susac syndrome: clinical characteristics and treatment … · susac syndrome: clinical...
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CME ARTICLE
Susac syndrome: clinical characteristics and treatment in 29new cases
F. J. Mateena,b, A. Y. Zubkovc, R. Muralidharana, J. E. Fugatea, F. J. Rodriguezd, J. L. Winterse
and G. W. Pettya
aDepartment of Neurology, Mayo Clinic, Rochester, MN; bDepartment of Neurology, Johns Hopkins Hospital, Baltimore, MD; cMinneapolis
Clinic of Neurology, Edina, MN; dDivision of Neuropathology, Department of Pathology, Johns Hopkins Hospital, Baltimore, MD; andeDivision of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Keywords:
cochlea, encephalopathy,
plasma exchange, retina,
stroke, susac syndrome,
treatment, vasculopathy,
young adults
Received 24 August 2011
Accepted 17 November 2011
Background and purpose: There are few clinical studies on the attempted treatments and
outcomes in patients with Susac syndrome (SS) (retinocochleocerebral vasculopathy).
Methods: A retrospective review was performed of all patients presenting with SS at
the Mayo Clinic in Rochester, Minnesota, USA (1 January 1998–1 October 2011).
Results: There were 29 cases of SS (24 women, mean age at presentation, 35 years;
range, 19–65; full triad of brain, eye, and ear involvement, n = 16; mean follow-up
time, 29 months). Thirty CSF analyses were performed in 27 cases (mean protein
130 mg/dl, range 35–268; mean cell count 14, range 1–86). MRI of the brain showed
corpus callosal involvement (79%), T2-weighted hyperintensities (93%), and gado-
linium enhancement (50%). Average lowest modified Rankin Scale score was 2.5
(median 2, range 0–5). Most patients (93%) received immunosuppressive treatment,
with a mean time to treatment of 2 months following symptomatic onset. Treatments
included intravenous methylprednisolone or dexamethasone (n = 23), oral corticos-
teroids (n = 24), plasma exchange (PLEX) (n = 9), intravenous immunoglobulin
(IVIg) (n = 15), cyclophosphamide (n = 6), mycophenolate mofetil (n = 5), aza-
thioprine (n = 2), and rituximab (n = 1). Most patients also received an antiplatelet
agent (n = 21). Improvement or stabilization was noted in eight of 11 cases treated
with IVIg in the acute period (three experienced at least partial deterioration) and
eight of nine cases of PLEX treatment (one lost to follow up).
Conclusions: Susac syndrome may be severe, disabling, and protracted in some
patients. PLEX may be an adjunct or alternative therapy for patients who do not
experience symptomatic improvement following steroid treatment.
Introduction
Susac syndrome (SS) is a rare disorder of unknown
pathogenesis that affects the pre-capillary arterioles of
the brain, retina, and cochlea. The associated syndrome
is a triad of hearing loss, branch retinal artery occlu-
sions leading to visual loss, and cerebral symptoms that
may include seizures, headaches, cognitive decline, and
personality changes. Since its initial description in 1979
[1], more than two hundred cases have been reported,
mostly involving young women [2].
Patients with SS usually experience discrete symp-
tomatic episodes that can recur [3,4]. Although some
episodes prove to be self-remitting without treatment,
the clinical course cannot be readily predicted and pa-
tients may experience sequelae of epilepsy, dementia,
permanent deafness, and/or visual loss. The heteroge-
neity and rarity of the disorder have prevented large
clinical case series that include treatment. Because of a
presumed autoimmune etiology, acute symptomatic
treatment has justifiably centered on corticosteroids.
There are no randomized trials on treatment efficacy to
date. Anecdotal reports have suggested a therapeutic
benefit from azathioprine, cyclophosphamide, myco-
phenolate mofetil, infliximab, nimodipine, antiplatelet
agents, intravenous immunoglobulin (IVIg), and/or
plasma exchange (PLEX) in some patients [5–18].
We aim to expand the knowledge of the clinical
course of patients with SS following various attempted
treatments by qualitatively and, where possible,
Correspondence: Farrah J. Mateen, Department of Neurology, Johns
Hopkins Hospital, Pathology Building, Room 627, 600 North Wolfe
Street, Baltimore, MD 21287, USA (tel.: +410 935 5181;
fax: +410 502 6736; e-mail: [email protected]).
