Susac syndrome (SS) is an occlusive arteriolar disease, leading to infarcts in the retina, cochlea and brain. The classic triad of the disease consists of subacute encephalopathy, visual disturbances and hearing loss. It is accepted as an autoimmune disease causing an endoteliopathy disturbing the microvasculature of the inner ear, retina and brain. The rarity and the clinical diversity of the disease can make cases challenging for clinicians to diagnose. There are no defined criteria for the diagnosis of SS. Diagnosis can be made based on the findings of brain magnetic resonance imaging (MRI), fundus fluorescein angiography (FFA) and audiometry. In brain MRI; small, roundish, multifocal T2-hyperintense lesions in the periventricular, subcortical and deep white matter areas with at least one of them centrally located in the corpus callosum (‘snowball’ appearance) can be observed. The callosal lesions are accepted as pathognomonic signs. There are no standardized treatment protocols. High doses of corticosteroids for 3–5 days and oral prednisolone treatment for the following 4 weeks are recommended in the acute phase. For patients who do not respond to this first line treatment, plasmapheresis or intravenous immunoglobulin can be chosen as an alternative option. If these treatment steps fail, more aggressive immunosuppression with agents of cylophosphamide and rituxumab can be considered. The usage of antiaggregant agents such as acetylsalicylic acid is also recommended for all patients with SS to decrease the risk of thrombosis

In this chapter we review several CNS disorders of probable autoimmune origin or of unclear aetiology that sometimes are considered in the differential diagnosis of autoimmune encephalitis. These syndromes include the CNS complications of systemic autoimmune disorders: IgG4-related disease, Behçet disease, systemic lupus erythematosus (SLE), and sarcoidosis. In each of them, neurological symptoms may precede the onset of systemic symptoms. Other ‘frontier disorders’ include several diseases associated with primary involvement of the vascular endothelium or blood vessels: cerebral amyloid angiopathy-related inflammation, Susac’s syndrome, and primary angiitis of the CNS, which can all present with isolated neurological manifestations. These syndromes are immune-mediated, do not present specific or pathogenic neuronal antibodies, and their diagnosis is based on well-established clinical criteria that sometimes include neuroimaging and histopathological features. The clinical presentation of these syndromes may mimic that of several autoimmune encephalitis: SLE can present with psychosis (thus, it may need the differential diagnosis with anti-NMDAR encephalitis); IgG4-related disease can present with meningoencephalitis; and Behçet disease can present with brainstem dysfunction and neuroimaging findings resembling those of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). The clinical presentation of primary angiitis of the CNS and Susac syndrome can be indistinguishable from that of autoimmune encephalitis.