Regular Exercise Improves Physical Capacity and Promotes Neurotrophins in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis; Exercise Intervention; Neuro-Degenerative Disease
MeSH terms: Multiple Sclerosis; Neurodegenerative Diseases; Sclerosis
Study type: Interventional

Summary: 
      ABSTRACT

      Objective:

      The investigators aimed to determine the effect of regular exercise on aerobic capacity,
      strength values, and plasma levels of nerve growth factor (NGF) and Neurotrophin-3 (NT-3) in
      patients with multiple sclerosis (MS), and investigate its effects on MS symptoms including
      cognitive impairment, fatigue, balance disorders and quality of life.

      Methods:

      Forty-three relapsing-remitting MS (RRMS) patients with an EDSS score of 4 or less
      participated in the study. Participants were divided into 3 groups as aerobic exercise,
      strength exercise and control groups. The patients in the exercise groups had exercise
      programs 3 days a week, for 3 months. Aerobic capacity (maximum VO2 value), strength
      measurements and balance tests were done, and NGF and NT-3 plasma levels were analyzed in all
      participants at the beginning and end of the study. MSQoL54 quality of life, fatigue impact
      scale (FIS), Pittsburgh Sleep Quality Index (PSQI) and BICAMS scale were applied to evaluate
      cognitive functions.
    

Detailed description: 
      INTRODUCTION Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder
      characterized by inflammation, demyelination, axonal damage and gliosis, particularly
      affecting white matter, and also gray matter 1. It is the most common disorder of the central
      nervous system (CNS) that causes neurological disability in young adults. Various degrees of
      physical and cognitive impairments are seen starting in the early period, and particularly in
      the progressive course of the disease 2.

      Physical inactivity may lead to progressive muscle atrophy in MS patients due to insufficient
      neural stimulation to the muscles 6. In MS patients, maximal oxygen consumption (VO2 max),
      which is a marker of cardiorespiratory fitness and functional performance, has been shown to
      decrease 7. All of these conditions may lead to worsening of MS symptoms and fatigue, which
      may result in a vicious cycle and cause reduced physical activity and an impairment in
      quality of life.

      Exercise has numerous neurobiological effects, including anatomical and physiological changes
      in the brains of healthy and unhealthy individuals 8. Exercise provides comprehensive
      alterations in cerebrovascular structures such as blood flow, nutrient delivery, development
      of angiogenesis and regeneration of blood vessels 9. These alterations facilitate
      neurogenesis, increase synaptic plasticity, and ultimately may improve brain health and
      MS-related symptoms 9. Neurotrophins (NT) are growth factors that provide the survival and
      hypertrophy of neurons, as well as neurogenesis and synaptic plasticity 10. They are
      synthesized by a number of cell types including peripheral nervous system neurons, peripheral
      tissues, and particularly in the CNS 11,12. It is believed that exercise activates molecules
      and cellular cascades that support and maintain brain plasticity, facilitates neurogenesis,
      and thus may be effective in neurodegenerative processes and cognitive disorders 13.

      In this study, the investigators aimed to investigate the effect of regular exercise on
      aerobic capacity and strength values, and to determine whether exercise contributes to the
      improvement of cognitive, balance, and sleep disorders and fatigue, and quality of life in MS
      patients. The investigators also investigated post-exercise changes in the plasma levels of
      neurotrophins, nerve growth factor (NGF) and neurotrophin-3 (NT-3), which are important
      biomarkers in neural regeneration and re-myelination.

      MATERIAL AND METHODS Study design A total of 53 relapsing remitting form MS (RRMS) patients
      between the ages of 18-55 years, diagnosed with definite MS according to 2017 McDonald
      criteria, and followed up in Ege University MS and Demyelinating Diseases Unit, without an MS
      attack in the last 3 months, had an EDSS score ≤ 4 that did not change with symptomatic or
      immunomodulatory treatments within 6 months were included in this prospective randomized
      controlled study. The procedures and possible side effects (such as exercise-related injuries
      and having an MS attack) were explained in detail to each participant candidate, and the
      "Informed Consent Form" was signed by the volunteers. "Ege University Clinical Research
      Ethics Committee" approved the study protocol (date: Apr 03, 2019, decree no: 19-4T/43).

      The patients who participated in the study and wished to be included in the exercise group
      were randomly allocated to the aerobic exercise and strength exercise groups. The patients
      who didn't want to exercise were included in the control group. Four patients in the aerobic
      group and 6 patients in the strength group could not complete the study due to reasons such
      as knee pain (1), not attending exercise sessions regularly (8), and not attending control
      measurements (1).

      Exercise Procedures:

      The patients in the exercise groups carried out tailor-made exercise programs, under the
      supervision of a faculty member of the Faculty of Sports Sciences. It was paid attention to
      keep the temperature of the exercise room at 20°C. The control patients did not participate
      in any exercise or physical activity program.

      In the first month, the patients in the aerobic group started to exercise at a heart rate
      corresponding to 60% of the maximal VO2, by adjusting the pedal resistance of the exercise
      bike, consistent with the Karvonen formula. This was followed by exercise cycling at a heart
      rate corresponding to 70% of maximal VO2 in the second month, and 80% of maximal VO2 in the
      third month, for 30 minutes, 3 days a week (Figure 1) 14.

      The patients included in the strength exercise group performed weight training exercises
      involving 10 large muscle groups (leg press, chest press, leg curl, lateral pull down, leg
      extension, dumbbell lateral raise, calf press, upright row, sit up, quadruped arm opposite
      leg raise), 3 days a week; including 1 set of 12-15 repetitions in the first month, 2 sets of
      12-15 repetitions in the second month, and 3 sets of 12-15 repetitions in the third month.
      Participants' working weights were set as 60% of the maximum weight they could lift.
    

Intervention name(s): Regular Exercise
Intervention type(s): Behavioral
Intervention description(s): the third month, for 30 minutes or 1 hour, 3 days a week
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized prospective study
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: multiple sclerosis; exercise; nerve growth factor; neurotrophin 3; cognition; quality of life