Multiple sclerosis prevalence is rising; updated diagnostics, emerging biomarkers, and innovative therapies—including CAR T-cell therapy and EBV vaccination—aim to enhance early intervention and address progressive disease challenges.

Italian MS specialists propose redefining MS as a continuum of inflammation and neurodegeneration, advocating for revised diagnostics, novel biomarkers, and therapies targeting smouldering disease beyond traditional relapsing and progressive classifications.

Discontinuing first-line DMT in long-term stable MS led to significantly higher inflammatory disease recurrence, even in younger patients, highlighting risks and informing decisions on treatment cessation. Trial terminated early due to safety concerns.

Immune checkpoint inhibitors (ICIs) in multiple sclerosis (MS) show low relapse rates but higher neuroradiological activity, mainly in those discontinuing disease-modifying treatments, with events occurring within six months of therapy.

This review highlights the hypoxia-inflammation cycle's role in multiple sclerosis progression, its mechanisms, and potential therapeutic strategies targeting hypoxia-inducible factors, vascular issues, and inflammation to mitigate disease progression.