Central Nervous System Involvement in ANCA-Associated Vasculitis

Abstract

Specific involvement of central nervous system (CNS) in ANCA-associated vasculitis (AAV) is rare and affects probably less than 10% of patients. CNS involvement is more frequently observed in granulomatosis with polyangiitis (GPA) than in microscopic polyangiitis (MPA) or in eosinophilic granulomatosis with polyangiitis (EGPA). In GPA, three main CNS involvements are observed: CNS vasculitis, pachymeningitis, and involvement of the pituitary gland. In MPA and EGPA, most reported cases are CNS vasculitis, responsible for cerebral infarcts and subarachnoid hemorrhages. Diagnosis relies on imaging, mainly MRI with complete sequences (T1, T2, T2∗, fluid-attenuated inversion recovery [FLAIR], diffusion-weighted imaging/apparent diffusion coefficient mapping, and gadolinium-enhanced T1). Angiography (CT angiography, MRA, or digital subtraction angiography) should be performed but can be normal in half of the patients given the involvement of small-sized vessels, which are beyond the detection capacity of the procedure. Biopsy is rarely performed in clinical practice but can help diagnosis. A complete workup including infective and autoimmune serologies (especially ANCA dosage) as well as cerebrospinal fluid analysis is required, especially in patients with isolated or inaugural CNS manifestations. In patients with concomitant systemic manifestations of AAV, diagnosis is easier, although investigations are also necessary to exclude other conditions affecting CNS. Finally, in absence of biopsy and/or demonstration of CNS vascular involvement, diagnosis is often probabilistic and relies on the systemic context and the ANCA positivity. Treatment of AAV-related CNS involvement requires combination of high-dose glucocorticoids and an immunosuppressant, mainly cyclophosphamide. Rituximab may be another option in patients with a contraindication for cyclophosphamide. A maintenance therapy is required after induction.