Clinical & Experimental

Neuroimmunology
Clinical and Experimental Neuroimmunology 10 (Suppl. 1), (2019) 32–48

REVIEW ARTICLE

Magnetic resonance imaging diagnosis of demyelinating diseases:

An update
Yukio Miki
Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan

Keywords Abstract
acute disseminating encephalomyelitis (ADEM); Major demyelinating diseases include multiple sclerosis (MS), neuromyelitis
demyelinating diseases; multiple sclerosis (MS);
optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis
myelin oligodendrocyte glycoprotein (MOG)
(ADEM) and myelin oligodendrocyte glycoprotein (MOG) encephalomyelitis.
encephalomyelitis; neuromyelitis optica
spectrum disorder (NMOSD) As treatment strategies differ among these diseases, precise diagnosis of
demyelinating diseases is crucial, and magnetic resonance imaging (MRI)
Correspondence plays a pivotal role in the diagnosis. In the present review, MRI appearances
Yukio Miki, MD, PhD, Department of Diagnostic of characteristic lesions of these demyelinating diseases, and differentiation
and Interventional Radiology, Osaka City between MS and other demyelinating diseases based on MRI findings are
University Graduate School of Medicine, 1-4-3,
discussed.
Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Tel: +81-6-6645-3831
Fax: +81-6-6646-6655
Email: yukio.miki@med.osaka-cu.ac.jp

This is an open access article under the terms

of the Creative Commons Attribution-
NonCommercial-NoDerivs License, which
permits use and distribution in any medium,
provided the original work is properly cited,
the use is non-commercial and no
modifications or adaptations are made.

Received: 6 December 2018; accepted: 14

December 2018.

patient prognosis.2,3,22–27 In the present review, char-

Introduction
Multiple sclerosis (MS), neuromyelitis optica spec-
trum disorder (NMOSD), acute disseminated
encephalomyelitis (ADEM) and myelin oligodendro-
cyte glycoprotein (MOG) encephalomyelitis are major
inflammatory demyelinating diseases. The most
important roles of magnetic resonance imaging (MRI)
in demyelinating diseases include: (i) diagnosis;1–5 (ii)
imaging biomarkers;5–17 and (iii) monitoring of side-
effects from disease-modifying drugs.18–21 The present
review will focus on the diagnostic role of MRI in
these diseases. Precise diagnosis of demyelinating dis-
eases is crucial, because treatment strategies differ
between pathologies and thus can greatly influence
*The copyright line for this article was changed on 10 April 2019 after
original online and print publication.
acteristic lesions of demyelinating diseases, and differ-
entiation between MS and other demyelinating
diseases are discussed.
Characteristic lesions of demyelinating diseases
MS
MRI plays a pivotal role in diagnosing MS.2
Although diagnosis of MS cannot be made solely
from MRI, an understanding of the characteristic
MRI findings of MS lesions is important for precise
diagnosis.
Ovoid lesions
These ovoid-shaped periventricular or deep white
matter lesion are spread long in the direction perpen-
dicular to the lateral ventricle wall (Fig. 1). This

32 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
on behalf of Japanese Society for Neuroimmunology
Y. Miki Magnetic resonance imaging diagnosis of demyelinating diseases

Figure 2 Callosal-septal interface lesions in multiple sclerosis. Sagittal

fluid-attenuated inversion recovery image shows intracallosal lesions
spread perpendicular to the ventricular wall.

Figure 1 Ovoid lesions in multiple sclerosis. Axial T2-weighted image

shows multiple ovoid-shaped lesions in the deep white matter.

