CME ARTICLE Susac syndrome: clinical characteristics and treatment in 29 new cases F. J. Mateen a,b , A. Y. Zubkov c , R. Muralidharan a , J. E. Fugate a , F. J. Rodriguez d , J. L. Winters e and G. W. Petty a a Department of Neurology, Mayo Clinic, Rochester, MN; b Department of Neurology, Johns Hopkins Hospital, Baltimore, MD; c Minneapolis Clinic of Neurology, Edina, MN; d Division 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 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 Ó 2012 The Author(s) European Journal of Neurology Ó 2012 EFNS European Journal of Neurology 2012, 19: 800–811 doi:10.1111/j.1468-1331.2011.03627.x
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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-
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-
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of Susac syndrome (retinocochleocerebral vasculopathy)after remission of 18 years. Mayo Clin Proc 2001; 76:
958–960.
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16. O�Halloran HS, Pearson PA, Lee WB, et al. Microangi-opathy of the brain, retina, and cochlea (Susac syndrome).A report of five cases and a review of the literature.Ophthalmology 1998; 105: 1038–1044.
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� 2012 The Author(s)European Journal of Neurology � 2012 EFNS European Journal of Neurology