Publication
Research Article
Endurance training may worsen functional mobility and spasticity immediately post training for people with multiple sclerosis. Functional mobility returns to baseline within 60 minutes after training.
Background: People with multiple sclerosis (MS) occasionally report deterioration of motor function after endurance training. Endurance training is recommended to help manage MS symptoms, but its immediate impact on functional mobility and spasticity is not well understood. Therefore, the aim of this exploratory pre/post analysis was to investigate the immediate effects of a single bout of endurance training on a bicycle ergometer on functional mobility and lower extremity spasticity in people with MS.
Methods: Forty people with MS (21 men and 19 women; Expanded Disability Status Scale score ≤ 6.0) were randomly assigned to perform either a single bout of high-intensity interval training (HIIT) or moderate continuous training (MCT) on a bicycle ergometer. Functional mobility and spasticity were assessed using the Timed Up and Go (TUG), Numeric Rating Scale for Spasticity (NRS-S), and Modified Ashworth Scale (MAS) at 5 timepoints: before exercise, up to 5 minutes after exercise, at 60 minutes, 180 minutes, and 300 minutes after exercise.
Results: A significant decline in functional mobility, as measured by the TUG (P < .001), and an increase in spasticity, as measured by NRS-S (P = .01), were observed immediately after exercise in both groups. However, within 1 hour, TUG reverted to baseline, whereas NRS-S and MAS improved beyond baseline at 180 minutes post exercise.
Conclusions: The findings of this study can be used to reassure patients that acute, exercise-related symptom worsening is short-lived and to inform them about the time course to performance and symptom recovery to baseline, or even beyond.
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system through inflammatory and neurodegenerative processes.1 MS leads to a wide range of symptoms reflecting the multifocal lesions of the central nervous system, including muscle weakness, muscle spasticity, impaired gait, and fatigue.2
The evidence for beneficial chronic effects of exercise, like endurance training, in people with MS is indisputable,3,4 specifically among people with mild to moderate MS.5-7 Endurance training is a form of aerobic exercise that is performed through various activities, including walking, swimming, or cycling, and is commonly referred to as aerobic or cardiorespiratory training. Any concerns that exercise may increase the risk of relapses or lead to disease exacerbations have proven to be unwarranted.8,9 Instead, endurance training is a safe and effective nonpharmacological intervention for improving cardiorespiratory fitness, walking capacity, and fatigue in people with MS.8,10,11 Guidelines recommend at least 30 minutes of moderate intensity endurance training 2 or 3 times per week.12,13 In people with MS, endurance training on a cycle ergometer has traditionally been prescribed as moderate continuous training (MCT), characterized by sustained exercise at a moderate intensity corresponding to approximately 60% to 70% of peak oxygen uptake (VO₂peak).14 Recently, high-intensity interval training (HIIT) has become popular. HIIT involves short, intense bursts of exercise (90%-100% of VO2peak) interspersed with periods of active or passive rest.14,15 As an emerging exercise modality, studies investigating HIIT remain highly heterogeneous in their training protocols.15
The effects of both endurance training modalities on MS symptoms have been investigated, with studies showing improvements in functional mobility,15-18 spasticity,19 and walking.20 In contrast to the lasting or sustained effects of repeated bouts of endurance training in people with MS (ie, training), little is known about the acute effects of a single bout of endurance training on motor symptoms in people with MS.
Our clinical experience shows that in some people with MS, endurance training leads to a transient deterioration in motor function and leg spasticity immediately after the session, which quickly resolves and may even improve within a few hours. In line with this anecdotal evidence, a single exploratory study indicates that feelings of leg exertion may persist longer in people with MS compared with individuals without MS after a single session of endurance training.21 However, this study only observed participants until 45 minutes after stopping exercise. The immediate effects of endurance training on motor function and spasticity have not been systematically investigated. Therefore, the principal aim of this study was to investigate the immediate effects of a single bout of endurance training on functional mobility and leg spasticity, and to examine the time course of changes in these parameters in high resolution up to 300 minutes after exercise.
Study Design
The Transient and Immediate Motor Effects of Endurance Training in People With Multiple Sclerosis (TIME) Study is a substudy of the larger randomized controlled trial Cycling in Primary Progressive Multiple Sclerosis (CYPRO; registered at ClinicalTrials.gov on February 8, 2022 [NCT05229861]).22 The TIME study is an exploratory pre/post analysis aimed at evaluating the overall effects of a single bout of endurance training on functional mobility and spasticity in people with MS, rather than directly comparing HIIT and MCT. The study was approved by the Ethics Commission of Eastern Switzerland (EKOS, 2022-00122).
Setting
TIME was performed in the Rehabilitation Center Valens, Switzerland. People with MS entered the clinic for inpatient rehabilitation that included a personalized therapy program. This program consisted of physiotherapy, occupational therapy, and strength and endurance training as the standard of care. Depending on individual needs, people with MS could also receive additional therapies, such as robotic-assisted therapy, equine-assisted therapy, gait training, speech therapy, neuropsychological support, yoga, or other specialized treatments.
Participants and Recruitment
The recruitment process targeted people with primary progressive multiple sclerosis (PPMS) who were included in CYPRO.22 Recruitment was extended to include people with secondary progressive multiple sclerosis (SPMS). Written informed consent was obtained from all participants before their inclusion in the study. Participants were recruited on their first day of rehabilitation by a member of the research team who was independent of data collection and statistical analysis.
The CYPRO inclusion criteria were as follows: participants were adults (age ≥ 18 years) with a definitive diagnosis of PPMS consistent with the 2017 revised McDonald criteria2 and the 2013 Lublin criteria,23 and an Expanded Disability Status Scale (EDSS) score of 6.0 or less.24
CYPRO’s main exclusion criteria were comorbidities and other specific contraindications that would have hindered safe or adherent participation in endurance training. These also included severe leg spasticity (ie, leg spasticity too severe to permit cycling at > 50 revolutions per minute).
The deliberate inclusion of people with SPMS extended the scope of the research beyond the original CYPRO cohort, while maintaining identical inclusion and exclusion criteria. Details on the recruitment process are given in the CYPRO
study protocol.22
Endurance Training
All participants were randomly distributed into either HIIT or MCT. The group assignments originated from the main CYPRO trial. In the exploratory TIME substudy, these groupings were retained solely to align with the original trial’s structure and to avoid interference with its design and intervention. Random distribution for CYPRO was conducted by blinded investigators using Randomization In Treatment Arms (RITA; version 1.51, Evidat). Using a quasi-randomized approach, additional people diagnosed with SPMS were randomly assigned to either HIIT or MCT to ensure an even distribution and to avoid interference with the CYPRO randomization. All participants completed their training on a bicycle ergometer (Ergoline 800, Ergometrics), with sessions scheduled on Saturdays to avoid interfering with their regular therapy regimens. Participants who were recruited for the TIME study (ie, people with SPMS) received their usual care, including MCT, during their rehabilitation stay. TIME participants in the HIIT group received a single HIIT session.
For CYPRO participants, exercise intensities were prescribed based on peak heart rate (HRpeak) determined through a cardiopulmonary exercise test (CPET). Details of the CPET protocol can be found in the CYPRO protocol.22 For all additional participants, HRpeak was estimated as 210 minus age (in years).25
Participants performed a single bout of HIIT or MCT. During HIIT, participants performed six 1.5-minute intervals at 95% of HRpeak, interspersed with approximately 1.5 minutes of active recovery of unloaded pedaling, until their heart rate (HR) had decreased to 60% HRpeak. Exercise sessions began with a 2-minute low-intensity warm-up at 60% of HRpeak and ended with a 2-minute low-intensity cooldown of unloaded pedaling. HR was continuously monitored using chest strap sensors (Polar Electro Oy). Exercise intensity was monitored using both HR and Borg CR-10 rate of perceived exertion (RPE) scale.26 The use of RPE for monitoring exercise intensity has been shown to be valid and reliable in people with MS.27,28 During HIIT, participants were encouraged to reach an RPE of 8 to 10, whereas during MCT, the target RPE was 4 to 6. The duration of HIIT was approximately 26 minutes. MCT participants continuously cycled at 60% HRpeak for a total of 26 minutes. An overview of the training sessions is given in Figure 1.
