Using Brain Connectomes to Predict Disease Progression and Treatment Response in Multiple Sclerosis: Ceren Tozlu, PhD

WATCH TIME: 4 minutes

"Clinico- radiological paradox has helped us understand that while lesion number and location are important, they are not sufficient for predicting how a [patient] will develop a disability. Rather than just looking at lesion number and size, we should assess how a lesion impacts connections."

The clinico-radiological paradox in multiple sclerosis (MS) refers to the disconnect between MRI-detected lesion burden and the severity of clinical symptoms. Recent research suggests that analyzing brain connectomes, such as using comprehensive maps of neural connections, may help resolve this paradox by revealing how MS lesions disrupt network integrity rather than just individual brain regions. Ultimately, this network-based approach may offer a more precise understanding of disease progression and disability risk, supporting the development of novel imaging markers for prognosis and treatment planning.¹

These insights were a key focus of a symposium 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 Eric Klawiter, MD and Ceren Tozlu, PhD, the session explored advancements in brain connectivity imaging for MS. Presentations covered multi-modal brain mapping techniques, the role of connectomes in explaining the clinico-radiological paradox, new methods for studying functional connectivity using OPM-MEG while standing, and microstructural imaging of network effects in MS-related neurodegeneration.² These discussions underscored the potential of network-based imaging to refine MS diagnosis, monitor disease progression, and guide treatment strategies.

Expanding on these concepts, Tozlu, an instructor in the department of radiology at Weill Cornell Medicine, sat down with NeurologyLive^® at the Forum to further discuss her presentation in the session on the role of brain connectomes in MS. She emphasized how structural and functional connectivity analyses can help identify compensation mechanisms that allow some patients to avoid disability. Additionally, she highlighted the potential of AI-driven models to enhance long-term disease prediction and explored how insights from functional connectomes could inform targeted treatment strategies, including neuromodulation techniques.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Chard D, Trip SA. Resolving the clinico-radiological paradox in multiple sclerosis. F1000Res. 2017;6:1828. Published 2017 Oct 12. doi:10.12688/f1000research.11932.1
2. Tozlu C. Unraveling the Clinico-Radiological Paradox Using Brain Connectomes in Multiple Sclerosis. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. AP2.2