Effects of Neuromuscular Electrical Stimulation Combined With Ultrasound on Stroke Patients With Sarcopenia

Background: Stroke is a leading cause of disability worldwide. Sarcopenia, characterized by loss of muscle mass and function, is a common complication after stroke, with a prevalence of approximately 46.7% within the first six months. Post-stroke sarcopenia significantly impairs patients' ability to walk independently, maintain balance, and perform daily activities. Current interventions primarily include exercise, physical therapy, and nutritional support, but these approaches have limitations, particularly for elderly patients who cannot tolerate vigorous exercise due to comorbidities or disability.

Therapeutic ultrasound (UT) is a non-invasive, safe, and cost-effective modality that promotes tissue regeneration and muscle repair through mechanical vibration and increased growth factor secretion. Neuromuscular electrical stimulation (NMES) induces involuntary muscle contraction, preventing disuse atrophy, preserving muscle thickness, and promoting protein synthesis. However, no study has systematically compared UT and NMES, or their combination, specifically in stroke-related sarcopenia.

Objective: This study aims to (1) compare the efficacy of UT versus NMES in improving muscle mass, strength, and physical function in stroke patients with sarcopenia; (2) evaluate whether combined UT and NMES therapy produces synergistic effects superior to either monotherapy; and (3) explore the potential mechanisms of action.

Study Design: This is a prospective, single-center, randomized, single-blind controlled trial. Eligible participants will be randomly assigned in a 1:1:1:1 ratio to one of four groups: (1) conventional rehabilitation alone (control), (2) UT + conventional rehabilitation, (3) NMES + conventional rehabilitation, or (4) combined UT + NMES + conventional rehabilitation. The intervention period is 4 weeks, with assessments performed at baseline and immediately after the intervention.

Sample Size: Based on prior literature (α = 0.05, 1-β = 0.80, effect size = 0.25), accounting for a 10% dropout rate, the total sample size is 152 participants (approximately 38 per group).

Interventions:

Conventional rehabilitation: Exercise therapy (30 min) and occupational therapy (30 min), twice daily, 6 days/week for 4 weeks.

UT group: In addition to conventional rehabilitation, UT (1 MHz, 0.5-0.8 W/cm², 20 min, 2 sessions/day, 6 days/week) applied to the affected wrist extensors and quadriceps.

NMES group: In addition to conventional rehabilitation, NMES (50 Hz, 300μs pulse width, intensity adjusted to visible muscle contraction, 20 min, 2 sessions/day, 6 days/week) applied to the same muscle groups.

Combined group: Both UT and NMES in addition to conventional rehabilitation.

Outcome Measures:

Primary outcomes: Muscle mass (muscle thickness via musculoskeletal ultrasound), muscle strength (handgrip strength, isokinetic torque), and physical function (Fugl-Meyer Assessment, Functional Independence Measure, modified Rankin Scale, balance, and gait tests).

Secondary outcomes: Surface electromyography (RMS and iEMG), Hamilton Depression Scale, and safety/adverse event monitoring.

Statistical Analysis: Data will be analyzed using SPSS 26.0. Intention-to-treat analysis will be applied. Between-group comparisons will use one-way ANOVA with post-hoc tests (LSD/Bonferroni), within-group changes will use paired t-tests, and correlation analyses will explore relationships between muscle mass improvement and functional recovery.

Ethics and Dissemination: The study has been approved by the Ethics Committee of Nanjing First Hospital (Approval Number: KY20250425-12). All participants will provide written informed consent. Results will be disseminated through peer-reviewed publications and conference presentations.

Inclusion criteria

• Diagnosis of first-ever stroke confirmed by CT or MRI, with stable vital signs, disease course between 3 weeks and 6 months.

Diagnosis of sarcopenia according to the 2019 Asian Working Group for Sarcopenia (AWGS) criteria: reduced handgrip strength (male < 28 kg, female < 18 kg) and/or gait speed < 1.0 m/s, and reduced appendicular skeletal muscle mass index (male < 7.0 kg/m², female < 5.4 kg/m²).

Age between 30 and 75 years.

Brunnstrom stage of affected upper and lower limbs ≥ III, and modified Ashworth scale ≤ 2.

No significant consciousness or cognitive impairment.

Willing and able to provide written informed consent.

Exclusion criteria

• Presence of significant emotional or cognitive impairment.

Obesity or overweight (body mass index > 25 kg/m²).

Unable to stand up from a chair with or without assistance.

Comorbidities including renal, hepatic, or heart failure.