Investigating of Effects of e-Based Physical Exercise in Patients With Multiple Sclerosis and Comorbidity

Background Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). MS is a potentially disabling disease and occurs as a consequence of immune attacks on myelin and nerve fibers and may lead to neuronal damage (neurodegeneration) and consequently to the clinical accumulation of neurological disability. Over the last two decades, the age-specific prevalence of people with MS (pwMS) has increased, and aging may amplify the risk of comorbidities and conversion to a progressive disease course. Emerging evidence underscores the high prevalence of comorbidity in pwMS, evident even at the time of MS diagnosis. Comorbidities can lead to delayed MS diagnosis, accelerated disease progression, and diminished efficacy and safety of MS treatments, subsequently increasing mortality. Vascular comorbidities, in particular, are prevalent among MS patients, with risk factors including type 2 diabetes mellitus (T2DM), obesity, hyperlipidemia and hypertension.

Physical exercise (PE) is advocated as an effective treatment for at least 26 chronic diseases, including MS. In pwMS, PE has been shown to positively modulate peripheral inflammatory markers such as Tumour Necrosis Factor alpha (TNF alpha), interferon-gamma, Interleukin-4, interleukin-10, etc., and to reduce the rate of relapse. PE directly enhances muscle strength and cardiorespiratory fitness, as well as walking speed, endurance, and balance in MS patients. Furthermore, reductions in fatigue, symptoms of depression, and improvements in cognitive dysfunction and quality of life have been associated with PE in MS patients.

Despite the clear benefits of PE for MS patients, a significant proportion drop out or fail to maintain an active lifestyle post-rehabilitation. This tendency is a serious challenge for integrating and sustaining PE in the daily lives of individuals with MS. Consequently, the effectiveness of electronic health devices, or digital healthcare tools, in addressing the challenge remains an important area of interest. The effectiveness of new technology in MS rehabilitation, including telerehabilitation, has shown promising results in improving fitness, gait, balance, and upper limb function, often equaling or exceeding traditional methods.

It may be concluded that PE represents an effective therapeutic strategy for pwMS, however, further research is required to investigate PE's long-term impact on managing pwMS with comorbidities.

Study design This protocol delineates a prospective, longitudinal randomized controlled trial (RCT) aimed at evaluating the effects of an e-based PE intervention at home in addition to usual care on the disability progression of pwMS, both as an independent factor and in the context of comorbid conditions. Furthermore, an aim is to assess associations between PE and levels of inflammatory, metabolic, and neurodegenerative mediators and as well as clinical status, in pwMS with or without comorbidities.