Evolving Approaches to Seronegative NMOSD in New Diagnostic Criteria: Álvaro Cobo-Calvo, MD, PhD

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"We observed that, although the inclusion of seronegative patients in clinical trials is low, most therapies—such as satralizumab and inebilizumab—did not reduce the risk of relapses in double-seronegative patients, while they were effective in aquaporin-4–positive patients."

A session presented at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, centered on proposed updates to the diagnostic framework for neuromyelitis optica spectrum disorder (NMOSD). The session, chaired by Brenda Banwell, MD, and Jacqueline Palace, MD, included presentations from Dean Wingerchuk, MD, on the 2025 International Panel for Neuromyelitis Optica Diagnosis diagnostic criteria; Álvaro Cobo-Calvo, MD, PhD, on implications for double-seronegative cases; and Sara Mariotto, MD, on the molecular characterization of seronegative disease.

In an interview with NeurologyLive^® at the Congress, Cobo-Calvo, a neurologist at the Multiple Sclerosis Center of Catalonia in Spain, described the work of an international panel tasked with revising NMOSD diagnostic criteria to reflect scientific advances and evolving clinical understanding. He noted that the panel examined distinctions between aquaporin-4–positive NMOSD and double-seronegative presentations, including differences in demographic patterns, clinical features, and biomarker profiles. According to Cobo-Calvo, this effort aimed to clarify whether seronegative presentations should remain in the NMOSD criteria or be considered separately.

During the conversation, Cobo-Calvo also discussed emerging evidence suggesting variable treatment responses between these patient groups. He highlighted that targeted therapies have demonstrated consistent efficacy in aquaporin-4–positive NMOSD but less so in double-seronegative cases, a pattern that may have implications for future diagnostic and therapeutic decision-making. He noted that the panel did not reach consensus on certain aspects of the criteria; thus, additional discussion might be required before the updated criteria are published.

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REFERENCES
1. Cobo-Calvo Á, et al. 2025 diagnostic criteria for NMOSD: implications for double seronegative cases. Presented at ECTRIMS Congress; September 24-26, 2025; Barcelona, Spain. Hot Topic 3: New NMOSD diagnostic criteria.