Download Susac syndrome: clinical characteristics and treatment in 29 new

European Journal of Neurology 2012, 19: 800–811
doi:10.1111/j.1468-1331.2011.03627.x
CME ARTICLE
Susac syndrome: clinical characteristics and treatment in 29
new cases
F. J. Mateena,b, A. Y. Zubkovc, R. Muralidharana, J. E. Fugatea, F. J. Rodriguezd, J. L. Winterse
and G. W. Pettya
a
Department 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; and
e
Division 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 gadolinium 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 corticosteroids (n = 24), plasma exchange (PLEX) (n = 9), intravenous immunoglobulin
(IVIg) (n = 15), cyclophosphamide (n = 6), mycophenolate mofetil (n = 5), azathioprine (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 occlusions 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].
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
Patients with SS usually experience discrete symptomatic episodes that can recur [3,4]. Although some
episodes prove to be self-remitting without treatment,
the clinical course cannot be readily predicted and patients may experience sequelae of epilepsy, dementia,
permanent deafness, and/or visual loss. The heterogeneity 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, mycophenolate 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,
2012 The Author(s)
European Journal of Neurology 2012 EFNS
Susac syndrome
quantitatively presenting our experience of the diagnosis, assessment, and management of a large series of
patients with SS at a high-volume referral center.
801
All procedures were performed on the COBE Spectra
(CaridianBCT; Roundlake, CO, USA).
Results
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 between 1 January 1998 and 1 October 2011 at the Mayo
Clinic in Rochester, Minnesota, USA. Keyword search
terms included ÔSusac SyndromeÕ and Ôretinocochleocerebral vasculopathyÕ, Ôcerebral vasculopathyÕ, ÔcerebroretinovasculopathyÕ, and Ôother encephalopathyÕ. The
institutional experience of SS prior to this time has been
reported [3]. None of the patients included in the previous report were included in this study.
Diagnoses were confirmed by review of the laboratory
tests, imaging studies, and treating cliniciansÕ diagnoses.
Demographic and clinical data included age, sex, and
details of the symptomatic presentation, methods of
diagnostic evaluation, treatment course, and any evidence of recurrence. Dates of birth, symptomatic onset,
first treatment, first signs of improvement, and last follow-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 hyperintense lesions in the cerebral parenchyma and subcortical 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 neurologist(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 pretreatment criteria. These were not necessarily more severe 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 examination, 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.
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 characteristic 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 extended 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 different 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 nervous system vasculitis, WegenerÕs granulomatosis, CoganÕs syndrome, retinal vasculitis, cerebral autosomal
dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL), cerebroretinal vasculopathy, 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 summarized in Table 1. There were 30 CSF analyses in 27
individuals with an average CSF protein of 130 mg/dl
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
51/F
26/F
5
6
36/F
3
35/F
32/F
2
4
34/F
1
Age/sex
Headaches,
numbness and
tingling of
hands and face,
visual field
defect, hearing
loss, tinnitus
Vertigo, diplopia,
visual loss,
tingling of
hands and feet,
and amnestic
episodes
Tongue
numbness,
TIA-like
episodes of
upper extremity
numbness,
tingling, and
weakness,
photosensitivity,
HA
Unilateral tinnitus,
hearing loss, unilateral
visual loss,
disequilibrium
memory loss,
uncontrollable
laughter
Segmental visual
loss, vertigo
Diplopia,
stroke-like
episodes of
right hemiparesis,
hearing loss,
episodic gait
instability,
slurred speech,
numbness in UE
Presenting
symptoms/
clinical
findings/first
symptom(s)
Out
Both
B, H, V
Out
Out
Out
In
Inpatient/
outpatient
evaluation
(episode #)
H, V
B, H, V
B, V
B, V
B, H, V
Involvement
of brain (B),
hearing
(H), and
vision (V)
185
Normal
47
105, 76
161
101
CSF
protein
70
5
2
86, 6
11
2
CSF
cell count
Table 1 Investigations and demographic features of patients with susac syndrome
0
n/a
0
<2
0
n/a
Oligoclonal
bands
Low-frequency
hearing loss
Bilateral
hearing loss;
right at 40 DB
(250–1000Hz,
80dB at
1000–6000 Hz)
Bilateral
asymmetric
hearing loss,
particularly in
lower
frequencies
n/a
Low- to
mid-frequency
hearing loss
n/a
Audiogram
ANA mildly
positive
Rheumatoid
factor mildly
positive; mild
diffuse lymph
adenopathy
(biopsy
negative for
malignant
cells)
EEG: diffuse
abnormalities
VEP:
abnormal
prolongation
bilaterally
Y
Y
N
Y
Y
N
Y
Y
Y
Y
Symptoms
began
postpartum
Positive FTA
· 2 (negative
RPR); elevated
IgG synthesis
rate
Y
Y
MRI T2
hyperintensities
(y/n)
Symptoms
during 3rd
trimester of
pregnancy
Other
findings
MRI
corpus
callosum
involvement
(y/n)
N
N
N
N
Y
N
MRI
gadolinium
enhancement
Normal
Normal
Normal
Normal
Normal
Normal
Cerebral
angiogram
or MRA
findings
802
F. J. Mateen et al.
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
30/M
46/M
23/F
50/F
36/F
20/F
7
8
9
10
11
12
Age/sex
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
Gait ataxia, uni
lateral hearing
loss, confusion,
pseudobulbar
affect, urinary
incontinence
Intractable HA,
unilateral hearing
loss, progressive
cognitive decline,
scintillating
scotoma,
photophobia,
N&V
Episodes of visual
loss, hearing loss,
disorientation,
imbalance,
memory loss,
hallucinations,
lethargy
Headaches, unilat
eral visual loss,
imbalance,
vertigo,
hemiparesis
Confusion, cognitive
difficulty,
new headaches,
unilateral hearing
loss, and tinnitus
Vertigo, numb
hands, vision
loss, hearing loss,
cognitive decline,
agitation
Presenting
symptoms/
clinical
findings/first
symptom(s)
Table 1 (Continued )
In
In
B, H, V
Out
B, H
B, H, V
Both
In
B, V, H
B, H, V
In
Inpatient/
outpatient
evaluation
(episode #)
H, B
Involvement
of brain (B),
hearing
(H), and
vision (V)
170
106
171, 157
133
Ôslightly
elevatedÕ
188
CSF
protein
20
2
12, 6
10
8
16
CSF
cell count
n/a
1
n/a
n/a
n/a
1
Oligoclonal
bands
50% reduced
hearing left ear
Sensorineural
hearing loss
(250–2000 Hz
range on one
ear, all
frequencies
other ear)
n/a
n/a
n/a
n/a
Audiogram
None
None
ANA positive
1:80,
CK = 5000,
LDH 338,
ESR 24.
Brain biopsy:
scant
perivascular
chronic
inflammation,
microglial
activation and
mild nonspecific gliosis
EEG:
generalized
slowing
None
Other
findings
Y
Y
Y
Y
Y
Y
n/a
Y
Y
Y
Y
MRI T2
hyperintensities
(y/n)
Y
MRI
corpus
callosum
involvement
(y/n)
Y
Y
N
n/a
N
Y
MRI
gadolinium
enhancement
n/a
Normal
Normal
Normal
Normal
Normal
Cerebral
angiogram
or MRA
findings
Susac syndrome
803
37/F
44/F
19/F
24/F
16
17
18
23/F
14
15
35/F
13
Age/sex
Headaches, R vi
sual loss, R
hearing loss,
cognitive
difficulty, gait
ataxia, R facial
sensory
disturbance,
confusion,
pseudobulbar
affect
Segmental visual
loss, dizziness,
weak and numb
UE
Episodic loss of
consciousness,
transient visual
disturbance,
progressive
cognitive decline,
and memory loss
Headache, hearing
loss, blurry
vision,
disorientation,
personality
change, and
cognitive decline
Vertigo, tinnitus,
bilateral hearing
loss, segmental
visual loss
Headaches, blurry
vision, hearing
loss, confusion,
memory loss, gait
instability
Presenting
symptoms/
clinical
findings/first
symptom(s)
Table 1 (Continued )
B, H, V
Out
In
Both
B, H, V
B, H, V
Out
Out
B, H, V
V, B
Out
Inpatient/
outpatient
evaluation
(episode #)
B, H, V
Involvement
of brain (B),
hearing
(H), and
vision (V)
n/a
126
131
n/a
59
177
CSF
protein
n/a
3
0
n/a
4
n/a
CSF
cell count
n/a
n/a
0
n/a
n/a
n/a
Oligoclonal
bands
Moderate left
hearing loss
250–1000 Hz
range
n/a
10% word
recognition in
left ear
Normal
n/a
n/a
Audiogram
Prothrombin
20 210 A
mutation
heterozygote
Y
N
N
Y
N
Y
Y
MRI T2
hyperintensities
(y/n)
Y
Y
None
None
N
Y
Y
None
Positive IgM
and IgG
anticardiolipin
antibody, V
Leiden
heterozygous
None
Other
findings
MRI
corpus
callosum
involvement
(y/n)
N
Y
Y
N
Y
N
MRI
gadolinium
enhancement
Normal
Normal
Normal
Normal
Normal
n/a
Cerebral
angiogram
or MRA
findings
804
F. J. Mateen et al.
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
46/F
28/F
27/M
43/F
20/F
33/F
57/F
39/M
25/F
19
20
21
22
23
24
25
26
27
Age/sex
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
Headache, nausea,
vomiting,
tinnitus, hearing
loss, dizziness,
short-term
memory loss
Visual loss,
hearing loss,
headache
Disorientation,
visual loss,
headache
Disorientation,
hearing loss
Disorientation,
urinary retention,
gait instabliity
Right ear discomfort,
gait instability,
disorientation
Scotomatous vi
sual loss, vertigo,
worsening gait,
tinnitus,
headache,
paresthesias of
face and
extremities
Hearing loss,
headache,
blurred vision
Hearing loss,
headache,
vertigo, left
numbness, gait
unsteadiness
Presenting
symptoms/
clinical
findings/first
symptom(s)
Table 1 (Continued )
In
B, V
Out
Out
B, H
B, H
Out
Out
Out
In
Out
Both
Inpatient/
outpatient
evaluation
(episode #)
B, V
H, V
B,H,V
B, H
H,V
B, H, V
Involvement
of brain (B),
hearing
(H), and
vision (V)
147
79
248
84
84
> 200
164
35
83, 57
CSF
protein
14
4
n/a
11
2
50
5
1
0, 0
CSF
cell count
0
0
n/a
n/a
0
0
0
0
n/a
Oligoclonal
bands
Not done but
had abnormal
brainstem
evoked
potentials
Sensorineural
hearing loss
bilaterally
(1000–8000 Hz
range)
n/a
Normal
Unilateral 6000
and 8000 Hz
loss
Mild R and
moderate–
severe left
sensorineural
hearing loss,
all frequencies
Mostly normal
but loss at
1500 Hz left
and 2000 Hz
right ear
n/a
Low-frequency
hearing loss
left, low- and
high-frequency
loss right
Audiogram
Y
Y
None
None
Y
Y
Y
None
None
None
Y
Y
None
None
N
Y
None
ANA (1:40)
Other
findings
MRI
corpus
callosum
involvement
(y/n)
Y
Y
Y
Y
Y
Y
Y
Y
Y
MRI T2
hyperintensities
(y/n)
Y
n/a
n/a
N
N
Y
Y
N
Y
MRI
gadolinium
enhancement
*Normal
Normal
Normal
Normal
*Normal
Normal
n/a
Normal
n/a
Cerebral
angiogram
or MRA
findings
Susac syndrome
805
65/M
29
*Digital subtraction angiography; ANA, antinuclear antibody; B, brain; EEG, electroencephalogram; FTA, fluorescent treponemal antibody absorption; H, hearing; HA, headache; MRI, magnetic resonance imaging study
of the brain; L, left; N, no; N&V, nausea and vomiting; n/a, not done; R, right; VEP, visual evoked potentials; V, vision; Y, yes.
