Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a rare and sometimes aggressive autoimmune encephalopathy caused by immune reaction directed to the beta-amyloid protein in cerebral small vessels. It has been described in the main cerebral amyloid-related diseases, cerebral amyloid angiopathy (CAA) and Alzheimer’s Disease (AD) as a spontaneous occurrence and a phenomenon triggered by immunological therapy in recent trials for AD. Indeed there are several similarities between the clinic-radiological syndrome described in CAA (CAA-ri) and the neuroradiological phenomenon described in AD patients as Amyloid-Related Imaging Abnormalities (ARIA). CAA-ri is probably underdiagnosed because many CAA patients are elderly and cognitively impaired before CAA-ri occurrence. In some cases a missed diagnosis means a missed possibility of treatment because in its most striking form it is known as steroid-responsive dementia. The clinical expression of CAA-ri is characterized by the acute/subacute onset of neurological symptoms, accompanied by the neuroimaging evidence of cerebral vasogenic edema on FLAIR-MR sequences, and cortical-subcortical microbleeds (MBs) and/or cortical superficial siderosis (CSS) on T2*-weighted gradient echo (T2*-GRE) or susceptibility weighted imaging (SWI). CSS is a marker of CAA included in modified Boston criteria for CAA diagnosis and it represents a neuroradiological sign highly specific of CAA and associated to an even higher ICH risk than MBs. Atypical forms of CAA-RI have also been reported including radiologically isolated CAA-ri, minimally symptomatic CAA-RI, CAA-RI with isolated leptomeningitis, and CAA-RI without MBs. There is a well-defined set of clinic-radiological criteria, validated vs hysto-pathological examination with a sensitivity of 82% and a specificity of 97% for the category of probable CAA-ri. The main differential diagnosis is represented by neoplastic, infectious, or other even more rare causes

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.