Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the central nervous system (CNS). While the inflammatory components of MS have been extensively studied, the progressive neurodegenerative aspect remains a critical factor contributing to long-term disability. Therefore, the identification and validation of biomarkers associated with neurodegenerative processes are essential for improved diagnosis, prognosis, and treatment monitoring. This review explores cerebrospinal fluid (CSF) and blood-based biomarkers, including neurofilaments, lipid markers, kynurenines, and other molecular indicators that provide insights into neurodegeneration in MS.

Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder with increasing global prevalence. Emerging evidence underscores the role of lifestyle interventions (particularly diet and physical activity) in modulating disease progression and improving quality of life. This narrative review synthesizes current scientific literature on the effects of dietary interventions, including the Mediterranean, ketogenic, Swank, Wahls, gluten-free, and fasting-based diets, alongside various physical activity regimens. The Mediterranean and ketogenic diets show promise in reducing inflammation, enhancing neuroprotection, and improving metabolic health. Similarly, structured physical activity (including aerobic, resistance, sensorimotor, and mind–body exercises) demonstrates benefits in mobility, fatigue, and mental well-being. The review highlights the need for personalized, sustainable approaches that integrate nutritional and exercise-based strategies for optimal MS management in the long term.

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies.