Supplementary Table 1 Existing literature of radiological findings associated with Balό’s concentric sclerosis.
Reference
Spiegel M et
al. (1989)1
Clinical characteristics and
treatment
Presentation: 39-year-old man with
mental deficits, mild spastic
tetraparesis, dysarthria, left central
facial palsy and gait disturbances
Treatment: intravenous
methylprednisolone
Hanemann
CO et al.
(1993)2
Outcome: improved gait, facial palsy
and mental deficit
Presentation: 32-year-old woman with
left hemiparesis, urinary retention,
fatigue and mental slowing
Conventional
neuroimaging (T1weighted and T2-weighted)
Initial imaging: multiple
concentric white matter
lesions consistent with BCS
Diffusionweighted imaging
(DWI)
Not performed
Magnetic resonance
spectroscopy
(MRS)
Not performed
Not performed
Not performed
6 months later: additional
reduction in all lesions; no
enhancement
Initial imaging: multiple high Not performed
signal foci with alternating
low and high signal areas;
one lesion enhanced
Not performed
10 weeks later: reduction in
the size and number of the
lesions
Initial imaging: hypointense
concentric lesions in right
frontal, left occipital and left
centroparietal lobes
Diagnosis: biopsy-proven BCS
Treatment: intravenous dexamethasone
followed by mitoxantrone
Outcome: improvement in disability
Revel MP et
al. (1993)3
Presentation: 22-year-old woman with
progressive left hemiparesis and right
lateral gaze palsy
Treatment: intravenous
6 weeks later: reduction in
size of all lesions
methylprednisolone followed by oral
taper
Revel MP et
al. (1993)3
Outcome: mild left hemiparesis 6
months later
Presentation: 27-year-old man with
right hemiparesis and dysarthria
Treatment: none
Tersegno MM
and Reich DR
(1993)4
Outcome: spontaneous recovery within
10 days; right facial paresis 3 months
later
Presentation: 32-year-old woman with
sudden left paresthesias
Diagnosis: autopsy-proven BCS
Treatment: steroids
Gharagozloo
et al. (1994)5
Outcome: clinical progression followed
by death 1 year later
Presentation: 32-year-old woman with
progressive left hemiparesis
hemiplegia, and left homonymous
heminanopsia over 2 weeks
Diagnosis: autopsy-confirmed BCS
Treatment: intravenous steroids
Initial imaging:
periventricular white matter
hyperintensities with
concentric foci
Not performed
Not performed
Initial imaging: large right
parietal mass with concentric
rings and peripheral
enhancement
Not performed
Not performed
Not performed
Not performed
8 months later: bilateral
frontal lesions with
concentric rings; atrophy in
region of initial lesion
Initial imaging: large right
parietal lesion with mass
effect and marginal
enhancement
Approximately 9 months
later: multiple large lesions
with concentric ring
appearance
Louboutin JP
and Elie B
(1995)6
Outcome: initial improvement followed
by increasing weakness and apathy
with relentless progression until death 1
year after symptom onset
Presentation: 16-year-old boy with
acute bilateral visual impairment,
headache, ataxia, right hemisensory
loss, alteration of consciousness, and
vertigo
Diagnosis: biopsy-proven BCS
Treatment: intravenous prednisone
(initially), followed by intravenous
cyclophosphamide and ACTH (after
worsening), followed by azathioprine
(maintenance)
Chen CJ et al.
(1996)7
Outcome: mild improvement after
steroids followed by worsening to
include left hemiparesis; further
improvement after cyclophosphamide
and ACTH and sustained improvement
after starting azathioprine
Presentation: 27-year-old woman with
rapidly progressive right hemiparesis
Initial imaging: multiple
white matter lesions of
varying size with
concentricity in a 3cm right
frontal lesion
Not performed
Not performed
Not performed
4 months later: all lesions
smaller; concentric pattern
still evident in right frontal
lesion
16 months after presentation:
loss of concentric pattern
2 years after presentation:
one new lesion near right
occipital horn
Initial imaging: multiple
concentric white matter
lesions
Diagnosis: biopsy-proven BCS
Treatment: none
Not performed
10 days later: bifrontal
alternating isointense and
hypointense or hyperintense
Outcome: nearly complete recovery
rings with partial
after 3 months with no weakness after 1 enhancement
year
20 days later: concentric
lesion with partial
enhancement in frontal lobe
Chen CJ et al.
