The Spectrum of Neuroimaging Findings on CT and MRI in
Adults With COVID-19
Gul Moonis, MD1, Christopher G. Filippi, MD2, Claudia F. E. Kirsch, MD3, Suyash Mohan, MD 4, Evan G. Stein, MD, PhD5,
Joshua A. Hirsch, MD6, Amit Mahajan, MBBS7
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N e uroradio lo g y/H e ad and N e c k Imaging · Review
Keywords
brain, coronavirus disease, COVID-19, CT,
MRI, neuroimaging, spine
Submitted: Sep 22, 2020
Revision requested: Oct 6, 2020
Revision received: Oct 27, 2020
Accepted: Nov 17, 2020
First published online: Nov 25, 2020
C. F. E. Kirsch is a consultant and receives
royalties from Primal Pictures 3D Head and
Neck Anatomy. S. Mohan is a consultant for
Northwest Biotherapeutics and has
received research grants from NovoCure
and Galileo CDS. The remaining authors
declare that they have no disclosures
relevant to the subject matter of this article.
Moonis et al.
COVID-19 Neuroimaging Findings on CT and MRI
Moonis G, Filippi CG, Kirsch C, et al.
Neuroradiology/Head and Neck Imaging
Review
doi.org/10.2214/AJR.20.24839
AJR 2021; 217:959–974
ISSN-L 0361–803X/21/2174–959
© American Roentgen Ray Society
AJR:217, October 2021
Neurologic involvement is well-recognized in COVID-19. This article reviews the
neuroimaging manifestations of COVID-19 on CT and MRI, presenting cases from the
New York City metropolitan region encountered by the authors during the first surge
of the pandemic. The most common neuroimaging manifestations are acute infarcts
with large clot burden and intracranial hemorrhage, including microhemorrhages.
However, a wide range of additional imaging patterns occur, including leukoenceph-
alopathy, global hypoxic injury, acute disseminated encephalomyelitis, cytotoxic
lesions of the corpus callosum, olfactory bulb involvement, cranial nerve enhance-
ment, and Guillain-Barré syndrome. The described CNS abnormalities largely repre-
sent secondary involvement from immune activation that leads to a prothrombotic
state and cytokine storm; evidence for direct neuroinvasion is scant. Comorbidities
such as hypertension, complications of prolonged illness and hospitalization, and as-
sociated supportive treatments also contribute to the CNS involvement in COVID-19.
Routine long-term neurologic follow-up may be warranted, given emerging evi-
dence of long-term microstructural and functional changes on brain imaging after
COVID-19 recovery.
COVID-19 is predominantly a respiratory illness, although neurologic involvement is
well recognized [1, 2]. This article reviews the neuroimaging manifestations of COVID-19,
presenting cases from the New York City metropolitan area encountered by the au-
thors during the first surge of the pandemic. The presented neuroradiologic findings en-
tail predominantly thromboembolic phenomena and intracranial hemorrhages in acute
COVID-19 and a range of subacute and chronic neurologic consequences of COVID-19.
Pathogenesis
The neurologic sequelae of COVID-19 can be broadly grouped into four categories: di-
rect viral effects through neuroinvasion, parainfectious immune response to the virus that
manifests as coagulopathy or cytokine storm, postinfectious delayed immune response,
and complications of prolonged illness or hospitalization (Table 1).
The evidence for direct neuroinvasion by the SARS-CoV-2 virus is scant, with neuroinvasion
not yet confirmed on histopathologic studies to our knowledge. SARS-CoV-2, a novel corona-
virus, gains intracellular entry via the spike protein interaction with the angiotensin-converting
enzyme 2 (ACE2) receptor on the mammalian cell surface [3, 4]. The ACE2 protein is expressed
on multiple cell surfaces, including the intestinal epithelium, renal tubular cells, heart, endo-
thelium, respiratory epithelium, neuronal glial cells, circumventricular organs, arterial smooth
muscle, and endothelial cells [5]. The possibility of direct viral invasion into neuronal cells was
raised by reports of CSF testing positive for SARS-CoV2 infection on reverse transcriptase poly-
Department of Radiology, Columbia University Irving Medical Center, New York, NY.
1
Department of Radiology, Lenox Hill Hospital–Northwell Health, Zucker School of Medicine at Hofstra-Northwell,
2
New York, NY.
3
Department of Radiology, Northwell Health, Zucker Hofstra School of Medicine at Northwell, North Shore University
Hospital, Hempstead, NY.
4
Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylva-
nia, Philadelphia, PA.
Department of Radiology, SUNY Downstate, Maimonides Medical Center, Brooklyn, NY.
5
6
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT 06520.
7
Address correspondence to A. Mahajan (amit.mahajan@yale.edu).
www.ajronline.org | 959
 Moonis et al.

merase chain reaction (RT-PCR) tests [6–8], as well as by a report of

intraneuronal virallike inclusions in one patient on autopsy [9]. How-
ever, a subsequent larger autopsy series of COVID-19 that showed
endothelial damage and microthrombi within small vessels of the
brain failed to show intraneuronal viral particles [10]. Nonetheless,
anosmia and dysgeusia are frequent symptoms of early COVID-19,
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HIGHLIGHTS
 The most common neuroimaging manifestations of
COVID-19 are acute infarcts with large clot burden and in-
tracranial hemorrhage, including microhemorrhages.

