Phenol and Botulinum Toxin vs Botulinum Toxin Alone for Post-Stroke Upper-Limb Spasticity

Официальное название

Combined Phenol and Botulinum Toxin vs Botulinum Toxin Alone for Upper-Limb Spasticity After Stroke: A Randomized Trial

Обзор

This study aims to evaluate the efficacy of a combined treatment approach for post-stroke upper limb spasticity using phenol neurolysis and botulinum toxin (BoNT). Spasticity is a common post-stroke complication that leads to muscle stiffness and significantly hinders functional recovery. While botulinum toxin is the standard treatment, its high cost often limits its application, particularly for large proximal muscles. The researchers will compare two treatment strategies in 60 adult stroke survivors: Group A (Combined Therapy): Patients will receive ultrasound-guided phenol neurolysis for the proximal nerves (pectoralis and musculocutaneous nerves) and botulinum toxin for the distal forearm flexors. Group B (Standard Care): Patients will receive botulinum toxin alone for all affected muscles in the upper limb. All procedures will be performed under ultrasound guidance to ensure anatomical precision. The study will also utilize Transcranial Magnetic Stimulation (TMS) to assess changes in cortical excitability (RMT, MEPs, and cortical silent period). The primary goal is to determine if this combined approach effectively reduces muscle stiffness (measured by the Modified Ashworth Scale) while potentially reducing the total dose of botulinum toxin required per patient.

Подробное описание

Background and Rationale:

Post-stroke spasticity is a manifestation of Upper Motor Neuron Syndrome, characterized by reduced cortical inhibition and maladaptive plastic changes in both the ipsilesional and contralesional hemispheres. While Botulinum Toxin Type A (BoNT-A) provides focal chemodenervation, its effect on central neurophysiology is an area of active research. This study evaluates a hybrid approach-proximal Phenol neurolysis combined with distal BoNT-A-compared to standard BoNT-A alone. By utilizing Transcranial Magnetic Stimulation (TMS), we aim to investigate how reducing peripheral spasticity influences central motor excitability and interhemispheric inhibition.

Methodology and Procedures:

Participants (n=60) will be randomized 1:1 into:

Group A (Hybrid): Ultrasound-guided Phenol neurolysis (5% aqueous) of the pectoralis and musculocutaneous nerves + distal BoNT-A.

Group B (Standard): Ultrasound-guided BoNT-A for all affected upper limb muscles.

Bilateral TMS Assessment \& Rationale:

Single-pulse TMS will be performed on both the ipsilesional and contralesional hemispheres to evaluate the entire motor network.

Ipsilesional Assessment: To measure corticospinal integrity via Resting Motor Threshold (RMT) and Motor Evoked Potential (MEP) amplitude.

Contralesional Assessment: To evaluate compensatory over-activity or maladaptive plasticity.

Rationale: the investigators hypothesize that effective reduction of spasticity via the hybrid approach will lead to a reduction in the Cortical Silent Period (CSP) and a shift toward normalized interhemispheric balance, potentially reflecting decreased "noise" from the spastic periphery to the cortex. If the ipsilesional MEP is absent, the contralesional hemisphere's excitability will serve as the primary neurophysiological marker.

Assessment Time Points:

All participants will undergo a comprehensive battery of assessments (Clinical, Functional, and Neurophysiological) at three specific intervals:

T0 (Baseline): prior to injection. T1 (Early Follow-up): 4 weeks post-injection (to capture peak BoNT-A and Phenol effect).

T2 (Late Follow-up): 12 weeks post-injection (to assess the sustainability of the clinical effect and central plastic changes).

Functional \& Clinical Outcomes:

Clinical response is measured via the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Functional recovery is assessed through the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and the Goal Attainment Scale (GAS).

