COVID-19-associated encephalitis, neuroimaging demonstrated orbitofrontal cortex and hippocampal and mesial temporal hyperintensity akin to that seen in autoimmune encephalitis.[63],[64],[65] Moriguchi and colleagues described a case of COVID-19-associated encephalitis; FLAIR images, in this case, demonstrated hyperintense signal abnormalities in the right mesial temporal lobe and hippocampus. Besides, DWI images demonstrated hyperintensity along the wall of the inferior horn of the right lateral ventricle. The CSF in this patient was positive for the SARS-CoV-2.[66] In another similar case, Efe and colleagues described an unusual case of COVID-19-associated encephalitis. MRI demonstrated marked T2/FLAIR hyperintensity in the left temporal lobe. The patient had uncontrolled seizures so anterior temporal lobectomy was done. Histopathological examination of resected brain tissue demonstrated inflammatory changes consistent with encephalitis.[67] Human brain gene-expression recently suggested that the hypothalamus and other structures of limbic system express ACE 2 receptor and transmembrane proteinase, serine 2. Both these receptors mediate SARS-CoV-2 entry in neurons.[68]

Cytotoxic lesions of the corpus callosum

Rasmussen and colleagues described dominant corpus callosum involvement in a 66-year-old patient with multiple comorbidities. MRI signal changes were dominantly present in the splenium. Patient was having encephalopathy and was admitted in intensive care unit. Cytokine storm was considered responsible for clinical manifestations and imaging changes.[69]

Splenium hyperintensity

Hayashi and colleagues described a 75-year-old man with COVID-19-associated encephalopathy. MRI of the brain, on DWI sequences, revealed a reversible abnormal hyperintensity in the splenium of corpus callosum.[70]

Splenium signal changes were noted in four severely ill pediatric patients having the pediatric multisystem inflammatory syndrome. All these patients had encephalopathy. Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to severe disease characterized by dysregulated immune response and extensive tissue damage.[71]

Cortical laminar lesions

Cortical laminar necrosis is a condition that indicates a state of hypoxia and brain energy depletion. Anzalone and colleagues reported four cases with COVID-19-associated subacute encephalopathy, neuroimaging in these patients revealed multiple areas of T2/FLAIR cortical laminar hyperintensity in the parietal, occipital and frontal lobes. In cortical laminar necrosis, T2/FLAIR hyperintensity followed the gyral pattern. After one month, all lesions had completely disappeared.[72]

Posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES) refers to a disorder with reversible posterior cortical white matter T2/FLAIR hyperintensity. MRI lesions predominantly involve bilateral parieto-occipital regions. In COVID-19-associated PRES, hemorrhage in demyelinating lesions are common.[73],[74] PRES in COVID-19 possibly caused because of blood pressure fluctuations indicating that manifestations of hypertensive encephalopathy may occur at lower blood pressure thresholds due to endothelial dysfunction [Figure 4].[75],[76],[77]
Figure 4: Axial sections of computed tomography (a and b) show posteriorly-predominant hypodensities (finger-like projections) suggestive of white matter involvement. Axial sections of MRI (Brain) show similar posteriorly-predominant hyperintensities on T2W (c) and FLAIR (d) sequences

Click here to view


Diffuse cerebral oedema

Fulminant diffuse cerebral oedema with chinked ventricles, effaced sulci, obliterated basal cisterns and herniated brain has been described in a severely ill patient of COVID-19.[78]

Leptomeningeal enhancement

In many patients, contrast-enhanced MRI revealed cerebral and spinal leptomeningeal enhancement. The precise reason for meningeal enhancement may be a not clear but either a direct viral meningeal invasion or an autoimmune meningeal inflammation may be a likely pathogenic mechanism.[24]

Olfactory tract changes

Anosmia is a common symptom of COVID-19. Frequently, anosmia is a heralding manifestation. Smell sensations are transmitted to the limbic system of the brain via olfactory nerve and olfactory bulb across the cribriform plate. Neuroimaging in a patient with COVID-19 and anosmia revealed a cortical hyperintensity in the right gyrus rectus in the olfactory bulbs.[79] In another patient, Laurendon and colleagues demonstrated olfactory bulb edema. Olfactory clefts showed mild hyperintensity. Rest of the olfactory pathway was normal.[80]