suggesting possible retrograde transsynaptic spread of viral parti-
cles adherent to nasal mucosa through direct infection of olfacto-
ry epithelium and subsequent transport into the CNS through the
olfactory nerve [11]. Indeed, nasal epithelial and goblet cells within
the nasal mucosa show the highest expression of ACE2 among sites
within the respiratory tree and may be important for efficient viral
transmission and early development of anosmia [12]. Aside from the
olfactory involvement, brain involvement in COVID-19 most likely
represents secondary involvement from immune activation.
Coagulopathy leading to thromboembolism is well described
in patients with COVID-19 and occurs in a higher fraction of pa-
tients with severe disease [13–19]. It is uncertain whether the hy-
percoagulability results primarily from direct viral interactions
with the endothelium (endotheliopathy), even in the absence of
neuroinvasion, or an abnormal inflammatory response incited by
the virus. Nonetheless, strokes have been reported in young pa-
tients with COVID-19 who did not have significant inflammatory
symptoms, suggesting the importance of endotheliopathy in the
pathogenesis of neurologic syndromes [13, 20].
Cytokine storm refers to a dysregulated and excessive immune
response that can cause immune-mediated tissue damage [21]. A
hyperinflammatory syndrome akin to secondary hemophagocytic
lymphohistiocytosis with monocyte activation has been described
in COVID-19 [10, 22, 23]. Proinflammatory cytokines can result in
endothelial dysfunction, vascular damage, and activation of coag-
ulation cascade, promoting a hypercoagulable state [24].
The sequelae of treatment of COVID-19 also contribute to neu-
roimaging findings. Severely affected patients may have extend-
ed stays in the ICU with prolonged intubation including extra-
 Additional imaging patterns include leukoencephalop-
athy, ADEM, cytotoxic lesions of the corpus callosum,
olfactory bulb involvement, cranial nerve enhance-
ment, and Guillain-Barré syndrome.
 Routine long-term neurologic follow-up may be war-
ranted given emerging evidence of long-term micro-
structural and functional changes on brain imaging af-
ter COVID-19 recovery.
corporeal membrane oxygenation (ECMO), which may result in
diffuse hypoxemic injury to the brain, microhemorrhages, and
delayed posthypoxic leukoencephalopathy.
Imaging Findings
Most patients with COVID-19 who undergo neuroimaging
show no specific imaging findings [25, 26]. For example, in a
study of 242 patients with COVID-19 who underwent brain CT or
MRI within 2 weeks of a positive RT-PCR test, the most common
finding was nonspecific white matter microangiopathy, with
acute or subacute infarct present in 5.4% and hemorrhage pres-
ent in 4.5% [25]. Table 2 summarizes representative studies de-
scribing the neuroimaging findings of COVID-19.
Thromboembolic Manifestations
In the early surge phase of the pandemic, acute thromboem-
bolic infarcts were the most commonly seen intracranial mani-
festations in patients with COVID-19 who had positive findings

TABLE 1: Neurologic Syndromes Associated With COVID-19

Category, Putative Pathogenesis Clinical Syndromes
Direct viral effect
Neuroinvasion Anosmia, possible encephalitis or meningoencephalitis
Endotheliopathy Thromboembolism
Parainfectious
Immune response
Coagulopathy Thromboembolism, hemorrhage
Cytokine storm Acute necrotizing leukoencephalopathy, encephalitis, cytotoxic lesions of corpus callosum,
thromboembolism, hemorrhage
Postinfectious
Delayed immune response Guillain-Barré syndrome, acute disseminated encephalomyelitis
Complications of prolonged illness or hospitalization
Anticoagulation Hemorrhage
Hypoxic changes Diffuse hypoxic damage, posthypoxic demyelination
Drug related Neurotoxicity
Dialysis related Posterior reversible encephalopathy syndrome

960 AJR:217, October 2021

 C O V I D -19 N e u r o i m a g i n g F i n d i n g s o n C T a n d M R I
on neuroimaging studies [27, 28]. Acute stroke was a strong prog-
nostic indicator of poor outcome [27]. In addition, in a case con-
trol study of 41 patients with COVID-19 and 82 control patients
who underwent stroke alert imaging, COVID-19 was an indepen-
dent risk factor for acute ischemic stroke [29]. One study identi-
fied 54 strokes in 3334 patients hospitalized at a single institu-
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tion between March 1 and April 17, 2020; 31 (3.7%) strokes in 829
patients in the ICU and 23 (0.9%) strokes in 2505 patients not in
the ICU [16]. Cerebral thromboembolic event may be the first pre-
sentation of COVID-19 [13, 30]. For example, one study described
five patients 50 years old or younger with COVID-19 who present-
ed with large vessel occlusion stroke [13]. Thromboembolic epi-
sodes may coincide with increased d-dimer levels and inflamma-
tory markers. For example, case reports describe an association
between stroke in COVID-19 and antiphospholipid antibod-
ies [31–34]. The commonly observed patterns of acute cerebral
thromboembolic disease are large vessel occlusion with territori-
al infarcts, branch vessel occlusion, small vessel occlusion, small
vessel infarcts, watershed infarcts, and extensive bilateral mul-
tivessel infarcts [26, 28, 35, 36] (Figs. 1 and 2).
Patients with COVID-19 and acute thromboembolic infarct
may have a high clot burden with thrombotic manifestations
elsewhere in the body, including cervical carotid artery, vertebral
artery, and subclavian artery thrombosis; pulmonary embolism;
and lower extremity venous thromboembolism (Fig. 1). Com-
pared with the common reports of cerebral arterial thrombotic
events, there are very limited reports of cerebral venous throm-
bosis in COVID-19 [37–41] (Fig. 3). One of these reports described
three fatal cases of COVID-19–related superficial and deep cere-
bral venous thrombosis [41]. Finally, one report describes a pa-
tient with COVID-19 who had a normal MRA but exhibited a CNS
vasculitislike pattern with multifocal ischemia in the hemispheric
deep white matter, middle cerebellar peduncles, cerebellar hemi-
spheres, and corpus callosum [42].
In summary, thromboembolic infarcts are common in patients
with COVID-19 who have an abnormal neuroimaging examina-
tion. These include acute large vessel, small vessel, and water-
shed infarcts. Venous infarcts are uncommon.
Hemorrhages
Intracranial hemorrhage is commonly observed on neuroimag-
ing examinations in patients with COVID-19 [43, 44]. Patients with
COVID-19 may present with lobar hemorrhage, microhemorrhag-
es, subarachnoid hemorrhage, or subdural hemorrhage. These in-
tracranial hemorrhages in COVID-19 likely result from a complex in-
terplay of an underlying prothrombotic state, cytokine storm, and
treatment-related complications. ACE2 plays a role in autoregula-
tion in addition to regulation of hormones and the sympathoad-
renal system [45]. Blood vessel dysregulation in COVID-19 could
potentially cause the vessels to become susceptible to changes in
blood pressure. Hemorrhagic transformation is a well-recognized
phenomenon in preexisting acute infarcts and has been observed
in COVID-19 [43]. Finally, patients with severe COVID-19 may have
underlying comorbidities, such as hypertension, that are indepen-
dent risk factors for intracranial hemorrhage.
A range of disease-related complications and interventions
may further contribute to intracranial hemorrhage in COVID-19.
For example, blood pressure changes, including elevations in
AJR:217, October 2021
blood pressure, commonly occur in the critical care setting [46].
In addition, disseminated intravascular coagulation, related to cy-
tokine storm, is common in severe COVID-19 and may cause intra-
cranial hemorrhage [47]. Patients with COVID-19 and severe acute
respiratory distress syndrome may be treated with continuous
venovenous ECMO; the resulting hematologic alterations may
contribute to intracranial bleeds, including microhemorrhages
in the corpus callosum [48] (Fig. 4). Anticoagulation started for
deep venous thrombus prevention can also predispose to hem-
orrhage. Patients with severe COVID-19 may develop acute kid-
ney injury and require dialysis, which may cause rapid changes in
blood pressure, cerebral edema, microembolization, and micro-
hemorrhages [49–51]. Finally, hemorrhagic posterior reversible
encephalopathy syndrome has been described in COVID-19 [52].
A series of 11 patients had microhemorrhages associated
with COVID-19 [53]. The microhemorrhages occurred predom-
inantly in the juxtacortical and callosal white matter (Fig. 5).
The distribution is similar to that of microhemorrhage in criti-
cal illness microangiopathy, in which hypoxia-induced disrup-
tion of the blood-brain barrier causes extravasation of eryth-
rocytes or disseminated intravascular coagulation [54, 55]. It is
also possible that the microhemorrhages represent a virus-in-
duced thrombotic microangiopathy in which the viral infec-
tion triggers a systemic microvascular aggregation of platelets
and platelet fibrin thrombi, leading to microvascular occlusion,
thrombocytopenia, microangiopathic hemolytic anemia, and
brain ischemia [56–58].
In summary, patients with COVID-19 commonly have acute
hemorrhages in different intracranial compartments related to
a combination of factors, including COVID-19 coagulopathy, dis-
seminated intravascular coagulation, and cytokine storm. Effects
of treatments such as thromboprophylaxis, hemodialysis, and
ECMO may also contribute to the hemorrhages. Critical illness
microangiopathy and virus-induced thrombotic microangiopa-
thy are additional factors contributing to microhemorrhages.
Leukoencephalopathy
White matter changes may occur in patients with prolonged
ICU stays for COVID-19 [53, 59] (Fig. 6). For example, the previous-
ly noted report of 11 patients with COVID-19 and microhemor-
rhages also described an associated diffuse leukoencephalopa-
thy in these patients. This leukoencephalopathy manifested as
symmetric confluent white matter hyperintensity on T2-weight-
ed sequences and restricted diffusion, with relative sparing of
juxtacortical and infratentorial white matter [53]. The findings, al-
though nonspecific, may represent a delayed posthypoxic phe-
nomenon. The previously described thrombotic microangiop-
athy that may lead to microhemorrhages in COVID-19 may also
uncommonly produce white matter lesions [60].
Global Hypoxic Injury
Along with the previously noted possible delayed posthypoxic
leukoencephalopathy that may occur in COVID-19, global hypox-
ic injury may occur in the acute setting. In one series global hy-
poxic injury in two of 3218 hospitalized patients during a 6-week
period [27]. Global hypoxic injury was observed typically mani-
fests on MRI as restricted diffusion of the basal ganglia, thalami,
hippocampi, and cortex [61]. Globus pallidus necrosis has been
961
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962
TABLE 2: Imaging Features From Representative Studies of Neuroimaging Findings in Patients With COVID-19
Moonis et al.

Patients With Neuroimaging No. (%) of Findings

First Author
[Reference], Patients With Total Type No. (%)
Country (City) COVID-19 No. of Imaging Abnormal Neurologic Manifestations Other Findings CSF
Helms [2], France 64 hospitalized with 13/58 Brain MRI 11 Leptomeningeal enhancement, 8 Perfusion abnormali- PCR negative, 7;
(Strasbourg) ARDS; 58 evaluable Infarct, 3 ties: 11/11 pleocytosis, 0
Radmanesh [25], 3661 diagnosed 242/3661 Head CT, 207; brain 206 Infarct, 13 (5.4) Diffuse anoxic injury, —
U.S. (NYC)a MRI, 11 Hemorrhage, 11 (4.5) 1 (5.4)
Nonspecific microangiopathy, 134 (55.4)
Klironomos [26], 2611 hospitalized 185/2611 CT, 174; brain MRI, 43; Total not Leptomeningeal enhancement, 3/20 (15) Olfactory bulb signal —
Sweden (Stockholm) spine MRI, 7 provided Infarct on CT,15/174 (8.6); on MRI, 10/41 (24) abnormality, 7/37
Hemorrhage on CT, 16/174 (9.2); on MRI, 11/39 (28) (19); prominent
Leukoencephalopathy, 23/41 (56) [periventricular, 18; optic nerve sheath,
juxtacortical, 10; corpus callosum, 11; middle cerebellar 20/36 (56)
peduncle, 7]
Microhemorrhage, 29/39 (74) [corpus callosum susceptibili-
ty, 23/39 (59) and juxtacortical susceptibility,14/39 (36)]
Guillain-Barré syndrome [cranial nerve enhancement, 2/20
(10); spinal nerve enhancement, 2/4 (50)]
Encephalitis [parenchymal enhancement, 3/20 (15); CLOCC,
1/41 (2.4)]
Jain [27], U.S. (NYC)a 6447 diagnosed, of 454/3218 Head CT, 586; head 38 (8.4) Infarct, 26 [large, 17 (44.5); lacunar, 9 (24)] PRES, 1 (5); diffuse —
which 3218 were and neck CTA, 34; Hemorrhage, 9 (24) anoxic injury, 2 (5)
admitted CT perfusion, 14; Guillain-Barré syndrome [Miller Fisher, 1 (10)]
brain MRI, 48; brain Encephalitis, 1 (2.5) [acute encephalopathy, 1 (5)]
MRA/MRV, 17; spine
MRI, 12
Mahammedi [28], Italy 725 hospitalized, of 108/119 Head CT, 107; head 51 (47) Leptomeningeal enhancement, 0/10 Acute MS, 2 (10); —
(Multicenter) which 119 had and neck CTA, 17; Infarct ,34 (31) cerebral venous
neurologic brain MRI, 2 Hemorrhage, 6 (6) thrombosis; 2/17
symptoms Chronic leukoencephalopathy, 7/20 (12); diffuse anoxic
Guillain-Barré syndrome, 2 (20) injury, 2
Nonspecific encephalopathy, 2 (10)
Yoon [35], U.S. (Boston) 641 admitted 150/641 CT, 141; brain MRI, 21 26 Infarct, 13 — —
Hemorrhage, 11 [microhemorrhage, 7]
Leukoencephalopathy, 7
Lin [36], U.S. (NYC) 2054 admitted or 278/2054 Head CT, 269; brain 58 (21) Leptomeningeal enhancement, 0 PRES, 3; olfactory —
presenting to MRI, 51 Infarct, 31 (11%) bulb abnormality: 4
emergency Hemorrhage, 10 [hematoma > 5 cm, 6]
department Microhemorrhage, 26 (51) [corpus callosum, 3]
Guillain-Barré syndrome [cranial nerve enhancement, 6]
(Table continues on next page)

AJR:217, October 2021

 C O V I D -19 N e u r o i m a g i n g F i n d i n g s o n C T a n d M R I

reported in COVID-19, presumably related to hypoxia [62] (Fig. 7).

PCR negative, 5;
Callosal microhemor- PCR negative, 1
Although isolated involvement of the globus pallidus is unusu-

Note—Values are provided as reported in the referenced articles. Dash indicates not reported. ARDS = acute respiratory distress syndrome, PCR = polymerase chain reaction, U.S. = United States, NYC = New
protein, 4
al, it has been described previously in global hypoxic injury [63].

elevated
CSF
—

York City, CLOCC = cytotoxic lesion of the corpus callosum, MRV = MR venogram, PRES = posterior reversible encephalopathy syndrome, MS = multiple sclerosis, AHNE = acute hemorrhagic necrotizing
TABLE 2: Imaging Features From Representative Studies of Neuroimaging Findings in Patients With COVID-19 (continued)

Meningitis and Encephalitis

Meningitis and encephalitis are less common than thrombo-
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embolic events in COVID-19 [27]. A systematic nationwide sur-

Other Findings

veillance system report from the United Kingdom [64] observed

Transvers sinus
thrombosis,1
encephalitis in 18% of 153 patients with neurologic symptoms
—

rhage, 4/7
identified over a 3-week period during the first phase of the ep-
idemic. Table 3 summarizes reported cases of encephalitis in
COVID-19. The radiologic presentations of such cases are myri-
ad. For example, one report described enhancement in the lep-
No. (%) of Findings

Microhemorrhage [cortical FLAIR signal abnormality, 10/27;

tomeningeal spaces in eight of 13 patients with severe COVID-19
[2]. Two cases of brainstem involvement have been described
Cortical DWI abnormality, 7 [acute right MCA infarct, 1

[65, 66]. Additional case reports describe COVID-19–related acute

necrotizing encephalopathy, manifested by increased signal in
Neurologic Manifestations

the thalami and medial temporal lobes [65, 67]. Acute necrotiz-
ing encephalopathy has been reported with other viral illnesses,
including SARS and influenza, and may relate to intracranial cyto-
Juxtacortical microhemorrhages, 5/7

Leptomeningeal enhancement, 5/8

kine storm and breakdown of the blood-brain barrier [68].

Various criteria have been used for diagnosing meningitis or
cortical blooming artifact, 1]

encephalitis resulting from COVID-19. Some studies showed diag-

Guillain-Barré syndrome, 7
Leukoencephalopathy, 10

Leukoencephalopathy, 3

nosis of meningitis or encephalitis in patients with COVID-19 and

Hemorrhage > 4 mm, 4

Encephalitis [AHNE, 1]

an RT-PCR test from the CSF that was positive for SARS CoV-2 in-
fection [6, 7]. On the other hand, one study attributed hyperin-
Hemorrhage, 33

tensity on cortical FLAIR to encephalitis in 10 patients in the ICU

who underwent MRI, of whom seven showed cortical restricted
diffusion and five showed leptomeningeal enhancement [59]; CSF
RT-PCR was negative for SARS-CoV-2infection in the five of 10 pa-
tients with cortical hyperintensity to whom the test was given.
Abnormal

Further, one multicenter study (ENCOVID) [69] reported 32 cases

No. (%)

12 (44)
33

11

of encephalitis associated with COVID-19. The diagnosis was ac-

Patients With Neuroimaging

cording to clinical features and the presence of at least two of sei-

zures, new focal neurologic abnormalities, CSF pleocytosis, ab-
755/3824 33 had hemorrhage;
CT, 24/33; MRI and

normal MRI, or abnormal EEG. According to MRI findings, cases

of Imaging

were classified as acute disseminated encephalomyelitis (ADEM)

Type

(n = 3), limbic encephalitis (n = 2), nonspecific changes (n = 7), or

Brain MRI

Brain MRI
CT, 9/33

normal imaging (n = 13). ADEM and limbic encephalitis had a de-

layed clinical onset compared with other encephalitides. Also, pa-
tients with MRI abnormalities had a worse response to treatment
and worse final outcome than patients with other encephalitides.
Total

27/27

27/50

Other studies [70, 71], along with the ENCOVID study [69], de-
No.

scribe ADEM in COVID-19. ADEM usually follows an infection

of the upper respiratory tract or immunization in children and
the ICU; of these, 50
which 235 were in

young adults and most likely represents an autoimmune re-

Kandemirli [59], Turkey 749 hospitalized, of
Patients With

had neurologic

encephalitis, MCA = middle cerebral artery.

sponse to these triggers. ADEM in COVID-19 may involve the brain

COVID-19
3824 admitted

or spinal cord (Figs. 8 and 9). ADEM typically manifests on imag-

symptoms

ing as subcortical and central white matter lesions and lesions at

27 ICU

the cortical gray-white matter junction, although periventricular

Studies from same institution.

white matter and gray matter of the cortex, thalamus, and basal
ganglia may also be involved [72]. Acute hemorrhagic leukoen-
a
Dogra [43], U.S. (NYC)

Radmanesh [53], U.S.

cephalitis, also known as Weston Hurst syndrome, is a fulminant

Country (City)
[Reference],
First Author

form of ADEM and has been reported in COVID-19 [73, 74]. On im-
aging, acute hemorrhagic leukoencephalitis exhibits confluent
(Istanbul)

large nonenhancing subcortical white matter lesions with rela-

(NYC)a

tive sparing of the cortex, with associated hemorrhagic foci and

variable enhancement and diffusion restriction [75, 76] (Fig. 10).
a

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964
Moonis et al.

TABLE 3: Case Reports or Series of Patients With COVID-19 With Presumed Encephalitis
First Author Naso­
[Reference], No. of pharyngeal
Country Diagnosis Cases Age (y) Sex Clinical Imaging RT-PCR Other Tests
Helms [2], Encephalopathy 49 NA NA Agitation, 40; confusion, 26; corticospinal MRI, 13; Positive in all CSF analysis, 7; no pleocytosis, 7;
France tract signs, 39; dysexecutive syndrome enhancement in leptomeninge- patients raised protein, 1; matched
at discharge, 15; neurologic disorders, al spaces, 8; bilateral frontotem- oligoclonal bands, 2; RT-PCR
including transient ischemic attack, poral hypoperfusion, 11/11; negative, 7
partial epilepsy, and mild cognitive acute ischemic stroke, 2; EEG, 8: diffuse bifrontal slowing
impairment, 7 subacute ischemic stroke, 1
Moriguchi [6], Encephalitis 1 24 M Generalized seizures, reduced conscious- MRI: DWI abnormality in right Negative CSF: positive RT-PCR
Japan ness, and meningism 9 days after temporal lobe
nonspecific symptoms
Zhou [7], China Encephalitis 1 56 NA COVID-19 pneumonia NA NA CSF: sequencing showing
SARS-CoV2
Paniz-Mondolfi Acute encephalo­ 1 74 M Two falls at home with fever, confusion, CT: no acute change Positive Electron microscopy of brain tissue:
[9], United pathy and agitation viral particles in endothelial cells
States and neurons of frontal lobe
Dixon [65], Acute necrotizing 1 59 F Aplastic anemia with seizures and CT: diffuse swelling of brainstem Positive —
United encephalitis reduced level of consciousness, 10 days MRI: symmetric hemorrhagic
Kingdom after onset of fever lesions in the brainstem,
amygdalae, putamen, and
thalamic nuclei
Wong [66], Rhombencephalitis 1 40 M Ataxia, diplopia, oscillopsia, and bilateral MRI: hyperintense lesion in right Positive CSF: normal cell count and protein;
United facial weakness 13 days after onset of inferior cerebellar peduncle CSF RT-PCR not performed
Kingdom fever and SOB extending to involve a small
portion of the upper cord with
associated microhemorrhage
Poyiadji [67], Acute necrotizing 1 Late 50s F Cough, fever, and altered mental status CT: symmetric hypoattenuation Positive CSF: bacterial culture negative
United States encephalitis in bilateral medial thalami after 3 days
MRI: T2-weighted FLAIR RT-PCR not performed; tests for
hyperintensity in bilateral HSV, VZV, and WNV, negative
medial temporal lobes, thalami,
subinsular regions with
hemorrhage and rim enhance-
ment on contrast-enhanced
images
Note—Dash indicates not reported. RT-PCR = reverse transcription polymerase chain reaction, NA = not available, EEG = electroencephalogram, SOB = shortness of breath, HSV = herpes simplex virus, VZV =
varicella-zoster virus, WNV = West Nile virus.

AJR:217, October 2021

 C O V I D -19 N e u r o i m a g i n g F i n d i n g s o n C T a n d M R I

In summary, meningitis and encephalitis are uncommon in pa-
tients with COVID-19 and neurologic symptoms or syndromes.
Cases described as encephalitis have a myriad of clinical and ra-
diologic presentations. Reported cases have not been routinely
confirmed by histopathology, such that the term “encephalitis” is
being used to describe neurologic involvement according to clin-
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and tract in 19% (7/37) of patients on MRI, with subtle contrast
enhancement in two of these patients [26]. Another study report-
ed significantly higher signal intensity on olfactory bulb normal-
ized T2-weighted FLAIR in 12 patients with COVID-19 than in 12
age-matched control patients [86]; in addition, four patients with
COVID-19, but none of the control patients, showed intraneural

ical or radiologic manifestations, without regard to the etiologic
or pathogenetic basis. Whether these cases represent direct viral
invasion or a sequela of cytokine storm is unclear.
Cytotoxic Lesions of the Corpus Callosum
Cytotoxic lesions of the corpus callosum have been described
in both adults [26, 77–81] and children [82–84] with COVID-19. For
example, one study reported this finding in 14.8% (4/27) of chil-
dren with multisystem inflammatory syndrome associated with
COVID-19 [84]. CSF examination was performed in two of these
children and showed a lack of CSF pleocytosis and a CSF RT-PCR
that was negative for SARS-CoV-2 infection. These lesions like-
ly relate to inflammatory damage from the coincident cytokine
storm and high level of cytokine and glutamate receptors in the
corpus callosum, particularly in the splenium [78]. Table 4 sum-
marizes case reports of this finding.
Olfactory Bulb Involvement
Anosmia is a clinical marker for COVID-19, although the imag-
ing correlates are not well described [85]. One study reported in-
creased T2-weighted signal abnormality in the olfactory bulbs
T2-weighted hyperintensity on the contrast-enhanced 3D FLAIR
sequence. Additional studies describe edema within the olfacto-
ry bulbs and tracts and increased signal on T2-weighted FLAIR
in the right gyrus rectus [87, 88]. Olfactory bulb atrophy after
COVID-19–induced anosmia has also been described in patients
with prolonged postinfectious anosmia, suggesting persistent
olfactory bulb damage [89].
Cranial Nerve Enhancement
Aside from olfactory bulb and nerve involvement, additional
cranial neuropathies reported in COVID-19 include optic neuri-
tis, oculomotor nerve enhancement, and Miller Fisher syndrome
[90–92] (Fig. 11). Miller Fisher syndrome, also known as Miller Fish-
er variant of Guillain-Barré syndrome, is an acute peripheral neu-
ropathy that can develop after exposure to infectious pathogens,
including viruses, and is characterized by a triad of ophthalmo-
plegia, ataxia, and areflexia. Miller Fisher syndrome in COVID-19
may appear as hyperintensity on T2-weighted MRI, enlargement,
and enhancement of the cranial nerves [93]. It is unclear wheth-
er the cranial nerve enhancement in COVID-19 is the result of im-
mune-mediated injury or viral neurotropism.

TABLE 4: Case Reports or Series Showing Cytotoxic Lesions of the Corpus Callosum (CLOCC)
First Author No. of Sex
[Reference] Cases Age (y) (No.) Country Clinical CSF Diagnosis of COVID-19
Klironomos 1 NA NA Sweden NA NA NA
[26]
Agarwal [77] 1 41 F U.S. Respiratory failure, internuclear NA “SARS-CoV-2 positive
ophthalmoplegia, and paralysis interstitial pneumonia”
with unequal pupils
Rasmussen [78] 1 66 F U.S. Deterioration 8 days after initial Not performed NP RT-PCR positive
symptoms of fever, followed by
respiratory symptoms
Forestier [79] 1 55 M France Acute onset of headache, dizziness, Mild proteinorrhachia NP swab positive
and impaired consciousness; MRI (no pleocytosis)
performed 3 days after symptom
onset
Moreau [80] 1 26 M Belgium Acute confusion and dry cough for CSF studies negative, Serum IgG positive
2 days normal
Edjlali [81] 2 49, 51 M (2) France Acute encephalopathy, 2 NA NP swab positive (2)
Lin [82] 1 13 F U.S. Fever, vomiting, diarrhea, cough, CSF studies negative; RT-PCR positive;
dizziness, auditory hallucinations CSF RT-PCR negative; serum IgG positive
and urinary retention; diagnosed increased CSF IgM by
with MIS-C ELISA
Gaur [83] 2 9, 12 M (2) UK Fever, headache, vomiting, Not performed, 2 Positive serum IgG;
abdominal pain, diarrhea, 1; BAL fluid RT-PCR positive
altered mental state, fever, and
lethargy, 1
Abdel-Mannan 4 8–15 M (2); F UK Encephalopathy (4) CSF studies negative, 2; Respiratory RT-PCR positive,
[84] (2) CSF RT-PCR negative, 2 4; serum IgG positive, 2
Note—NA = not available, F = female, U.S. = United States, NP = nasopharyngeal, RT-PCR = reverse transcription polymerase chain reaction, M = male, MIS-C =
multisystem inflammatory syndrome in children, ELISA = enzyme-linked immunosorbent assay, UK = United Kingdom, BAL = bronchoalveolar lavage.

