ABSTRACT
Aim
The aim of this study was to investigate the effects of botulinum toxin injection on upper extremity muscle thickness and motor recovery in stroke patients.
Materials and Methods
The study was conducted retrospectively. Twenty stroke patients (11 males, 9 females) who received botulinum toxin injections into the forearm muscles of the upper extremity were included in the study. Muscle thickness measurements, brunnstrom motor recovery stages, and modified Ashworth scale scores were assessed before and one month after botulinum toxin injection.
Results
There were no significant change in the brunnstrom upper extremity and hand stages before or after botulinum toxin application (p>0.05). No significant change in forearm muscle thickness was observed in measurements taken from the proximal third of the volar surface of the forearm before or after the injections (p>0.05). A significant decrease in spasticity levels was observed in wrist flexor group and finger flexor group muscles after botulinum toxin application (p=0.001).
Conclusion
The study shows that botulinum toxin reduces spasticity but has no effect on brunnstrom motor recovery and muscle thickness.
INTRODUCTION
Stroke is the second leading cause of death worldwide. It poses a significant risk of disability among survivors. It is particularly prevalent in developing countries1. There are significant changes in muscle tone in patients after a stroke. Spasticity, which is defined as an increase in muscle tone depending on speed, is one of the most common conditions2. Spasticity that occurs during patients’ recovery from a stroke can help maintain limb functionality when it is at reasonable levels. However, if it becomes severe, it can lead to a deterioration in motor activity and limitations in daily life participation, as well as the development of various physical impairments3. There are many treatment options for spasticity. Botulinum toxin (BoNT-A) injection treatment is one of the preferred options4. When treating spasticity, the clinical presentation and functional impairments must be carefully evaluated in order to develop an appropriate management strategy. Treatment goals should be determined based on the patient’s current clinical status and functional capacity2. Opinions differ regarding the effects of BoNT-A injections on motor function during stroke rehabilitation.
A systematic review found that BoNT-A injections combined with post-stroke rehabilitation had a limited effect on motor function. Nevertheless, it has been suggested that BoNT-A could help to improve motor function5. A exploratory meta-analysis study involved 47 patients from two randomised trials who received BoNT-A injections for post-stroke spasticity. The study showed that reducing spasticity in the arm was significantly associated with improvement in motor function6. Shaw et al.7 reported that BoNT-A type A did not significantly improve upper extremity motor function one month after treatment for post-stroke spasticity. Another meta-analysis study, compiled from a limited number of studies investigating the effects of BoNT-A type A injections on muscle elasticity, muscle thickness, and structure, revealed a significant improvement in muscle elasticity as assessed by ultrasound in the short term. Furthermore, no significant difference was found in muscle structure (muscle thickness, pennation angle) in the short term. However, a decrease in normalized muscle volume was observed in the long term8. In a study by Picelli et al.9 examining the ultrasonographic features of the medial gastrocnemius muscle following BoNT-A treatment in post-stroke patients, no significant change in muscle thickness was observed after one month. However, some studies indicate a decrease in muscle mass in the early stages after BoNT-A injections. A study in rats found that a decrease in gastrocnemius muscle mass began in the second week after BoNT-A injections10. In a prospective study conducted on cerebral palsy patients who received BoNT-A injections for the first time, a decrease in gastrocnemius muscle volume was observed in all follow-ups at 4 weeks, 13 weeks, and 25 weeks11. Another study by Tok et al.12 evaluated the medial gastrocnemius muscle on the hemiplegic side and observed a reduction in muscle thickness two months after treatment. Similarly, Yi et al.13 observed a decrease in medial gastrocnemius muscle thickness for up to 12 weeks following BoNT-A injection in children with spastic hemiplegic cerebral palsy.
The use of BoNT-A in the treatment of spasticity has been investigated in systematic review and meta-analysis studies containing many studies. However, these generally focus on the effectiveness of the treatment14-16. To our knowledge, no study has examined the effect of BoNT-A application on upper extremity forearm muscle thickness and motor recovery in stroke patients. The aim of this study was to investigate the early effects of BoNT-A injections on upper extremity forearm muscle thickness and motor recovery in stroke patients.
MATERIAL AND METHODS
This retrospective cross-sectional study was conducted in accordance with the Ethical Principles of the Declaration of Helsinki and was approved by the Bolu Abant Izzet Baysal University Clinical Research Ethics Committee (approval number: 2023/429, date: 19.12.2023). This study was registered as a clinical trial on ClinicalTrials.gov.
Selection and Description of the Cases
Patient charts were scanned to identify patients who were hospitalised for neurological rehabilitation at the Bolu Abant Izzet Baysal University Physical Medicine and Rehabilitation Training and Research Hospital between 1 January 2022 and 1 December 2023 and who received BoNT-A injections treatment. Twenty patients who met these criteria were identified and included in the study. All of the patients included were also receiving neurological rehabilitation.
