A Case of <scp>AQP4</scp> Antibody–Positive <scp>NMOSD</scp> Initially Manifesting as Extensive, Asymptomatic Cerebral White Matter Lesions and Subsequently Developing Cognitive Impairment

ABSTRACT Background The original diagnostic criteria for neuromyelitis optica (NMO) required both optic neuritis and myelitis. The subsequent recognition of cases with either one of these features or other central nervous system lesions, including brain involvement, gave rise to the concept of NMO spectrum disorder (NMOSD). Cerebral involvement has been reported in various forms, including extensive lesions, asymptomatic lesions, and cases in which brain pathology represents the initial clinical manifestation. Despite this, asymptomatic individuals are not currently included within the 2015 NMOSD diagnostic criteria. Case Presentation A 74‐year‐old man was referred to our hospital due to abnormal findings on brain MRI, despite the absence of neurological deficits. Brain magnetic resonance imaging (MRI) demonstrated multifocal extensive cerebral white matter lesions with multiple ill‐defined, patchy, mild, and irregular gadolinium‐enhancing lesions, consistent with “cloud‐like enhancement.” Aquaporin‐4 (AQP4) antibodies were negative by enzyme‐linked immunosorbent assay (ELISA) but positive on a cell‐based assay (CBA). At that time, the patient was asymptomatic and therefore did not meet the diagnostic criteria for NMOSD. After exhaustive exclusion of alternative diagnoses and the subsequent development of cognitive impairment, the patient was diagnosed with NMOSD. Conclusions To our knowledge, this is the first reported case in which extensive, asymptomatic cerebral white matter lesions served as the initial manifestation of NMOSD, emphasizing the clinical importance of considering such cases in the differential diagnosis, evaluating appropriate treatment strategies, and potentially informing future revisions of the NMOSD diagnostic criteria.