Susac syndrome (ORPHA:838)
A rare systemic or rheumatologic disease characterized by the triad of central nervous system (CNS) dysfunction, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss (SNHL) due to autoimmune-mediated occlusions of microvessels in the brain, retina, and inner ear.
Epidemiology
Susac syndrome (SuS) prevalence is still unknown. To date more than 500 cases have been reported worldwide. Young females (20-40 years) are more affected (female: male ratio 3.5:1). The age at onset ranges from 8 to 72 years (mean age: 32 years).
Clinical description
Characteristic is a triad of encephalopathy (cognitive and behavioral disturbances, personality changes, psychosis, preceding headaches) and/or focal CNS dysfunction, visual dysfunction due to BRAO and SNHL. The components of the triad may not be concomitantly present and may develop successively. Three major disease courses have been suggested: monocyclic (fluctuating disease that self-limits after a maximum period of 2 years), polycyclic (relapses that continue beyond a 2 years period) and chronic-continuous.
Etiology
The etiology and precise pathophysiology are not yet clear. According to recent data, clonally expanding autoreactive cytotoxic CD8+ T cells cause inflammation-mediated injury of the microvascular endothelium which leads to swelling of endothelial cells, vessel occlusion in the affected organ and finally micro-ischaemic damage and dysfunction.
Diagnostic methods
The diagnosis is based on the demonstration of the typical triad. There is no singular ''marker'' of SuS. Beside the clinical examination, most relevant diagnostic tools are brain magnetic resonance imaging (MRI), retinal fluorescein angiography (FA), and audiometry. In the acute phase, T2 weighted brain MRI often shows blurry lesions in the central fibers of the corpus callosum (''snowball lesions'') which later convert into sharply defined ''punched out'' lesions. Periventricular lesions and involvement of cerebellum, brain stem and deep grey matter nuclei are also often present. FA demonstrates BRAO and fluorescein leakage, often in the retinal periphery (may then be clinically silent). Audiometry analysis reveals uni- or bilateral SNHL. Cerebrospinal fluid analysis often shows mild pleocytosis and moderate protein elevation, oligoclonal bands are uncommon. Anti endothelial cell antibodies have been reported in some cases. An early and reliable diagnosis is facilitated by application of the validated diagnostic criteria of the European Susac Consortium (EUSAC).
Differential diagnosis
Inflammatory demyelinating CNS disease (such as multiple sclerosis, acute disseminated encephalitis, neuromyelitis optica spectrum disorders), autoimmune encephalitis, and various other diseases involving CNS, retina, and inner ear (including infections, malignancies, psychotic disorders, cerebrovascular disease, migraine, Meniere disease, isolated BRAO) and a variety of autoimmune diseases such as Cogan syndrome, Eales disease, autoimmune inner-ear disease, polyarteritis nodosa, Wegener granulomatosis, Churg-Strauss syndrome, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome and Behçet disease.
Management and treatment
No evidence-based treatment strategies exist. Empirically, pulsed glucocorticosteroid treatment is effective in the acute phase. In severe cases treatment may be complemented by cyclophosphamide and/or intravenous immunoglobulins (ivIG), methotrexate (MTX), azathioprine (AZA) or mycophenolate mofetil (MMF). After stabilization glucocorticosteroids should be very slowly tapered. Long term immunosuppressive treatment by MTX, AZA, MMF, and/or ivIG is usually necessary. More recently, positive experiences have been reported with monoclonal antibodies such as rituximab, natalizumab, and infliximab. Patients with severe hearing loss may benefit from cochlear implants.
Prognosis
The disease usually self-limits after 2-4 years, Late relapses after decades have been reported. The final outcome shows a large variability of disability ranging from unimpairment to dementia, deafness and blindness. The majority of patients retains variable degrees of cognitive, visual and/or hearing deficits.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Dr Jan-Markus DÖRR