Miller Fisher syndrome

Miller Fisher syndrome is a post-infectious autoimmune disorder. Lately, several cases of Miller Fisher syndrome have been described in association with COVID-19. Miller Fisher syndrome is clinically characterized by ophthalmoplegia, ataxia, and areflexia. In a recent report, neuroimaging demonstrated enlargement, T2 hyperintensity, and enhancement of third cranial nerve throughout its course from the cavernous sinus to the orbit.[81]

Myelitis

In many reports of isolated cases, imaging abnormalities of the spinal cord have been described. In COVID-19, spinal cord can be affected by several pathogenic processes viz., acute inflammatory transverse myelitis, acute disseminated encephalomyelitis, and acute flaccid myelitis [Figure 3]. MRI of spinal cord in COVID-19-associated myelitis often demonstrates longitudinally extensive transverse myelitis. Acute flaccid myelitis is a polio-like illness, that is characterized by acute flaccid paraparesis and long T2/FLAIR hyperintensity of the gray matter of the spinal cord.[82],[83],[84]

Incidental MRI findings

Imaging of spine and CT angiography performed for non-pulmonary indications may occasionally demonstrate unsuspected lung findings, consistent with the COVID-19. Now experts recommend that routine lung imaging should be included the neuroimaging protocol.[85]

Incidental gadolinium enhancement of bilateral abducens and right ophthalmic veins were noticed along with bilateral facial nerve enhancement in a patient with bifacial weakness in a variant of Guillain-Barrè syndrome.[86] Another case presenting with ophthalmoparesis demonstrated enhancement of multiple cranial nerves.[87]

Siddiqui and co-workers noted that assessment of apical portion of lungs, while performing carotid computed tomography angiography in patients of stroke, can help in detecting unsuspected COVID-19. Apical ground-glass shadows were observed in 22.2% (50/225) patients.[88]


 » Pathogenesis Top


Cytokine storm

The sudden unexpected massive influx of proinflammatory cytokines is the hallmark feature of severe COVID-19 infection. High plasma levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β have been observed in critically ill patients leading to vascular hyperpermeability, multiorgan failure, and death. Cytokine storm disrupts blood-brain barrier leading to brain injury and neuroimaging abnormalities.[89],[90]

Coagulopathy

Cytokine storms can induce coagulopathy.[91] COVID-19-associated coagulopathy is often held responsible for cerebral vascular complications, like large vessel occlusion, cerebral venous thrombosis, and intracerebral hemorrhage. Elevated levels of fibrinogen, D-dimer, and C-reactive protein are common in patients with COVID-19 related strokes.[92],[93]

The characteristic feature of COVID-19-associated coagulopathy is markedly elevated D-dimer and fibrin degradation product levels. A D-dimer level of more than 1000 ng/mL is a strong predictor of death. In COVID-19, prothrombin time (PT) is mildly prolonged. while the activated partial thromboplastin time (aPTT) is either normal or less. Platelet count usually remains unaffected.[94] In severe cases, the course of illness may be complicated by disseminated intravascular coagulation (DIC). DIC is characterized by thrombocytopenia, prolonged prothrombin time, and increased D-dimer. DIC is generally associated with multiple organ dysfunction.[95] Zayet and colleagues described 2 cases of ischemic stroke with infarcts in multiple arterial territories. where laboratory investigations demonstrated increased antiphospholipid antibodies in blood.[96]

Endothelial dysfunction

Vascular injury, in the form of endotheliitis, endothelial cell damage, and dysfunction is a key element in the pathogenesis of SARS-CoV-2 induced organ injury. Endothelial cells profusely express the ACE2 receptor, the target receptor for SARS-CoV-2 cell entry. Endothelial injury damage facilitates the cerebral vascular thrombosis and injury to the blood-brain barrier, resulting in either brain edema or microhemorrhages.[97]

The SARS-CoV-2 has capability to infect brain cells, especially the brain microvascular endothelial cells of the blood–brain barrier. Blood–brain barrier damage by SARS-CoV-2 usually occurs in combination with neuronal cell damage, edema, glial proliferation, and inflammatory cell infiltration of the vascular walls and neuronal tissue.[98] In a recent investigation, high-tites of anti-SARS-CoV-2 antibodies were observed in the CSF of patients with encephalopathy indicating blood–brain barrier damage as well as intrathecal synthesis of antiviral antibodies. A disrupted blood–brain barrier allows the entry of inflammatory mediators inside the brain with potential to harm the brain by process of neuroinflammation and neuronal cell damage.[99]

Hypoxia

In COVID-19, majority of neurological complications happened in older age groups or the elderly with various comorbidities like diabetes mellitus and chronic hypertension. Cerebral microvasculature (both arterioles and venules) in the elderly population is commonly associated with cerebral amyloid angiopathy leading to microangiopathy. Hypoxic brain damage in severe COVID-19 can further damage small vessels resulting in white matter microhemorrhages or periventricular neuronal demyelination. Prolonged hypoxia results in widespread small vessel thrombosis and tissue damage.[100],[101]

Neurotropism

The SARS-CoV-2 can invade the brain through several mechanisms. ACE2 receptors in humans are expressed in the lung, kidney, intestine, and vascular endothelium. The SARS-CoV-2 can reach the brain either transsynaptically or through blood vessels. Transsynaptically virus can travel to the brain via the olfactory nerve across the cribriform plate. Parts of the limbic system, basal ganglia and the midbrain have a direct neuronal link with the olfactory nerve. In many cases, imaging abnormalities in the hypothalamus and other related structures have also been noted. Viruses can also spread to the brain via a hematogenous route.[102] The hematogenous spread can occur through infected endothelial cells or migration of infected leukocytes across the blood-brain barrier.[90]

Autoimmune

Post-infectious immune-mediated complications like ADEM are considered to be caused by an autoimmune mechanism. Molecular mimicry between neuronal and viral proteins directs an inadvertent immune reaction towards host cells.[103]

Genetics

The ε2/ε4 alleles of the apolipoprotein E gene, because of greater amyloid deposition, is one of the potential risk factors for recurrent intracerebral hemorrhage. A recent investigation noted that apolipoprotein e4e4 allele increases risks of severe COVID-19 infection.[104]


 » Conclusion Top


Neuroimaging findings in patients having COVID-19-associated neurological complications are now increasingly being reported. Neuroimaging abnormalities are common in old age and patients with comorbidities. None of the neuroimaging abnormality is peculiar for COVID-19 encephalopathy. Periventricular white-matter MR hyperintensity, microbleeds, arterial and venous infarcts, and hemorrhages are apparently distinctive abnormalities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
World Health Organization. Coronavirus disease (COVID-19) outbreak situation. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. [Last assessed on 2020 Oct 11].  Back to cited text no. 1
    
2.
The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19)—China 2020. Available from: http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51. [Last accessed 2020 May 31].  Back to cited text no. 2
    
3.
Castellano A, Anzalone N, Pontesilli S, Fominskiy E, Falini A. Pathological brain CT scans in severe COVID-19 ICU patients. Intensive Care Med 2020;46:2102-4.  Back to cited text no. 3
    
4.
Yoon BC, Buch K, Lang M, Applewhite BP, Li MD, Mehan WA Jr, et al. Clinical and neuroimaging correlation in patients with COVID-19. AJNR Am J Neuroradiol 2020.  Back to cited text no. 4
    
5.
Conklin J, Frosch MP, Mukerji S, Rapalino O, Maher M, Schaefer PW, et al. Cerebral microvascular injury in severe COVID-19. medRxiv [Preprint] 2020. doi: 10.1101/2020.07.21.20159376.  Back to cited text no. 5
    
6.
Freeman CW, Masur J, Hassankhani A, Wolf RL, Levine JM, Mohan S. COVID-19-related disseminated leukoencephalopathy (CRDL): A retrospective study of findings on brain MRI. AJR Am J Roentgenol 2020. doi: 10.2214/AJR.20.24364.  Back to cited text no. 6
    
7.
Agarwal S, Jain R, Dogra S, Krieger P, Lewis A, Nguyen V, et al. Cerebral microbleeds and leukoencephalopathy in critically Ill patients with COVID-19. Stroke 2020;51:2649-55.  Back to cited text no. 7
    
8.
Lin E, Lantos JE, Strauss SB, Phillips CD, Campion TR Jr, Navi BB. Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City. AJNR Am J Neuroradiol 2020;41:2001-8.  Back to cited text no. 8
    
9.
Klironomos S, Tzortzakakis A, Kits A, Öhberg C, Kollia E, Ahoromazdae A, et al. Nervous System involvement in COVID-19: Results from a retrospective consecutive neuroimaging cohort. Radiology 2020;297:e324-34.  Back to cited text no. 9
    
