Recognizing and Investigating the Prodromal Phase in MS and NMOSD: Dalia Rotstein, MD, MPH

WATCH TIME: 6 minutes

"Recognizing prodromal symptoms in an individual, especially a younger adult, could inspire further investigations into the possibility of demyelinating disease."

Prodromes in central nervous system (CNS) demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), refer to early, nonspecific symptoms that precede more defined clinical manifestations. Recent evidence suggests that recognizing these early symptoms like fatigue, musculoskeletal pain, and sensory disturbances could provide valuable opportunities for early diagnosis and intervention. For instance, studies have shown that the detection of aquaporin-4 antibodies during the preclinical phase of NMOSD may help guide timely therapeutic strategies, potentially improving patient outcomes.¹ Identifying these prodromal phases may be crucial for facilitating earlier interventions that can alter the disease's progression.

This concept of prodromes was explored in greater detail during the "Connecting to Diseases Beyond MS" session at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida. Chaired by Douglas Sato, MD, and Jodie Burton, MD, the session included presentations on genetic risk, transcriptomic changes, and immunopathology. Dalia Rotstein, MD, MPH, discussed the emerging role of prodromes in central nervous system (CNS) demyelinating diseases while other speakers, including Matthew Lincoln, MD, DPhil, and Kevin O’Connor, PhD, highlighted shared genetic risk loci, transcriptomic differences, and the distinct immunopathology of MOG antibody-associated disease (MOGAD).

Together, these presentations underscored the importance of cross-disease comparisons to enhance our understanding of demyelinating conditions. At the Forum, Rotstein, an assistant professor of medicine at the University of Toronto, also sat down for an interview with NeurologyLive^® to discuss the latest evidence suggesting that prodromal symptoms could aid in early identification of CNS demyelinating diseases. She elaborated on how recognizing these early features might influence clinical decision-making and disease-modifying treatment strategies, while also addressing the challenges in distinguishing these symptoms from those of other neurological or systemic conditions.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Fadda G, Flanagan EP, Cacciaguerra L, et al. Myelitis features and outcomes in CNS demyelinating disorders: Comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD. Front Neurol. 2022;13:1011579. Published 2022 Nov 7. doi:10.3389/fneur.2022.1011579
2. Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Program Agenda. Accessed February 27, 2025. https://forum.actrims.org/program
3. Zandee S. Linking MS Immune Cell Protein Signature With Clinical Progression. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. S5.1