This is a Continuing Medical Education article, and can be found with
corresponding questions on the Internet at http://www.efns.org/EFNS
Continuing-Medical-Education-online.301.0.html. Certificates for
correctly answering the questions will be issued by the EFNS.
800� 2012 The Author(s)
European Journal of Neurology � 2012 EFNS
European Journal of Neurology 2012, 19: 800–811 doi:10.1111/j.1468-1331.2011.03627.x
quantitatively presenting our experience of the diag-
nosis, assessment, and management of a large series of
patients with SS at a high-volume referral center.
Methods
The Mayo Clinic Institutional Review Board approved
this study. A retrospective medical record review was
performed of all patients with the diagnosis of SS be-
tween 1 January 1998 and 1 October 2011 at the Mayo
Clinic in Rochester, Minnesota, USA. Keyword search
terms included �Susac Syndrome� and �retinocochleoce-rebral vasculopathy�, �cerebral vasculopathy�, �cerebro-retinovasculopathy�, and �other encephalopathy�. The
institutional experience of SS prior to this time has been
reported [3]. None of the patients included in the pre-
vious report were included in this study.
Diagnoses were confirmed by review of the laboratory
tests, imaging studies, and treating clinicians� diagnoses.Demographic and clinical data included age, sex, and
details of the symptomatic presentation, methods of
diagnostic evaluation, treatment course, and any evi-
dence of recurrence. Dates of birth, symptomatic onset,
first treatment, first signs of improvement, and last fol-
low-up were collected. A modified Rankin Scale score
[19] was assigned retrospectively by the authors, based
on detailed clinical notes. Magnetic resonance images of
the brain were analyzed for the following: (i) evidence of
lesions consistent with SS, notably punctuate T2 hy-
perintense lesions in the cerebral parenchyma and sub-
cortical structures, (ii) T2 hyperintense lesions involving
the corpus callosum thought to be highly characteristic
of SS, and (iii) gadolinium enhancement of the T2
hyperintense lesions noted in (i) and (ii).
Patient therapy was determined by the treating neu-
rologist(s) at the time of evaluation in conjunction with
a consultant rheumatologist, ophthalmologist, and/or
otolaryngologist when appropriate. Use of PLEX was
determined by the treating physician without any pre-
treatment criteria. These were not necessarily more se-
vere cases. There are no standard algorithms for the use
of steroids, IVIg, or PLEX in SS at our institution.
Treatment course was assessed by the presence of
symptomatic improvement documented in the medical
records, corroborated by audiogram, retinal examina-
tion, and brain imaging when performed. PLEX is an
extracorporeal technique for removing humoral factors
such as immunoglobulins, complement, or cytokines
from the blood. At our institution, the usual course of
PLEX for SS consisted of a one-volume PLEX
administered every other day for a planned course of
five treatments. Replacement fluid was 5% albumin
with the anticoagulant consisting of either acid citrate
dextrose solution A (ACDA) or heparin and ACDA.
All procedures were performed on the COBE Spectra
(CaridianBCT; Roundlake, CO, USA).
Results
Search results and patient characteristics
There were 43 case records retrieved that had SS within
the differential diagnosis. A total of 29 patients (24
women (83%), mean age at symptomatic presentation
35 years, range 19–65) had a diagnosis of SS. All
patients were diagnosed or had the diagnosis confirmed
by a neurologist. All patients underwent an extensive
workup to exclude other diagnoses that may mimic SS.
Patients were seen as an inpatient (n = 10), outpatient
(n = 15), or both (n = 4). One patient was diagnosed
during pregnancy.
Patients included in this series had at least two of the
three retinal, cochlear, or cerebral symptoms charac-
teristic of SS, including 16 (55%) with the full triad of
brain, vestibulocochlear, and eye involvement at the
time of first assessment. Hearing was involved in 24
cases (83%), vision in 24 cases (83%), and cerebral
symptoms in 26 cases (90%) (Table 1). Follow-up
ranged from a single visit with further treatment and
care by local physicians to more than 10 years of ex-
tended follow-up at this institution (mean 29 months
(2.4 years), median 13 months, range < 1–
128 months). Average lowest modified Rankin Scale
score reported was 2.5 (mRS 2 = slight disability, able
to look after own affairs without assistance but unable
to carry out all previous activities) [median 2, range 0
(no symptoms) to 5 (severe disability, incontinent,
bedridden, and requiring constant attention for care)].