10.
Chougar L, Shor N, Weiss N, Galanaud D, Leclercq D, Mathon B, et al. Retrospective observational study of brain magnetic resonance imaging findings in patients with acute SARS-CoV-2 infection and neurological manifestations. Radiology 2020;29:E13-23.  Back to cited text no. 10
    
11.
Kremer S, Lersy F, Anheim M, Merdji H, Schenck M, Oesterlé H, et al. Neurologic and neuroimaging findings in COVID-19 patients: A retrospective multicenter study. Neurology 2020;95:e1868-82.  Back to cited text no. 11
    
12.
Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, et al. The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings. Brain 2020;143:3104-20.  Back to cited text no. 12
    
13.
Hernández-Fernández F, Valencia HS, Barbella-Aponte RA, Collado-Jiménez R, Ayo-Martín Ó, Barrena C, et al. Cerebrovascular disease in patients with COVID-19: Neuroimaging, histological and clinical description. Brain 2020;143:3089-103.  Back to cited text no. 13
    
14.
Pilotto A, Masciocchi S, Volonghi I, del Zotto E, Magni E, De Giuli V, et al. The clinical spectrum of encephalitis in COVID-19 disease: The ENCOVID multicentre study. medRxiv 2020. doi: https://doi.org/10.1101/20200.06.19.20133991.  Back to cited text no. 14
    
15.
Kremer SA, Lersy F, de Sèze J, Ferré JC, Maamar A, Carsin-Nicol B, et al. Brain MRI findings in severe COVID-19: A retrospective observational study. Radiology 2020; 297:E242-E251. doi: 10.1148/radiol. 2020202222.  Back to cited text no. 15
    
16.
Pons-Escoda A, Naval-Baudín P, Majós C, Camins A, Cardona P, Cos M, et al. Neurologic involvement in COVID-19: Cause or coincidence? A neuroimaging perspective. Am J Neuroradiol 2020. doi: 10.3174/ajnr.A6627.  Back to cited text no. 16
    
17.
Scullen T, Keen J, Mathkour M, Dumont AS, Kahn L. Coronavirus 2019 (COVID-19)-associated encephalopathies and cerebrovascular disease: The new orleans experience. World Neurosurg 2020;141:e437-46.  Back to cited text no. 17
    
18.
Radmanesh A, Raz E, Zan E, Derman A, Kaminetzky M. Brain imaging use and findings in COVID-19: A single academic center experience in the Epicenter of disease in the United States. AJNR Am J Neuroradiol 2020;41:1179-83  Back to cited text no. 18
    
19.
Mahammedi A, Saba L, Vagal A, Leali M, Rossi A, Gaskill M, et al. Imaging in neurological disease of hospitalized COVID-19 patients. An Italian multicenter retrospective observational study. Radiology 2020;29:e270-3.  Back to cited text no. 19
    
20.
Jain R, Young M, Dogra S, Kennedy H, Nguyen V, Jones 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.  Back to cited text no. 20
    
21.
Radmanesh A, Derman A, Lui YW, Raz E, Loh JP, Hagiwara M, et al. COVID-19-associated diffuse leukoencephalopathy and microhemorrhages. Radiology 2020;297:E223-7.  Back to cited text no. 21
    
22.
Kandemirli SG, Dogan L, Sarikaya ZT, Kara S, Akinci C, Kaya D, et al. Brain MRI findings in patients in the intensive care unit with COVID-19 infection. Radiology 2020;29:e242-51.  Back to cited text no. 22
    
23.
Giorgianni A, Vinacci G, Agosti E, Mercuri A, Baruzzi F. Neuroradiological features in COVID-19 patients: First evidence in a complex scenario. J Neuroradiol 2020;47:474-6.  Back to cited text no. 23
    
24.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020;382:2268-70.  Back to cited text no. 24
    
25.
Nalleballe K, Reddy Onteddu S, Sharma R, Dandu V, Brown A, Jasti M, et al. Spectrum of neuropsychiatric manifestations in COVID-19. Brain Behav Immun 2020;88:71-4.  Back to cited text no. 25
    
26.
Mao L, Jin H, Wang M, Hu Yu, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.  Back to cited text no. 26
    
27.
Xiong W, Mu J, Guo J, Lu L, Liu D, Luo J, et al. New onset neurologic events in people with COVID-19 infection in three regions in China. Neurology 2020;95:e1479-87.  Back to cited text no. 27
    
28.
Williams OH, Mohideen S, Sen A, Martinovic O, Hart J, Brex PA, et al. Multiple internal border zone infarcts in a patient with COVID-19 and CADASIL. J Neurol Sci 2020;416:116980.  Back to cited text no. 28
    
29.
Khandelwal P, Mufti FA, Tiwari A, Singla A, Dmytriw A Piano M, et al. Characteristics and outcomes of large vessel stroke in COVID-19 cohort: A multicentric international study. (June 2, 2020). SSRN. Available from:https://ssrn.com/abstract=3617195 or http://dx.doi.org/10.2139/ssrn.3617195.  Back to cited text no. 29
    
30.
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020;382:e60.  Back to cited text no. 30
    
31.
Goldberg D. AIDS and the general practitioner. J R Coll Gen Pract 1988;38:476.  Back to cited text no. 31
    
32.
Guillan M, Villacieros-Alvarez J, Bellido S, Peremarch CPJ, Suarez-Vega VM, Aragones-Garcia M, et al. Unusual simultaneous cerebral infarcts in multiple arterial territories in a COVID-19 patient. Thromb Res 2020;193:107-9.  Back to cited text no. 32
    
33.
Escalard S, Chalumeau V, Escalard C, Redjem H, Delvoye F, Hébert S, et al. Early brain imaging shows increased severity of acute ischemic strokes with large vessel occlusion in COVID-19 patients. Stroke 2020;51:3366-70.  Back to cited text no. 33
    
34.
Cavalcanti DD, Raz E, Shapiro M, Dehkharghani S, Yaghi S, Lillemoe K, et al. Cerebral venous thrombosis associated with COVID-19. AJNR Am J Neuroradiol 2020;41:1370-6.  Back to cited text no. 34
    
35.
Hughes C, Nichols T, Pike M, Subbe C, Elghenzai S. Cerebral venous sinus thrombosis as a presentation of COVID-19. Eur J Case Rep Intern Med 2020;7:001691.  Back to cited text no. 35
    
36.
Chougar L, Mathon B, Weiss N, Degos V, Shor N. Atypical deep cerebral vein thrombosis with hemorrhagic venous infarction in a patient positive for COVID-19. AJNR Am J Neuroradiol 2020;41:1377-9.  Back to cited text no. 36
    
37.
Benger M, Williams O, Siddiqui J, Sztriha L. Intracerebral haemorrhage and COVID-19: Clinical characteristics from a case series. Brain Behav Immun 2020;88:940-4.  Back to cited text no. 37
    
38.
Carroll E, Lewis A. Catastrophic intracranial hemorrhage in two critically ill patients with COVID-19. Neurocrit Care 2020;1-5. doi: 10.1007/s12028-020-00993-5.  Back to cited text no. 38
    
39.
Heman-Ackah SM, Su YS, Spadola M, Petrov D, Chen HI, Schuster J, et al. Neurologically devastating intraparenchymal hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation: A case series. Neurosurgery 2020;87:E147-51.  Back to cited text no. 39
    
40.
Wee NK, Fan EB, Lee KCH, Chia YW, Lim TCC. CT Fluid-blood levels in COVID-19 intracranial hemorrhage. AJNR Am J Neuroradiol 2020;41:E76-7.  Back to cited text no. 40
    
41.
García-García S, Cepeda S, Arrese I, Sarabia R. Letter: Hemorrhagic conditions affecting the central nervous system in COVID-19 patients. Neurosurgery 2020;87:E394-6.  Back to cited text no. 41
    
42.
Dogra S, Jain R, Cao M, Bilaloglu S, Zagzag D, Hochman S, et al. Hemorrhagic stroke and anticoagulation in COVID-19. J Stroke Cerebrovasc Dis 2020;29:104984.  Back to cited text no. 42
    
43.
Ghani MU, Kumar M, Ghani U, Sonia F, Abbas SA. Intracranial hemorrhage complicating anticoagulant prophylactic therapy in three hospitalized COVID-19 patients. J Neurovirol 2020;26:602-4.  Back to cited text no. 43
    
44.
Nicholson P, Alshafai L, Krings T. Neuroimaging findings in patients with COVID-19. AJNR Am J Neuroradiol 2020;41:1380-83.  Back to cited text no. 44
    
45.
Melmed KR, Cao M, Dogra S, Zhang R, Yaghi S, Lewis A, et al. Risk factors for intracerebral hemorrhage in patients with COVID-19. J Thromb Thrombolysis 2020. doi: 10.1007/s11239-020-02288-0.  Back to cited text no. 45
    
