Treatment of Susac’s syndrome

Abstract

Susac's syndrome (SS) consists of the triad of encephalopathy, branch retinal artery occlusions (BRAO), and hearing loss. It usually affects women aged 20 to 40, but men are also affected, and the age range extends from 9 to 72 years. It tends to be unrecognized, even in major academic centers. The complete triad may not be present at the onset, which makes diagnosis more difficult. However, since this disorder is treatable, early diagnosis is important. The encephalopathy is usually associated with headaches, multifocal neurologic manifestations, and psychiatric features (particularly paranoia). MRI shows a white matter disturbance that is frequently confused with multiple sclerosis and acute disseminated encephalomyelitis. During the encephalopathy, the corpus callosum is always affected and shows central involvement--small to large "snowballs" and linear defects, "spokes." As the acute changes (microinfarcts) resolve, central callosal "holes" develop, a pathognomonic finding. The deep gray matter (70%) and leptomeninges (33%) also may be involved. Dilated fundus examination will reveal branch retinal artery occlusions. Fluorescein angiography may disclose pathognomonic staining of the arterioles proximal to the occlusions and of nonoccluded arterioles. The cochlear hearing loss, sometimes associated with vertigo, is usually bilateral, and deafness becomes a major disabling problem. Brain biopsies, anatomic observations, and responses to immunosuppressive therapy suggest that SS represents an autoimmune endotheliopathy in the microvasculature of the brain, retina, and cochlea. Treatment requires immunosuppression. High-dose corticosteroid therapy is the mainstay, but additional therapies such as intravenous immunoglobulin, mycophenolate mofetil, and cyclophosphamide are often necessary. Rituximab is the newest therapy to consider. Treatment should be prompt, aggressive, and sustained to avoid the dreaded residuals of dementia, deafness, and blindness.

Diagnostic criteria for Susac syndrome

“…Treatment is empirical and based on the hypothesis of an autoimmune inflammatory endotheliopathic aetiology1 15 and some similarity to juvenile dermatomyositis 1 4 5. In the acute episode, treatment comprises high-dose corticosteroids.…”

“…In the acute episode, treatment comprises high-dose corticosteroids. To avoid further disease attacks or progression, a continuous immunosuppressive therapy is currently recommended 1 4 15 16. Response to immune treatment was not chosen for the criteria as an 'ex juvantibus' prove of the diagnosis.…”

“…Consequently, the complete triad is present in only 13% of patients at disease onset 1. The lack of diagnostic criteria often leads to a delayed or wrong diagnosis and a critical protraction of an appropriate treatment 4 5. Of particular note, immune treatment for multiple sclerosis (MS), which is the most common misdiagnosis of SuS,6 may lead to exacerbation of the disease 7…”

Skin involvement in Susac's syndrome

“…Yet, permanent deafness, blindness or dementia may persist [11]. Natural history can be monocyclic (particularly in patients presenting with encephalopathy), polycyclic, or chronic continuous [12]. Treatment is empirical and relies on immunosuppressive agents and aspirin [12].…”

Looking out for the blind spot

“…However, there are no randomised controlled trials evaluating treatment options in Susac's syndrome. Based on clinical experience and case series and reports, recommendations include high-dose corticosteroids as first-line treatment, followed by aggressive early immunosuppression with other agents, including cyclophosphamide and intravenous immunoglobulin 8 9. Some authors recommend slow taper of corticosteroids on remission, with continuation of immunomodulatory treatment with azathioprine, mycophenolate mofetil or cyclophosphamide.…”