Rethinking prognosis in multiple sclerosis: a multiaxial perspective

Multiple sclerosis (MS) is a condition marked by considerable prognostic uncertainty, despite advances in therapeutic strategies and biomarker development. Current approaches to prognosis are largely focused on disease burden, failing to consider the influence of compensatory mechanisms, which complicate the evaluation of long-term outcomes. No unified framework currently exists to guide the integration of diverse prognostic factors, ranging from lesion burden and location to neuroaxonal injury, structural and cognitive reserve, lifestyle and digital biomarkers. To address this gap, a consortium from the Magnetic Resonance Imaging in MS (MAGNIMS) network has reviewed the latest research on MS prognosis and, in this Expert Recommendation, proposes a multiaxial conceptual model that incorporates the overall burden of damage, the topography of injury and the capacity for compensation. These three axes can be explored with different tools, such as clinical history and neurological examination, MRI-based tools, biofluid markers and additional techniques, including multimodal evoked potentials, optical coherence tomography and technology-based passive monitoring systems. The MAGNIMS consortium evaluated the existing tools, their limitations and potential future directions across each axis, proposing an integrated, non-prescriptive framework for individualized risk prediction. This work is intended not as a clinical guideline but as a conceptual roadmap to inform future research and refinement of prognostic models in MS.