finding is considered to reflect inflammation around

the long axis of the medullary veins (Dawson’s fin-
ger).1 Although this type of lesion is frequently (63%)
seen in MS,28 similar lesions can be seen in other dis-
eases, such as NMOSD and ischemia, so the specificity
of this type of lesion is not very high. Veins running
through MS lesions (central vein sign) are frequently
seen on T2*-weighted images, susceptibility-weighted
images and fluid-attenuated inversion recovery
(FLAIR) T2*-weighted images (combined T2*-
weighted and FLAIR images), which could be useful
for differentiation from diseases, such as NMOSD,
cerebral small vessel disease, Susac syndrome,
migraine and inflammatory vasculopathies (Behcßet’s Figure 3 Isolated U-fiber lesion in multiple sclerosis. Sagittal fluid-atte-
disease, primary angitis of the central nervous system, nuated inversion recovery image shows a lesion extending along sub-
antiphospholipid syndrome, Sj€ ogren’s syndrome and cortical U-fiber (arrow).
systemic lupus erythematosus).29–31
syndrome, but are usually large in those diseases,
Callosal-septal interface lesions which can help in differentiation from MS.22,35,36
These intracallosal lesions spread perpendicularly to
the ventricular wall (Fig. 2).32,33 This type of lesion is Isolated U-fiber lesions, juxtacortical lesions
seen in more than half of MS patients.28,32 The corpus These MS lesions extend along the subcortical U-
callosum is resistant to ischemia and can provide a fibers.37–39 They are considered to represent perive-
point of differentiation from ischemic lesions. Both nous inflammation along the subcortical U-fibers
sensitivity and specificity are considered high for MS. (Fig. 3).37 Approximately half of MS patients have at
As these findings are well depicted on thin sagittal least one isolated U-fiber lesion.37 This type of lesion
FLAIR images, sagittal FLAIR imaging is included in is relatively specific for MS, and has thus been
the standard MRI sequences for diagnosing MS.34 Cal- adopted as an MRI criterion for demonstrating dis-
losal lesions are also seen in NMOSD and Susac semination in space in the McDonald criteria.2

© 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd 33
on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
Figure 4 Cortical lesion in multiple sclerosis. Double inversion recovery
image clearly shows a cortical lesion in the left frontal lobe.
Cortical lesions
MS lesions involve not only cerebral white matter, but
also gray matter, including the cortex (Fig. 4). Double
inversion recovery40 and phase-sensitive inversion
recovery41 are sensitive sequences for detecting
Figure 5 T1-black holes in multiple sclerosis. Axial T1-weighted image
shows multiple hypointense deep white matter lesions (arrows).
34 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
Y. Miki
cortical lesions. Cortical lesions are rarely seen in
NMOSD, migraine patients or healthy individuals,
and are thus useful for differentiation from these
diseases.42 Cortical lesions have been added to the
MRI criteria for dissemination in space in the 2017
McDonald criteria.2
T1 black holes
Approximately 10–20% of T2-hyperintense MS
lesions are hypointense on T1-weighted images
(Fig. 5).43 This hypointensity is considered to repre-
sent severe pathological changes, including axonal
loss,44 although acute lesions with significant edema
can be temporally hypointense on T1-weighted
images.43
Enhancing lesions
Active MS lesions might be enhanced after injection
of gadolinium.45 The sensitivity of gadolinium-
enhanced MRI for detecting disease activity is 5–10-
fold higher than that of clinical relapse,12,46 and con-
trast enhancement thus offers an index of ongoing
disease activity.6 Most enhancing lesions show a
solid enhancement pattern.47 Ring enhancement is
also frequently seen, and the ring is often discontin-
uous (open-ring sign; Fig. 6).47,48 Enhancement of
each lesion disappears within 6 months.47
Brain atrophy
Brain atrophy might be identified in the early stage of
the disease, and becomes more prominent in the
chronic stage.49 Brain volume decreases at a rate of
0.5–1.6% per year in MS patients,21,50 but occurs at a
Figure 6 Enhancing lesion with open-ring sign in multiple sclerosis.
Coronal gadolinium-enhanced image shows a periventricular ring-
enhancing lesion. Note that the enhancing ring is discontinuous (arrow).
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Y. Miki Magnetic resonance imaging diagnosis of demyelinating diseases

Figure 7 Dirty-appearing white matter in multiple sclerosis. Axial fluid-

attenuated inversion recovery image shows diffuse, subtle hyperintensi-
ties in the deep white matter (arrows), in addition to typical periventric-
ular and deep white matter lesions.

rate of 0.1–0.3% in healthy controls.21 Tissue loss of

gray matter is considered more prominent than that
of white matter.49,51 A temporal decrease in brain vol-
ume (pseudoatrophy) might be seen after administra-
tion of steroids, interferon beta and natalizumab.21 A
recent report stated that the speed of decrease in
whole brain volume is slower in Japanese patients,49
but another recent report stated that the speed of
decrease in deep gray matte volume was faster in
Japanese patients than in Caucasian patients.52 Fur-
ther studies with a larger number of patients might be
required to clarify the details and mechanisms of brain
atrophy processes in Japanese MS patients.

Dirty-appearing white matter (diffusely abnormal white

matter)
Diffuse, subtle hyperintensities are sometimes identi-
fied in the periventricular or deep white matter on
T2-weighted images (Fig. 7).28,53–55 This type of
lesions might represent mild axonal loss, myelin loss
and gliosis.54,56
Tumefactive lesions
These large (>2 cm) demyelinating lesions show a
mass effect, edema and/or ring enhancement that
mimic primary brain tumors, including high-grade
Figure 8 Tumefactive multiple sclerosis lesion. (a) Axial T2-weighted
image shows a large lesion involving the left frontal lobe. (b) Coronal
gadolinium enhanced image shows peripheral enhancement of the
white-matter side of this lesion (arrow). Reprinted with permission from
Miki et al.58
glioma or lymphoma (Fig. 8).57,58 Approximately
70% of patients with tumefactive lesions fulfill the
McDonald criteria at follow up (median time to sec-
ond attack: 4.8 years).57 Tumefactive lesions can also
be seen in patients with NMOSD, particularly in

© 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd 35
on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
(a)
(b)
Figure 9 Spinal cord lesion in multiple sclerosis. (a) Sagittal T2-
weighted image shows a hyperintense lesion involving the cervi-
cal spinal cord (arrow). (b) Axial T2-weighted image shows that
this lesion involves the peripheral portion of the spinal cord (ar-
row).
36 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
Y. Miki
aquaporin-4 (AQP4)-seropositive patients, and in
those with ADEM.22,59 Cases of tumefactive lesions in
patients receiving disease-modifying drugs have also
been reported.60–63 A variety of gadolinium-enhan-
cing patterns, such as homogeneous, heterogeneous,
patchy and diffuse, open-ring, and irregular rim, are
seen according to different pathologies.64 Tumefactive
demyelinating lesions can be differentiated from
tumors, such as glioblastoma or lymphoma, by the
following points: (i) tumefactive lesions have less
mass effect compared with tumors;57 (ii) surrounding
enhancement of tumefactive lesions is often discon-
tinuous (open-ring sign);64,65 (iii) a T2-hypointense
rim is seen in approximately half of tumefactive
lesions;66 (iv) perilesional edema is mild or absent in
57% of tumefactive lesions;66 (v) relative cerebral
blood volume on perfusion MRI is lower in tumefac-
tive lesions than tumors;67 (vi) density on non-con-
trast-enhanced computed tomography of MRI
enhancing portions is lower in tumefactive lesions
than in tumors;68 (vii) intralesional susceptibility sig-
nals (dot-like hypointensities) are not seen in tume-
factive lesions, although these signals are almost
always seen in glioblastomas;69 and (viii) a dilated
vein coursing within the lesion might be seen.70,71
Tumefactive lesions usually diminish on follow-up
MRI, in contrast to continual enlargement seen in real
tumors.45
Balo’s concentric sclerosis
This is a rare variant in which white matter is
destroyed in concentric layers. This used to be con-
sidered as a monophasic rapidly progressive and fatal
disease, but an increasing number of cases with bet-
ter outcomes have been reported.72,73 Bal
o’s concen-
tric sclerosis has been reported in patients with
NMOSD.74,75 A recent study showed that Bal o’s con-
centric sclerosis might be immunologically distinct
from MS, and could be similar to NMOSD or MOG
encephalomyelitis.76
Spinal cord lesions
Spinal cord lesions are seen in up to 90% of MS
patients.45,77 The cervical spinal cord is most fre-
quently involved.45 The lesions are typically well-cir-
cumscribed in the acute stage and often involve the
periphery (Fig. 9).45,77 The lesions are usually small
and short, and longitudinally extensive transverse
myelitis (LETM) extending three or more vertebral
segment lengths is very rare in MS, in contrast to
NMOSD, ADEM and MOG encephalomyelitis.22,28
Spinal cord atrophy is also frequently seen in the
chronic stage.45,77
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Y. Miki Magnetic resonance imaging diagnosis of demyelinating diseases

Optic nerve lesions

In the acute stage, swelling of the optic nerve and
enhancement of the optic sheath are frequently
identified.78 Dilatation of the subarachnoid space at
the anterior end of the optic nerve might also be
seen.78 In the chronic stage, optic nerve atrophy
might be seen.77,79 In MS, optic neuritis is typically
unilateral and involves a shorter segment, with less
extension to the optic chiasm.22 Short-inversion-
time recovery and fat-suppressed gadolinium-
enhanced imaging are useful for observing optic
nerve lesions in the intraorbital segments.77,79

NMOSD
Brain lesions are seen in 43–70% of patients with
NMOSD at the disease onset, and the prevalence of
brain lesions becomes more frequent with increasing
duration of the disease.26,80 NMOSD patients with
associated autoimmune disease show a relatively
high frequency of brain lesions.81 Brain lesions can
be seen not only in areas with high AQP4 expres-
sion, but also in those without high AQP4 expres-
sion.26 MRI is mandatory for diagnosing NMOSD.3

Dorsal brainstem lesions adjacent to the fourth ventricle

including the area postrema
This is one of the most characteristic MRI lesions of
NMOSD, seen in 7–46% of patients.3,22,26 Patients
with this lesion often develop intractable hiccups,
nausea and/or vomiting. The area postrema, as the
location of the emetic reflex center, lacks a blood–
brain barrier, and is vulnerable to AQP4-immunoglo- Figure 10 A dorsal brainstem lesion including the area postrema in
bulin (Ig)G attack. This type of lesion is often con- neuromyelitis optica spectrum disorder. Sagittal T2-weighted short-inver-
tiguous with upper cervical cord lesions (Fig. 10).22,26 sion-time recovery image shows a lesion involving the dorsal medulla
oblongata extending into the upper cervical spinal cord.

Diencephalic lesions surrounding the third ventricles and

cerebral aqueduct
Lesions involving the hypothalamus, thalamus and
periaqueductal area of the midbrain.22,26 Patients
with these lesions might present with symptoms
related with hypothalamic/pituitary dysfunction,
including hypothermia, hypotension, hypersomnia,
obesity, narcolepsy, syndrome of inappropriate
antidiuretic hormone secretion, hyperprolactinemia
(amenorrhea, galactorrhea), hypothyroidism and
behavioral changes.26
Periependymal corpus callosal lesions
Callosal lesions are seen in 12–40% of NMOSD
patients.26 Callosal lesions in NMOSD typically
involve its ependymal surface, often affecting most of
its length.22 This differs from the “callosal-septal
interface lesions” typically seen in MS. In the acute
phase, callosal lesions might be edematous and
heterogeneous (marbled pattern);82 sometimes exten-
sively involving the splenium (arch bridge pattern).83
Lesions involving the corticospinal tract
This is one of the most common MRI findings in
NMOSD, found in 23–44% of patients (Fig. 11).26,83
The corticospinal tracts are not regions where AQP4
is highly expressed, so why these regions are fre-
quently involved in NMOSD remains unclear.22
Hemispheric white matter lesions
Extensive and confluent lesions involving the cerebral
hemisphere are seen in 29% of NMOSD patients.83
Lesions are often tumefactive, but mass effects are

© 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd 37
on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
Figure 11 Corticospinal tract lesion in neuromyelitis optica spectrum
disorder. Coronal T2-weighted short-inversion-time recovery image
shows a lesion extending along the left corticospinal tract, including the
internal capsule and cerebral peduncle (arrow).
usually absent.26 Extensive lesions are more frequently
seen in AQP4 antibody seropositive patients than in
seronegative patients.26 Non-specific dot-like or patchy
lesions are also seen in cerebral white matter at high
frequency (35–84%; Fig. 12).26,83 These lesions do not
abut onto and are not perpendicular to the lateral ven-
tricles, which can help distinguish from MS.83
Cortical lesions
Cortical lesions are usually considered as a “red flag”
for the diagnosis of NMOSD,22 but are rarely (3.1%)
seen in AQP4-positive NMOSD.84 Cortical lesions
might involve the subpial layer, and leptomeningeal
enhancement can be seen.22,84,85 As described later,
cortical lesions are more frequently seen in MOG
encephalomyelitis.
Enhancing lesions
The enhancement pattern of brain lesions in NMOSD
is variable; patchy and inhomogeneous with poorly-
defined margins (cloud-like), periependymal linear
patterns (pencil-thin enhancement), and lep-
tomeningeal and nodular enhancements have been
reported.22,26,86,87 Ring and open-ring enhancement
are rare in NMOSD.22
Spinal cord lesions
The most typical spinal cord lesion is acute LETM
(Fig. 13a).3,22,26,88 However, non-longitudinally
extensive myelitis is also often identified (Fig. 14).28
Upper thoracic cord involvement is most frequent.28
38 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
Y. Miki
Figure 12 Non-specific dot-like or patchy lesions in neuromyelitis
optica spectrum disorder. Axial fluid-attenuated inversion recovery
image shows multiple patchy lesions and tiny lesions.
The central gray matter is preferentially involved
(Fig. 13b). Bright spotty lesions on T2-weighted
images corresponding to dark lesions on T1-weighted
images are often identified, and might reflect necro-
tic and microcystic changes.22 Cord swelling
(Fig. 13a) and gadolinium enhancement can be
shown in the acute stage, and focal cord atrophy can
be observed in the chronic stage (Fig. 15).22,88
Optic nerve lesions
In AQP4-positive NMOSD patients, optic nerve invol-
vement with swelling and gadolinium enhancement
is often identified. Optic nerve involvement might
affect more than half of the length of the optic nerve
(longitudinally extensive optic neuritis), predomi-
nantly affecting the posterior part and/or involving
the optic chiasm, and optic tracts with bilateral visual
disturbance can be seen.22,88 In the chronic stage,
optic nerve atrophy with signal hyperintensity can be
observed on T2-weighted images.22,88
ADEM
Brain lesions
Typical brain lesions in ADEM include bilateral, asym-
metrical, poorly demarcated, large lesions involving
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Y. Miki
(a)
(b)
Figure 13 Longitudinally extensive transverse myelitis in neuromyelitis
optica spectrum disorder. (a) Sagittal T2-weighted image shows longitu-
dinally extensive lesions involving the cervical and thoracic spinal cord.
(b) Axial T2-weighted image shows a hyperintense lesion involving the
central part of the spinal cord.
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on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
supra- and infratentorial white matter (Fig. 16).4,22,59
The thalami and basal ganglia are also frequently
involved.22 T1 black holes are rare (5%).89 Callosal
lesions are sometimes seen, and are larger than in
MS.45 As ADEM is usually a monophasic disease, MRI
should not show evidence of previous demyelinating
lesions or evidence of more than one relapse.45,59 Fol-
low-up MRI usually shows complete or near-com-
plete lesion resolution.90 Gadolinium enhancement is
seen in up to 30% of patients.59 Acute lesions might
show enhancement, and these lesions enhance simul-
taneously.45
Severe cases of ADEM might show petechial hem-
orrhage. In a more aggressive form of ADEM (i.e.
acute hemorrhagic leukoencephalitis), lesions are
larger with a greater mass effect and hemorrhages
are seen.45 Whether acute hemorrhagic leukoen-
cephalitis is a variant of ADEM or separate entity
remains controversial.59
Spinal cord lesions
Spinal cord lesions are seen in 11–28% of patients,
and LETM is the typical spinal cord lesion, similar
to that in NMOSD.22,59,91 Gadolinium enhancement is
variable.91 The thoracic cord is most often involved.91
Optic nerve lesions
Patients with ADEM on rare occasions later develop
optic neuritis, as “ADEM followed by optic
neuritis”.59,92 MOG-IgG is positive in most of these
patients.92–94
MOG encephalomyelitis (MOG-IgG disease)
MOG encephalomyelitis (MOG-IgG disease) was
recently proposed as a new, distinct disease entity
among the demyelinating diseases.95,96 This disorder
presents with a variety of clinical phenotypes, and
optic symptoms are the most frequent manifestation.
It has been reported that 21–42% of AQP4-IgG-nega-
tive NMOSD patients are MOG-IgG-positive.97–99
MOG-IgG positivity is found in patients who have
previously been diagnosed with a variety of clinical
phenotypes, such as ADEM, MS, optic neuritis and
transverse myelitis.92,98,100,101 A significant percentage
of patients previously diagnosed with multiphasic
demyelinating encephalomyelitis and ADEM followed
by optic neuritis are also MOG-IgG-positive.92,94 MRI
features of the brain, spinal cord and optic nerves in
patients with MOG encephalomyelitis are distinct
from those of AQP4-IgG-positive NMOSD and typical
MS.97,102
39
Magnetic resonance imaging diagnosis of demyelinating diseases Y. Miki

Figure 14 Non-longitudinally extensive myelitis in neuromyelitis optica

spectrum disorder. Sagittal T2-weighted image shows a hyperintense
lesion involving the upper cervical spinal cord and extending just one
vertebral segment length (arrow).