No patient is known to have died.
Twenty-four additional patients had SS within the
differential diagnosis of their condition but had a dif-
ferent final diagnosis. These alternative diagnoses were
confirmed by the treating physicians to be multiple
sclerosis, central nervous system lymphoma, primary
central nervous system vasculitis, probable central ner-
vous system vasculitis, Wegener�s granulomatosis, Co-
gan�s syndrome, retinal vasculitis, cerebral autosomal
dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL), cerebroretinal vas-
culopathy, episodic vertigo with sensorineural hearing
loss, conversion syndrome, or indeterminate symptoms
that lacked at least two features of the triad of SS.
Investigations
The diagnostic evaluation of patients with SS is sum-
marized in Table 1. There were 30 CSF analyses in 27
individuals with an average CSF protein of 130 mg/dl
Susac syndrome 801
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
1Investigationsanddem
ographic
featuresofpatients
withsusacsyndrome
Age/sex
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvem
ent
ofbrain
(B),
hearing
(H),and
vision(V
)
Inpatient/
outpatient
evaluation
(episode#)
CSF
protein
CSF
cellcount
Oligoclonal
bands
Audiogram
Other
findings
MRI
corpus
callosum
involvem
ent
(y/n)
MRIT2
hyperintensities
(y/n)
MRI
gadolinium
enhancement
Cerebral
angiogram
orMRA
findings
134/F
Headaches,
numbnessand
tinglingof
handsandface,
visualfield
defect,hearing
loss,tinnitus
B,H,V
In101
2n/a
n/a
Symptoms
during3rd
trim
esterof
pregnancy
YY
NNorm
al
232/F
Vertigo,diplopia,
visualloss,
tinglingof
handsandfeet,
andamnestic
episodes
B,V
Out
161
11
0Low-to
mid-frequency
hearingloss
Symptoms
began
postpartum
YY
YNorm
al
336/F
Tongue
numbness,
TIA
-like
episodes
of
upper
extrem
ity
numbness,
tingling,and
weakness,
photosensitivity,
HA
B,V
Out
105,76
86,6
<2
n/a
PositiveFTA
·2(negative
RPR);elevated
IgG
synthesis
rate
YY
NNorm
al
435/F
Unilateraltinnitus,
hearingloss,unilateral
visualloss,
disequilibrium
mem
ory
loss,
uncontrollable
laughter
B,H,V
Out
47
20
Bilateral
asymmetric
hearingloss,
particularlyin
lower
frequencies
EEG:diffuse
abnorm
alities
VEP:
abnorm
al
prolongation
bilaterally
YY
NNorm
al
551/F
Segmentalvisual
loss,vertigo
H,V
Out
Norm
al
5n/a
Low-frequency
hearingloss
ANA
mildly
positive
NY
NNorm
al
626/F
Diplopia,
stroke-like
episodes
of
righthem
iparesis,
hearingloss,
episodic
gait
instability,
slurred
speech,
numbnessin
UE
B,H,V
Both
185
70
0Bilateral
hearingloss;
rightat40DB
(250–1000Hz,
80dBat
1000–6000Hz)
Rheumatoid
factormildly
positive;
mild
diffuse
lymph
adenopathy
(biopsy
negativefor
malignant
cells)
NY
NNorm
al
802 F. J. Mateen et al.
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
1(C
ontinued
)
Age/sex
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvem
ent
ofbrain
(B),
hearing
(H),and
vision(V
)
Inpatient/
outpatient
evaluation
(episode#)
CSF
protein
CSF
cellcount
Oligoclonal
bands
Audiogram
Other
findings
MRI
corpus
callosum
involvem
ent
(y/n)
MRIT2
hyperintensities
(y/n)
MRI
gadolinium
enhancement
Cerebral
angiogram
orMRA
findings
730/M
Confusion,cognitive
difficulty,
new
headaches,
unilateralhearing
loss,andtinnitus
H,B
In188
16
1n/a
None
YY
YNorm
al
846/M
Vertigo,numb
hands,vision
loss,hearingloss,
cognitivedecline,
agitation
B,V,H
In�slightly
elevated�
8n/a
n/a
Brain
biopsy:
scant
perivascular
chronic
inflammation,
microglial
activationand
mildnon-
specificgliosis
YY
NNorm
al
923/F
Episodes
ofvisual
loss,hearingloss,
disorientation,
imbalance,
mem
ory
loss,
hallucinations,
lethargy
B,H,V
Both
133
10
n/a
n/a
EEG:
generalized
slowing
Yn/a
n/a
Norm
al
10
50/F
Headaches,unilat
eralvisualloss,
imbalance,
vertigo,
hem
iparesis
B,H,V
Out
171,157
12,6
n/a
Sensorineural
hearingloss
(250–2000Hz
rangeonone
ear,all
frequencies
other
ear)
ANA
positive
1:80,
CK
=5000,
LDH
338,
ESR
24.
YY
NNorm
al
11
36/F
Gaitataxia,uni
lateralhearing
loss,confusion,
pseudobulbar
affect,urinary
incontinence
B,H
In106
21
n/a
None
YY
YNorm
al
12
20/F
Intractable
HA,
unilateralhearing
loss,progressive
cognitivedecline,
scintillating
scotoma,
photophobia,
N&V
B,H,V
In170
20
n/a
50%
reduced
hearingleft
ear
None
YY
Yn/a
Susac syndrome 803
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
1(C
ontinued
)
Age/sex
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvem
ent
ofbrain
(B),
hearing
(H),and
vision(V
)
Inpatient/
outpatient
evaluation
(episode#)
CSF
protein
CSF
cellcount
Oligoclonal
bands
Audiogram
Other
findings
MRI
corpus
callosum
involvem
ent
(y/n)
MRIT2
hyperintensities
(y/n)
MRI
gadolinium
enhancement
Cerebral
angiogram
orMRA
findings
13
35/F
Headaches,blurry
vision,hearing
loss,confusion,
mem
ory
loss,gait
instability
B,H,V
Out
177
n/a
n/a
n/a
PositiveIgM
andIgG
anticardiolipin
antibody,V
Leiden
heterozygous
YY
Nn/a
14
23/F
Headaches,R
vi
sualloss,R
hearingloss,
cognitive
difficulty,gait
ataxia,R
facial
sensory
disturbance,
confusion,
pseudobulbar
affect
B,H,V
Out
59
4n/a
n/a
None
YY
YNorm
al
15
37/F
Segmentalvisual
loss,dizziness,
weakandnumb
UE
V,B
Out
n/a
n/a
n/a
Norm
al
None
NN
NNorm
al
16
44/F
Episodic
loss
of
consciousness,
transientvisual
disturbance,
progressive
cognitivedecline,
andmem
ory
loss
B,H,V
Both
131
00
10%
word
recognitionin
left
ear
None
YY
YNorm
al
17
19/F
Headache,
hearing
loss,blurry
vision,
disorientation,
personality
change,
and
cognitivedecline
B,H,V
In126
3n/a
n/a
None
YY
YNorm
al
18
24/F
Vertigo,tinnitus,
bilateralhearing
loss,segmental
visualloss
B,H,V
Out
n/a
n/a
n/a
Moderate
left
hearingloss
250–1000Hz
range
Prothrombin
20210A
mutation
heterozygote
NN
NNorm
al
804 F. J. Mateen et al.
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
1(C
ontinued
)
Age/sex
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvem
ent
ofbrain
(B),
hearing
(H),and
vision(V
)
Inpatient/
outpatient
evaluation
(episode#)
CSF
protein
CSF
cellcount
Oligoclonal
bands
Audiogram
Other
findings
MRI
corpus
callosum
involvem
ent
(y/n)
MRIT2
hyperintensities
(y/n)
MRI
gadolinium
enhancement
Cerebral
angiogram
orMRA
findings
19
46/F
Scotomatousvi
sualloss,vertigo,
worseninggait,
tinnitus,
headache,
paresthesiasof
face
and
extrem
ities
B,H,V
Both
83,57
0,0
n/a
Low-frequency
hearingloss
left,low-and
high-frequency
loss
right
ANA
(1:40)
YY
Yn/a
20
28/F
Hearingloss,
headache,
blurred
vision
H,V
Out
35
10
Unilateral6000
and8000Hz
loss
None
NY
NNorm
al
21
27/M
Hearingloss,
headache,
vertigo,left
numbness,gait
unsteadiness
B,H
In164
50
MildR
and
moderate–
severeleft
sensorineural
hearingloss,
allfrequencies
None
YY
Yn/a
22
43/F
Righteardiscomfort,
gaitinstability,
disorientation
B,H
,VOut
>200
50
0Mostly
norm
al
butloss
at
1500Hzleft
and2000Hz
rightear
None
YY
YNorm
al
23
20/F
Visualloss,
hearingloss,
headache
H,V
Out
84
20
n/a
None
YY
N*Norm
al
24
33/F
Disorientation,
visualloss,
headache
B,V
Out
84
11
n/a
Norm
al
None
YY
NNorm
al
25
57/F
Disorientation,
hearingloss
B,H
Out
248
n/a
n/a
n/a
None
YY
n/a
Norm
al
26
39/M
Disorientation,
urinary
retention,
gaitinstabliity
B,V
In79
40
Notdonebut
hadabnorm
al
brainstem
evoked
potentials
None
YY
n/a
Norm
al
27
25/F
Headache,
nausea,
vomiting,
tinnitus,hearing
loss,dizziness,
short-term
mem
ory
loss
B,H
Out
147
14
0Sensorineural
hearingloss
bilaterally
(1000–8000Hz
range)
None
YY
Y*Norm
al
Susac syndrome 805
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
(median 129, range 35–268, normal range 15–45 mg/dl)
and an average cell count of 14 cells/ml (median 5,
range 0–86, normal range 0–5 cells/ml). MRI was per-
formed in all cases (Fig. 1). Corpus callosal involve-
ment of lesions was noted in 23/29 cases (79%).
Punctate T2-weighted hyperintense lesions were seen in
26 individuals (absent in two cases, not available in one
case, 93%). Gadolinium enhancement of lesions oc-
curred in 13 cases (available in 26 cases, 50%). One
patient had the diagnosis confirmed by brain biopsy
(Fig. 2).
Treatment and outcomes
Two patients (cases 4 and 20) were untreated. Mean
time to treatment was 2 months (median 1 month)
amongst the 27 cases who received immunosuppressive
therapy (Table 2). PLEX was used in nine cases (range
of 3–10 exchanges). Symptomatic improvement was
observed in six cases, stabilization was in two cases, and
one case was lost to follow up. No patient continued to
worsen. Amongst the patients treated with IVIg, there
were 11 cases who received initial treatment with IVIg
(cases 6, 9, 10, 11, 14, 17, 22, 24, 26, 28, and 29) and
three cases who were observed whilst receiving main-
tenance monthly IVIg (cases 21, 23, and 25). Amongst
the 11 cases who were evaluated in the acute symp-
tomatic treatment phase and treated with IVIg,
improvement was noted in six cases, stability or modest
improvements in two cases, deterioration in symptoms
in two cases, and mixed results (both improvement and
deterioration) in one case. Additional treatments
included intravenous methylprednisolone or dexa-
methasone (n = 23), oral corticosteroids (n = 24),
mycophenolate mofetil (n = 5), cyclophosphamide
(n = 5), azathioprine (n = 2), and rituximab (n = 1).
Most patients also received an antiplatelet agent: aspi-
rin (n = 18), clopidogrel (n = 2), and aspirin and
dipyridamole (n = 1). Nimodipine was taken by five
individuals.
Discussion
Given the variable course and rarity of SS, there are no
prospective studies on the best treatment of patients.
Retrospective studies are also challenging given the
wide range of symptomatic manifestations of SS, delay
to diagnosis in many cases, lack of diagnostic biomar-
kers, and limited literature on the natural history of the
disease. In our experience, which is subject to referral
bias, not all patients with SS have a symptomatic re-
sponse to corticosteroids. Most patients were treated
with additional immunosuppressive therapy with the
goal of achieving symptomatic remission in the acuteTable
1(C
ontinued
)
Age/sex
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvem
ent
ofbrain
(B),
hearing
(H),and
vision(V
)
Inpatient/
outpatient
evaluation
(episode#)
CSF
protein
CSF
cellcount
Oligoclonal
bands
Audiogram
Other
findings
MRI
corpus
callosum
involvem
ent
(y/n)
MRIT2
hyperintensities
(y/n)
MRI
gadolinium
enhancement
Cerebral
angiogram
orMRA
findings
28
32/F
Acute
unilateral
hearingloss,
visualloss,
disorientation
B,H,V
In268
19
0n/a
None
YY
NNorm
al
29
65/M
Headache,
disori
entation
B,H,V
In96
20
Moderate–se
verebilateral
sensorineural
hearingloss
None
NY
NNorm
al
*Digitalsubtractionangiography;ANA,antinuclearantibody;
B,brain;EEG,electroencephalogram;FTA,fluorescenttreponem
alantibodyabsorption;H,hearing;HA,headache;MRI,magneticresonance
imagingstudy
ofthebrain;L,left;N,no;N&V,nauseaandvomiting;n/a,notdone;
R,right;VEP,visualevoked
potentials;V,vision;Y,yes.
806 F. J. Mateen et al.
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
period. This is especially true for patients with severe
presentations, including dementia, recurrent seizures,
and recurrent visual loss despite treatment with corti-
costeroids.
There are several reports of refractory cases of SS
treated with IVIg in the acute period [7,8,10–12].
Rarely, IVIg may cause additional ischaemic changes in
the microvasculature [20,21], which is a theoretical
concern in SS, given the arteriolar distribution of the
disease. By contrast, reports of patients with SS treated
with PLEX are exceptional. Five patients with SS are
reported to have been treated with PLEX [3,5–8]. The
positive therapeutic effects probably involve removal of
humoral factors from the patient�s blood including
immunoglobulins, complement, and/or cytokines [22].
The putative pathogenic antibody or antibodies are
probably removed or reduced in this process.
Many cases of SS are treated with antiplatelet agents
including aspirin and clopidogrel given the arteriolar
involvement seen under fluorescein angiography of the
retina and cerebral pathology [3,4]. Possible arteriolar
vasospasm has prompted the use of the calcium channel
blocker nimodipine, which is almost always an adjunct
treatment. These treatments are difficult to assess for
efficacy independently of immunosuppressive treat-
ment.
These findings are not definitive evidence for the use
of PLEX in the treatment of SS. Our observations are
rather intended to be foundational for prospective
studies on the treatment of patients with SS. Based on
our data alone, we cannot confirm that any treatment
improved the course of patients with Susac syndrome.
There are only occasional cases of untreated individu-
als, including just two in this series, some of whom
experience spontaneous resolution of symptoms with-
out immunosuppressive treatment. It is unclear whether
the currently employed treatments hasten symptomatic
recovery. The appropriate duration of treatment
requires proper study and presently is anecdotal.
Our study had limitations. This was a retrospective,
observational study and, at times, had incomplete data.
Follow-up was not consistent amongst patients, and
not all patients received their complete care for SS at
this institution. There are no defined criteria for SS.
Therefore, we considered cases to have SS if they had at
least two of the three features of the triad of retinal,
cochlear, or brain involvement during our observation
period. Deficits from SS are difficult to quantify with
standard functional outcome scales, such as the modi-
fied Rankin Scale; therefore, the degree of cognitive and
functional deficits can be underestimated.
However, our findings report the largest series of SS
to date including the careful evaluation and confirma-
tion of this diagnosis in a large referral center over the
Figure 1 Axial view of a T1-weighted MRI of the brain with
gadolinium contrast, demonstrating involvement of the cochlea in
a patient with diagnosed Susac syndrome.
(a) (b)
Figure 2 Pathologic features of Susac
syndrome in brain biopsy of case 21.
Histologic sections demonstrate aggre-
gates of macrophages representing a
subacute microinfarct (arrowheads)
associated with a small vessel (large
arrow). Rare isolated acute ischaemic
neurons are also present (small arrows)
(a). Distinct microthrombi were also
identified within leptomeningeal vessels
(arrow) (b).
Susac syndrome 807
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
2Treatm
entandclinicalcourseofpatients
withsusacsyndrome
Age
(years
/sex)
Durationof
symptoms
priorto
treatm
ent
months)
Antiplatelet
medication
Oral
steroids
(Y/N
)
IV steroids
Other
treatm
ents
IVIg
(#ofdays)
PLEX
Lowest
modified
rankin
scale
score
Improvem
ent
following
treatm
ent
Outcome
No.of
monthsof
follow-up
available
134/F
2ASA
YN
––
Everyother
day
·5
0Stabilized
symptoms
postpartum
Recurrence
after
oral
steroid
taper
9
232/F
0.25
ASA
YY
––
Everyother
day
·5
0Im
proved
Laterepisodes
ofvisualand
hearingloss
128
336/F
1ASA
2pills
only
YNim
odipine
–Daily
·3
0Weaknessim
proved
withIV
steroids
butlaterhadvisual
changes
(halos
aroundobjects),
earpressure,and
objectivehearing
loss
Recommended
tohave
PLEX
but
LFU
13
435/F
5ASA
NN
––
–5
Initialepisode
resolved
without
treatm
ent;later
episodetreated
withIV
Ig
Improvem
ent
without
treatm
ent
then
recurrenteye
symptoms
6years
later
88
551/F
1ASA-D
ipyri
damole
NY
––
Everyother
day
·5
0Im
proved
hearing
andsight
Norecurrent
symptoms
62
626/F
Uncertain
Clopidogrel
YY
–3
–2
Improved
n/a
95
730/M
1–
YY
––
–2
Improved
following
IVsteroidson2
occasions
Improved
32
846/M
3–4
ASA
NY
Cyclophosphamide
––
5Stable
Stable
but
poorbaseline
9
923/F
6ASA
NY
Nim
odipine,
recommended
to
have
cyclophosphamide
2mg/kgPO
daily
·6months
Daily
·5days
Daily
·5,then
1month
later
4more
doses
5Initiallyreturned
to
baselinewithIV
Ig
maintained
on
monthly
IVIg
and
Solu-M
edrol;
recurrence
1year
laterwithsome
improvem
entwith
PLEX
butdid
not
return
tobaseline
Some
improvem
ent
withIV
Ig
andPLEX
butcontinually
worsening
baselineover
15months
15
808 F. J. Mateen et al.
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
2(C
ontinued
)
Age
(years
/sex)
Durationof
symptoms
priorto
treatm
ent
months)
Antiplatelet
medication
Oral
steroids
(Y/N
)
IV steroids
Other
treatm
ents
IVIg
(#ofdays)
PLEX
Lowest
modified
rankin
scale
score
Improvem
ent
following
treatm
ent
Outcome
No.of
monthsof
follow-up
available
10
50/F
<1
–Y
NCyclophosphamide
5doseson2
different
occasions
–0
Symptomatic
response
toIV
Ig
reported
inpast
Continued
progression
then
LFU
<1
11
36/F
2–
YY
–Everyother
day
·5
–4
Noresponse
toIV
/
PO
steroids,
4weekslaterhad
response
toIV
Ig
Improvem
ent
3
12
20/F
1.25
ASA
YY
––
Everyother
day
·5
4Im
proved
objective
gaitspeedand
coordination
LFU
<1
13
35/F
0.5
ASA
YY
Nim
odipine
––
2Im
proved
Nonew
symptoms
76
14
23/F
1.5
ASA
YY
Mycophenolate
mofetil,Nim
odipine
5everyother
daythanweekly
–4
Deteriorated
n/a
73
15
37/F
1ASA
YN
––
Everyother
day
·5
0Im
proved
Nonew
symptoms
9
16
44/F
3ASA
YN
––
Everyother
day
·5,then
relapse
then
2
more
doses
4Im
proved
following
PLEX,then
cognitiveandgait
deficits
relapsed
andthen
repeat
treatm
ent
Cognitive
improvem
ent
butrequired
wheelchairat
7months
15
17
19/F
1ASA
YY
Nim
odipine
2doses,then
relapse
then
5
everyother
daywith
improvem
ent,
then
3·per
week
–2
Improved
Nonew
symptoms
43
18
24/F
3.5
Clopidogrel
YY
Azathioprine
–Everyother
day
·5;2
separate
occasion
0Stable,unclear
whether
improvem
ent
occurred
Visualchanges
off
immuno
suppression
nearly
2years
later
treatedwith
repeatPLEX
24
19
36/F
3ASA
YY
Cyclophosphamide
100mgdaily
––
1Onerelapse
while
ona15-m
onth
courseof
cyclophospha
mide,
treatedwith
steroids
Norecurrent
symptomsfor
nearly5years,
persistent
mildvisual
loss
59
Susac syndrome 809
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