(1996)8
Presentation: 54-year-old man with
unsteady gait, progressing to hiccups,
slurred speech and choking within 2
weeks
3 months later: marked
resolution of all lesions
Initial imaging: multiple
round lesions in a concentric
or mosaic pattern with mild
rim enhancement
Not performed
Not performed
Not performed
Not performed
Treatment: corticosteroids for 2 weeks
Morioka C et
al. (1996)9
Outcome: full recovery after 2 weeks of
therapy; stable at 8 month follow-up
Presentation: 22-year-old man with
Initial imaging: concentric
nausea and vomiting, bowel and
patterns of low signal lesions
bladder incontinence, quadriparesis,
with enhancement
and altered level of consciousness
3 weeks later: enlarged
Treatment: glycerin (initially) followed lesions with presumed
by prednisone (after second MRI)
necrosis on T1-weighted
MRI
Outcome: normalization of function
except for residual euphoria and severe 9 weeks later: regression of
cognitive abnormalities at 3 weeks;
hyperintensities with
after treatment with steroids had mild
concentric lesions
cognitive dysfunction
16 weeks later: lesions were
"remarkably" improved
Sekijima Y et
al. (1997)10
Presentation: 28-year-old woman with
confusion and impaired level of
consciousness, progressive gait
disturbance, aphasia, right leg
weakness, and right homonymous
hemianopsia
Treatment: intravenous
methylprednisolone then oral taper
followed by plasmapheresis
Outcome: marked improvement in
symptoms; no further demyelinating
events 3 years after onset of symptoms
Kim MO et al. Presentation: 52-year-old woman with
(1997)11
right hemiparesis
12 days after onset: multiple
lesions with ‘fried egg’
appearance; no enhancement
Outcome: gradual resolution of
hemiparesis over 5 months; no further
events after 17 months
Not performed
Not performed
Initial: decrease in
NAA:Cr ratio,
increased Cho:Cr
ratio, elevated lipid
peak
21 days after onset: slight
enlargement of existing
lesions; some with enhancing
concentric rings
53 days after onset:
regression of lesions with no
enhancement
Initial imaging: multiple
white matter lesions with
marginal enhancement
Diagnosis: biopsy-proven BCS
Treatment: intravenous dexamethasone
Not performed
14 days later: increased size
of initial lesion
9 months later:
Decreased lipid
peak, increased
myoinositol peak, no
significant changes
in NAA:Cr or
Cho:Cr ratios
Murakami Y
et al. (1998)12
Presentation: 4-year-old boy with
headaches, drowsiness, and right
hemiparesis
Initial imaging: concentric
Not performed
enhancing lesions in centrum
semiovale and occipital lobes
Treatment: intravenous dexamethasone
3 weeks later: non-enhancing
hyperintensities in occipital
lobe
Outcome: complete resolution of
symptoms in two weeks
Singh S et al.
(1999)13
Presentation: 45-year-old woman with
cognitive decline, seizures and
abnormal limb movements
Treatment: intravenous
methylprednisolone and intravenous
immunoglobulin (IVIg) followed by
high-dose intravenous
methylprednisolone and azathioprine
Singh S et al.
(1999)13
Outcome: slight improvement after 1
month, followed by slowly progressive
worsening
Presentation: 38-year-old man with
alexia, aphasia and right hemiparesis
Treatment: dexamethasone and
plasmapheresis followed by oral
steroids and azathioprine
6 months later: nonenhancing hyperintensities in
occipital lobe
Initial imaging: multiple
concentric lamellar rings in
left frontal, temporal and
parietal lobes, with
additional lesions in corpus
callosum
Not performed
Not performed
Not performed
Not performed
Not performed
9 months later: reduction in
lesion size and absence of
concentric layers
Initial imaging: left frontal
lesion consisting of
alternating concentric rings
and surrounding edema with
peripheral enhancement
6 weeks later: reduction in
Ng SH et al.
(1999)14
Outcome: mild cognitive recovery after
treatment; no long-term follow-up
reported
Presentation: 56-year-old woman with
right-sided weakness, dysarthria and
gait abnormalities
Treatment: oral prednisolone followed
by slow taper
Outcome: resolution of hemiparesis
after 1 month; subsequent recurrence of
right hand clumsiness
Chen CJ et al.
(1999)15
Presentation: 27-year-old woman with
right hemiparesis and memory
impairments
Diagnosis: biopsy-proven BCS
lesion size with persistent
rings and widening of
lamellae
Initial imaging: left
frontoparietal lesions with
edema and concentric ring
enhancement; right frontal
subcortical lesion with
concentric rings and
enhancing lamellae
Not performed
12 months later: persistence
of concentric ring pattern in
left frontoparietal cortex
Initial imaging:
Not performed
frontoparietal lesions with
concentric rings; outer two to
three layers had incomplete
enhancement
Not performed
Not performed
Treatment: not reported
Chen CJ et al.
