Objective: To study the effect of botulinum toxin A in the subscapular muscle on shoulder pain and humerus external rotation.
Methods: 22 stroke patients with spastic hemiplegia, substantial shoulder pain and reduced external rotation of the humerus participated in a randomised, double blind, placebo controlled effect study. Injections of either botulinum toxin A (Botox, 2×50 units) or placebo were applied to the subscapular muscle at two locations. Pain was scored on a 100 mm vertical Visual Analogue Scale; external rotation was recorded by means of electronic goniometry. Assessments were carried out at 0 (baseline), 6 and 12 weeks.
Results: 21 patients completed the study. We observed no significant changes in pain or external rotation as a result of administration of botulinum toxin A. External rotation improved significantly (p = 0.001) for both the treatment group (20.4° (16.6) to 32.1° (14.0)) and the control group (10.3° (19.5) to 23.7° (20.7)) as a function of time.
Conclusions: Application of botulinum toxin A into the subscapular muscle for reduction of shoulder pain and improvement of humeral external rotation in spastic hemiplegia does not appear to be clinically efficacious.
Statistics from Altmetric.com
Shoulder pain after stroke is a common complication that influences quality of life.1 Associated with shoulder pain and limited external rotation of the humerus2 3 are shoulder subluxation, adhesive capsulitis, rotator cuff injury, reflex sympathetic dystrophy4–7 and spasticity (ie, hypertonia of the subscapular muscle).8 Uncontrolled studies indicate benefits of subscapular muscle nerve blocking with phenol.9 10 Systematic surveys of intra-articular glycosteroids or botulinum toxin A application showed no or contradictory effects.11–14
Simultaneously with the study of Yelnik and co-workers,13 we conducted a double blind, randomised, placebo controlled, clinical trial to study the effect of botulinum toxin A (Botox) into the subscapular muscle on shoulder pain and external rotation of the humerus in patients with post stroke shoulder pain. We expected a beneficial effect of botulinum toxin A on pain and humeral external rotation.
We performed a randomised, double blind, placebo controlled study. Between October 2003 and November 2006, 22 adult stroke patients, aged 18 years or over, were included.
Inclusion criteria were: (1) significant shoulder pain with a minimal score of 40 mm on a pain Visual Analogue Scale (VAS), lasting for at least 1 week; (2) restricted passive external rotation of the humerus ⩾50% relative to the unaffected arm; and (3) an Ashworth Score15 at the elbow of ⩾1. Exclusion criteria were: (1) unable to reliably fill in the VAS score (checked beforehand by means of dummy questions); (2) an International Normalised Ratio ⩾3; (3) glenohumeral infiltration in the last 4 weeks; and (4) shoulder pathology in the medical history (affected or unaffected side). One patient did not attend after inclusion.
Pain and humeral external rotation were recorded as primary outcome variables at inclusion and after 6 and 12 weeks of follow-up. At inclusion, functionality (Brunnström’s six stages of recovery16) and spasticity (Ashworth Score15) were assessed as potential confounders.
The maximal passive external rotation of the humerus was recorded by means of an electrical goniometer, fixed to the wrist. Patients lay in a supine position with the upper arm along the body and the elbow at 90° flexion. The humerus was then passively moved into external rotation. The maximal range of motion was recorded when the patient reported that further external rotation was impossible. Humerus rotation angle was defined as zero (0°) when the forearm was positioned vertically and to be increasing during external rotation. A vertical pain VAS score was used instead of a horizontal one to exclude bias from hemi-inattention. At each assessment the measurements were repeated three times by two observers to correct for interobserver and inter-trial variability. The mean of all measurements at each assessment was used for further analysis.