Brain lesions
Typically, lesions appear as a small number (≤3) of
poorly demarcated infratentorial lesions,103 and tha-
lamic and pontine lesions are distinctive MRI find-
ings.104 Supratentorial deep white matter lesions can Figure 15 Spinal cord atrophy in chronic neuromyelitis optica spec-
be seen (Fig. 17).102 Children tend to show a greater trum disorder. Sagittal T2-weighted image shows significant atrophy of
frequency of a higher number of lesions, bilateral the thoracic spinal cord.
lesions and larger lesions, especially in the deep gray
matter and brainstem.22,103 Ovoid lesions are not
usually seen.27 presenting with unilateral cortical encephalitis with
Cortical lesions and leptomeningeal enhancement epileptic seizure. Wang et al.106 reported that 21%
are seen in 16% and 6% of patients, respectively of MOG-IgG-positive patients presented with
(Fig. 18).104 Ogawa, et al.105 reported cases encephalitis, and one-third of these patients also

40 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
on behalf of Japanese Society for Neuroimmunology
Y. Miki Magnetic resonance imaging diagnosis of demyelinating diseases

Figure 16 Cerebral lesions in acute disseminated encephalomyelitis.

Axial T2-weighted image shows poorly demarcated lesions involving the
deep white matter and deep gray matter.

showed anti-N-methyl d-aspartase receptor antibody.

MOG antibody-positive cortical encephalitis might
have other distinct mechanisms beyond simple
MOG-related immunopathology.105,107,108

Optic nerve lesions

MRI abnormalities of the optic nerve have been found
in 44–83% of patients.102,109,111 Bilateral, longitudi-
nally extensive, symmetrical optic neuritis in the
intraorbital segments is characteristic.97,102,112,113 An
edematous appearance of the involved optic nerves and
gadolinium enhancement are often seen in the acute
phase (Fig. 19).112 The optic chiasm is involved in 12%
of patients, and the optic tract is involved in 2% of
patients.114 Peri-optic nerve enhancement (nerve
sheath enhancement) is also often apparent.102,112,114
Enhancement of the surrounding orbital fat might be
identified.102 Approximately 80% of patients experi-
ence ≥2 attacks of optic neuritis, although the majority
of patients show significant recovery.114

Spinal cord lesions

Most spinal cord lesions present LETM (Fig. 20), but
non-longitudinally extensive myelitis is also sometimes
seen.102,110 The central portion of the spinal cord on
axial images is involved in 50–83% of patients.97,102,110
The peripheral portion might also be involved.102
The frequency of spinal cord abnormalities is
reportedly variable (12–78%).97,109,111 This variety
might be due to different patient selection criteria (if
Figure 17 Supratentorial lesion in myelin oligodendrocyte glycoprotein
encephalomyelitis. (a) Axial T2-weighted image shows a large hyperin-
tense lesion involving the right frontal lobe. (b) Axial gadolinium-
enhanced image shows peripheral enhancement of this lesion.
MOG-IgG testing is limited to patients with AQP4-
IgG-negative NMOSD, the frequency of spinal cord
lesion should be higher), patient ethnicity and/or
different MRI scanning locations (i.e. some spinal

© 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd 41
on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
Figure 18 Cortical lesions and leptomeningeal enhancement in
myelin oligodendrocyte glycoprotein encephalomyelitis. (a) Cortices
in the right parietal lobe appear thickened and are hyperintense on
an axial fluid-attenuated inversion recovery image. (b) Gadolinium-
enhanced image shows leptomeningeal enhancement in the right
parietal lobe.
cord lesions might be missed if the whole spinal cord
is not scanned); further studies are required to con-
firm the frequency of spinal cord lesions among
MOG encephalomyelitis patients who are diagnosed
according to international preliminary criteria for
the diagnosis of MOG encephalomyelitis or
42 © 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
Y. Miki
Figure 19 Optic nerve lesion in myelin oligodendrocyte glycoprotein
immunoglobulin G disease. (a) Axial T2-weighted image shows edema-
tous appearance of the right optic nerve. (b) Gadolinium-enhanced
image shows enhancement of this nerve and nerve sheath.
diagnostic criteria that might be established in the
near future.27
According to earlier reports, lower portions of the
spinal cord are more frequently involved than the
upper spinal cord.97,110 However, a recent multi-
institutional study of 50 patients showed that the
upper spinal cord is more frequently involved than
the lower spinal cord.102
Clues to differentiating between MS and other
white matter lesions
MS versus NMOSD
MS patients are significantly more likely to have
periventricular lesions than NMOSD patients, and
NMOSD patients are more likely to have deep white
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Y. Miki
Figure 20 Spinal cord lesion in myelin oligodendrocyte glycoprotein
encephalomyelitis. Sagittal T2-weighted shows extensive hyperintensity
(longitudinally extensive transverse myelitis) involving the cervical spinal
cord. Mild cord swelling is also seen.
28,115
matter lesions. Criteria of: (i) at least one lesion
adjacent to the body of the lateral ventricle and in
the inferior temporal lobe; (ii) presence of a subcor-
tical U-fiber lesion; or (iii) a Dawson’s finger-type
lesion can distinguish MS from AQP4-positive
NMOSD with 91% sensitivity and 87% specificity.23
A recent multi-institutional study in Japan con-
firmed that periventricular white matter lesions,
© 2019 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd
on behalf of Japanese Society for Neuroimmunology
Magnetic resonance imaging diagnosis of demyelinating diseases
Table 1 Red flags for magnetic resonance imaging diagnosis of multi-
ple sclerosis
• Few periventricular WM lesions
• Absence of ovoid lesions
• No isolated U-fiber lesions despite
the presence of many subcortical lesions
• Absence of posterior fossa, corpus callosum
and spinal cord lesions
• Only very small (<3 mm) lesions
• Symmetrical/semi-symmetrical lesions
• No change on successive MRI
• No gadolinium enhancement on any MRI
• Persistent gadolinium enhancement
• Continuous gadolinium enhancement over 6 months
• No T1-black hole(s)
• Overly large corpus callosum lesion(s)
• Family members with similar “identical” MRI
• Lesions with prominent mass effect
• Up/downward (edematous) extension
of large brainstem lesion(s)
• LETM
LETM, longitudinally extensive transverse myelitis; MRI, magnetic resonance
imaging; WM, white matter. Modified from Siva et al.36
ovoid lesions, T1-black hole lesions, callosal-septal
interface lesions and isolated U-fiber lesions are
more frequently present in MS than in NMOSD.28
Spinal cord lesions in NMOSD preferentially
involve the central gray matter, whereas those in
MS preferentially involve peripheral white matter,116
although peripheral white matter is also sometimes
involved in NMOSD.117 The aforementioned multi-
institutional study also showed that more thoracic
cord lesions are present in NMOSD than in MS, and
that thoracic cord lesions are significantly longer
than cervical cord lesions in NMOSD.28 Of note,
lesions involving the cervical spinal cord in NMOSD
do not always represent LETM, and a significant
number of lesions are non-longitudinally extensive
myelitis (median length: 23 mm for cervical cord
lesions; 63 mm for thoracic cord lesions; Fig. 14).28
MS versus ADEM
MRI appearances of ADEM and MS in pediatric
patients are often similar, so differentiating between
these diseases is not straightforward.118 Callen
et al.89 proposed criteria (Callen MS-ADEM criteria)
to distinguish MS from ADEM in children. In these
criteria, MS is to be distinguished from ADEM by
any two of: (i) absence of a diffuse bilateral lesion
pattern; (ii) presence of black holes; and (iii)
43
Magnetic resonance imaging diagnosis of demyelinating diseases
presence of two or more periventricular lesions.
These are currently considered the most useful crite-
ria, offering relatively high sensitivity and speci-
ficity.119
MS lesions versus non-specific white matter lesions
Misdiagnosis of MS remains a matter of concern.35,120
Rates of misdiagnosis have been reported to be up to
10%.121 The most common lesions that can be misdi-
agnosed as MS are non-specific white matter
lesions.122 Red flags for MRI diagnosis for MS are
listed in Table 1, which could be useful for distin-
guishing MS lesions from non-specific white matter
lesions.36
Conclusions
The present review provides an update of character-
istic lesions for major demyelinating diseases, as well
as clues to differentiating between MS and other
demyelinating diseases, which might be helpful for
differential diagnoses.
Acknowledgements
The author thanks Drs Takahiko Saida, Taro Shi-
mono, Hiroyuki Tatekawa and Satoshi Doishita, and
Ms Hiroko Nakano for their kind assistance and
invaluable suggestions.
Conflict of Interest
None declared.
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