Вмешательства

• Процедура phenol neurolysis
  A chemical neurolysis procedure using a 5% aqueous phenol solution. Under real-time ultrasound (US) guidance, the needle is advanced until it is adjacent to the target nerve trunk. The phenol is then injected to induce protein denaturation and axonal degeneration (Wallerian degeneration), effectively interrupting the spastic reflex arc. Targets: The pectoralis nerves (to address shoulder adduction and internal rotation) and the musculocutaneous nerve (to address elbow flexion). Volume: Typical
• Процедура Botulinum Toxin - A injections
  A focal chemodenervation procedure using Botulinum Toxin Type A. The toxin is reconstituted with 0.9% sterile saline. Using ultrasound guidance, the medication is injected directly into the motor points of the hypertonic muscles. The toxin acts by inhibiting the release of acetylcholine at the neuromuscular junction, resulting in localized muscle relaxation. Targets (Experimental Group): Distal muscles only (e.g., Flexor Carpi Radialis, Flexor Digitorum Superficialis/Profundus). Targets (Compa

Первичные конечные точки

• Change from Baseline in the Modified Ashworth Scale (MAS) at 4 and 12 weeks. [Срок оценки: Baseline, 4 weeks, and 12 weeks.]

Вторичные конечные точки (5)

• Change from Baseline in Fugl-Meyer Assessment for Upper Extremity (FMA-UE). [Срок оценки: Baseline, 4 weeks, and 12 weeks.]
• Goal Attainment Scale (GAS). [Срок оценки: 4 weeks and 12 weeks.]
• Change from Baseline in Resting Motor Threshold (RMT) of both hemispheres. [Срок оценки: Baseline, 4 weeks, and 12 weeks.]
• Change from Baseline in Cortical Silent Period (CSP) duration. [Срок оценки: Baseline, 4 weeks, and 12 weeks.]
• Total Dose of Botulinum Toxin Type A (BoNT-A) administered. [Срок оценки: Day 0 (at time of injection).]

Критерии участия

• Inclusion criteria :

• Adults aged 18 to 70 years.
• Diagnosis: Documented Ischemic or Hemorrhagic stroke (with a duration of at least 6 months post-stroke to ensure a chronic, stable phase).
• Spasticity Severity: A score of 2 on the Modified Ashworth Scale (MAS) in at least one proximal muscle group (Shoulder adductors or Elbow flexors).
• Functional Status: Evidence of upper limb motor impairment but with enough stability to participate in follow-up.
• Cognitive Ability: Ability to understand and follow instructions (Mini-Mental State Examination score typically 24) to ensure cooperation during TMS and functional testing.
• Consent: Signed informed consent provided by the patient or a legal guardian.
• Exclusion Criteria :

• Fixed Contractures: Any permanent joint deformity or fixed contracture in the target limb that would prevent range of motion improvement.
• Prior Treatment: Received Botulinum Toxin or phenol injections in the affected limb within the last 6 months.
• TMS Contraindications: History of seizures.
• Presence of metallic implants in the head or neck (e.g., clips, shunts).
• Cardiac pacemakers or implanted medication pumps.
• Local Factors:Skin infection or inflammation at the planned injection sites.
• Medical Co-morbidities: Significant peripheral nerve disease (other than the stroke-related upper motor neuron lesion) or severe psychiatric disorders.
• Phenol Sensitivity: Known hypersensitivity to phenol or its derivatives.

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

Список центров уточняется — проверьте первичный протокол.

Публикации

• Anwar F, Ramanathan S. Combined Botulinum Toxin Injections and Phenol Nerve / Motor Point Blocks to Manage Multifocal Spasticity in Adults. British Journal of Medical Practitioners. March 2017;10(1):a1002.
• Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004 Mar;55(3):400-9. doi: 10.1002/ana.10848. PMID 14991818
• Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principl PMID 25797650
• Gonnade N, Lokhande V, Ajij M, Gaur A, Shukla K. Phenol Versus Botulinum Toxin A Injection in Ambulatory Cerebral Palsy Spastic Diplegia: A Comparative Study. J Pediatr Neurosci. 2017 Oct-Dec;12(4):338-343. doi: 10.4103/jpn.JPN_123_17. PMID 29675072
• Wissel J, Ward AB, Erztgaard P, Bensmail D, Hecht MJ, Lejeune TM, Schnider P, Altavista MC, Cavazza S, Deltombe T, Duarte E, Geurts AC, Gracies JM, Haboubi NH, Juan FJ, Kasch H, Katterer C, Kirazli Y, Manganotti P, Parman Y, Paternostro-Sluga T, Petropoulou K, Prempeh R, Rousseaux M, Slawek J, Tieranta N. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil PMID 19197564

Идентификаторы

NCT: NCT07440173 · NuroRehabSpasticity

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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