Effect of botulinum toxin injection on lower limb function in chronic stroke patients: A pilot study

INTRODUCTION

Stroke is a leading cause of disability worldwide.^[1] Stroke is the number one cause of dependence and disability in Portugal, with 50% of the patients experiencing some form of disability in daily activities.^[2] Of all disabilities, walking is usually referred to stroke survivors as one of their priorities and with a big impact on their daily autonomy. It is estimated that 20–25% of survivors are unable to walk without physical assistance. Randomized trials have demonstrated that patients can improve walking with task-oriented exercise from 3 months to more than 12 months after stroke, beyond the expected neurologic recovery.^[3] In addition, other authors noted that brisk walking can improve endurance and balance in chronic stroke survivors.^[4]

Post-stroke lower limb spasticity has a prevalence of 28–37%. Spasticity can significantly interfere with mobility and functional abilities, like walking, in multiple ways such as increase in muscle tone, involuntary spasm, poor motor control, reduced range of motion, and altered gait patterns. It has been shown that intensive exercise training, especially task-specific, can enhance brain neuroplasticity and improve mobility, balance, and walking endurance.^[5]

Botulinum toxin type A (BoNT-A) is a safe and effective modality to treat spasticity, and it has been shown to improve muscle tone in the ankle.^[6] However, that benefit did not translate to walking speed and gait pattern scale. The authors attributed this result to the long mean duration of stroke, which meant that a lot of physical changes and patterns were already accommodated by the patients. They adapted their walking to make use of spasticity. A change in the motor pattern occurs by rearranging the underlying neural circuits, which proved ineffective in this short time frame.^[7] Some studies reported positive functional lower limb outcomes with the injection of botulinum toxin. Tao et al.,^[8] showed improvements in gait speed, cadence, step length, and walking distance in the treatment group. Another randomized controlled trial by Johnson et al.,^[9] demonstrated beneficial differences in walking speed in the treatment group. Yu et al.,^[10] also studied the effects of BoNT-A injection on lower limb function with significant results in mobility, stride length, walking speed, and forefoot pressure. Despite these results, it seems variability across studies regarding inclusion criteria, outcome measures, and methods challenges the conduction of good quality meta-analysis as reported by Gupta et al.,^[11] Even in the absence of clinical changes, there are improvements in laboratory and instrumental measures of gait with BoNT therapy.^[12]

Chronic stroke is defined as the period of rehabilitation after 6 months of the initial event.^[13] In gait rehabilitation, most studies recommend moderate intensity exercise; nonetheless, a recent study showed that with high intensity interval training with short bursts of maximum safe walking speed, chronic stroke patients have greater improvement in their walking capacity after 12 weeks compared to moderate intensity aerobic training.^[14]

A large Cochrane review concluded that ambulatory stroke patients can benefit from treadmill training to improve walking velocity and endurance in the short term without persistent beneficial effects.^[15] Backward treadmill training seems to prove greater improvement in gait and balance after the administration of botulinum toxin than forward treadmill training.^[16] Robot-assisted training after BoNT-A therapy appears to lead to better results in walking capacity, mobility, and balance than only conventional physical therapy in chronic stroke patients.^[17,18]

The aim of this study was to determine the effect of BoNT-A injection on lower limb function through tests of gait speed, walking ability, mobility, balance, activities of daily living, and quality of life in patients with chronic stroke and lower limb spasticity.

MATERIALS AND METHODS

A total of 17 patients with chronic stroke and lower limb spasticity were submitted to BoNT-A injection. Patients were recruited in a single center at the Medical Rehabilitation Center of the South in the Local Health Unit Algarve. These former inpatients were selected to participate in our study.

RESULTS

During the follow-up, one patient did not complete the study because it could not complete the 6-min walking test. Thus, 17 patients completed the follow-up. No adverse effects were reported. Baseline characteristics are shown in Table 1. Statistical results are shown in Table 2. Berg balance scale increased significantly at 1 month (P = 0.003) and 4 months (P = 0.007) evaluation compared to baseline by 2 points (4.5%). Quality of life using SF-12 increased significantly 2 points (6.2%) at 4 months (P = 0.012). At 1 month, there was no difference. There were no differences in the modified Ashworth scale between evaluations, contrasting with the expected effect of BoNT-A. There was no difference in gait speed measured by the 10 m walking distance test, with the speed decreasing at 1 month and increasing by 0,032 m/s (5.2%) not significantly at 4 months. Walking distance increased at both 1 (9 m) and 4 months (24 m–13.7%) evaluation however with no statistical significance. There was a slight decrease in time to perform timed and go without significance. FIM^® in gait instrument remained equal with the value 6 (modified independence) at baseline, 1 and 4 months. GAS T score increased from 36.3 to 40.9 (11.7%) in both evaluations without significance.

DISCUSSION

Our results show that injection with BoNT-A in the treatment of spasticity in chronic stroke survivors might have a positive impact in balance, walking capacity, and quality of life. Despite the primary effect of BoNT-A is reducing spasticity, we did not observe that in our study. We postulate that baseline values were low, patients were already in the BoNT-A regime with regular injections, and at the chronic stroke phase, there might already be some musculoskeletal retraction which interferes with results. This population is more resistant to functional improvements as they have established gait patterns, due to the chronic lack of motor control and altered muscle tone. Improved balance means better protection against falls, which, in the stroke population, is one of the most common causes of morbidity. Falls in this population can have nefarious consequences, including hospitalization, less mobility, pain, and overall decrease in activities and participation.^[19] We observed a small benefit in gait speed and walking capacity, this has not been demonstrated in a meta-analysis. Despite the increasing number of randomized controlled trials, considering the variability in protocols, doses, and injection muscles, there is no sufficient evidence to allow robust conclusions. There was, however, evidence of improvement in sensory motor function.^[20]

We observed a small increase in quality of life 4 months post-injection. A systematic review showed no conclusive evidence for the impact of BoNT-A on quality of life.^[21] This is in part due to the heterogeneity of the questionnaires that were used in the different studies which make comparisons difficult.

Goal setting is a frequently used tool in stroke rehabilitation which is tailored to individual patients. It is a standardized measure of outcome. Our study showed a small increase in GAS T score which meant some objectives accorded with patients were attained successfully.^[22]

It has been difficult to prove functional benefit when treating spasticity with BoNT-A injection alone; we know that it decreases spasticity, but also decreases muscle strength.^[23] This is the reason why it is so important to add a rehabilitation program after the injection. In our study, there was no control of post-injection rehabilitation program which can be a confounding variable. Roche et al.,^[24] compared two groups, one with botulinum toxin and self-rehabilitation program and the other with botulinum toxin alone. The former one had greater gait velocity, gait capacity, and stair climbing. It is hypothesized that training compensates for the decrease in muscle strength caused by BoNT-A and facilitates its positive effects. This training was task-oriented, focused on walking and turning.

Overall, this is a preliminary study with major limitations (small sample size, lack of control group, and unmonitored rehabilitation and so results have limited utility).

CONCLUSION

Botulinum toxin type A may provide modest improvements in gait, balance and quality of life in chronic stroke patients with spasticity. However, due to small sample size, lack of control group, and unmonitored rehabilitation, further controlled studies are needed to confirm these preliminary findings.