After baseline assessments, botulinum toxin A (Botox) or placebo was injected at two locations into the subscapular muscle with the patient sitting in an upright position. The affected arm was held in internal rotation to achieve sufficient winging of the medial edge of the scapula. At one-third and two-thirds of the distance between the superior and inferior scapular angle, a curved 90 mm needle was inserted and guided under the scapula just until the tip of the needle reached the scapular periosteum, marked by a bony resistance felt by the injector and/or the sensation of a sudden sharp pain by the patient.17 The needle was then retracted a few millimetres before application of 50 units of Botox dissolved in 1 ml of saline 0.9% or placebo (1 ml 0.9% of saline only, control group) at each injection site. All injections were given by the same investigator (KdB). Injection time did not exceed 15 min. The study was approved by the medical ethics committee of Leiden University Medical Centre and all patients gave their informed consent.
A General Linear Model repeated measurements ANOVA (SPSS V.11.5, alpha 0.05) was used for comparisons of mean pain scores and external rotation between the two groups at each visit. Sensitivity of the statistical procedure to missing data (one and two occasions at, respectively, 6 and 12 weeks of follow-up for both external rotation and VAS) was investigated by filling in extreme values. This did not affect the significance of the results. Interrelations between parameters were investigated by linear regression.
The treatment and control groups did not differ with respect to relevant confounding variables: age, sex distribution, baseline spasticity (Ashworth Score 0–4), time after stroke, arm function (Brunnström stages 1–6) (table 1), baseline pain and glenohumeral external rotation (fig 1).
All patients still received some form of (physical) therapy. At the end of the follow-up period, an average improvement of external rotation (p = 0.001) and lowering of the VAS pain score (p = 0.08) was observed. However, both the improvement in external rotation and VAS pain score were not modified by botulinum toxin A therapy (interaction p = 0.81 and p = 0.61, respectively) (fig 1).
Time after stroke was not related to VAS pain score (r = 0.05, p = 0.82) or external rotation of the humerus (r = 0.08, p = 0.72). VAS score and external rotation of the humerus were not interrelated (r = 0.03, p = 0.91). The baseline Ashworth Score showed no significant correlation to external rotation of the humerus (r = 0.39, p = 0.081) or VAS pain score (r = 0.04, p = 0.86).
The goal of this study was to demonstrate the effects of botulinum toxin A on shoulder pain and humerus external rotation. The effect of botulinum toxin A did not appear to be clinically efficacious. We observed an overall improvement by 3 months, explained by natural recovery and ongoing therapy. Our results do not agree with those of Yelnik and colleagues13 who reported a significant improvement of 7.5° of external rotation following botulinum toxin after 4 weeks. This improvement is of the same order of magnitude as the overall improvement observed in this study (12.5° in 12 weeks). Methodological aspects may explain the different outcomes of Yelnik et al’s study and ours as there were differences in terms of the type of botulinum toxin (Dysport vs Botox), the method of botulinum toxin delivery (straight needle versus curved needle), control of “initial” needle tip position (electrostimulation vs periosteum detection), assessment of pain (10 point verbal scale vs vertical VAS), measurement of external rotation of the humerus (hand vs electronic goniometry), and time of assessment and duration of follow-up. We consider periosteum detection to be valid to ensure correct needle position in the subscapular muscle. From an anatomical point of view, there is no other muscle located at the injection site, and subscapular muscle stimulation may not necessarily be directly related to internal rotation of the humerus.
Of overriding importance seems to be the small sample size combined with the multi-causal nature of post stroke shoulder pain involving capsular and neuromuscular factors. This is underlined by the lack of association between external rotation, pain and spasticity score. Injection into other isolated muscles, such as the biceps and pectoralis major muscle, does not seem to be the panacea either.14 We should aim for greater understanding of the pathophysiology of post stroke shoulder pain.
In current clinical trials, statistical power is too low to reach conclusions. Individual improvement may coincidentally result in significant (false positive) findings. We should focus on the criteria for pre-trial selection based on the pathophysiology of post stroke shoulder pain. Otherwise, identification of the prominent factors of shoulder pain in post stroke hemiplegic patients will require large scale multicentre clinical trials, in view of the low inclusion rate (10 or less patients per year) of both the current and two previous studies.13 14 The clinical relevance of botulinum toxin A injection alone into the subscapular muscle has not been established.
Funding: The study was approved by the medical ethics committee of Leiden University Medical Centre, Leiden, The Netherlands.
Competing interests: None.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.