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

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

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.

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).

• 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.