AJR:217, October 2021 965

 Moonis et al.
Spinal Manifestations
Guillain-Barré syndrome may occur in association with
COVID-19 [94]. The syndrome is characterized by hyperintensity
on T2-weighted MRI in the distal cord and enhancement of the
caudal nerve roots on contrast-enhanced sequences (Fig. 12). In
a systematic review of 73 patients with Guillain-Barré syndrome
Downloaded from www.ajronline.org by 182.1.181.175 on 03/01/23 from IP address 182.1.181.175. Copyright ARRS. For personal use only; all rights reserved
spectrum associated with COVID-19, CSF RT-PCR was negative
for SARS-CoV-2 infection in all patients in whom it was tested
[95]. Cranial and spinal MRI examinations were performed in 23
of these 73 patients. Spinal nerve root and leptomeningeal en-
hancement were observed in eight and two patients with low-
er extremity involvement, respectively, whereas cranial nerve
and leptomeningeal enhancement were seen in five and two pa-
tients with clinical cranial nerve involvement, respectively. Most
patients’ neurologic symptoms occurred from 2 to 33 days after
onset of respiratory symptoms. However, neurologic symptoms
occurred in four patients before or concurrently with the respira-
tory symptoms, suggesting a parainfectious phenomenon.
Possible Long-Term Diffusion-Tensor Imaging Changes
A diffusion-tensor imaging study of 60 patients who recovered
after neurologic symptoms of COVID-19 revealed possible disrup-
tion to microstructural and functional brain integrity in the recov-
ery stage. The observation suggests that long-term neurologic
and neuroimaging follow-up may be warranted [96].
Conclusion
COVID-19 results in CNS abnormalities, largely representing
secondary involvement from immune activation leading to a pro-
thrombotic state and cytokine storm. Comorbidities such as hy-
pertension and complications from critical illness and prolonged
ICU admission also contribute to the CNS involvement. Evidence
for direct neuroinvasion is scant. The neuroimaging findings in
COVID-19 have been reviewed using representative cases en-
countered by the authors in the New York City metropolitan re-
gion in the pandemic’s first phase. The most common neuroim-
aging manifestations are acute infarcts with large clot burden
and intracranial hemorrhage. However, a wide range of addition-
al patterns are encountered, including leukoencephalopathy,
global hypoxic injury, meningitis and encephalitis, cytotoxic le-
sions of the corpus callosum, olfactory bulb involvement, crani-
al nerve enhancement, spinal manifestations, and long-term dif-
fusion-tensor imaging changes of the brain. Routine long-term
neurologic follow-up may be warranted given emerging evi-
dence of long-term microstructural and functional changes on
brain imaging after COVID-19 recovery.
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(Figures begin on next page)
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 C O V I D -19 N e u r o i m a g i n g F i n d i n g s o n C T a n d M R I
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A B C
Fig. 1—Large vessel occlusion with large infarct. 64-year-old man with history of prostate cancer presented to emergency department (ED) with abdominal pain,
fever, and cough for 1 day. While in ED, he developed dysarthria and right-sided weakness. Unenhanced CT was normal.
A and B, Sagittal images from concurrent CTA revealed occluded left internal carotid artery (ICA) at its origin (arrow, A) and lack of flow in left middle cerebral artery
(MCA) and anterior cerebral artery territory (B). Inferior images of CTA showed left main pulmonary artery embolus (not shown).
C, Digital subtraction angiogram shows large left MCA thrombus (arrow) in addition to smaller thrombus in proximal ICA. Patient underwent mechanical
thrombectomy with thrombolysis in cerebral infarction grade 2b reperfusion. His hospital course was complicated by hemorrhagic transformation of left MCA infarct
and brainstem herniation.

Fig. 2—Acute small vessel hemorrhagic infarction.

30-year-old man presented with acute right
hemiparesis and slurred speech in setting of normal
blood pressure.
A, Axial CT through basal ganglia shows 2-cm acute
hemorrhage (arrow) in posterior globus pallidus.
B, Concurrent DWI shows restricted diffusion
(arrow) medial to region of hemorrhage, suggesting
hemorrhagic conversion of basal ganglia infarct. CTA
was negative for large vessel occlusion (not shown).
However, reverse transcriptase polymerase chain
reaction test was performed because of incidental
findings suggestive of COVID-19 pneumonia at lung
apices on CTA performed for stroke and was positive
for SARS-CoV-2.
A B

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 Moonis et al.
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A B C
Fig. 3—Venous sinus thrombosis and venous infarct. 35-year-old woman, who tested positive for SARS-CoV-2
on reverse transcriptase polymerase chain reaction test, presented with increasing right temporooccipital
headache for 1 week.
A, Unenhanced CT shows low attenuation and hemorrhage (arrow) in right temporal lobe.
B–D, Brain MR images (B and C) show hemorrhagic lesion (arrow, B) on gradient-recalled echo image;
predominant T2-weighted prolongation (arrow, C) on FLAIR, and no reduced diffusivity on DWI (not shown),
consistent with acute venous infarct secondary to thrombosis of right transverse and sigmoid sinus, as also
shown on MR venogram (arrow, D).

Fig. 4—Hemorrhage related to extracorporeal

membrane oxygenation (ECMO). 64-year-old
woman with rheumatoid arthritis, diabetes mellitus
type 2, hyperlipidemia, hypertension, and obesity
presented with change in mental status. She was
transferred to tertiary care hospital with fever
and tested positive for SARS-CoV-2 infection. She
was administered convalescent plasma on day 15,
and venovenous ECMO at bedside for persistent
hypoxia was started on day 21. Emergency
unenhanced head CT was performed for fixed right
pupil during ECMO and showed large right basal
ganglia intraparenchymal hemorrhage (arrow) with
associated vasogenic edema, mass effect, leftward
midline shift, uncal and subfalcine herniation,
intraventricular extension, and obstructive
hydrocephalus. Additional smaller hemorrhages
throughout brain and scattered subarachnoid
hemorrhage were also present (not shown). Patient
died on day 22.

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A B C
Fig. 5—Watershed infarcts and microhemorrhages. 68-year-old man presenting with fever and respiratory distress, with positive reverse transcriptase polymerase
chain reaction test for SARS-CoV-2 infection, was intubated and admitted to ICU. Brain MRI was performed after 5 weeks of hospitalization.
A, DWI shows rings of high signal intensity with corresponding central high signal and intermediate signal intensity on ADC map (not shown), compatible with
subacute-to-chronic infarcts in bilateral centrum semiovale watershed territories.
B and C, Susceptibility-weighted imaging at supraventricular (B) and ventricular (C) levels shows patchy, linear, and nodular low signal intensity at gray-white junctions
in centrum semiovale (arrow, B) and in corpus callosum (arrow, C). There was no abnormal enhancement after contrast administration.

A B C
Fig. 6—Diffuse posthypoxic leukoencephalopathy with microhemorrhages. 65-year-old man with history of diabetes mellitus and hypertension was admitted for
COVID-19–related hypoxic respiratory failure and had prolonged hospital course complicated by pneumonia and acute kidney injury requiring peritoneal dialysis.
Patient was transferred to neurology ICU for left extremity shaking, at which time MRI was performed (1 month after admission).
A, Axial FLAIR image shows diffuse white matter hyperintensity.
B, DWI shows slowed diffusion in white matter.
C, Susceptibility-weighted image shows microhemorrhages (arrows) in putamen and splenium of corpus callosum.

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A B C
Fig. 7—Hemorrhagic necrosis of globus pallidus. 69-year-old man with COVID-19 with prolonged intubations had poor neurologic status after removal of all sedation.
A, Axial FLAIR image shows increased signal (arrows) in bilateral globus pallidi.
B, DWI shows restricted diffusion in area designated in A.
C, Susceptibility-weighted image shows low signal compatible with blood products.

Fig. 8—Acute disseminated encephalomyelitis.

57-year-old woman with COVID-19 was intubated
for respiratory failure for 21 days. Laboratory values
showed elevated interleukin-6 several days after
admission. She was given trial with remdesivir and
extubated on day 21. After extubation, patient was
not following instructions or communicating and
MRI was performed.
A and B, Axial FLAIR (A) and DW (B) images
show multiple foci (arrows) of increased signal in
periventricular white matter without restricted
diffusion on ADC maps (not shown), suggestive of
demyelinating disease after COVID-19.
A B

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A B C
Fig. 9—Acute disseminated encephalomyelitis lesion within spinal cord. 44-year-old man was admitted with first presentation of conus myelitis (paraparesis, bladder
and bowel dysfunction), left eye visual deficits, dysarthria, ataxia, and possible lethargy. He tested positive for SARS-CoV-2 infection, although he had no respiratory
symptoms on admission.
A, Sagittal STIR image of thoracic spine shows multifocal cord lesions (arrows), one of which at conus showed mild enhancement (not shown).
B and C, Subsequently performed brain FLAIR MRI (B) and DWI (C) show multiple small hyperintense periventricular and juxtacortical lesions (arrows) on T2-weighted
FLAIR imaging with one enhancing lesion in left parietal lobe (not shown), suggestive of multifocal demyelinating disorder. DWI showed only T2-weighted shine-
through effect without restricted diffusion on ADC maps (not shown).

A B C
Fig. 10—Possible acute hemorrhagic leukoencephalitis. 45-year-old woman with COVID-19 required intubation. Stroke code was initiated 2 days after extubation for
left arm numbness. Her hospital course was complicated by acute kidney injury requiring intermittent hemodialysis.
A, Axial FLAIR image shows lesion to be predominantly in white matter with some gray matter involvement.
B, Susceptibility-weighted image shows blood products manifested by low signal (arrow).
C, Contrast-enhanced MRI shows patchy enhancement. DWI (not shown) showed T2-weighted shine-through effect without restricted diffusion.

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Fig. 11—Leptomeningitis and cranial nerve enhancement.
23-year-old woman with asthma and COVID-19 had
encephalopathy with mental status change, decreased verbal
output, and difficulty talking. Axial contrast-enhanced T1-
weighted MRI shows enhancement along optic nerve tracts
(white arrows) and basal cisterns (black arrows). Enhancement
was also noted in cisternal segments of cranial nerve V (not
shown).
974
A B
Fig. 12—Guillain-Barré syndrome.
A, Thoracic sagittal STIR image of 62-year-old woman with COVID-19 and ascending paraparesis
shows lower thoracic intramedullary cord hyperintensity (arrow). Gadolinium was not administered
owing to renal failure.
B, 27-year-old woman with COVID-19 and complex disease course including acute respiratory
distress syndrome and cytokine storm presented with subacute onset of flaccid quadriplegia.
Sagittal contrast-enhanced T1-weighted MRI shows smooth enhancement of cauda equina nerve
roots (arrow) consistent with Guillain-Barré syndrome.
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