ESTIM-UL: FES for Upper Limb Recovery After Stroke

Официальное название

Efficacy of Functional Electrical Stimulation (FES) Combined With Task- Oriented Training on Upper Limb Recovery in Post-Stroke Patients With Spastic Hemiparesis: A Randomized Controlled Trial

Обзор

Stroke is a leading cause of long-term disability, frequently resulting in impaired upper limb motor function and spasticity. Although Botulinum Toxin Type A (BoNT-A) is effective in reducing focal spasticity, functional recovery of the upper limb often remains limited without intensive, task-specific rehabilitation. Functional Electrical Stimulation (FES), when synchronized with voluntary movement during Task-Oriented Training, may enhance motor recovery by facilitating muscle activation and neuroplasticity. This randomized controlled trial aims to evaluate whether FES combined with Task-Oriented Training is superior to conventional Task-Oriented Training alone in improving upper limb function in post-stroke patients treated with BoNT-A.

Подробное описание

Stroke remains one of the leading causes of long-term disability worldwide. Among its most disabling and persistent sequelae is impairment of upper limb motor function, affecting approximately 50-80% of stroke survivors in the acute phase and persisting in a substantial proportion of patients over time. Incomplete recovery of manual dexterity and fine motor control significantly limits independence in activities of daily living and negatively impacts quality of life. A major factor limiting upper limb recovery after stroke is the development of spasticity, a sensorimotor disorder resulting from upper motor neuron lesions. Upper limb spasticity typically evolves toward pathological flexor synergies which, if left untreated, lead to increased muscle tone, altered muscle-tendon properties, soft tissue shortening, and fixed joint deformities. These changes interfere with voluntary motor control, functional use of the limb, hygiene, and caregiving.

Current international guidelines identify focal injection of Botulinum Toxin Type A (BoNT-A) as the first-line treatment for focal upper limb spasticity. By blocking presynaptic acetylcholine release at the neuromuscular junction, BoNT-A induces a temporary chemical denervation that effectively reduces muscle overactivity. However, clinical experience and scientific evidence consistently demonstrate a frequent dissociation between technical success, defined as reduction in spasticity scores, and functional success, defined as improved active use of the upper limb. Reduction of muscle tone alone, although necessary, is not sufficient to restore voluntary motor control in a damaged central nervous system unless it is integrated into an intensive neuromotor rehabilitation program.

This observation has led to the concept of a "therapeutic window," in which BoNT-A reduces peripheral biomechanical resistance, creating favorable conditions that must be exploited through targeted adjunctive rehabilitation therapies. Among these, Task-Oriented Training (TOT), based on repetitive and intensive practice of meaningful functional tasks, represents one of the most effective approaches to promote post-stroke neuroplasticity.

Nevertheless, in patients with moderate to severe paresis, insufficient voluntary muscle activation often limits the effective execution of task-oriented exercises.

In this context, Functional Electrical Stimulation (FES) emerges as a key rehabilitative technology. Beyond inducing muscle contraction through peripheral nerve stimulation, FES acts as a powerful modulator of cortical plasticity. When synchronized with the patient's voluntary movement attempts, FES provides enhanced somatosensory feedback to the sensorimotor cortex. The coupling of motor intention, assisted execution, and afferent feedback reinforces synaptic connections according to Hebbian learning principles. Despite a strong neurophysiological rationale, there remains a lack of rigorous randomized controlled trials quantifying the specific added value of FES when combined with task- oriented rehabilitation in patients treated with BoNT-A. The present study is based on the hypothesis that applying FES to wrist and finger extensor muscles during Task-Oriented Training, in post-stroke patients previously treated with BoNT-A to inhibit spastic flexor muscles, produces a synergistic effect superior to conventional task-oriented rehabilitation alone. By simultaneously reducing spasticity-related resistance and enhancing muscle recruitment and cortical plasticity, this multimodal approach is expected to result in greater improvements in manual dexterity and overall upper limb function.

Вмешательства

• Устройство Functional Electrical Stimulation (FES)
  Functional Electrical Stimulation is applied to wrist and finger extensor muscles of the paretic upper limb using a surface electrode system. Electrical stimulation is synchronized with the participant's voluntary movement attempts during Task-Oriented Training to facilitate active motor execution and sensorimotor integration. Stimulation is delivered during 60-minute rehabilitation sessions, 5 days per week for 2 consecutive weeks.
• Другое Conventional Rehabilitation
  Conventional rehabilitation consists of therapist-assisted Task- Oriented Training of the paretic upper limb, including manual facilitation and guidance as needed to support task execution. No electrical stimulation is applied. Sessions last 60 minutes and are performed 5 days per week for 2 consecutive weeks.

Первичные конечные точки

• Change in Gross Manual Dexterity [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]

Вторичные конечные точки (5)

• Fine Manual Dexterity [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]
• Upper Limb Muscle Strength [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]
• Upper Limb Muscle Tone [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]
• EQ-5D-5L Index [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]
• EQ-5D Visual Analogue Scale (VAS) [Срок оценки: Baseline (T0, prior to randomization) to Post-Treatment (T1, within 24-48 hours after completion of the 2-week rehabilitation program)]

Критерии участия

Критерии включения

• Age 18 years or older.
• Diagnosis of ischemic or hemorrhagic stroke, documented by CT or MRI.
• Clinical presence of focal upper limb spasticity, defined as a score ≥ 1+ on the Modified Ashworth Scale (MAS) in at least one target muscle group (elbow, wrist, or finger flexors), treated with Botulinum Toxin Type A injection.
• Presence of residual voluntary muscle activation (minimal active movement) sufficient to initiate the motor task required by the training (Box and Block score > 1).
• Preserved cognitive function, defined as a Mini-Mental State Examination (MMSE) score ≥ 24 or clinical judgment confirming adequate comprehension and cooperation.

Критерии исключения

• Absolute contraindications to Functional Electrical Stimulation (FES), including the presence of a cardiac pacemaker or implantable cardioverter defibrillator (ICD), pharmacologically uncontrolled epilepsy, or skin lesions/dermatitis at the electrode application sites.
• Presence of severe muscle-tendon contractures or fixed joint deformities (ankylosis) that mechanically limit passive movement and make active functional recovery unlikely.
• Severe cognitive impairment, global aphasia, or severe unilateral spatial neglect that prevents task comprehension or active participation in the training program.
• Concomitant orthopedic or rheumatologic conditions affecting the upper limb (e.g., recent fractures, severe arthritis) that could interfere with treatment delivery or outcome assessment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• Università degli studi di Foggia — Foggia

Публикации

• Timmermans AA, Seelen HA, Willmann RD, Kingma H. Technology-assisted training of arm-hand skills in stroke: concepts on reacquisition of motor control and therapist guidelines for rehabilitation technology design. J Neuroeng Rehabil. 2009 Jan 20;6:1. doi: 10.1186/1743-0003-6-1. PMID 19154570
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• Reebye R, Jacinto LJ, Balbert A, Biering-Sorensen B, Carda S, Draulans N, Molteni F, O'Dell MW, Picelli A, Santamato A, Verduzco-Gutierrez M, Walker H, Wissel J, Francisco GE. Multimodal therapy and use of adjunctive therapies to BoNT-A in spasticity management: defining terminology to help enhance spasticity treatment. Front Neurol. 2024 Aug 30;15:1432330. doi: 10.3389/fneur.2024.1432330. eCollec PMID 39281409
• Chen HM, Chen CC, Hsueh IP, Huang SL, Hsieh CL. Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke. Neurorehabil Neural Repair. 2009 Jun;23(5):435-40. doi: 10.1177/1545968308331146. Epub 2009 Mar 4. PMID 19261767
• Kwakkel G, van Wegen EEH, Burridge JH, Winstein CJ, van Dokkum LEH, Alt Murphy M, Levin MF, Krakauer JW; ADVISORY group. Standardized Measurement of Quality of Upper Limb Movement After Stroke: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2019 Nov;33(11):951-958. doi: 10.1177/1545968319886477. Epub 2019 Oct 29. PMID 31660781
• Eraifej J, Clark W, France B, Desando S, Moore D. Effectiveness of upper limb functional electrical stimulation after stroke for the improvement of activities of daily living and motor function: a systematic review and meta-analysis. Syst Rev. 2017 Feb 28;6(1):40. doi: 10.1186/s13643-017-0435-5. PMID 28245858
• Picelli A, Santamato A, Chemello E, Cinone N, Cisari C, Gandolfi M, Ranieri M, Smania N, Baricich A. Adjuvant treatments associated with botulinum toxin injection for managing spasticity: An overview of the literature. Ann Phys Rehabil Med. 2019 Jul;62(4):291-296. doi: 10.1016/j.rehab.2018.08.004. Epub 2018 Sep 13. PMID 30219307
• Mills PB, Finlayson H, Sudol M, O'Connor R. Systematic review of adjunct therapies to improve outcomes following botulinum toxin injection for treatment of limb spasticity. Clin Rehabil. 2016 Jun;30(6):537-48. doi: 10.1177/0269215515593783. Epub 2015 Jul 21. PMID 26198891

Идентификаторы

NCT: NCT07513714 · FoggiaFisiatria02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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