46.
Bryce C, Grimes Z, Pujadas E, Ahuja S, Beasley MB, Albrecht R, et al. Pathophysiology of SARS-CoV-2: Targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience. medRxiv 2020. doi: 10.1101/2020.05.18.20099960.  Back to cited text no. 46
    
47.
Shindo A, Ishikawa H, Ii Y, Niwa A, Tomimoto H. Clinical features and experimental models of cerebral small vessel disease. Front Aging Neurosci 2020;12:109.  Back to cited text no. 47
    
48.
Coolen T, Lolli V, Sadeghi N, Rovaï A, Trotta N, Taccone FS, et al. Early postmortem brain MRI findings in COVID-19 non-survivors. Neurology 2020;95:e2016-27.  Back to cited text no. 48
    
49.
Chen HM, Chen CC, Wang HC, Chang YC, Pan KJ, Chen WH, et al. Novel automated method for the detection of white matter hyperintensities in brain multispectral MR images. Curr Med Imaging 2020;16:469-78.  Back to cited text no. 49
    
50.
Sachs JR, Gibbs KW, Swor DE, Sweeney AP, Willaims DW, Burdette JH, et al. COVID-19-associated leukoencephalopathy. Radiology 2020;296:E184-5.  Back to cited text no. 50
    
51.
Lang M, Buch K, Li MD, Mehan Jr WA, Lang AL, Leslie-Mazwi TM, et al. Leukoencephalopathy associated with severe COVID-19 infection: Sequela of hypoxemia?. AJNR Am J Neuroradiol 2020;41:1641-5.  Back to cited text no. 51
    
52.
Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, et al. Neuropathological features of Covid-19. N Engl J Med 2020;383:989-92.  Back to cited text no. 52
    
53.
Fitsiori A, Pugin D, Thieffry C, Lalive P, Vargas MI. Unusual microbleeds in brain MRI of Covid-19 patients. J Neuroimaging 2020;30:593-7.  Back to cited text no. 53
    
54.
von Weyhern CH, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. Lancet 2020;395:e109.  Back to cited text no. 54
    
55.
Dixon L, Varley J, Gontsarova A, Mallon D, Tona F, Muir D, et al. COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. Neurol Neuroimmunol Neuroinflamm 2020;7:e789.  Back to cited text no. 55
    
56.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020;296:E119-20.  Back to cited text no. 56
    
57.
Stoyanov GS, Lyutfi E, Dzhenkov DL, Petkova L. Acute necrotizing encephalitis in viral respiratory tract infection: An autopsy case report. Cureus 2020;12:e8070.  Back to cited text no. 57
    
58.
Virhammar J, Kumlien E, Fällmar D, Frithiof R, Jackmann S, Sköld MK, et al. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology 2020;95:445-9.  Back to cited text no. 58
    
59.
Delamarre L, Gollion C, Grouteau G, Rousset D, Jimena G, Roustan J, et al. COVID-19-associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network. J Neurol Neurosurg Psychiatry 2020;91:1004-6.  Back to cited text no. 59
    
60.
Novi G, Rossi T, Pedemonte E, Saitta L, Rolla C, Roccoatgliata L, et al. Acute disseminated encephalomyelitis after SARS-CoV-2 infection. Neurol Neuroimmunol Neuroinflamm 2020;7:e797.  Back to cited text no. 60
    
61.
Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M. COVID-19-associated acute disseminated encephalomyelitis (ADEM). J Neurol 2020;267:2799-802.  Back to cited text no. 61
    
62.
Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF. Neuropathology of COVID-19: A spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol 2020;140:1-6.  Back to cited text no. 62
    
63.
Le Guennec L, Devianne J, Jalin L, Cao A, Galanaud D, Navarro V, et al. Orbitofrontal involvement in a neuroCOVID-19 patient. Epilepsia 2020;61:e90-4.  Back to cited text no. 63
    
64.
Pascual-Goñi E, Fortea J, Martínez-Domeño A, Rabella N, Tecame M, Gómez-Olivaet C, et al. COVID-19-associated ophthalmoparesis and hypothalamic involvement. Neurol Neuroimmunol Neuroinflamm 2020;7:e823.  Back to cited text no. 64
    