(1999)15
Outcome: no clinical relapse after 1
year
Presentation: 56-year-old woman with
right hemiparesis and dysphagia
Diagnosis: biopsy-proven BCS
Treatment: not reported
Initial imaging:
frontoparietal lesions with
multiple lamellae that
enhanced
Not performed
Not performed
Chen CJ et al.
(1999)15
Outcome: no clinical relapse after 1
year
Presentation: 22-year-old man with
tetraparesis and confusion
Initial imaging: multiple
concentric lesions with
enhancement
Not performed
Not performed
Not performed
Not performed
Not performed
Not performed
Not performed
Not performed
Treatment: not reported
Outcome: no clinical relapse after 1
year
Chen CJ et al.
(1999)15
Presentation: 42-year-old man with left
hemiparesis
2 weeks later: outward
expansion of lesions with
loss of internal enhancement
but new peripheral
enhancement
Initial imaging:
frontoparietal and temporal
rings without enhancement
Treatment: not reported
Chen CJ et al.
(1999)15
Outcome: no clinical relapse after 2
years
Presentation: 33-year-old woman with
left hemiplegia
Treatment: not reported
Outcome: no clinical relapse after 1
year
Manelfe C et
al. (1999)16
Presentation: 44-year-old man with
rapid onset of cerebellar and
‘hemispheric’ symptoms and signs
Treatment: mitoxantrone
Initial imaging:
frontoparietal lesions with
enhancement of all layers
except at the margins.
1 month later: new
hypointensity in frontal lobe
within one lesion
Initial imaging: multifocal
superficial and deep white
matter lesions, some of
which enhanced in a ringlike manner; rare gray matter
Iannucci G et
al. (2000)17
Outcome: improvement in the
subsequent months without complete
resolution (some remaining ataxia, arm
incoordination, and memory and
attention deficits)
Presentation: 31-year-old with
weakness
Treatment: not reported
Caracciolo JT
et al. (2001)18
involvement (insula, caudate,
putamen)
Initial imaging: two lesions
with alternating concentric
rings with an intermediate
ring that enhanced
Outcome: not reported
4 months later: coalescence
of lesion
Presentation: 34-year-old woman with
seizures and expressive aphasia
Initial imaging: concentric
demyelinating lesion in left
frontal lobe with enhancing
concentric rings
Diagnosis: biopsy-proven BCS
Initial imaging:
Not performed
diffusivity values (x
10-3 mm2/s):
center, 1.234;
inner ring, 1.295;
intermediate ring,
1.099; outer ring,
1.146
Not performed
Not performed
Treatment: not reported
Karaarslan E
et al. (2001)19
Outcome: not reported
Presentation: 52-year-old man with
ataxia, left hemiparesis and confusion
Diagnosis: biopsy-proven BCS
Treatment: not reported
Outcome: residual left hemiparesis and
no further events after 3 years
Initial imaging: concentric
rings in right centrum
semiovale with focal
peripheral enhancement
13 months later: residual
concentric lesion
Not performed
Not performed
Karaarslan E
et al. (2001)19
Presentation: 20-year-old woman with
left hemiparesis
Treatment: corticosteroids
Karaarslan E
et al. (2001)19
Outcome: no further relapses after 6
months
Presentation: 48-year-old man with
aphasia
Treatment: intravenous
methylprednisolone
Initial imaging: concentric
rings adjacent to right lateral
ventricle with prominent
peripheral enhancement
Not performed
Not performed
Initial imaging: multiple
white matter lesions with an
enhancing left concentric
temporoparietal lesion
Not performed
Not performed
Not performed
Not performed
Not performed
Initial:
increased Cho:Cr
ratio, decreased
NAA:Cr ratio;
possibly increased
lipid and lactate
1 month later: no new lesions
Outcome: mild clinical improvement
after 1 month
Karaarslan E
et al. (2001)19
Presentation: 38-year-old man with
dysarthria, dysphagia and fatigue
Treatment: intravenous
methylprednisolone
Karaarslan E
et al. (2001)19
Outcome: normal neurological
examination after 4 years without
further clinical events
Presentation: 15-year-old woman with
left hemiparesis
Treatment: intravenous
methylprednisolone
4 years later: no new lesions;
gliosis within old lesions
Initial imaging: multiple
white matter lesions with
concentric enhancing pattern
3 weeks later: multiple
concentric lesions with no
enhancement
Initial imaging: concentric
lesion in right centrum
semiovale
Chen CJ et al.
