Effects of Resistance Exercises in Hereditary Sensory-Motor Neuropathy (Charcot-Marie-Tooth Disease)

Measurements will be performed on the tibialis anterior muscle of both lower limbs using ultrasonography (GE Logiq e BT11, General Electric, Boston, MA, USA) with a 10-MHz linear transducer by an evaluator experienced in muscle ultrasound analysis. For the assessment, participants will be positioned in a seated posture with knees flexed in neutral position and feet supported without footwear. The head of the fibula and the center of the lateral malleolus will be used as anatomical landmarks, where the total length will be measured and divided into three portions. Measurements will be obtained with the transducer placed transversely on the muscle belly located in the upper third of the distance measured between the two aforementioned bony landmarks. The analysis of muscle architecture will be performed using the public-domain software NIH ImageJ. This quantification will also be carried out by a blinded evaluator.

Blood samples will be collected in the morning after a 12-hour fasting period from a superficial vein in the cubital fossa. Samples will be obtained on the first evaluation day (1 week before starting training) and 48 hours after the final training session. They will be drawn into serum-separator tubes without anticoagulant, centrifuged at 2500 rpm for 15 minutes, and the resulting serum will be aliquoted into microtubes and stored at -80 °C for subsequent analysis of Creatine Kinase levels.

Total and regional lean body mass will be assessed by bioelectrical impedance analysis (HBF-514C, Omron©, Japan) after overnight fasting, with participants standing. Lean body mass will be expressed in kilograms (kg) and as a percentage of total body mass (%).

anthropometric measurements will include body weight measured in kilograms (Kg), height, waist to hip, chest, thigh, and calf circumferences, as well as knee height and leg length mesuared in milimiters (mm). Weight and height will be obtained with a SECA® platform scale and stadiometer (Madison, WI, USA), while circumferences will be measured with a retractable SECA® measuring tape at standardized anatomical landmarks. Weight and height will be combined to report BMI in kg/m^2

Oxygen consumption (VO₂) will be measured during the 6-Minute Walk Test (6MWT) using a portable metabolic analyzer (PNOE, ENDO Medical, Palo Alto, CA). Breath-by-breath respiratory gas exchange kinetics will be recorded, while heart rate will be continuously monitored with an ECG-activated POLAR® chest strap (Finland). VO₂, VCO₂ and tidal volume, be assessed via a face mask equipped with a flow sensor and gas analyzer with minimal dead space (<70 ml). Data will be transmitted in real time to a laptop through a harness-secured system, enabling continuous monitoring throughout the tests.

Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) will be assessed using a portable handheld spirometer (MicroRPM, Micro Medical/CareFusion, Kent, UK). Measured in centimeters of water (cmH₂O)

Handgrip strength will be measured using a JAMAR dynamometer (model BK-7498, Fred Sammons, Inc., Burr Ridge, IL) for both upper limbs. Each hand will be tested three times with a 30-second rest between trials, and the highest value from the six attempts will be recorded

This will be assessed using the Sit-to-Stand Test (STST). The participant will sit on a chair with arms crossed over the chest and, upon the command 'ready, go,' will stand up and sit down as many times as possible within 1 minute. The total number of repetitions will be recorded.

Upper-limb strength will be assessed with the 30-s Arm Curl Test using a dumbbell (2.5 kg for women, 3.5 kg for men), recording the number of full elbow flexion-extension repetitions completed in 30 seconds

Maximal voluntary isometric strength of the ankle dorsiflexors will be assessed bilaterally using a force transducer (Load Cell -500 lb, Sensortronics, USA). After a 5-minute ankle mobility warm-up, participants will be seated with the trunk supported, hip at 90°, knee extended, and foot perpendicular to the transducer. The best of three maximal dorsiflexion trials, performed at high speed with verbal encouragement, will be recorded.

This will be assessed using the Heel Raise Test. The participant will stand facing a platform or step, keeping the body upright and feet parallel with the forefoot placed on the platform edge, while supporting themselves on the wall with both hands. They will be instructed to rise onto the toes as many times as possible within 30 seconds, and the total number of repetitions will be recorded.

Maximal strength will be determined through a one-repetition maximum (1RM) test for the lower limbs using leg press and knee extension machines (TuffStuff Fitness International), as well as free weights for ankle dorsiflexion and plantarflexion exercises

Blance and Gait will be assessed with the Tinetti Performance-Oriented Mobility Assessment (POMA), which includes 22 items divided into gait (12 points) and balance (16 points), for a total of 28 points. Scores of 19-24 indicate minimal fall risk, while scores <19 indicate high fall risk.

Health-related quality of life will be assessed with the SF-36, a validated 36-item questionnaire covering 8 domains and 2 summary components (Physical Component Summary and Mental Component Summary). Scores range from 0 to 100%, with higher scores indicating better quality of life.

The International Physical Activity Questionnaire (IPAQ) assesses physical activity levels across four domains: work, domestic, transport, and leisure time. Physical activity is expressed both continuously, in metabolic equivalent (MET)-minutes/week, and categorically, classifying activity level as low, moderate, or high. METs provide a way to estimate energy expenditure as multiples of basal metabolic rate, and the unit used, MET-minutes, is calculated by multiplying the MET value of an activity by the minutes performed per day or per week. In this study, results will be expressed in MET-minutes/week.