Study inclusion criteria were as follows: patients with hemiplegia due to first stroke who had BoNT-A injections for spasticity in the upper extremity muscles (flexor carpi ulnaris, palmaris longus, flexor carpi radialis, pronator teres, flexor digitorum superficialis, flexor digitorum profundus); patients aged between 30 and 75; and patients who had been at least 3 months post-stroke. No upper limit has been set for the duration of the disease. Exclusion criteria were having a neurological disease other than stroke, malignancy, and having a preexisting musculoskeletal deformity or disease in the upper extremity of the patient who had received BoNT-A injections.
The patients received neurological rehabilitation including range of motion, strengthening, balance-coordination, and stretching exercises during the period between BoNT-A injections and a one-month follow-up. Rehabilitation sessions were held five days a week, with each session lasting one hour.
All of these patients gave informed consent before the BoNT-A injections.
Evaluation Parameters
Patient data were retrospectively retrieved from the hospital’s medical record system.
Patients’ demographic data, the names of the upper extremity muscles injected with BoNT-A, and the injection doses were recorded.
Information on the brunnstrom motor recovery stage of the upper extremity and hand, the spasticity level of the upper extremity muscles according to the modified Ashworth scale (MAS), and the thickness of the forearm muscles measured by ultrasound was obtained from medical records kept before and one month after BoNT-A injections. The reason for using the first month evaluation data is to examine early effects, as this is the period when the effect of BoNT-A is most pronounced.
Primary Outcomes
Brunnstrom Stage: It was used to evaluate motor recovery in the upper extremity, hand and lower extremity, and also to indicate which motor level the patient is at. The brunnstrom stage consists of six stages, each representing progressively improving movement patterns. Higher scores indicate better motor recovery17.
Muscle thickness measurements were performed using a Falcon 2101 EXL 2003 ultrasound device equipped with an 8 MHz linear probe, both before and one month after BoNT-A application.
In patients who received BoNT-A injections into the musculus (m) palmaris longus, m. pronator teres, m. flexor carpi radialis, m. flexor carpi ulnaris, m. flexor digitorum profundus, and m. flexor digitorum superficialis, muscle thickness was measured using ultrasound from the proximal one-third of the volar side of the forearm. Measurements were taken before and one month after the application. The forearm muscles were at rest during the measurements. Muscle thickness was recorded by measuring the vertical distance between the subcutaneous tissue and the radius and ulna bone borders on the ultrasound image. Two measurements were taken, radial and ulnar side, and recorded in millimeters (Figure 1). Ultrasound measurements showed good to excellent intra-rater reliability (intraclass correlation coefficient= 0.89; 95% confidence interval: 0.80-0.94).
Secondary Outcomes
MAS: It involves scoring the amount of resistance that specific muscle groups offer to passive movement by manually moving the extremity. A 5-stage scale has been defined to rate resistance during passive muscle tension. Higher scores indicate greater levels of spasticity18.
Statistical Analysis
For statistics the SPSS 23 program was used. The normality of the data was assessed using the Shapiro-Wilk test. The mean, standard deviation, frequency, median, minimum and maximum values were recorded. The Paired Samples t-test was used to compare normally distributed data, while the Wilcoxon Signed-Rank test was used to compare non-normally distributed data. A p-value of less than 0.05 was considered statistically significant.
RESULTS
In this retrospective cross-sectional study, 20 patients (11 males, 9 females) were included. The mean age of the patients was 60 years. Other demographic data are presented in Table 1. The muscles injected with BoNT-A and the mean dosages were indicated in the Table 2.
Muscle thickness measurements, brunnstrom stages, and MAS scores were assessed before and one month after BoNT-A injections.
There was no significant change in the brunnstrom upper extremity stage before or after BoNT-A application (p>0.05). Similarly, the brunnstrom hand stage did not show any significant change (p>0.05) (Table 3).
No significant change in muscle thickness was observed in measurements taken from the proximal third of the ulnar side of the volar surface of the forearm before or after the injections (p=0.198). Similarly, no significant change in muscle thickness was observed in measurements taken from the proximal third of the radial side of the volar surface of the forearm (p=0.775) (Table 3).
Wrist Flexor Group Muscles: A significant decrease in spasticity levels was observed in this muscle group after BoNT-A application (p=0.001).
Finger Flexor Group Muscles: Similarly, a significant decrease in spasticity levels was observed in this muscle group after treatment. (p=0.001) (Table 3).
DISCUSSION
This study found that injecting BoNT-A into the upper extremity muscles of stroke patients significantly reduced spasticity after a 1-month follow-up, but did not significantly affect motor recovery or muscle thickness.
The use of BoNT-A the treatment of post-stroke spasticity is widely accepted in the literature19, 20. A study by Sun et al.14 demonstrated that BoNT-A was superior to placebo in reducing upper or lower limb spasticity after stroke. In a study conducted by Varvarousis et al.19, which evaluated lower limb spasticity (using MAS) and gait pattern (10-metre walk test) after stroke, it was observed that BoNT-A reduced the degree of lower limb spasticity. In this recent study, a significant decrease was observed in wrist and finger flexor spasticity levels, as assessed by MAS, in patients treated with BoNT-A.