Figure 1. Study Overview
Data Collection
Motor assessment occurred at 5 time points: 5 minutes before the start of the training session (T0), directly after cooldown (T1), and 60 minutes (T2), 180 minutes (T3), and 300 minutes (T4) after the single bout of endurance training (Figure 1). A blinded research assistant performed all motor assessments that were conducted in the fixed order of the Timed Up and Go (TUG), Numeric Rating Scale for Spasticity (NRS-S), and Modified Ashworth Scale (MAS). There was no rest period between the motor assessments.
Assessments and Measurements
Functional Mobility
Functional mobility was assessed using the TUG. Participants were asked to get up from a chair, walk 3 m, perform a 180° turn, return to the chair, and sit down again as quickly as possible.29 The time required to complete the test was measured in seconds using a stopwatch. A faster TUG performance indicated greater functional mobility. The TUG is widely used in clinical practice as it requires minimal equipment, space, and training.30 The TUG has been validated and shown to be a highly reliable tool (intraclass correlation coefficient [ICC] = 0.98) in people with MS.31
Spasticity
Lower-extremity spasticity was assessed with 2 measurements. First, self-reported leg spasticity was evaluated using the NRS-S, which ranges from 0, no spasticity, to 10, worst possible spasticity. The NRS was originally developed as a pain scale32 but is a commonly used and reliable tool (ICC = 0.83) for assessing spasticity.33
In addition to the NRS-S, an examiner used the MAS to assess spasticity of the knee and ankle flexors and extensors, as it is the most commonly used test to rate spasticity.34 The examiner passively stretched the respective muscle groups at a controlled speed and graded muscle tone on a 6-category ordinal scale (0, 1, 1+, 2, 3, 4). Examiners measured the knee flexors (hamstrings), knee extensors (quadriceps), ankle plantar flexors (primarily the gastrocnemius muscle and soleus muscle), and ankle dorsiflexors (primarily the tibialis anterior muscle), as these muscle groups are commonly affected by spasticity in people with MS, and they play a key role in lower limb function and mobility.35 Studies have demonstrated that the interrater reliability of the MAS for lower extremities is acceptable, with an ICC of 0.686, supporting its use as a clinically applicable measure of spasticity in populations with neurological diseases.36
Statistical Analysis
Normality was assessed through visual inspection of the data distribution; as the data deviated from normality, subsequent analyses were conducted using nonparametric statistical tests. Mean MAS knee and ankle spasticity scores were determined.37 Within-group changes over time were assessed using paired-sample Wilcoxon signed-rank tests for the T1-T0, T2-T1, T3-T2, T3-T0, and T4-T0 intervals, with Benjamini-Hochberg corrections for multiple testing applied to all outcomes.
NRS-S and MAS scores were analyzed separately for participants with spasticity present at baseline (NRS-S > 0 and MAS > 0 at T0) and for all participants regardless of baseline status. The analysis included calculating median MAS scores, enabling a quantitative assessment of the overall change in spasticity. In Table S1, an overview of the MAS values for the separate muscle groups is given (all supplemental materials are available in a PDF at the end of the online article).
A multifaceted approach was used to detect clinically relevant changes in TUG, NRS-S, and MAS scores. For TUG, no minimal clinically important difference (MCID) has been reported in the literature. A comparative sample of 256 persons, obtained from the inpatient database at the Valens clinic and meeting the inclusion criteria for this study, was used. Half an SD between TUG at admission and TUG at discharge was assumed to be a reasonable approximation for the MCID.38 In our case, this amounted to 2.92 seconds. We did not have comparable inpatient data records for the MAS and NRS-S, so MCID was set at 10%.39
All statistical analyses were performed in RStudio version 4.3.0 (Posit Software, PBC; R Core Team). Graphs were generated using GraphPad version 10.0.3 (GraphPad Software).
Baseline Characteristics
Forty people with MS were included in TIME. A detailed breakdown of participant characteristics can be found in Table 1. Table S2 contains the MCT and HIIT participant characteristics. All MCT participants completed 26 minutes of training. The average participant's HR was 71% of their HRpeak. All HIIT participants completed all 6 intervals. The average HR of the participants during the intervals was 93% of their HRpeak. No adverse events occurred during the exercise sessions.
Table 1. Participant Characteristics
Functional Mobility
All data presented as median (IQR) unless otherwise specified. A decline in functional mobility was observed immediately after training, as shown by an increase in the time to complete the TUG from T0 (9.9 s [range, 8-12.3]) to T1 (12.8 s [range, 9.6-18.2]) (adjusted [adj] P < .001; effect size [ES], 0.75). Of the participants, 40% showed a clinically relevant decline (> 2.92 s) in TUG performance from T0 to T1. In the overall study population, the initial decline was followed by a return to baseline values from T1 (12.8 s [range, 9.6-18.2]) to T2 (9.5 s [range, 8.0-12.5]) (adj P < .001; ES, 0.80), which persisted at T3 (9.3 s [range, 7.7-12.3]) (adj P = .338; ES: 0.17). A detailed overview can be found in Figure 2, Table 2, and Table 3.
Figure 2. Functional Mobility as Measured by TUG
Table 2. Outcome Scores Per Measurement Time Point
Table 3. Median Differences, P Values, and ES for TUG, NRS-S, and MAS
Self-Reported Spasticity
From T0 (4.0 [range, 2.0-6.5]) to T1 (7.0 [range, 3.5-8.0]), NRS-S scores rose significantly in participants who reported spasticity at baseline (NRS-S > 0), indicating an acute worsening of self-reported leg spasticity (adj P = .046; ES, 0.43). This significant increase was also observed among all participants (adj P = .009; ES, 0.46). Eighteen participants (45%) had a clinically relevant increase in NRS-S scores (at least 0.9 points) immediately after training. This increase was followed by a return to baseline at T2 (4.0 [range, 2.0-6.0]) that persisted and slightly improved at T3 (3.0 [range, 1.0-5.5]) (adj P = .049; ES, 0.47). Thirteen participants (32.5%) showed clinically relevant improvements from T0 to T4 (decrease of at least 0.9 points). For a more detailed overview, see Figure 3, Table 2, and Table 3.
Figure 3. Spasticity Measurements
Clinician-Assessed Spasticity
From T0 (0.4 [range, 0.1-0.7]) to T1 (0.4 [range, 0.3-0.8]), MAS scores did not increase significantly (adj P = .252; ES, 0.21). From T0 to T3, MAS scores significantly decreased in participants who had a MAS score of greater than 0 (adj P = .014; ES, 0.44). MAS scores of all participants were also significantly lower at T3 compared with T0 (adj P = .014; ES, 0.41). For a more detailed overview, see Figure 3, Table 2, and Table 3.
The aim of TIME was to assess the acute effects of a single bout of endurance training on functional mobility and spasticity in people with MS. Based on our observations in clinical practice, we hypothesized that in some people with MS, endurance training would cause a slight and transient deterioration in functional mobility and spasticity in the leg muscles, which would quickly resolve. Our findings confirm this hypothesis, indicating an initial decline in these parameters immediately after training. Yet both TUG performance and the severity of spasticity returned to baseline within 60 minutes. Notably, spasticity, as measured by NRS-S and MAS, showed improvements beyond baseline at
180 minutes after exercise (T3).
To our knowledge, this is the first study to assess the acute effects of endurance training on motor symptoms in people with MS until 300 minutes post exercise. The initial decline in functional mobility may be explained by greater leg muscle exertion and/or an increase in spasticity. Unfortunately, we did not assess leg muscle exertion. However, other research data show that feelings of leg exertion following endurance training may persist after session completion and resolve in an intensity-dependent manner for approximately 35 minutes after participating in HIIT and for 15 minutes after participating in MCT.21 Other data show that an increase in spasticity of the plantar flexors, as assessed using the MAS, is associated with reduced TUG performance. However, in our study, median MAS scores remained below 1, indicating that endurance exercise did not induce pronounced spasticity in our mildly spastic cohort. Moreover, changes in TUG performance might not be attributable solely to changes in spasticity and might be due to changes in 1 or more additional systems that determine functional mobility, such as balance.
Although the primary aim of TIME was not to directly compare HIIT and MCT, the observed acute responses may have been subtly influenced by training modality. For example, participants assigned to HIIT may have experienced slightly higher transient fatigue or neuromuscular challenge immediately post session, whereas MCT might have elicited more modest, rapidly resolving exertion effects. Nevertheless, in our study, the recovery trajectories for functional mobility and spasticity appear broadly similar across groups, suggesting that the acute beneficial and transient responses are generally consistent regardless of the type of endurance training. We have provided supplementary tables and figures to allow exploratory observation of potential modality-related patterns, offering additional context for readers interested in the differential effects of HIIT and MCT.
Study Limitations
Limitations must be considered when interpreting TIME findings.
Due to its exploratory nature, the study was conducted within a relatively small cohort, and no formal sample size calculations were performed. This limits the generalizability of the results.
HRpeak was determined using CPET for CYPRO participants; for TIME participants (ie, participants with SPMS), it was estimated with a formula (210 minus age in years). This difference may have introduced variability in exercise intensities between groups. However, to ensure that participants trained at the intended intensity, the Borg RPE was used in both exercise modalities. Based on RPE scores, participants reached the desired exercise intensities irrespective of group allocation or HR estimation methods.
As indicated by MAS values less than 1, TIME participants presented with very mild clinician-assessed spasticity.Therefore, any statement on a subacute exercise-related alleviation of spasticity at 300 minutes after training requires cautious interpretation. Future studies are needed to investigate similar acute and subacute changes in spasticity level in study cohorts presenting with moderate or severe spasticity at baseline.
The effect of neuroplasticity was not examined; Chaves et al reported that a single session of exercise is associated with acute changes in corticospinal excitability in people with MS, indicating potential short-term neurophysiological adaptations.40 Thus, the inclusion of neurophysiological markers such as transcranial magnetic stimulation–derived measures of corticospinal excitability and intracortical inhibition in this study might have offered complementary insights into the mechanisms underlying the observed transient changes in mobility and spasticity here.
There is increasing evidence that repeated TUG performances lead to learning effects, in which participants completing TUG become increasingly faster as a result of increased familiarity, confidence, and motor adaptation, as opposed to genuine changes in functional mobility. This has been
demonstrated in geriatric cohorts41 and may also apply to people with MS.
Participants were not familiarized with the MCT or HIIT protocols before testing, which may have influenced initial performance due to learning effects. TUG assessment, on the other hand, is performed in every patient upon admission to the clinic, so the cohort was already acquainted with the procedure.
Finally, muscle exertion was not directly assessed during the exercise sessions. While prior literature suggests that perceived exertion can contribute to transient declines in functional mobility, practical and logistical constraints prevented its measurement in this study. Finally, while no public patient investigator was directly involved, the research team carefully designed this study based on extensive prior experience working with people with MS, ensuring the relevance and applicability of the findings to this population.
Implications for Clinical Practice and Future Research
TIME provides valuable insights for clinicians, therapists, and patients regarding acute motor effects induced by a single bout of endurance exercise and the time course of changes during the subacute phase, defined here as the 180 minutes following exercise completion. Based on the results of this study, clinicians and therapists should counsel their patients to expect a temporary worsening of gait and leg spasticity immediately after training. However, it is crucial to reassure them that these symptoms resolve within 1 hour after exercise. In this sense, TIME’s results alleviate patients’ concerns about lasting motor deterioration from participating in (intense) exercise. Equipping people with MS with this knowledge will help them make informed decisions regarding their participation in endurance training. Future research should include a larger study cohort and investigate the comparative effects among different endurance training modalities. In addition, further studies are warranted to validate the findings and elucidate the underlying mechanisms of the initial deterioration in functional mobility and spasticity, as well as their subsequent improvement. Furthermore, as TIME focused solely on people with MS with PPMS or SPMS, a point of interest for future research is the effects of MCT and HIIT in other cohorts, specifically in people with relapsing-remitting MS.
A single bout of endurance training on a bicycle ergometer led to a short-term decline in functional mobility and leg spasticity immediately after training. Functional mobility resolved to baseline levels within 60 minutes. Furthermore, patient-reported leg spasticity might improve beyond baseline levels at 180 minutes after 1 bout of endurance training. The findings of this study can reassure people with PPMS and SPMS about the short-lived nature of acute, exercise-related symptom worsening and inform them about the time course to performance and symptom recovery to baseline, or even beyond.
Funding: This study was funded by the foundation Grenzen überschreiten, led by Christian Rusterholz. Additionally, this research was supported by the Swiss Multiple Sclerosis Society (Research Grant No. 2021-06). The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Conflicts of interest: The authors have declared no relevant conflicts
of interest.
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