While there is broad consensus that immediate immunotherapy after diagnosis is indicated in AQP4-IgG+NMOSD given the high risk of recurrence and poor prognosis if left untreated (93–95), the situation is less clear in MS and MOGAD (96, 97), and finally, in light of the rapidly changing treatment landscape with approved drugs for AQP4-IgG+NMOSD and several clinical trials in MOGAD currently underway, the ACON study will collect clinically useful data on individual treatment sequences for on-label or off-label immunotherapies in patients with acute ON (97–100). This evidence concerns the gene AQP4 and myeloid sarcoma.