Studies investigating the effects of BoNT-A on motor function have produced mixed results. While some studies indicate that BoNT-A has a positive effect on improving motor function21, 22, others suggest that it has no significant effect23, 24. In a study by Lim et al.25 comparing the effects of BoNT-A injections in subacute and chronic stroke patients, no change was observed in brunnstrom stages in either group, while an improvement was observed in Fugl-Meyer scores. In a study by Devier et al.26, an improvement in motor function was observed in patients receiving rehabilitation alongside BoNT-A treatment for chronic upper extremity spasticity following a stroke. In a study by Çelebi et al.27 investigating the effects of ultrasound-guided BoNT-A injections on pain, functionality, spasticity, and range of motion in patients with upper extremity spasticity following a stroke, motor function was evaluated using the Fugl-Meyer scale at the second week and third month of treatment. It was observed that motor function had improved significantly. In a study by Hesse et al.28investigating the effects of BoNT-A injections treatment for upper extremity spasticity within 12 weeks of a stroke, no significant change in motor function values was observed when evaluated using the modified Rankin Scale and the Motor Function Assessment scale. In Hesse et al.28 study examining the effect of early BoNT-A treatment on finger flexors six weeks after subacute stroke, arm motor function was evaluated using the Fugl-Meyer scale, and no significant change was observed. In our study, no significant change in motor function recovery was observed. This result is consistent with some previous studies and shows that BoNT-A has a limited effect on motor function. As the patients in this study were chronic stroke patients, no change may have been observed in their Brunnstom motor recovery stages after BoNT-A. Furthermore, brunnstrom staging may not be the optimal method for assessing motor recovery after BoNT-A application. Although frequently used to assess motor recovery, it may be insufficient in capturing minor functional changes and fine motor movements outside of synergy in the patient. More detailed scales such as Fugl-Meyer may yield different results.
The effect of BoNT-A on muscle thickness has been investigated mostly in lower extremity muscles, and there are limited studies in the literature. No significant changes were observed in the ultrasonographic features of the muscle 4 weeks after BoNT-A injections into the gastrocnemius medialis and lateralis muscles due to spastic equinus in stroke patients11. However, there are studies showing that the thickness of the gastrocnemius muscle decreases 2 months after BoNT-A administration in stroke patients and approximately 4 weeks after BoNT-A administration in patients with cerebral palsy12, 13. However, no significant change in muscle thickness was observed in our study due to BoNT-A. The main difference between this study and other studies is the evaluation of the upper extremity muscles. While upper limb muscles are subjected to short bursts of low-intensity activity throughout the day, lower limb muscles require stronger contractions to maintain body balance29. The lower limb muscle architecture has a wide pennate angle, allowing for greater force generation30. However, age-related sarcopenia has been found to be more severe in lower extremity muscles than in upper extremity muscles31. These differences between upper and lower limb muscles may have differentiated the effect of BoNT-A injections on muscle thickness.
Repeated BoNT-A administration has been shown to cause muscle volume reduction and fibrosis over time in the masseter muscle and in experimental animals32, 33. Ultrasonographic examinations in stroke patients revealed decreased muscle thickness in the spastic extremity compared to the contralateral muscles34. Another study found that spastic muscles were thinner than non-spastic muscles, but no significant differences were found in muscle and fascial properties between the spastic flexor carpi ulnaris with and without BoNT-A injections35.
A review has indicated that repeated BoNT-A injections can cause permanent muscle atrophy and negatively impact BoNT-A long-term effectiveness. Therefore, it has been emphasized that further studies examining the muscle properties of BoNT-A-treated muscles are needed, and that this monitoring can be achieved especialy through ultrasound, a non-invasive method36. In summary, the present study adds to the limited evidence on early changes in muscle thickness and motor recovery at the 1-month follow-up BoNT-A treatment in stroke patients.
Study Limitations
One of the limitations of this study is that the number of patients is low, and the etiology is not uniform. The small sample size and the retrospective nature of the study limit the generalizability of the findings. Due to the limited sample size, the study may have been underpowered to detecting small effects, especially changes in muscle thickness. The short follow-up period (1 month) and the application of only a single dose of BoNT-A injection do not allow the evaluation of the long-term effects of the treatment. Due to the retrospective design of the study, there was insufficient data available on patient evaluations from the second or third month. This is one of the study’s limitations, as it does not reflect the medium- and long-term effects of BoNT-A. Therefore, long-term studies with larger samples, prospective designs and repeated injections are needed to evaluate the long-term effects of BoNT-A more accurately. In addition to evaluating muscle thickness using ultrasound, we suggest evaluating muscle volume using magnetic resonance imaging in future studies.
CONCLUSION
The study shows that BoNT-A reduces spasticity after a 1-month follow-up, significant changes in motor recovery and muscle thickness were not observed.