(2001)20
Outcome: improvement with no further
events after 6 months
Presentation: 37-year-old woman with
right face and hand numbness and
weakness
peaks
Initial imaging:
frontoparietal lesions with
marginal enhancement
Not performed
Initial: decreased
NAA:Cr ratio,
increased Cho:Cr
ratio
Treatment: not reported
Not performed
7 months later:
incomplete
improvement
Initial: decreased
NAA:Cr ratio and
increased Cho:Cr
peak
Not performed
14 months later:
persistent
abnormalities
Initial: decreased
NAA:Cr ratio,
increased choline:Cr
ratio
Outcome: no further events at 8 months
Chen CJ et al.
(2001)20
Presentation: 56-year-old woman with
progressive right hemiparesis and
dysphagia
Initial imaging:
frontoparietal lesions with
concentric ring enhancement
Treatment: not reported
Outcome: no further events at 1 year
Chen CJ et al.
(2001)20
Presentation: 42-year-old man with
progressive left hemiparesis and
concentration problems
Initial imaging:
frontoparietal and temporal
lesions with no enhancement
Treatment: not reported
Outcome: no further events at 2 years
Chen CJ et al.
(2001)20
Presentation: 33-year-old woman with
left hemiplegia
Treatment: not reported
Initial imaging:
frontoparietal lesions with
concentric rings and
marginal enhancement
Not performed
8 months later:
incomplete
improvement
Decreased NAA/Cr
ratio, increased
choline/Cr peak
Two months later:
Kastrup O et
al. (2002)21
Outcome: no further events at 1 year
Presentation: 43-year-old man with
inattention, memory deficits, and rightsided clumsiness
Treatment: intravenous prednisolone
Outcome: gradual improvement of
symptoms
Gu J et al.
(2003)22
Presentation: 35-year-old man with left
hemiparesis
Treatment: repeated courses of
intravenous dexamethasone
Outcome: mild clinical improvement
after first steroid course and nearly
complete restoration of strength after
second course of steroids
Gu J et al.
(2003)22
Presentation: 38-year-old woman with
bifacial paresis, quadriplegia, apathy
and seizures
Initial imaging: right parietal
lesion with concentric rings
and mild surrounding edema;
marked contrast
enhancement of lamellae
4 weeks later: confluence of
lesions with patchy
enhancement
Initial imaging: multiple
concentric rings in right
frontal, parietal and temporal
lobes with no enhancement
Not performed
limited improvement
Not performed
Not performed
Not performed
Not performed
Not performed
Not performed
Not performed
1 month after symptoms:
concentric rings remaining
3 years after presentation:
small, non-specific, plaquelike lesion remained
Initial imaging: concentric
rings with no enhancement
Treatment: corticosteroids
Gu J et al.
(2003)22
Outcome; death resulting from
pulmonary embolism
Presentation: 40-year-old man with
subacute headaches and left
Initial imaging: left
frontoparietal concentric
hemiparesis
lesions with no enhancement
Treatment: intravenous dexamethasone
Pohl D et al.
(2005)23
Outcome: significant improvement
after therapy with no relapses after 2
years
Presentation: 5-year-old girl with acute
anomia and right hemianopsia after a
viral illness; subsequent clinical decline
over one month; evidence of human
herpesvirus 6 acute seroconversion
Treatment: intravenous
methylprednisolone and foscarnet; then
high-dose steroids and foscarnet,
followed by monthly intravenous IVIg
(after further clinical deterioration 7
months later)
Nagi S et al.
(2005)24
Outcome: persistent hemianopsia after
treatment but stable for 6 months,
followed by further deterioration that
improved markedly after IVIg
Presentation: 22-year-old man with
tetraparesis and horizontal diplopia
Treatment: intravenous
methylprednisolone
Outcome: no further relapses after 18
Initial imaging: multiple
Not performed
white matter lesions with one
having ring-like
enhancement
Not performed
1 month later: striking
enlargement of lesions with
garland-like enhancement
7 months later: new right
frontal lesion without
enhancement
8 months later: enlargement
of all lesions with garlandlike enhancement
Initial imaging: bilateral
concentric centrum
semiovale lesions with
lamellar enhancement
Not performed
Not performed
Bruneteau G
et al. (2005)25
months
Presentation: 28-year-old man with
right hemiparesis and hypoesthesia
Treatment: intravenous
methylprednisolone followed by oral
steroid taper
Outcome: improvement of symptoms:
at 6 months only hyperreflexia and
mild spasticity remained
Airas L et al.
(2005)26
Presentation: 23-year-old pregnant
woman with blurry vision, alexia and
visuospatial disturbance, followed 1
month later by right homonymous
hemianopsia, memory disturbance and
right leg paresthesias
Treatment: intravenous
methylprednisolone followed by
plasma exchange (five exchanges)
Outcome: partial resolution of
symptoms, followed by relapse
consisting of gait ataxia, leg
paresthesias, weakness, and right
asteroagnosia and homonymous
hemianopsia. 4 months after initial
onset: improvement in all deficits after
Initial imaging: left
frontoparietal lesion with
concentric enhancement
1 month later: reduction in
size of lesion with no
enhancement
6 months later: unchanged
from 1 month
Initial imaging: bilateral
confluent parieto-occipital
white matter and splenium
lesions with laminar pattern
and partially-laminar
enhancement; multiple small
multiple sclerosis-like
lesions
1 month later: lesions
reduced in size
4 months later: new lesions
in the superior parietal white
matter with ring-like
enhancement
Not performed
Initial: decreased
NAA:Cr ratio,
increased Cho:Cr
ratio, elevated lactate
and lipid peaks
6 months later:
decreased Cho:Cr
peak, absent lactate
peak, elevated
myoinositol, NAA
peak still low
1 month after onset: 4 months after onset:
no diffusion
“active biochemical
restriction
changes associated
with active
4 months after
demyelination”
onset: facilitated
diffusion in
enhancing regions
Wiendl H et
al. (2005)27
plasma exchange
Presentation: 28-year-old woman with
right hemiparesis and hypoesthesia
Treatment: intravenous
methylprednisolone
Outcome: improvement, but mild
residual right hemiparesis, spasticity
and hyperreflexia at 6 months
Kavanagh EC
et al. (2006)28
Presentation: 45-year-old woman with
dysarthria and right upper extremity
weakness
Initial imaging: nonenhancing left centrum
semiovale lesions
14 days later: enhancing left
centrum semiovale lesions
10 weeks later:
hyperintensity remained; no
enhancement
Initial imaging: left posterior
corona radiata lesion with
concentric enhancing rings
Initial imaging:
severe restriction of
diffusion in left
centrum semiovale
Not performed
14 days later:
enlargement of
restricted diffusion
lesion
10 weeks later: no
restricted diffusion
Initial imaging:
restricted diffusion
in outer ring
Not performed
Treatment: oral steroids
Anschel DL
(2006)29
Outcome: improvement of symptoms
after steroids
Presentation: 32-year-old man with
left-sided tingling followed by gait
disturbance and left upper extremity
weakness
Initial imaging: multiple T2
hyperintensities in brain and
spine; two brain lesions with
lamellar appearance and a
ring of enhancement
Initial imaging:
no restricted
diffusion
Not performed
Initial imaging: right
periventricular
Initial imaging:
restricted diffusion
2 weeks after
presentation: normal
Treatment: not reported
Mowry EM et
al. (2007)30
Outcome: not reported
Presentation: 37-year-old woman who
presented with acute left-sided
weakness and numbness
in a ring around a
nidus of facilitated
diffusion
Cho peak, decreased
NAA peak, elevated
lactate peak
2 weeks later: concentric
Outcome: nearly complete resolution of rings of hyperintensity with
symptoms without new clinical events
patchy enhancement
after 3 years
3 months after presentation:
disorganization of concentric
ring with new edema
surrounding the lesion; less
enhancement than before
2 weeks later: band
of restricted
diffusion
surrounding nidus
of facilitated
diffusion; decreased
perfusion around
the lesion (contrast
perfusion study)
5 months after
presentation: further
decrease in NAA
peak, less prominent
lactate doublet peak,
mild increase in Cho
peak
5 months after presentation:
reduced lesion size with less
enhancement
3 months after
presentation:
facilitated diffusion
in region that
previously had
restricted diffusion;
thin rim of
diffusion restriction
remaining at the
periphery
Treatment: intravenous
methylprednisolone
hyperintensity with rings and
faint hyperintensities before
and after contrast
7 months after presentation:
continued reduction in lesion
size
Additional imaging (up to 3
years after presentation): no
new lesions
7 months after
presentation:
continued decrease
in NAA peak with
slight increase in
Cho peak and only a
small lactate peak
5 months after
presentation: no
restricted diffusion
Abbreviations: BCS, Balo’s concentric sclerosis; ACTH, adrenocorticotropic hormone; NAA, N-acetylaspartate; Cr, creatine; Cho,
choline; IVIg, intravenous immunoglobulin.
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