Table
2(C
ontinued
)
Age
(years
/sex)
Durationof
symptoms
priorto
treatm
ent
months)
Antiplatelet
medication
Oral
steroids
(Y/N
)
IV steroids
Other
treatm
ents
IVIg
(#ofdays)
PLEX
Lowest
modified
rankin
scale
score
Improvem
ent
following
treatm
ent
Outcome
No.of
monthsof
follow-up
available
20
28/F
No Treatm
ent
ASA
NN
––
–1
Improved
Hearingloss
andvision
improved
8
21
27/M
4–
YY
Azathioprine
Maintained
on
once
monthly
dose
–2
Cognition
significantly
improved
Slightresidual
mem
ory
deficits
24
22
43/F
1.75
–Y
Y–
5dosesdaily,
then
once
weekly
–4
Stable
Persistent
mem
ory
problems,
improved
gait
3
23
20/F
�months�
ASA
YY
Mycophenolate
mofetilwhen
symptomsremitted
Maintained
on
2g/kgmonthly
–1
Improved
vision
andhearingloss
Norm
al
examination
3
24
33/F
0.25
–Y
Y5dosesdays,then
weekly
·3
–4
Improved
Gait
improvem
ent,
cognitive
gainsto
nearly
norm
al
11
25
57/F
0.25
–Y
YMycophenolate
mofetilwhen
symptomsremitted
Maintained
on
0.25g/kgevery
3weeks
–4
Improved
cognition
Markedly
improved
cognition,
legsweak,
walker
dependent
13
26
39/M
0.75
ASA
YY
Cyclophosphamide,
laterrituxim
ab
Daily
·7
–5
Stable
––
27
25/F
0.25–0.5
ASA
YY
Mycophenolate
mofetil
––
3Im
proved
Mild
improvem
ent
inhearing
loss
and
headaches
9
28
32/F
0.5
ASA
YY
Cyclophosphamide
recommended
post-dismissal
Daily
·5
–4
Cognitionsubtly
improved
––
29
65/M
0.5
–Y
YMycophenolate
mofetil
Daily
·5,then
once
monthly
–4
Cognition
improved,hearing
loss
worsened
Persistent
cognitivedef
icits
8
ASA,aspirin;F,female;LFU,lost
tofollow
up;IV
,steroids;
IVIg,intravenousim
munoglobulins;
M,male;mRS,modified
Rankin
Scale
score;N,no;n/a,notavailable;PLEX,plasm
aexchange;
PO,bymouth;Y,yes.
810 F. J. Mateen et al.
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology
course of nearly 14 years. Our findings help establish
the clinical spectrum of SS, including a depiction of the
treated history of the disease. Our qualitative analysis
also suggests that PLEX is worthy of further evalua-
tion, perhaps in a matched case control design com-
pared to IVIg. Given that SS may rarely be fatal and is
often disabling and severe [8,13], we propose that
PLEX should be considered as an adjunct or alternative
treatment to steroids in patients who do not improve
with IVIg.
Our clinical cohort underscores the value and
necessity of prospective studies of this rare condition.
Such studies would be most effectively achieved
through an international collaboration of researchers,
so that patients can participate in the acute symptom-
atic period from multiple centers. The use of stan-
dardized and uniform clinical assessment tools – where
possible, also including audiogram and visual testing –
will further help clarify the degree of impairment and
long-term disability. Such tests must be carried out at
sufficiently timed intervals to capture the fluctuating
and occasionally recurrent nature of the disorder. In the
longer term, outcome studies of the degree of disability
and recovery through proposed international registries
will provide valuable new information to the growing
number of patients diagnosed with SS.
Acknowledgements
Dr. Mateen is supported by the American Academy of
Neurology Practice Research Fellowship grant.
Disclosure of conflict of interests
The authors declare no financial or other conflict of
interests.
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Susac syndrome 811
� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology