Inductive Therapeutic Exercise in Multiple Sclerosis

Scientific rationale. ETOTUR combines the development of an accessible biomechanical assessment tool with an exploratory investigation of Inductive Therapeutic Exercise (ETI, from its Spanish name) in multiple sclerosis. The project addresses two related research needs: obtaining reproducible quantitative measurements of limb pendular behavior and investigating whether an intervention intended to elicit involuntary neuromuscular responses can influence muscle tone, postural control, and health-related quality of life. The rationale for the measurement component is to complement clinical assessment with instrumented recordings that can be obtained using portable technology. The pendulum test characterizes the movement of a relaxed limb after release, including its initial excursion and subsequent oscillations. ETOTUR will investigate whether a mobile tool can capture these features consistently and with sufficient agreement with laboratory reference systems to support its intended research use. The therapeutic component investigates ETI as an approach combining specific active movements, positioning, and breathing patterns to elicit neuromuscular responses beyond the body region performing the voluntary movement. The working hypothesis is that these responses may influence tonic and postural regulation. This proposed mechanism provides the rationale for the intervention but is not considered established, and the clinical study is not designed to demonstrate the underlying neurophysiological mechanism directly. Relationship between the two studies. The project comprises two sequential studies with distinct populations and objectives. Study 1 is an observational, cross-sectional measurement-validation study in healthy adults. Study 2 is a pilot, nonrandomized, controlled intervention study in adults with multiple sclerosis. The methodological study will inform the subsequent clinical use of the measurement tool. The healthy participants will provide measurement-validation data and preliminary reference values; they will not constitute a treatment comparison group for participants with multiple sclerosis. Analyses will be conducted separately for each study. The clinical intervention study is the focus of this trial registration. The preparatory validation study is described here to explain the development of the assessment approach and its role within the wider ETOTUR project. Study 1: development and measurement validation. The first study will develop and evaluate a mobile assessment system for upper- and lower-limb pendulum testing, incorporating portable inertial sensing. Measurements will be compared with laboratory reference recordings obtained using three-dimensional optical motion capture and high-precision triaxial accelerometry, as appropriate to the measurement being evaluated. Standardized positioning, calibration, synchronization, and limb-release procedures will be used to reduce avoidable variation. Repeated recordings will allow assessment of measurement consistency under the study conditions. The analysis will distinguish reliability from agreement between systems. Intraclass correlation coefficients will characterize reliability, while agreement analyses, including Bland-Altman methods, will examine systematic differences and the dispersion of differences between the mobile tool and the reference systems. Correlation analyses will provide complementary information about associations between measurements. The study will also describe the distribution of pendulum-test measurements in the healthy sample. Demographic and anthropometric characteristics will be considered when exploring variation in these measurements. The resulting reference values will be regarded as preliminary and specific to the population and procedures studied. Validation in healthy adults will provide initial evidence about measurement performance. It will not, by itself, establish diagnostic accuracy for neurological disorders or demonstrate that all measurement properties are preserved in people with abnormal muscle tone. These limits will be considered when interpreting the subsequent clinical findings. Study 2: exploratory clinical evaluation. The second study will investigate whether changes following ETI differ from those following a simulated intervention. The sham comparison is intended to account partly for therapist attention, interpersonal interaction, and expectations associated with receiving treatment. The intervention is individualized within a standardized framework, with maneuver selection informed by the participant's initial postural assessment. The therapeutic rationale involves eliciting responses in the lower limbs through maneuvers performed in another limb, supported by the breathing pattern specified for ETI. The sham intervention preserves external similarities while omitting the principal components intended to produce induction. Group assignment will use a sequential balancing procedure that considers relevant baseline characteristics. This approach seeks to improve initial comparability but does not constitute randomization or eliminate the possibility of selection bias and residual confounding. To reduce variation related to treatment delivery, the treating physiotherapists will follow agreed protocols and each will provide interventions in both groups. Outcome assessment will be performed by a physiotherapist who is not involved in intervention delivery and is unaware of group assignment. Treating physiotherapists cannot be blinded to the procedures they deliver. Interpretation and analytical approach. The clinical analysis will examine changes over time and differences in change between groups. Longitudinal analyses will consider intervention group and assessment time, with methods selected according to the characteristics of the data and the assumptions of the statistical models. Effect sizes will complement significance testing to characterize the magnitude of observed differences. Exploratory analyses will examine whether the neuromuscular responses recorded during treatment are associated with changes in biomechanical, postural, or patient-reported outcomes. Such associations will be interpreted as hypothesis-generating and will not establish a causal mechanism. Session completion, perceived effort, and recorded clinical incidents will inform the assessment of feasibility and tolerability. These findings will help determine whether the intervention and assessment procedures are suitable for a larger study and which aspects require refinement. Given the pilot sample, nonrandom allocation, and short follow-up period, the clinical findings will be interpreted as preliminary. The project is intended to provide initial measurement evidence, estimates of possible treatment effects, and practical information for planning subsequent confirmatory research.