Combined Whole-Body Cryotherapy and Exercise vs Exercise Alone for Lower Limb Strength and Mobility in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disease in which the immune system contributes to damage of the central nervous system []. Regardless of disease subtype, MS can result in increasing disability. The disease is characterized by a chronic inflammatory and demyelinating process driven by complex neuroimmunological mechanisms and is the leading cause of neurological disability and the second cause of disability, after injuries, in young adults [,]. MS can progress through relapses, with subsequent stages of exacerbation and remission, and can follow a secondary progressive or primary progressive course. However, regardless of the form, disability tends to increase []. The pathogenesis of MS is neuroimmunological in nature, encompassing autoimmune processes and secondary neurodegenerative mechanisms. Within the immune system, autoreactive T cells and B cells play a key role. Through the production of proinflammatory cytokines and autoantibodies, they initiate and sustain central nervous system (CNS) inflammation, leading to demyelination and axonal damage. This process is associated with dysfunction of the blood-brain barrier, which facilitates the migration of immune cells into neural tissue and the activation of microglia, which secrete cytotoxic mediators and chemokines. Chronic neuroimmune inflammation contributes to acute flares and the gradual progression of neurodegeneration, independent of flare activity. Multilevel immunological studies, encompassing immune cell signaling and their interactions with resident CNS cells, are currently the subject of intensive analysis in the context of the development of precise immunomodulatory therapies for MS []. The primary goal of rehabilitation for patients with MS is to improve muscle strength and overall physical fitness, compensate for coordination disorders, maintain a full range of active joint movements, normalize muscle tone, maintain balance, prevent muscle atrophy, and counteract fatigue [].