Susac syndrome (SuS) is a rare microvascular disease characterized by a clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. J.O. Susac described the first cases in 1979 [1]. In 2013, 304 diagnosed cases were collected worldwide [2], but this syndrome's true incidence and prevalence are unknown. SuS affects predominantly young adults from 20 to 40 years old, primarily women with a sex ratio of 3:1. The complete clinical presentation is rare at symptom onset – around 13% [2] – which, combined with insufficient knowledge of the disease, often leads to underdiagnosis or misdiagnosis. Thus, delaying the diagnosis and treatment may worsen the prognosis and lead to severe complications such as irreversible deafness and cognitive impairment.

The pathophysiology of SuS still needs to be understood. Our neuropathological knowledge of the disease is limited to describing a few brain biopsies. The first autopsy case was described in 2019 on a 24-year-old female patient with a highly severe presentation and a fatal outcome in a few months [3]. Neuropathological analysis showed multiple infarcts and vascular alterations such as basement membrane thickening, endothelial loss, and perivascular inflammation. The presence of CD8+ lymphocytes around small leptomeningeal and parenchymal arteries favors the hypothesis of a vasculitis phenomenon. Interestingly, this perivascular inflammation is described as moderate or absent in most cases [3].

Studies suggest an autoimmune mechanism leading to microvascular inflammation responsible for microvessel occlusions. The autoimmune hypothesis is based on the anti-endothelial cell antibodies IgG1 class findings in serum. However, their direct implication remains unclear since they may be found in multiple autoimmune disorders such as Sjögren syndrome or dermatomyositis [4].

Regarding treatment, there are, to date, no randomized trials or prospective studies. Recent guidelines were published in 2017 based on clinical experience and a follow-up of a large cohort of patients [5]. High doses of intravenous methylprednisolone or immunoglobulins are frequently used in the acute phase, with oral maintenance corticosteroids for several months up to several years to prevent relapses with slow tapering. The treatment of SuS is also associated with acetylsalicylic acid. In the case of refractory disease, immunosuppressants such as mycophenolate mofetil, cyclophosphamide, or azathioprine have been used. Some recent case reports have shown an interest in treatment by rituximab after a 12-month follow-up [6]. In these cases, it is still being determined how long the immunosuppressive therapy should be maintained.