Health Care Utilization Patterns May Signal Onset Years Before Clinical Symptoms: Gianmarco Bellucci, MD, PhD

Prodromal phases are well recognized in several inflammatory and neurodegenerative diseases, including multiple sclerosis (MS). In MS, much of that evidence came from health administrative data showing more health care use in the years before the first attack.¹ Whether a similar early phase exists in neuromyelitis optica spectrum disorder (NMOSD) has been less clear.

Although NMOSD, like MS, is an inflammatory disorder of the central nervous system, it is far rarer and is most often driven by antibodies against aquaporin-4 (AQP4-IgG). Some patients with NMOSD have tested positive for aquaporin-4 antibodies (AQP4-IgG) as long as 16 years before their first attack.2 However, earlier studies were limited by relatively small sample sizes and short lookback periods.

Building on this work, investigators presented data at the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto 2026), held October 21-23, 2026, in Toronto, Ontario, Canada. The study analyzed 7 million longitudinal electronic health records to look for a prodromal signature in NMOSD. those who later developed NMOSD used more health care starting about 5 to 6 years before their first clinical manifestation. This may point toward autoimmune associations with future NMOSD, as well as possible infectious triggers of clinical disease.

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“It is very important to think about ways of preventing disease, or if not preventing, intervening—identifying patients as soon as we can in order to avoid the accumulation of potential tissue damage and clinical disability.”

To discuss the findings of the study, NeurologyLive® spoke with Gianmarco Bellucci, MD, PhD, post doctoral researcher at the University of California. Bellucci described the challenge of identifying NMOSD in administrative data, where billing codes have lagged behind evolving diagnostic definitions. The team had to confirm true cases, pinpoint actual disease onset, and account for AQP4-IgG testing. To add biological context to the findings, researchers mapped them onto a biomedical knowledge graph, which revealed signals such as complement activation, B-cell activation, and myelin damage.

Bellucci also explained why recognizing a prodrome matters. Early red flags could allow clinicians to identify and treat at-risk patients sooner, before tissue damage and disability accumulate. He framed the work as part of the fast-growing field of preventive neurology.

REFERENCES
1. Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol.2017;16(6):445-451. doi:10.1016/S1474-4422(17)30076-5