65.
Zambreanu L, Lightbody S, Bhandari M, Hoskote C, Kandil H, Houlihan CF, et al. A case of limbic encephalitis associated with asymptomatic COVID-19 infection. J Neurol Neurosurg Psychiatry 2020;91:1229-30.  Back to cited text no. 65
    
66.
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-8.  Back to cited text no. 66
    
67.
Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K. COVID-19-associated encephalitis mimicking glial tumor. World Neurosurg 2020;140:46-8.  Back to cited text no. 67
    
68.
Nampoothiri S, Sauve F, Ternier G, Fernandois D, Coelho C, Imbernon M, et al. The hypothalamus as a hub for putative SARS-CoV-2 brain infection. bioRxiv 2020 Jan 1;2020.06.08.139329. doi: 10.1101/2020.06.08.139329.  Back to cited text no. 68
    
69.
Rasmussen C, Niculescu I, Patel S, Krishnan A. COVID-19 and involvement of the corpus callosum: Potential effect of the cytokine storm?. AJNR Am J Neuroradiol 2020;41:1625-8.  Back to cited text no. 69
    
70.
Hayashi M, Sahashi Y, Baba Y, Okura H, Shimohata T. COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. J Neurol Sci 2020;415:116941.  Back to cited text no. 70
    
71.
Abdel-Mannan O, Eyre M, Löbel U, Bamford A, Eltze C, Hameed B, et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol 2020;e202687.  Back to cited text no. 71
    
72.
Anzalone N, Castellano A, Scotti R, Scandroglio AM, Filippi M, Tresoldi M, et al. Multifocal laminar cortical brain lesions: A consistent MRI finding in neuro-COVID-19 patients. J Neurol 2020;267:2806-9.  Back to cited text no. 72
    
73.
Princiotta Cariddi L, Tabaee Damavandi P, Carimati F, Banfi P, Clemenzi A, Marelli M, et al. Reversible encephalopathy syndrome (PRES) in a COVID-19 patient. J Neurol 2020;267:3157-60.  Back to cited text no. 73
    
74.
Franceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol 2020;41:1173-6.  Back to cited text no. 74
    
75.
Kaya Y, Kara S, Akinci C, Kocaman AS. Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report. J Neurol Sci 2020;413:116858.  Back to cited text no. 75
    
76.
Kishfy L, Casasola M, Banankhah P, Pervez A, Jan YJ, Shenoy AM, et al. Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe Covid-19. J Neurol Sci 2020;414:116943.  Back to cited text no. 76
    
77.
Pinna P, Grewal P, Hall JP, Tavarez T, Dafer RM, Garg R, et al. Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline. J Neurol Sci 2020;415:116969.  Back to cited text no. 77
    
78.
van den Enden AJM, van Gils L, Labout JAM, van der Jagt M, Moudrous W. Fulminant cerebral edema as a lethal manifestation of COVID-19. Radiol Case Rep 2020;15:1705-8.  Back to cited text no. 78
    
79.
Politi LS, Salsano E, Grimaldi M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol 2020;77:1028-9.  Back to cited text no. 79
    
80.
Laurendon T, Radulesco T, Mugnier J, Géraultet M, Chagnaud C, Ahmadi AE, et al. Bilateral transient olfactory bulbs edema during COVID-19-related anosmia. Neurology 2020;95:224-5.  Back to cited text no. 80
    
81.
Lantos JE, Strauss SB, Lin E. COVID-19-associated miller fisher syndrome: MRI findings. AJNR Am J Neuroradiol 2020;41:1184-6.  Back to cited text no. 81
    
82.
Baghbanian SM, Namazi F. Post COVID-19 longitudinally extensive transverse myelitis (LETM)-a case report. Acta Neurol Belg 2020. doi: 10.1007/s13760-020-01497-x.  Back to cited text no. 82
    
83.
AlKetbi R, AlNuaimi D, AlMulla M, AlTalai N, Samir M, Kumar N, et al. Acute myelitis as a neurological complication of Covid-19: A case report and MRI findings. Radiol Case Rep 2020;15:1591-5.  Back to cited text no. 83
    
84.
Abdelhady M, Elsotouhy A, Vattoth S. Acute flaccid myelitis in COVID-19. BJR Case Rep 2020;6:20200098.  Back to cited text no. 84
    
85.
Jain R, Young M, Dogra S, Kennedy H, Nguyen V, Raz E. Surprise diagnosis of COVID-19 following neuroimaging evaluation for unrelated reasons during the pandemic in hot spots. AJNR Am J Neuroradiol 2020;41:1177-8.  Back to cited text no. 85
    
86.
Hutchins KL, Jansen JH, Comer AD, Scheer RV, Zahn GS, Capps AE, et al. COVID-19–associated bifacial weakness with paresthesia subtype of Guillain-Barré syndrome. Am J Neuroradiol 2020;41:1707-11.  Back to cited text no. 86
    
87.
Dinkin M, Gao V, Kahan J, Bobker S, Simonetto M, Wechsler P, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020;95:221-3.  Back to cited text no. 87
    
88.
Siddiqui J, Bala F, Sciacca S, Falzon AM, Benger M, Matloob SA, et al. COVID-19 stroke apical lung examination study: A diagnostic and prognostic imaging biomarker in suspected acute stroke. AJNR Am J Neuroradiol 2020;42:138-43.  Back to cited text no. 88
    
89.
Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I. COVID-19 cytokine storm: The anger of inflammation. Cytokine 2020. doi: 10.1016/j.cyto. 2020.155151.  Back to cited text no. 89
    
90.
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;77:1018-27.  Back to cited text no. 90
    
91.
Jose RJ, Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation. Lancet Respir Med 2020;8:e46-7.  Back to cited text no. 91
    
92.
D'Anna L, Kwan J, Brown Z, Halse O, Jamil S, Kalladke D, et al. Characteristics and clinical course of Covid-19 patients admitted with acute stroke. J Neurol 2020;267:3161-5.  Back to cited text no. 92
    
93.
Jayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A. COVID-19-associated coagulopathy: An exacerbated immunothrombosis response. Clin Appl Thromb Hemost 2020;26:1076029620943293.  Back to cited text no. 93
    
94.
Colling ME, Kanthi Y. COVID-19-associated coagulopathy: An exploration of mechanisms. Vasc Med 2020;25:471-8.  Back to cited text no. 94
    
95.
Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost 2020;18:2103-9.  Back to cited text no. 95
    
96.
Zayet S, Klopfenstein T, Kovács R, Stancescu S, Hagenkötter B. Acute Cerebral Stroke with Multiple Infarctions and COVID-19, France, 2020. Emerg Infect Dis 2020;26:2258-60.  Back to cited text no. 96
    
97.
Huertas A, Montani D, Savale L, Pichon J, Tu L, Parent F, et al. Endothelial cell dysfunction: A major player in SARS-CoV-2 infection (COVID-19)?. Eur Respir J 2020;56:2001634.  Back to cited text no. 97
    
98.
Alquisiras-Burgos I, Peralta-Arrieta I, Alonso-Palomares LA, Zacapala-Gómez AE, Salmerón-Bárcenas EG, Aguilera P. Neurological complications associated with the blood-brain barrier damage induced by the inflammatory response during SARS-CoV-2 infection. Mol Neurobiol 2020. doi: 10.1007/s12035-020-02134-7.  Back to cited text no. 98
    
99.
Alexopoulos H, Magira E, Bitzogli K, Kafasi N, Vlachoyiannopoulos P, Tzioufas A, et al. Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients. Neurol Neuroimmunol Neuroinflamm 2020;7:e893.  Back to cited text no. 99
    
100.
Parry AH, Wani AH, Yaseen M. Neurological dysfunction in coronavirus disease-19 (COVID-19). Acad Radiol 2020;27:1329-30.  Back to cited text no. 100
    
101.
Jaunmuktane Z, Mahadeva U, Green A, Sekhawat V, Barrett NA, Childs L, et al. Microvascular injury and hypoxic damage: Emerging neuropathological signatures in COVID-19. Acta Neuropathol 2020;140:397-400.  Back to cited text no. 101
    
102.
Cheng Q, Yang Y, Gao J. Infectivity of human coronavirus in the brain. EBioMedicine 2020;56:102799.  Back to cited text no. 102
    
103.
Angileri F, Legare S, Marino Gammazza A, Conway de Macario E, Jl Macario A, Cappello F. Molecular mimicry may explain multi-organ damage in COVID-19. Autoimmun Rev 2020;19:102591.  Back to cited text no. 103
    
104.
Kuo CL, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Kuchel GA, et al. APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort. J Gerontol A Biol Sci Med Sci 2020;75:2231-2.  Back to cited text no. 104
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow