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Acute Neurological Complications of Coronavirus Disease

  • Sanders Chang
    Affiliations
    Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1176 5th Avenue MC Level, New York, NY 10029, USA
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  • Michael Schecht
    Affiliations
    Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1176 5th Avenue MC Level, New York, NY 10029, USA
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  • Rajan Jain
    Affiliations
    Department of Radiology, NYU Grossman School of Medicine, 660 1st Avenue, 1st Floor, New York, NY 10016, USA

    Department of Neurosurgery, NYU Grossman School of Medicine, 660 1st Avenue, 1st Floor, New York, NY 10016, USA
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  • Puneet Belani
    Correspondence
    Corresponding author. 1176 5th Avenue MC Level, New York, NY 10029.
    Affiliations
    Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1176 5th Avenue MC Level, New York, NY 10029, USA

    Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, 1176 5th Avenue MC Level, New York, NY 10029, USA
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      Keywords

      Key points

      • Acute/subacute stroke is the most common neuroimaging finding seen in patients with coronavirus disease (COVID-19). Other vascular findings include dural venous sinus thrombosis, arterial dissection, and vasculitis.
      • Intracerebral hemorrhage may manifest as a large hemorrhage or microhemorrhages, the latter being more predominant in the hemispheres or corpus callosum.
      • Leukoencephalopathies may manifest as posterior reversible encephalopathy syndrome.
      • Neuropathies may be multiple or single, ranging from anosmia, facial nerve palsy, to Guillain-Barré syndrome.
      • Multisystem inflammatory syndrome can be seen in the pediatric population.

      Introduction

      The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has affected hundreds of millions people globally and led to several million deaths.
      COVID-19 Map. Coronavirus Resource Center - John Hopkins University n.d..
      In addition to respiratory sequelae (eg, interstitial pneumonia and acute respiratory distress syndrome), neurologic manifestations have been observed with COVID-19, including encephalopathy, acute cerebrovascular disease, and sensory abnormalities.
      • Vogrig A.
      • Gigli G.L.
      • Bnà C.
      • et al.
      Stroke in patients with COVID-19: Clinical and neuroimaging characteristics.
      ,
      • Helms J.
      • Kremer S.
      • Merdji H.
      • et al.
      Neurologic features in severe SARS-CoV-2 Infection.
      The frequency of neurologic symptoms has been observed in up to 36.4% of COVID-19 patients and is more common in patients with severe stages of infection.
      • Mao L.
      • Jin H.
      • Wang M.
      • et al.
      Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China.
      Recognizing the neuroradiological features associated with COVID-19 is crucial, as they have implications on diagnosis and management. This article reviews the various acute neuroradiological patterns that have been observed with SARS-CoV-2 infections (Table 1).
      Table 1Neuroimaging findings in acute coronavirus disease infection
      Clinical SyndromeImaging Findings (Computed Tomography or MRI)Proposed Pathogenesis
      Stroke
      • Anterior circulation most common
      • Multiterritorial involvement
      • Large vessel occlusions, especially in uncommonly affected vessels: subclavian artery and pericallosal gyrus
      • Higher prevalence among younger patients and those without traditional risk factors for stroke
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interactions
      • Indirect propagation of thrombosis and plaque rupture from immune response to the virus
      Dural vein thrombosis
      • Multifocal involvement: superior sagittal , transverse, and sigmoid sinuses, internal jugular vein
      • Associated parenchymal hemorrhage, cerebral edema, venous infarcts
      • Indirect propagation of thrombosis and plaque rupture from immune response to the virus
      Arterial dissection
      • Extracranial carotid and vertebral arteries, commonly bilateral
      • Absence of typical risk factors such as connective tissue disorders or trauma
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interactions
      Vasculitis
      • Long segment vessel wall enhancement of multiple arteries
      • Focal cerebral arteriopathy: pediatric patient with focal stenosis, irregular narrowing, concentric contrast enhancement of a large vessel
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interactions
      Intraparenchymal hemorrhage
      • Unifocal or multifocal involvement with extension into subarachnoid and intraventricular spaces
      • Associated diffuse edema and mass effect
      • Microhemorrhages: cortical, juxtacortical, deep white matter (WM), perivenular, and corpus callosal involvement
      • Dysregulation of blood pressure control through virus-related downregulation of ACE-2 receptors
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interactions
      • Iatrogenic: anticoagulation, ECMO, mechanical ventilation
      • Hypoxic-induced injury to the blood-brain barrier
      PRES
      • CT hypoattenuation, T2/FLAIR signal abnormality, and diffusion restriction in the subcortical WM of posterior temporal and occipital lobes
      • Associated parenchymal hemorrhages and microhemorrhages
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interaction
      • Dysregulation of blood pressure control through virus-related downregulation of ACE-2 receptors
      Leukoencephalopathy
      • Multifocal WM lesions with diffusion restriction and T2/FLAIR hyperintensity, predominantly in the posterior WM
      • • Central restricted diffusion greater for COVID-19 lesions
      • Associated enhancement and microhemorrhages
      • Severe: central expansile T2/FLAIR hyperintensity in the basal ganglia and thalami
      • Endothelial cell dysfunction via immune-mediated cytokine storm or direct viral interactions
      • Cranial neuropathy
        • Anosmia/dysgeusia
        • Facial and abducens nerve palsy
      • Anosmia/dysgeusia: T2/FLAIR signal abnormality in the gyrus rectus and olfactory bulbs
      • Facial and abducens nerve palsy: affected cranial nerves demonstrating STIR hyperintensity, gadolinium enhancement, and diffusion restriction
      • Autoimmune-mediated

      Stroke

      Stroke has been observed in 1% to 3% of all hospitalized patients with COVID-19.
      • Chou S.H.-Y.
      • Beghi E.
      • Helbok R.
      • et al.
      Global incidence of neurological manifestations among patients hospitalized with COVID-19-a report for the GCS-NeuroCOVID consortium and the ENERGY consortium.
      ,
      • Yaghi S.
      • Ishida K.
      • Torres J.
      • et al.
      SARS-CoV-2 and stroke in a New York healthcare system.
      From a meta-analysis of published articles detailing MRI neuroimaging findings during the peak of the pandemic, acute and subacute strokes were the most common neuro-radiological abnormality.
      • Gulko E.
      • Oleksk M.L.
      • Gomes W.
      • et al.
      MRI brain findings in 126 patients with COVID-19: initial observations from a descriptive literature review.
      Development of strokes bears important implications in the clinical course of the COVID-19 patient. Their detection signifies poor prognosis with reported rates of mortality up to 50%.
      • 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.
      Severe disability has been seen in COVID-19 survivors with ischemic strokes upon discharge, significantly greater than those with non-COVID-19-related ischemic strokes.
      • Ntaios G.
      • Michel P.
      • Georgiopoulos G.
      • et al.
      Characteristics and outcomes in patients with COVID-19 and acute ischemic stroke: the Global COVID-19 stroke registry.
      Moreover, studies have shown that COVID-19 represents a significant independent risk factor in stroke development among hospitalized patients, even greater than traditional comorbidities such as cardiovascular disease and obesity.
      • Belani P.
      • Schefflein J.
      • Kihira S.
      • et al.
      COVID-19 is an independent risk factor for acute ischemic stroke.
      ,
      • Katz J.M.
      • Libman R.B.
      • Wang J.J.
      • et al.
      Cerebrovascular complications of COVID-19.
      Certain neuroradiological characteristics are linked to COVID-19-related strokes. These features include multiterritorial involvement, involvement of atypical vessels, and large vessel occlusions.

      Stroke Distribution

      Strokes in COVID-19 patients more commonly involve the anterior circulation compared with the posterior circulation.
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      • Radmanesh A.
      • Raz E.
      • Zan E.
      • et al.
      Brain imaging use and findings in COVID-19: A single academic center experience in the epicenter of disease in the United States.
      • Yoon B.C.
      • Buch K.
      • Lang M.
      • et al.
      Clinical and neuroimaging correlation in patients with COVID-19.
      Multivascular distribution is a common feature, observed in up to 40% of cases.
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      This rate is higher than that observed in the prepandemic era (10.7%).
      • Kaesmacher J.
      • Mosimann P.J.
      • Giarrusso M.
      • et al.
      Multivessel occlusion in patients subjected to thrombectomy: prevalence, associated factors, and clinical implications.
      The high prevalence of multiterritorial strokes is consistent with the induced prothrombotic environment and increased embolic risk associated with the SARS-COV-2 virus, and had been reported in the previous 2003 outbreak of SARS-COV-1 virus infection.
      • Umapathi T.
      • Kor A.C.
      • Venketasubramanian N.
      • et al.
      Large artery ischaemic stroke in severe acute respiratory syndrome (SARS).
      Infection severity is also likely correlated with risk for multiterritorial strokes. In 1 study, multiterritorial strokes were significantly more frequent among hospitalized patients with severe infection compared to outpatients with less severe infections (56.4% vs 33.3%).
      • Katz J.M.
      • Libman R.B.
      • Wang J.J.
      • et al.
      COVID-19 severity and stroke: correlation of imaging and laboratory markers.

      Large Vessel Occlusions

      Large vessel occlusions (LVOs) have been observed in up to around 60% of COVID-19 patients with ischemic infarctions.
      • Hernández-Fernández F.
      • Sandoval Valencia H.
      • Barbella-Aponte R.A.
      • et al.
      Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
      ,
      • Kihira S.
      • Schefflein J.
      • Mahmoudi K.
      • et al.
      Association of coronavirus disease (COVID-19) with large vessel occlusion strokes: a case-control study.
      In comparison, arterial occlusions were historically observed in up to 46% of ischemic strokes in the prepandemic era.
      • Rennert R.C.
      • Wali A.R.
      • Steinberg J.A.
      • et al.
      Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke.
      In 1 study, proximal large vessel occlusions were significantly more common among COVID-19 patients compared with historic controls.
      • Yaghi S.
      • Ishida K.
      • Torres J.
      • et al.
      SARS-CoV-2 and stroke in a New York healthcare system.
      The relatively high prevalence of LVOs among COVID-19-related acute ischemic strokes suggests the prothrombotic nature of the SARS-COV-2 virus.
      LVOs in COVID-19 patients most commonly involve the anterior circulation, particularly the middle cerebral artery (MCA) and internal carotid artery (Fig. 1).
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      ,
      • Radmanesh A.
      • Raz E.
      • Zan E.
      • et al.
      Brain imaging use and findings in COVID-19: A single academic center experience in the epicenter of disease in the United States.
      Other locations include the posterior cerebral artery (PCA), basilar artery, vertebral artery, and common carotid arteries.
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      ,
      • Beyrouti R.
      • Adams M.E.
      • Benjamin L.
      • et al.
      Characteristics of ischaemic stroke associated with COVID-19.
      ,
      • Franceschi A.M.
      • Arora R.
      • Wilson R.
      • et al.
      Neurovascular complications in COVID-19 infection: case series.
      Significant thrombotic burden and occlusions of otherwise uncommonly affected vessels have also been observed in the subclavian artery
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      and the pericallosal artery.
      • Morassi M.
      • Bagatto D.
      • Cobelli M.
      • et al.
      Stroke in patients with SARS-CoV-2 infection: case series.
      Occlusions can appear in tandem, which was seen in up to 40% of patients in 1 case series.
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      Figure thumbnail gr1
      Fig. 133-year-old woman with ongoing COVID-19 infection experienced sudden onset left hemiparesis and sensory loss. Axial CT angiography (CTA) image of the neck (A) and sagittal maximum intensity projection (MIP) (B) demonstrated a large noncalcified thrombus (arrows) in the proximal right internal carotid artery (ICA) causing moderate stenosis. Subsequent MRI diffusion weighted imaging (DWI) (C) demonstrated a large acute infarct involving the right MCA territory (star).