Normal
N
N
In
B, H, V
96
2
0
Moderate–se
vere bilateral
sensorineural
hearing loss
None
Y
Normal
N
Y
Y
n/a
0
19
In
32/F
28
Age/sex
Acute unilateral
hearing loss,
visual loss,
disorientation
Headache, disori
entation
B, H, V
268
Other
findings
Audiogram
Oligoclonal
bands
CSF
cell count
Inpatient/
outpatient
evaluation
(episode #)
Presenting
symptoms/
clinical
findings/first
symptom(s)
Involvement
of brain (B),
hearing
(H), and
vision (V)
CSF
protein
None
MRI
gadolinium
enhancement
MRI
corpus
callosum
involvement
(y/n)
MRI T2
hyperintensities
(y/n)
Cerebral
angiogram
or MRA
findings
F. J. Mateen et al.
Table 1 (Continued )
806
(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 performed in all cases (Fig. 1). Corpus callosal involvement 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 occurred 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 maintenance monthly IVIg (cases 21, 23, and 25). Amongst
the 11 cases who were evaluated in the acute symptomatic 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 dexamethasone (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: aspirin (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 biomarkers, 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 response to corticosteroids. Most patients were treated
with additional immunosuppressive therapy with the
goal of achieving symptomatic remission in the acute
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
Susac syndrome
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.
period. This is especially true for patients with severe
presentations, including dementia, recurrent seizures,
and recurrent visual loss despite treatment with corticosteroids.
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 patientÕs blood including
immunoglobulins, complement, and/or cytokines [22].
807
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 treatment.
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 individuals, including just two in this series, some of whom
experience spontaneous resolution of symptoms without 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 modified 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 confirmation of this diagnosis in a large referral center over the
(a)
Figure 2 Pathologic features of Susac
syndrome in brain biopsy of case 21.
Histologic sections demonstrate aggregates 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).
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
(b)
26/F
30/M
46/M
23/F
8
9
35/F
4
6
7
36/F
3
51/F
32/F
2
5
34/F
1
Age
(years
/sex)
6
3–4
Uncertain
1
1
5
1
0.25
2
Duration of
symptoms
prior to
treatment
months)
ASA
ASA
ASA-Dipyri
damole
Clopidogrel
–
ASA
ASA
ASA
ASA
Antiplatelet
medication
N
N
Y
Y
N
N
2 pills
only
Y
Y
Oral
steroids
(Y/N)
Y
Y
Y
Y
Y
N
Y
Y
N
IV
steroids
Nimodipine,
recommended to
have
cyclophosphamide
2 mg/kg PO
daily · 6 months
Cyclophosphamide
–
–
–
–
Nimodipine
–
–
Other
treatments
Table 2 Treatment and clinical course of patients with susac syndrome
–
Daily · 5, then
1 month later
4 more doses
Daily · 5 days
Every other
day · 5
–
–
5
5
2
2
0
5
0
Daily · 3
–
0
0
Every other
day · 5
Every other
day · 5
PLEX
–
3
–
–
–
–
–
–
IVIg
(# of days)
Lowest
modified
rankin
scale score
Initially returned to
baseline with IVIg
maintained on
monthly IVIg and
Solu-Medrol;
