What is Susac syndrome?

Susac Syndrome: Clinical Features, Diagnosis, and Management

Susac syndrome is a rare autoimmune disorder characterized by a clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss caused by microvessel occlusions in the brain, retina, and inner ear. 1

Clinical Presentation

• Susac syndrome predominantly affects young women with a mean age at diagnosis of 35 years 2
• The classic clinical triad includes:
  • Encephalopathy (brain involvement)
  • Visual disturbances due to branch retinal artery occlusions
  • Sensorineural hearing impairment 1
• Only 13-30% of patients present with the complete triad at initial evaluation, making diagnosis challenging 1
• Symptoms may develop sequentially rather than simultaneously 3

Diagnostic Features

Brain Involvement

• MRI findings show characteristic multifocal, rounded brain lesions, often centrally located in the corpus callosum ("snowball-like" lesions) 4
• These lesions are considered a red flag that distinguishes Susac syndrome from multiple sclerosis 4

Ocular Involvement

• Branch retinal artery occlusions (BRAOs) are characteristic 5
• Gass plaques (yellow-white plaques in the arteriolar wall) may be observed on fundus examination 5
• Fluorescein angiography reveals arteriolar wall hyperfluorescence and branch retinal arterial occlusions without other signs of intraocular inflammation 5
• Punctate or miliary enhancement patterns may be seen on MRI 4

Auditory Involvement

• Bilateral perceptual hearing loss is common, often asymmetric 3
• Tinnitus and recurrent vertigo may occur 3
• Audiometry is essential to document sensorineural hearing loss 1

Pathophysiology

• Susac syndrome is believed to be an immune-mediated endotheliopathy affecting the microvasculature 1, 6
• Cytotoxic CD8+ T cells adhere to microvessels, causing endothelial cell swelling, vascular narrowing, and occlusion 1
• Anti-endothelial cell antibodies (AECAs) are present in approximately 25% of patients, though their exact role remains unclear 1, 6
• Microinfarcts with atrophy of white and gray matter occur due to microangiopathy with arteriolar wall proliferation, lymphocytic infiltration, and basal lamina thickening 6

Diagnostic Approach

• The diagnosis requires a high index of suspicion, especially when the full triad is not present 1
• Essential diagnostic tests include:
  • Brain MRI to identify characteristic corpus callosum "snowball" lesions 4
  • Retinal fluorescein angiography to detect branch retinal artery occlusions 1
  • Optical coherence tomography angiography to identify obstruction in deep layer retina arteries 3
  • Audiometry to document sensorineural hearing loss 1
• Testing for anti-endothelial cell antibodies may provide diagnostic support 6

Differential Diagnosis

• Multiple sclerosis (distinguished by different MRI lesion patterns) 4
• Neuromyelitis optica spectrum disorders 4
• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy 4
• Systemic lupus erythematosus 4
• Other causes of retinal artery occlusion 4

Treatment

• Immunosuppression is the mainstay of treatment, with high-dose corticosteroids as first-line therapy. 1, 2
• Initial treatment typically consists of high-dose intravenous or oral corticosteroids (e.g., methylprednisolone 1000 mg/day for 5 days) 3
• Additional immunosuppressive agents may be necessary in severe or refractory cases:
  • Intravenous immunoglobulin 1, 2
  • Mycophenolate mofetil 1, 3, 5
  • Cyclophosphamide 1, 5
  • Rituximab 1
  • Azathioprine 5
• Recent evidence suggests that the combination of glucocorticoids with immunosuppressive agents or intravenous immunoglobulin may not significantly reduce relapse risk compared to glucocorticoids alone 2

Prognosis and Monitoring

• The disease can cause irreversible organ damage if not treated promptly 1
• Relapse rates are high, with 72% of patients experiencing at least one relapse (median relapse-free survival time of 3.96 months) 2
• Residual symptoms commonly include scotoma and hearing loss 5
• Regular monitoring should include:
  • Retinal fluorescein angiography 1
  • Optical coherence tomography 1
  • MRI 1
  • Tonal audiometry 1
• There are currently no reliable objective immune markers to monitor disease activity during treatment 1

Clinical Pearls

• Early diagnosis and treatment are crucial to prevent irreversible sequelae including dementia, blindness, and hearing loss 1
• Consider Susac syndrome in young patients presenting with unexplained encephalopathy, visual disturbances, or hearing loss, even if the full triad is not present 1, 3
• Retinal findings may be the first manifestation of the disease 5
• The disease is often misdiagnosed due to its variable presentation and rarity 1