      Strokes in Younger Patients

      Younger age onset of strokes has been observed in COVID-19 patients. In 1 study, 73.3% of patients with large vessel occlusions were younger than 50 years old.
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      Median age of stroke-onset in COVID-19 patients was found to be significantly lower than that of patients without COVID-19 (median age of 63 vs 70).
      • Yaghi S.
      • Ishida K.
      • Torres J.
      • et al.
      SARS-CoV-2 and stroke in a New York healthcare system.
      In addition, the mean age of COVID-19 patients with emergency large vessel occlusions was also significantly less than that of patients without COVID-19 (mean age of 59 vs 74 years).
      • Majidi S.
      • Fifi J.T.
      • Ladner T.R.
      • et al.
      Emergent large vessel occlusion stroke during New York City’s COVID-19 outbreak.
      Certain clinical factors are shared among younger patients with COVID-19 and stroke, such as the absence of traditional risk factors for stroke (eg, diabetes, hypertension, hyperlipidemia, and coronary artery disease),
      • John S.
      • Kesav P.
      • Mifsud V.A.
      • et al.
      Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke.
      and minimal to absent respiratory symptoms during the initial stage of the disease course.
      • Cavallieri F.
      • Marti A.
      • Fasano A.
      • et al.
      Prothrombotic state induced by COVID-19 infection as trigger for stroke in young patients: a dangerous association.
      In 1 study, a significantly higher number of patients younger than 50 years old experienced an ischemic stroke in the absence of any prior respiratory symptoms (50.0%, P=.014).
      • Fridman S.
      • Bullrich M.B.
      • Jimenez-Ruiz A.
      • et al.
      Stroke risk, phenotypes, and death in COVID-19.

      Pathophysiology of Stroke

      The mechanism behind the development of strokes in COVID-19 patients is presumed to be multifactorial. Interaction between the SARS-COV-2 virus with endothelial angiotensin converting enzyme 2 (ACE-2) receptors is thought to result in direct endothelial damage, predisposing to occlusive events.
      • Mohamud A.Y.
      • Griffith B.
      • Rehman M.
      • et al.
      Intraluminal carotid artery thrombus in COVID-19: another danger of cytokine storm?.
      Indirectly, a proinflammatory state induced by a misdirected immune response to the SARS-COV-2 virus can result in propagation of thrombosis and plaque rupture. Inflammatory infiltrates have been found within the intima of surgically removed thrombosis on pathology, consistent with endotheliitis.
      • Esenwa C.
      • Cheng N.T.
      • Lipsitz E.
      • et al.
      COVID-19-Associated carotid atherothrombosis and stroke.
      It is unclear whether arterial thrombosis is a de novo phenomenon or related to worsening of pre-existing atheromatous plaque. Many COVID-19-related strokes have been observed in patients with prior atherosclerotic disease.
      • Franceschi A.M.
      • Arora R.
      • Wilson R.
      • et al.
      Neurovascular complications in COVID-19 infection: case series.
      ,
      • Mohamud A.Y.
      • Griffith B.
      • Rehman M.
      • et al.
      Intraluminal carotid artery thrombus in COVID-19: another danger of cytokine storm?.
      ,
      • Esenwa C.
      • Cheng N.T.
      • Lipsitz E.
      • et al.
      COVID-19-Associated carotid atherothrombosis and stroke.
      However, patients without any significant medical history, especially those younger than the observed population, have presented with strokes and large vessel occlusions. Direct endothelial damage may be the primary mechanism behind occlusive events in these patients. In addition, acute extracranial events, such as pulmonary embolism or cardiac arrests, may be triggers for strokes. In 1 meta-analysis, younger COVID-19 patients (<50 years) had a higher frequency of elevated cardiac troponin, suggesting that acute myocardial injury is a possible risk factor for the development of strokes.
      • Fridman S.
      • Bullrich M.B.
      • Jimenez-Ruiz A.
      • et al.
      Stroke risk, phenotypes, and death in COVID-19.

      Dural vein thrombosis

      Dural vein thrombosis is a relatively rare presentation among COVID-19 patients; in 1 large study, the prevalence was only 0.02% (Fig. 2).
      • Siegler J.E.
      • Cardona P.
      • Arenillas J.F.
      • et al.
      Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the SVIN COVID-19 Multinational Registry.
      When present, sinus vein thrombosis tends to involve multiple sites, most commonly the superior sagittal, transverse, and sigmoid sinuses.
      • Cavalcanti D.D.
      • Raz E.
      • Shapiro M.
      • et al.
      Cerebral venous thrombosis associated with COVID-19.
      • Gonçalves B.
      • Righy C.
      • Kurtz P.
      Thrombotic and hemorrhagic neurological complications in critically ill COVID-19 patients.
      • Kihira S.
      • Schefflein J.
      • Pawha P.
      • et al.
      Neurovascular complications that can be seen in COVID-19 patients.
      Other sites include the cortical veins, vein of Galen, and internal cerebral veins.
      • Chougar L.
      • Mathon B.
      • Weiss N.
      • et al.
      Atypical deep cerebral vein thrombosis with hemorrhagic venous infarction in a patient positive for COVID-19.
      Complications from the venous thrombosis may also be seen, such as surrounding parenchymal hemorrhage, cerebral edema, and hemorrhagic venous infarcts.
      • Gonçalves B.
      • Righy C.
      • Kurtz P.
      Thrombotic and hemorrhagic neurological complications in critically ill COVID-19 patients.
      ,
      • Poillon G.
      • Obadia M.
      • Perrin M.
      • et al.
      Cerebral venous thrombosis associated with COVID-19 infection: causality or coincidence?.
      Figure thumbnail gr2
      Fig. 240-year-old man presented with severe headache in the setting of a recent COVID-19 diagnosis. MR venogram coronal MIP image (A) showed thrombosis of the left transverse and sigmoid sinuses (circle). MRI DWI (B) showed hyperintense acute venous infarct in the right temporal lobe (arrow) corresponding to the region of the venous thrombosis.
      Given the low number of cases, the relationship between the development of dural vein thrombosis and SARS-COV-2 virus has yet to be elucidated. In many case series, dural venous thrombosis and its associated complications were seen in patients with predisposing risk factors, such as hypertension, diabetes, obesity, oral contraceptive pill (OCP) use, and hormonal therapy for cancer. However, sinus thrombosis can present in patients without prior risk factors or inciting events.
      • Hughes C.
      • Nichols T.
      • Pike M.
      • et al.
      Cerebral venous sinus thrombosis as a presentation of COVID-19.
      Its pathogenesis is likely tied to the prothrombogenic state associated with COVID-19.

      Arterial dissection

      Arterial dissections are rarely observed among COVID-19 patients, typically occurring in the extracranial carotid and vertebral arteries, and often bilaterally.
      • Hernández-Fernández F.
      • Sandoval Valencia H.
      • Barbella-Aponte R.A.
      • et al.
      Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
      ,
      • Patel P.
      • Khandelwal P.
      • Gupta G.
      • et al.
      COVID-19 and cervical artery dissection- A causative association?.
      • Morassi M.
      • Bigni B.
      • Cobelli M.
      • et al.
      Bilateral carotid artery dissection in a SARS-CoV-2 infected patient: causality or coincidence?.
      • Romero-Sánchez C.M.
      • Díaz-Maroto I.
      • Fernández-Díaz E.
      • et al.
      Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry.
      One report noted extension of the dissection from the distal cervical part to the petrous segment of the internal carotid arteries.
      • Morassi M.
      • Bigni B.
      • Cobelli M.
      • et al.
      Bilateral carotid artery dissection in a SARS-CoV-2 infected patient: causality or coincidence?.
      Patients were also noted to lack typical risk factors for dissection, such as connective tissue disorders, or inciting events, such as trauma (Fig. 3).
      Figure thumbnail gr3
      Fig. 334-year-old woman with no significant past medical history and no recent trauma presented with acute onset of left facial droop, dysarthria, right gaze deviation, and left hemiparesis/hemisensory loss. Sagittal view from a CTA of the head and neck (A) and lateral view from a catheter angiogram arterial phase injection of the right ICA (B) demonstrated an acute dissection in the right ICA shortly after its origin (arrows). Axial DWI (C) showed an acute right ganglionic infarct. COVID-19 polymerase chain reaction (PCR) test was positive.
      Although the mechanism remains unclear, endothelial damage propagated by the cytokine storm and direct infection by the SARS-COV-2 virus likely play a role. Dissections at other sites, such as the aorta and coronary arteries, have been observed in the context of COVID-19 and likely follow a similar pathogenesis.
      • Gasso L.F.
      • Maneiro Melon N.M.
      • Cebada F.S.
      • et al.
      Multivessel spontaneous coronary artery dissection presenting in a patient with severe acute SARS-CoV-2 respiratory infection.
      ,
      • Fukuhara S.
      • Rosati C.M.
      • El-Dalati S.
      Acute type A aortic dissection during the COVID-19 outbreak.

      Vasculitis and focal cerebral arteriopathy

      Acute vasculitis is a rare neuroradiologic manifestation observed in COVID-19 patients. Typical imaging features include long segment vessel wall enhancement of multiple arteries. In 1 case of a 64-year-old patient, vasculitis was observed in MCAs, anterior cerebral arteries (ACAs), vertebral arteries, and the basilar artery, and was associated with multiterritorial infarcts.
      • Dixon L.
      • Coughlan C.
      • Karunaratne K.
      • et al.
      Immunosuppression for intracranial vasculitis associated with SARS-CoV-2: therapeutic implications for COVID-19 cerebrovascular pathology.
      In pediatric COVID-19 patients, several cases of focal cerebral arteriopathy of childhood-inflammatory type have been reported.
      • Gulko E.
      • Overby P.
      • Ali S.
      • et al.
      Vessel wall enhancement and focal cerebral arteriopathy in a pediatric patient with acute infarct and COVID-19 infection.
      ,
      • Mirzaee S.M.M.
      • Gonçalves F.G.
      • Mohammadifard M.
      • et al.
      Focal cerebral arteriopathy in a pediatric patient with COVID-19.
      Imaging findings include focal stenosis and irregular narrowing of a large vessel, such as the M1 segment, with associated wall thickening and concentric contrast enhancement. In lieu of typical cardiovascular factors and pre-existing disease, focal cerebral arteriopathy may represent a possible mechanism for which strokes can develop in children. One case of stroke has been observed in a COVID-19 patient as young as 5 years old.
      • Kihira S.
      • Morgenstern P.F.
      • Raynes H.
      • et al.
      Fatal cerebral infarct in a child with COVID-19.

      Intracerebral hemorrhage

      Intracranial hemorrhage is a neurologic complication seen in approximately 0.2% of COVID-19 patients.
      • Siegler J.E.
      • Cardona P.
      • Arenillas J.F.
      • et al.
      Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the SVIN COVID-19 Multinational Registry.
      It has been observed in up to 42% of patients with abnormal neuroradiological findings.
      • Yoon B.C.
      • Buch K.
      • Lang M.
      • et al.
      Clinical and neuroimaging correlation in patients with COVID-19.
      Typical imaging features of intracranial hemorrhage include massive intraparenchymal hemorrhage, usually with extension into the subarachnoid and intraventricular spaces, multifocal intraparenchymal hemorrhages, and microhemorrhages.
      • 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.
      ,
      • Morassi M.
      • Bagatto D.
      • Cobelli M.
      • et al.
      Stroke in patients with SARS-CoV-2 infection: case series.
      ,
      • Gonçalves B.
      • Righy C.
      • Kurtz P.
      Thrombotic and hemorrhagic neurological complications in critically ill COVID-19 patients.
      ,
      • Kihira S.
      • Schefflein J.
      • Pawha P.
      • et al.
      Neurovascular complications that can be seen in COVID-19 patients.
      ,
      • Sharifi-Razavi A.
      • Karimi N.
      • Rouhani N.
      COVID-19 and intracerebral haemorrhage: causative or coincidental?.
      Diffuse edema is often associated with foci of hemorrhage,
      • Morassi M.
      • Bagatto D.
      • Cobelli M.
      • et al.
      Stroke in patients with SARS-CoV-2 infection: case series.
      ,
      • Gonçalves B.
      • Righy C.
      • Kurtz P.
      Thrombotic and hemorrhagic neurological complications in critically ill COVID-19 patients.
      and may contribute to significant mass effect with increased risk of brain herniation.
      • Dogra S.
      • Jain R.
      • Cao M.
      • et al.
      Hemorrhagic stroke and anticoagulation in COVID-19.
      Rarely, acute parenchymal hematomas can involve the bilateral basal ganglia.
      • Daci R.
      • Kennelly M.
      • Ferris A.
      • et al.
      Bilateral basal ganglia hemorrhage in a patient with confirmed COVID-19.
      The mechanism behind this distribution of hemorrhage is hypothesized to be disrupted drainage of the basal ganglia secondary to occlusion of the great cerebral vein.
      Intracranial hemorrhage may result spontaneously, which typically occurs in critically ill patients with severe infections and multiorgan failure.
      • Morassi M.
      • Bagatto D.
      • Cobelli M.
      • et al.
      Stroke in patients with SARS-CoV-2 infection: case series.
      ,
      • Gonçalves B.
      • Righy C.
      • Kurtz P.
      Thrombotic and hemorrhagic neurological complications in critically ill COVID-19 patients.
      Hemorrhage can also result secondarily from other pathologic processes, such as hemorrhagic transformation of ischemic strokes,
      • 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.
      ,
      • Katz J.M.
      • Libman R.B.
      • Wang J.J.
      • et al.
      COVID-19 severity and stroke: correlation of imaging and laboratory markers.
      ,
      • Hernández-Fernández F.
      • Sandoval Valencia H.
      • Barbella-Aponte R.A.
      • et al.
      Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
      ,
      • Dogra S.
      • Jain R.
      • Cao M.
      • et al.
      Hemorrhagic stroke and anticoagulation in COVID-19.
      rupture of dissecting aneurysms
      • Al Saiegh F.
      • Ghosh R.
      • Leibold A.
      • et al.
      Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke.
      and pseudoaneurysms,
      • Savić D.
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      Ruptured cerebral pseudoaneurysm in an adolescent as an early onset of COVID-19 infection: case report.
      hemorrhagic infarction associated with venous sinus thrombosis,
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      Atypical deep cerebral vein thrombosis with hemorrhagic venous infarction in a patient positive for COVID-19.
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      reversible cerebral vasoconstriction syndrome,
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      Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection.
      posterior reversible encephalopathy syndrome (PRES),
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      Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection.
      ,
      • Doo F.X.
      • Kassim G.
      • Lefton D.R.
      • et al.
      Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis.
      and iatrogenic causes.

      Pathophysiology of Hemorrhage

      The pathophysiology for the development of intracranial hemorrhage is multifactorial. COVID-19 is associated with coagulopathies, such as thrombocytopenia and disseminated intravascular coagulation, which increase the risk for hemorrhage.
      • Polimeni A.
      • Leo I.
      • Spaccarotella C.
      • et al.
      Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients.
      More directly, SARS-COV-2 virus is known to bind to the angiotensin-converting enzyme 2 (ACE-2) receptor in order to enter host cells. ACE-2 receptors are expressed on various organs, including cerebrovascular endothelial cells, and are integral components of the renin-angiotensin pathway. SARS-COV-2-induced downregulation of ACE-2 receptors can result in dysregulation of blood pressure control and lead to blood pressure spikes, potentially causing arterial wall rupture and hemorrhage in the brain.
      • Sharifi-Razavi A.
      • Karimi N.
      • Rouhani N.
      COVID-19 and intracerebral haemorrhage: causative or coincidental?.
      Alternatively, the mechanism of diffuse thrombotic microangiopathy has been proposed.
      • Nicholson P.
      • Alshafai L.
      • Krings T.
      Neuroimaging findings in patients with COVID-19.
      Diffuse thrombosis and vascular endothelial damage can lead to breakdown of the blood-brain barrier, facilitating the development of microhemorrhages that eventually coalesce into large intraparenchymal hematomas.
      Iatrogenic causes most likely play a role in the pathogenesis of intracranial hemorrhage. Anticoagulation therapy has been determined to be the cause of a substantial number of cases of intracranial hemorrhage in COVID-19 patients.
      • Hernández-Fernández F.
      • Sandoval Valencia H.
      • Barbella-Aponte R.A.
      • et al.
      Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
      ,
      • Lin E.
      • Lantos J.E.
      • Strauss S.B.
      • et al.
      Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City.
      In 1 study, most parenchymal hemorrhages were attributed to anticoagulation (60%), whereas a few cases were related to indeterminate mechanisms (30%).
      • Lin E.
      • Lantos J.E.
      • Strauss S.B.
      • et al.
      Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City.
      Other case series indicated that all patients with observed hemorrhagic transformation of ischemic strokes were on anticoagulation therapy.
      • Hernández-Fernández F.
      • Sandoval Valencia H.
      • Barbella-Aponte R.A.
      • et al.
      Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
      ,
      • Dogra S.
      • Jain R.
      • Cao M.
      • et al.
      Hemorrhagic stroke and anticoagulation in COVID-19.
      Characteristic imaging features can help distinguish coagulopathic intracranial hemorrhages from other etiologies. The presence of a fluid-blood level, represented by a meniscus separating dependent hyperattenuating blood products from lighter hypoattenuating serous fluid, is a highly specific finding for anticoagulation or antiplatelet therapy in COVID-19 patients.
      • Nicholson P.
      • Alshafai L.
      • Krings T.
      Neuroimaging findings in patients with COVID-19.
      ,
      • Wee N.K.
      • Fan E.B.
      • Lee K.C.H.
      • et al.
      CT fluid-blood levels in COVID-19 intracranial hemorrhage.
      High prevalence of intracranial hemorrhage has been reported in COVID-19 patients on extracorporeal membrane oxygenation (ECMO) therapy. In 1 case series, up to 41.7% of COVID-19 patients on veno-venous ECMO therapy had subarachnoid, intraparenchymal, or intraventricular hemorrhage.
      • Masur J.
      • Freeman C.W.
      • Mohan S.
      A double-edged sword: neurologic complications and mortality in extracorporeal membrane oxygenation therapy for COVID-19–related severe acute respiratory distress syndrome at a tertiary care center.
      ECMO therapy is associated with derangements of hematologic and coagulation pathways, resulting from continuous contact between the patient’s blood and extracorporeal circuit.
      • Kowalewski M.
      • Fina D.
      • Słomka A.
      • et al.
      COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review.
      These factors, possibly compounded by the coagulopathic environment associated with the SARS-COV-2 virus, promote the development of hemorrhagic complications.

      Microhemorrhages

      Microhemorrhages make up approximately 11.1% of abnormal neuroimaging findings in COVID-19 patients.
      • Gulko E.
      • Oleksk M.L.
      • Gomes W.
      • et al.
      MRI brain findings in 126 patients with COVID-19: initial observations from a descriptive literature review.
      Distribution patterns are various and include cortical, juxtacortical, subcortical, deep white matter, perivenular, and corpus callosal involvement.
      • Gulko E.
      • Oleksk M.L.
      • Gomes W.
      • et al.
      MRI brain findings in 126 patients with COVID-19: initial observations from a descriptive literature review.
      ,
      • Franceschi A.M.
      • Arora R.
      • Wilson R.
      • et al.
      Neurovascular complications in COVID-19 infection: case series.
      ,
      • Kihira S.
      • Schefflein J.
      • Pawha P.
      • et al.
      Neurovascular complications that can be seen in COVID-19 patients.
      Microhemorrhages attributable to COVID-19 can be made by deduction through the exclusion of other etiologies, such as hypertensive coagulopathy, diffuse axonal injury, or cerebral amyloid angiopathy, based on atypical distribution patterns and absence of clinical factors, such as hypertension or trauma.
      • Yoon B.C.
      • Buch K.
      • Lang M.
      • et al.
      Clinical and neuroimaging correlation in patients with COVID-19.
      Corpus callosum involvement, particularly the splenium, is a commonly reported finding in multiple case series of COVID-19 patients.
      • Franceschi A.M.
      • Ahmed O.
      • Giliberto L.
      • et al.
      Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection.
      ,
      • Lin E.
      • Lantos J.E.
      • Strauss S.B.
      • et al.
      Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City.
      ,
      • Sachs J.R.
      • Gibbs K.W.
      • Swor D.E.
      • et al.
      COVID-19–associated Leukoencephalopathy.
      Microhemorrhages in the corpus callosum have been previously described in other patient populations, such as in delayed posthypoxic leukoencephalopathy from acute respiratory distress syndrome,
      • Riech S.
      • Kallenberg K.
      • Moerer O.
      • et al.
      The pattern of brain microhemorrhages after severe lung failure resembles the one seen in high-altitude cerebral edema.
      ,
      • Breit H.
      • Jhaveri M.
      • John S.
      Concomitant delayed posthypoxic leukoencephalopathy and critical illness microbleeds.
      high-altitude cerebral edema,
      • Kallenberg K.
      • Dehnert C.
      • Dörfler A.
      • et al.
      Microhemorrhages in nonfatal high-altitude cerebral edema.
      and in critical illness-associated microbleeds,
      • Fanou E.M.
      • Coutinho J.M.
      • Shannon P.
      • et al.
      Critical illness–associated cerebral microbleeds.
      in which there is additional involvement of the juxtacortical white matter with sparing of the deep and periventricular white matter. The underlying mechanism is multifactorial, related to hypoxic-induced injury to the blood-brain barrier and impaired cerebral venous return from increased intracranial pressures. COVID-19-related microhemorrhages likely follow similar mechanisms; however, the pervasive use of mechanical ventilation among COVID-19 patients represents a confounding factor. Increased intrathoracic pressures related to ventilator use can reduce cerebral venous return in critically ill patients, which may better explain the development of microhemorrhages than direct effects from the SARS-COV-2 virus.
      • Lin E.
      • Lantos J.E.
      • Strauss S.B.
      • et al.
      Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City.

      Coronavirus disease-related leukoencephalopathies

      Leukoencephalopathies have been observed in up to 27% of abnormal neuroimaging findings among COVID-19 patients.
      • Yoon B.C.
      • Buch K.
      • Lang M.
      • et al.
      Clinical and neuroimaging correlation in patients with COVID-19.
      These include white matter abnormalities that are similar imaging patterns described in the literature associated with other infectious diseases, PRES, acute disseminated encephalomyelitis (ADEM), and acute hemorrhagic leukoencephalitis (AHLE). There are several pathologic findings described in COVID-19-related leukoencephalopathy that may relate to the different imaging patterns. However, the definite mechanisms are as yet incompletely understood.
      • Reichard R.R.
      • Kashani K.B.
      • Boire N.A.
      • et al.
      Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.

      Posterior Reversible Encephalopathy Syndrome

      PRES manifestations are typically seen as reversible confluent white matter changes in the posterior cerebrum. These appear as striking areas of hypoattenuation on noncontrast computed tomography (CT), correlating with findings of T2/fluid attenuated inversion recovery (FLAIR) signal abnormality on MRI. The distribution is typically in the areas associated with PRES, predominantly the subcortical white matter of the posterior temporal and occipital lobes.
      • Franceschi A.M.
      • Ahmed O.
      • Giliberto L.
      • et al.
      Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection.
      ,
      • D’Amore F.
      • Vinacci G.
      • Agosti E.
      • et al.
      Pressing issues in COVID-19: probable cause to seize SARS-CoV-2 for its preferential involvement of posterior circulation manifesting as severe posterior reversible encephalopathy syndrome and posterior strokes.
      ,
      • Conte G.
      • Avignone S.
      • Carbonara M.
      • et al.
      COVID-19–associated PRES–like encephalopathy with perivascular gadolinium enhancement.
      Corresponding high diffusivity is seen in these regions. Areas of hemorrhage are also described, including small parenchymal hemorrhages visible on CT and microhemorrhages best visualized on gradient echo (GRE)/susceptibility weighted imaging (SWI) (Fig. 4).
      • Doo F.X.
      • Kassim G.
      • Lefton D.R.
      • et al.
      Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis.
      ,
      • Kishfy L.
      • Casasola M.
      • Banankhah P.
      • et al.
      Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe COVID-19.
      ,
      • Rogg J.
      • Baker A.
      • Tung G.
      Posterior reversible encephalopathy syndrome (PRES): another imaging manifestation of COVID-19.
      The pathologic mechanism is thought to be related to direct binding of the virus to surface ACE-2 receptors on neurovascular endothelial cells, leading to breakdown of the blood brain barrier.
      • Lin E.
      • Lantos J.E.
      • Strauss S.B.
      • et al.
      Brain imaging of patients with COVID-19: Findings at an academic institution during the height of the outbreak in New York City.
      Blood pressure dysregulation caused by ACE-2 dysfunction is also a possibility.
      • Doo F.X.
      • Kassim G.
      • Lefton D.R.
      • et al.
      Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis.
      Interestingly, the PRES-like findings of COVID-19 may be associated with lower blood pressure elevations than seen in other PRES etiologies.
      • Kishfy L.
      • Casasola M.
      • Banankhah P.
      • et al.
      Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe COVID-19.
      ,
      • Rogg J.
      • Baker A.
      • Tung G.
      Posterior reversible encephalopathy syndrome (PRES): another imaging manifestation of COVID-19.
      Figure thumbnail gr4
      Fig. 464-year-old man with ongoing COVID-19 pneumonia requiring intubation developed rhythmic jerking and status epilepticus. MRI FLAIR sequence (A) demonstrated extensive symmetric cerebral edema with a parieto-occipital dominance (stars) and scattered small foci of recent hemorrhage on the GRE sequence (circles) (B). Findings were consistent with a posterior reversible syndrome-like leukoencephalopathy with hemorrhage.

      Acute Leukoencephalopathy

      Several ADEM-type lesions have been described secondary to COVID-19.
      • Reichard R.R.
      • Kashani K.B.
      • Boire N.A.
      • et al.
      Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.
      ,
      • Kihira S.
      • Delman B.N.
      • Belani P.
      • et al.
      Imaging features of acute encephalopathy in patients with COVID-19: A Case Series.
      ,
      • Lang M.
      • Buch K.
      • Li M.D.
      • et al.
      Leukoencephalopathy associated with severe COVID-19 infection: sequela of hypoxemia?.
      Findings generally include multifocal areas of white matter restricted diffusion (Fig. 5) with associated T2/FLAIR hyperintensity. These predominate in the posterior white matter, in a similar distribution to PRES-like findings. However, the less confluent distribution of these lesions helps to make the distinction between these pathologies. Of note, the degree of central restricted diffusion is greater in COVID-19 lesions when compared with findings of ADEM seen secondary to other viral infections. Lesions are also reported in the corpus callosum, basal ganglia, brain stem, and cerebellum.
      • Sachs J.R.
      • Gibbs K.W.
      • Swor D.E.
      • et al.
      COVID-19–associated Leukoencephalopathy.
      ,
      • Kihira S.
      • Delman B.N.
      • Belani P.
      • et al.
      Imaging features of acute encephalopathy in patients with COVID-19: A Case Series.
      Enhancement may be associated with these lesions, as well as multiple microhemorrhages visualized on GRE/SWI imaging.
      • Kandemirli S.G.
      • Dogan L.
      • Sarikaya Z.T.
      • et al.
      Brain MRI findings in patients in the intensive care unit with COVID-19 infection.
      Upon follow-up imaging after the acute episode, lesions may demonstrate more confluence on T2/FLAIR as well as development of cavitation and volume loss.
      • Agarwal S.
      • Conway J.
      • Nguyen V.
      • et al.
      Serial imaging of virus-associated necrotizing disseminated acute leukoencephalopathy (VANDAL) in COVID-19.
      Figure thumbnail gr5
      Fig. 560-year-old woman with morbid obesity, hypertension, and asthma admitted with COVID-19 with hospital course complicated by acute renal failure requiring hemodialysis, respiratory failure, and flaccid quadriparesis. Brain MRI axial diffusion sequence showed restricted diffusion in the centrum semiovale bilaterally (arrows). Findings likely reflect a combination of hypoxia and critical illness-related encephalopathy.
      More severe manifestations have also been described with imaging findings similar to AHLE. A case report of a patient with severe acute respiratory syndrome and altered mental status described more central expansile T2/FLAIR hyperintensity involving the basal ganglia and thalami. There was more frank evidence of hemorrhage than seen in less severe ADEM-like cases. Predominantly peripheral enhancement was also seen.
      • Poyiadji N.
      • Shahin G.
      • Noujaim D.
      • et al.
      COVID-19–associated acute hemorrhagic necrotizing encephalopathy: imaging features.
      The underlying pathologic mechanism shares some similarity to the PRES-like syndrome, including suspected ACE-2-related endothelial dysfunction. Cytokine storms with elevated bloodstream cytokines and interleukins may also play a central role.
      • Agarwal S.
      • Conway J.
      • Nguyen V.
      • et al.
      Serial imaging of virus-associated necrotizing disseminated acute leukoencephalopathy (VANDAL) in COVID-19.
      On pathology, a range of lesions are identified, including those that share features of ADEM and AHLE.
      • Reichard R.R.
      • Kashani K.B.
      • Boire N.A.
      • et al.
      Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.
      It may be that acute leukoencephalopathy in the setting of COVID-19 represents a spectrum of disorders rather than 1 entity.

      Neuropathies

      Anosmia/Dysgeusia

      Sudden onset and persistent alterations of taste and smell have been frequently reported in the setting of COVID-19 respiratory illness. In fact, loss of smell is reported as a helpful symptom in initial diagnosis of COVID-19. Several case reports and case series describe abnormal imaging findings in the anterior cranial fossa/olfactory bulbs seen in the early stages of infection (Fig. 6). An initial case report described T2/FLAIR signal abnormality in the gyrus rectus and olfactory bulbs at 3 days following presentation. At 28 days, the cortical edema had resolved, and atrophy was demonstrated in the olfactory bulbs.
      • Politi L.S.
      • Salsano E.
      • Grimaldi M.
      Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia.
      A follow-up case series identified intrinsic T1 hyperintensity and possible enhancement in the olfactory bulbs in 5 patients. Earlier work has shown central nervous system involvement via olfactory bulb invasion in experimental mouse models. This phenomenon has also been described in other viral infections.
      • Aragão M.F.V.V.
      • Aragão M.F.V.
      • Leal M.C.
      • et al.
      Anosmia in COVID-19 associated with injury to the olfactory bulbs evident on MRI.
      More recent case series evaluating patients with persistent anosmia at least 1 month after presentation described variable findings of volume loss, morphologic change, and signal abnormality.
      • Kandemirli S.G.
      • Altundag A.
      • Yildirim D.
      • et al.
      Olfactory bulb MRI and paranasal sinus CT findings in persistent COVID-19 anosmia.
      The pathologic mechanism is not yet completely understood. One possibility is injury of olfactory epithelial cells bearing ACE-2 receptors. Direct nerve invasion with retrograde tracking along the olfactory pathway has also been suggested, as seen in herpes simplex virus (HSV) infections; however, it remains unproven.
      • Kandemirli S.G.
      • Altundag A.
      • Yildirim D.
      • et al.
      Olfactory bulb MRI and paranasal sinus CT findings in persistent COVID-19 anosmia.
      Figure thumbnail gr6
      Fig. 637-year-old man suffered from anosmia following COVID-19 infection with loss of smell worse on the right side. Coronal T2-weighted (A) and FLAIR (B) MR images 6 months after infection showed atrophy and hyperintensity of the olfactory bulbs bilaterally (arrows), worse on the right side.

      Other Cranial Neuropathies

      Other cranial neuropathies have been observed in COVID-19, such as palsy of the facial nerve
      • Corrêa D.G.
      • Hygino da Cruz Jr., L.C.
      • Lopes F.C.R.
      • et al.
      Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.
      • Goh Y.
      • Beh D.L.L.
      • Makmur A.
      • et al.
      Pearls & oysters: facial nerve palsy in COVID-19 infection.
      • Lima M.A.
      • Silva M.T.T.
      • Soares C.N.
      • et al.
      Peripheral facial nerve palsy associated with COVID-19.
      and abducens nerve.
      • Corrêa D.G.
      • Hygino da Cruz Jr., L.C.
      • Lopes F.C.R.
      • et al.
      Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.
      These manifestations can occur as the initial symptom or develop more subacutely, usually up to 2 weeks from the initial onset of COVID-19 symptoms. Patients typically present with mild or absent respiratory or constitutional symptoms.
      Characteristic imaging features include short-T1 inversion recovery (STIR) hyperintensity with gadolinium enhancements of the affected cranial nerve. Diffusion restriction may also be observed.
      • Corrêa D.G.
      • Hygino da Cruz Jr., L.C.
      • Lopes F.C.R.
      • et al.
      Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.
      In facial nerve palsies, enhancement of the facial nerve may actually be normal and reflect anatomy, such as the circumneural venous plexus.
      • Corrêa D.G.
      • Hygino da Cruz Jr., L.C.
      • Lopes F.C.R.
      • et al.
      Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.
      However, presence of asymmetric enhancement and correlation with clinical symptoms can increase confidence that the enhancement is actually pathologic.
      As with olfactory neuropathies, the pathogenesis of these other cranial neuropathies is not well understood, but may be similar to that of neurotropic viruses, such as HSV and varicella zoster virus (VZV), in which direct viral invasion of the nerve can lead to axonal spread and subsequent inflammation and demyelination.
      • Eviston T.J.
      • Croxson G.R.
      • Kennedy P.G.E.
      • et al.
      Bell’s palsy: aetiology, clinical features and multidisciplinary care.
      Immune-mediated injury of the nerve from proinflammatory cytokines may additionally play a role.
      • Corrêa D.G.
      • Hygino da Cruz Jr., L.C.
      • Lopes F.C.R.
      • et al.
      Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.

      Summary

      COVID-19 infections are associated with a myriad of acute neuroradiological features, many of which necessitate careful and prompt diagnoses. Cerebrovascular disease is a predominant complication of COVID-19 infection, attributing to the prothrombotic environment engendered by the SARS-COV-2 virus. Acute and subacute strokes, the most common neuroradiological findings, share typical features, including multiterritorial distributions, involvement of atypical vessels, and prevalence among younger patients. Appearances of intracerebral hemorrhages are more variable, although predilection for the cerebral hemispheres and corpus callosum are salient features. COVID-19-related leukoencephalopathies share similar imaging patterns with white matter diseases observed in other infections, such as PRES, ADEM, and AHLE. Acute cranial nerve neuropathies, such as anosmia and dysgeusia, can present with pathologic enhancement and nerve atrophy. Radiologists and clinicians alike should be aware of the typical neuroimaging features of COVID-19 infections as these findings can play a significant role in patient management and treatment outcomes.

      Clinics care points

      • Given that neurological manifestations in COVID-19 patients can be associated with poor prognosis, radiologists and clinicians should have a lower threshold to pursue neuroimaging in these patients
      • Promptly recognizing characteristic imaging features of COVID-19-related strokes and intracranial hemorrhages can allow for earlier intervention and improved patient outcomes

      Disclosure

      The authors have nothing to disclose.

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