recurrence 1 year
later with some
improvement with
PLEX but did not
return to baseline
Improved hearing
and sight
Improved
Improved following
IV steroids on 2
occasions
Stable
Weakness improved
with IV steroids
but later had visual
changes (halos
around objects),
ear pressure, and
objective hearing
loss
Initial episode
resolved without
treatment; later
episode treated
with IVIg
Improved
Stabilized symptoms
postpartum
Improvement
following
treatment
Stable but
poor baseline
Some
improvement
with IVIg
and PLEX
but continually
worsening
baseline over
15 months
Improvement
without
treatment
then
recurrent eye
symptoms
6 years later
No recurrent
symptoms
n/a
Improved
Recurrence
after oral
steroid taper
Later episodes
of visual and
hearing loss
Recommended
to have
PLEX but
LFU
Outcome
15
9
95
32
62
88
13
128
9
No. of
months of
follow-up
available
808
F. J. Mateen et al.
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
50/F
36/F
20/F
35/F
23/F
37/F
44/F
19/F
24/F
36/F
10
11
12
13
14
15
16
17
18
19
Age
(years
/sex)
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
3
3.5
1
3
1
1.5
0.5
1.25
2
<1
Duration of
symptoms
prior to
treatment
months)
Table 2 (Continued )
ASA
Clopidogrel
ASA
ASA
ASA
ASA
ASA
ASA
–
–
Antiplatelet
medication
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Oral
steroids
(Y/N)
Y
Y
Y
N
N
Y
Y
Y
Y
N
IV
steroids
Cyclophosphamide
100mg daily
Azathioprine
Nimodipine
–
Mycophenolate
mofetil, Nimodipine
–
Nimodipine
–
–
Cyclophosphamide
Other
treatments
–
2 doses, then
relapse then 5
every other
day with
improvement,
then 3· per week
–
–
5 every other
day than weekly
–
–
–
5 doses on 2
different
occasions
Every other
day · 5
IVIg
(# of days)
–
–
Every other
day · 5; 2
separate
occasion
–
Every other
day · 5
Every other
day · 5, then
relapse then 2
more doses
–
–
Every other
day · 5
Stable, unclear
whether
improvement
occurred
0
1
One relapse while
on a 15-month
course of
cyclophospha
mide, treated with
steroids
Improved following
PLEX, then
cognitive and gait
deficits relapsed
and then repeat
treatment
Improved
4
2
Improved
Deteriorated
Symptomatic
response to IVIg
reported in past
No response to IV/
PO steroids,
4 weeks later had
response to IVIg
Improved objective
gait speed and
coordination
Improved
Improvement
following
treatment
0
4
2
4
4
0
PLEX
–
Lowest
modified
rankin
scale score
24
Visual changes
off immuno
suppression
nearly
2 years later
treated with
repeat PLEX
No recurrent
symptoms for
nearly 5 years,
persistent
mild visual
loss
59
43
15
9
73
76
<1
3
<1
No new
symptoms
No new
symptoms
Cognitive
improvement
but required
wheelchair at
7 months
No new
symptoms
n/a
LFU
Continued
progression
then LFU
Improvement
Outcome
No. of
months of
follow-up
available
Susac syndrome
809
32/F
65/M
28
29
0.5
0.5
0.25–0.5
0.75
0.25
0.25
ÔmonthsÕ
1.75
4
No
Treatment
–
ASA
ASA
ASA
–
–
ASA
–
–
ASA
Antiplatelet
medication
Y
Y
Y
Y
Y
Y
Y
Y
Y
N
Oral
steroids
(Y/N)
Y
Y
Y
Y
Y
Y
Y
Y
Y
N
IV
steroids
Cyclophosphamide
recommended
post-dismissal
Mycophenolate
mofetil
Cyclophosphamide,
later rituximab
Mycophenolate
mofetil
Mycophenolate
mofetil when
symptoms remitted
Mycophenolate
mofetil when
symptoms remitted
–
Azathioprine
–
Other
treatments
–
–
–
Daily · 5
Daily · 5, then
once monthly
–
Daily · 7
–
–
–
–
–
–
–
PLEX
Maintained on
0.25 g/kg every
3 weeks
5 doses days, then
weekly · 3
Maintained on
2 g/kg monthly
5 doses daily,
then once weekly
Maintained on
once monthly
dose
–
IVIg
(# of days)
4
4
3
5
4
4
1
4
2
1
Lowest
modified
rankin
scale score
Cognition
improved, hearing
loss worsened
Cognition subtly
improved
Improved
Stable
Improved cognition
Improved
Improved vision
and hearing loss
Cognition
significantly
improved
Stable
Improved
Improvement
following
treatment
Persistent
cognitive def
icits
Mild
improvement
in hearing
loss and
headaches
–
Gait
improvement,
cognitive
gains to
nearly
normal
Markedly
improved
cognition,
legs weak,
walker
dependent
–
Hearing loss
and vision
improved
Slight residual
memory
deficits
Persistent
memory
problems,
improved gait
Normal
examination
Outcome
–
–
8
9
13
11
3
3
24
8
No. of
months of
follow-up
available
ASA, aspirin; F, female; LFU, lost to follow up; IV, steroids; IVIg, intravenous immunoglobulins; M, male; mRS, modified Rankin Scale score; N, no; n/a, not available; PLEX, plasma exchange;
PO, by mouth; Y, yes.
25/F
27
33/F
24
39/M
20/F
23
26
43/F
22
57/F
27/M
21
25
28/F
20
Age
(years
/sex)
Duration of
symptoms
prior to
treatment
months)
Table 2 (Continued )
810
F. J. Mateen et al.
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology
Susac syndrome
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 evaluation, perhaps in a matched case control design compared 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 symptomatic period from multiple centers. The use of standardized 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.
References
1. Susac JO, Hardman JM, Selhorst JB. Microangiopathy of
the brain and retina. Neurology 1979; 29: 313–316.
2. Rennebohm R, Susac JO, Egan RA, Daroff RB. SusacÕs
syndrome – update. J Neurol Sci 2010; 299: 86–91.
3. Petty GW, Engel AG, Younge BR, et al. Retinocochleocerebral vasculopathy. Medicine (Baltimore) 1998; 77:
12–40.
4. Petty GW, Matteson EL, Younge BR, et al. Recurrence
of Susac syndrome (retinocochleocerebral vasculopathy)
after remission of 18 years. Mayo Clin Proc 2001; 76:
958–960.
811
5. Bogousslavsky J, Gaio JM, Caplan LR, et al. Encephalopathy, deafness and blindness in young women: a distinct retinocochleocerebral arteriolopathy? J Neurol
Neurosurg Psychiatry 1989; 52: 43–46.
6. Vila N, Graus F, Blesa R, Santamaria J, Ribalta T, Tolosa E. Microangiopathy of the brain and retina (SusacÕs
syndrome): two patients with atypical features. Neurology
1995; 45: 1225–1226.
7. Do TH, Fisch C, Evoy F. Susac syndrome: report of four
cases and review of the literature. AJNR Am J Neuroradiol
2004; 25: 382–388.
8. Hahn JS, Lannin WC, Sarwal MM. Microangiopathy of
brain, retina, and inner ear (SusacÕs syndrome) in an
adolescent female presenting as acute disseminated
encephalomyelitis. Pediatrics 2004; 114: 276–281.
9. Snyers B, Boschi A, De Potter P, et al. Susac syndrome in
four male patients. Retina 2006; 26: 1049–1055.
10. Fox RJ, Costello F, Judkins AR, et al. Treatment of
Susac syndrome with gamma globulin and corticosteroids.
J Neurol Sci 2006; 251: 17–22.
11. Rennebohm RM, Susac JO. Treatment of SusacÕs Syndrome. J Neurol Sci 2007; 257: 215–220.
12. Maillart E, Deschamps R, Moulignier A, et al. [Susac
syndrome: study of five cases]. Rev Neurol (Paris) 2009;
165: 575–582.
13. Saux A, Niango G, Charif M, et al. SusacÕs syndrome,
a rare, potentially severe or lethal neurological disease.
J Neurol Sci 2010; 297: 71–73.
14. Wildemann B, Schülin C, Storch-Hagenlocher B, et al.
SusacÕs syndrome: improvement with combined antiplatelet and calcium antagonist therapy. Stroke 1996; 27: 149–
151.
15. Papo T, Biousse V, Lehoang P, et al. Susac syndrome.
Medicine (Baltimore) 1998; 77: 3–11.
16. OÕHalloran HS, Pearson PA, Lee WB, et al. Microangiopathy of the brain, retina, and cochlea (Susac syndrome).
A report of five cases and a review of the literature.
Ophthalmology 1998; 105: 1038–1044.
17. Aubart-Cohen F, Kelin I, Alexandra JF, et al. Long-term
outcome in Susac syndrome. Medicine (Baltimore) 2007;
86: 93–102.
18. Hardy TA, Garsia RJ, Halmagyi GM, et al. Tumor
necrosis factor (TNF) inhibitor therapy in SusacÕs syndrome. J Neurol Sci 2011; 302: 126–128.
19. Rankin J. Cerebrovascular accidents in patients over the
age of 60. I. General considerations. Scott Med J 1957;
2(4): 127–136.
20. Marie I, Maurey G, Herve F, et al. Intravenous immunoglobulin-associated arterial and venous thrombosis:
report of a series and review of the literature. Br J Dermatol 2006; 155: 714–721.
21. Paran D, Herishanu Y, Elkayam O, et al. Venous and
arterial thrombosis following administration of intravenous immunoglobulins. Blood Coagul Fibrinolysis 2005;
16: 313–318.
22. Linker RA, Gold R. Use of intravenous immunoglobulin
and plasma exchange in neurological disease. Curr Opin
Neurol 2008; 21: 358–365.
2012 The Author(s)
European Journal of Neurology 2012 EFNS European Journal of Neurology