Laboratory Isolated Syndrome (LIS) in NMOSD - A Case Report
Document Type
Conference Proceeding - Restricted Access
Publication Date
5-8-2026
Abstract
Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune astrocytopathy strongly associated with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies and classically presents with core clinical syndromes such as optic neuritis or longitudinally extensive transverse myelitis (LETM). While AQP4-IgG is considered highly specific for NMOSD, AQP4-IgG seropositivity in the absence of any prior NMOSD-defining clinical syndrome has not been previously reported, nor is it addressed in current diagnostic criteria. We report a case of prolonged, asymptomatic AQP4-IgG seropositivity preceding the first clinical attack of NMOSD, suggesting a potential pre-clinical "laboratory isolated syndrome."
A 69-year-old right-handed woman with a history of focal epilepsy, myasthenia gravis (MG), and paroxysmal atrial fibrillation was found to have a transient ring-enhancing right frontal white matter lesion on brain MRI following a breakthrough seizure. Cerebrospinal fluid evaluation was unrevealing. Serologic testing confirmed acetylcholine receptor antibodies and unexpectedly demonstrated markedly positive AQP4-IgG on cell-based assay, with negative myelin oligodendrocyte glycoprotein antibodies. At the time of antibody detection, the patient had no clinical features of NMOSD, raising concern for a false-positive result. Repeat AQP4-IgG testing remained positive. Several years later, she developed acute bilateral lower-extremity paresthesias and genital sensory loss.
This case represents the first reported instance of prolonged asymptomatic AQP4-IgG seropositivity preceding the initial clinical manifestation of NMOSD, introducing the concept of a pre-clinical "laboratory isolated syndrome." The findings challenge existing diagnostic paradigms and raise important questions regarding the prognostic significance of isolated AQP4-IgG positivity, the temporal relationship between seroconversion and disease onset, and whether earlier recognition could allow for risk stratification or preventative therapeutic strategies.
Recommended Citation
Al Asaad K, Lannen N. Laboratory isolated syndrome (LIS) in NMOSD - A case report. Presented at: Research Day Corewell Health West; 2026 May 8; Grand Rapids, MI.
Comments
2026 Research Day Corewell Health West, Grand Rapids, MI, May 8, 2026. Abstract 2152