Evaluating The Efficiency Of Treatment Of Pain In Post-Stroke Spasticity By Botulinum Group A In Patients With Brain Stroke – Bui Van Nam

Journal of military pharmaco-medicine n o 3-2019 120 EVALUATING THE EFFICIENCY OF TREATMENT OF PAIN IN POST-STROKE SPASTICITY BY BOTULINUM GROUP A IN PATIENTS WITH BRAIN STROKE Bui Van Nam1; Le Van Quan1 SUMMARY Objectives: To assess the clinical characteristics and outcomes of treatment of pain in post- stroke spasticity with botulinum group A. Subjects and methods: 102 patients with spasticity after a stroke at Stroke Department, 103 Military Hospital from May 2014 to December 2017. Results: Pain in post-stroke spasticity was 55.9%, pain level with VAS score was 2.35 ± 1.22 points. After botulinum injection, the pain was significantly reduced at 1st and 3rd month of hospitalization, with p < 0.05. Pain at injection was 59.6% and there was no pain after 3 days. Conclusion: The pain level in post-stroke spasticity was moderate, common after stroke. Botulinum treatment was effective and the unwanted effects disappeared quickly after injection. * Keywords: Pain; Spasticity; Stroke; Botulinum group A. INTRODUCTION Stroke has long been considered a major contributor to the global disease burden due to high prevalence and incidence. Among the sequelae of stroke, chronic pain syndromes after cerebral stroke are common, accounting for 50 - 72%. There are many types of pain after cerebral stroke, including central pain, shoulder pain and secondary pain due to muscle spasticity, which is many authors’ great concerns. Muscle spasticity is very common (43%) and leaves a lot of serious physical and mental effects on the patient and society [5]. Thesedays, there are many treatments for muscle spasticity after strokes such as rehabilitation, systemic medications, alcohol or phenol blockers and surgery. But these methods are still limited. Botulinum toxin type A is used in the treatment of muscle spasticity in many countries around the world [6]. Being easy to use, botulinum type A is gradually becoming the first choice in the treatment of muscle spasticity after stroke in many stroke and rehabilitation centers in the country. Therefore, we conducted the study of the treatment of post-stroke muscle pain with botulinum A in order to: Evaluate clinical characteristics and assess the efficiency of treatment of pain in post-stroke spasticity with botulinum toxin type A. SUBJECTS AND METHODS 1. Subjects. 102 patients with stroke had Ashworth scores of 1 to 3, receiving inpatient treatment at Department of Stroke, 103 Military Hospital from May 2014 to December 2017. 1. 103 Military Hospital Corresponding author: Bui Van Nam (doctornambv103@gmail.com) Date received: 10/12/2018 Date accepted: 02/02/2019 Journal of military pharmaco-medicine n o 3-2019 121 2. Research methods. The interventional study was evaluated at 1, 3 and 6 months. With some research indicators, the sample was divided into two groups: patients with painful spasticity and patients with painless spasticity. Research only used simply botulinum toxin group A, did not use background. * Some diagnostic criteria: - Patients with cerebral infarction stroke were diagnosed according to the World Health Organization’s definition of stroke in 1970 [2]. - Muscle spasticity was diagnosed according to WM Lance 1980 [4]. - Muscle pain was diagnosed by Winstein's definition in 2016. - Dosage of botulinum toxin in group A: Use the injection dosage for muscle contraction by Huber M and Heck G (2002), which is approved and recommended for use by Vietnam Ministry of Health. - Pain assessment: Diagram 1: Pain level. To assess the pain of patients with visual scale (VAS) ranging from 0 to 10, the patients assessed their pain level in degrees corresponding to the pain level. The pain was calculated as either natural pain or in passive motion. * Data analysis: Data was analyzed by the medical statistical methods using SPSS software 20.0. RESULTS AND DISCUSSION 1. General characteristics of the research group. Table 1: Characteristics Painful spasticity (n = 57) Painless spasticity (n = 45) p Age (years) 57.12 ± 9.0 55.1 ± 11.0 > 0.05 Sex (male) 56.16% 51.9% > 0.05 38.3 ± 8.1 17.9 ± 9.4 < 0.05 Time of stroke (months) Median 31.3; the lowest 1; the highest 58 Journal of military pharmaco-medicine n o 3-2019 122 There was no difference in age between two groups of painful and painless spasticity after stroke: Mean age with spasticity after stroke was 55.1 ± 11.0, average 41 years old, the highest age 89; mean age in the group of patients with muscle pain after stroke was 57.2 ± 9.0 years, the lowest was 41 years, the highest age was 82 years (p > 0.05). Similarly to Wissel Jửrg et al (2000), when the pain was studied in patients with an average age of 41.5 years and severe muscle spasticity were present in younger patients, there was no difference between the painful and painless spasticity group [9]. However, the age in Wissel Jửrg's study was lower than that in our study, which was due to the choice of subjects. In our study, we selected patients right after cerebral stroke, whereas those in Wissel Jửrg’s study included both patients with stroke and traumatic brain injury, traumatic brain injury is more common in younger adults than those at the age of stroke. In terms of gender, males in the group of patients with painful spasticity were 56.6% compared to 51.9% in the group of patients with painless spasticity, the difference was not statistically significant with p > 0.05. The gender ratio in our study was equivalent to other authors’ [4, 9] (p > 0.05). 2. Clinical characteristics of pain due to muscle spasticity. Table 2: Clinical characteristics of patients with pain due to muscle spasticity following a stroke at admission. Clinical characteristics n; ratio % (n = 102) VAS ( X± SD) Pain in at least one position 57; 55.9% 2.35 ± 1.22 Adduction muscles of shoulder joint 53; 51.9% 2.98 ± 1.34 Flexor muscles of elbow joint 49; 48.0% 2.67 ± 1.51 Flexor muscles of wrist joint 35; 34.3% 1.98 ± 1.37 Flexor muscles of knee joint 45; 44.1% 2.06 ± 1.28 Flexor muscles of ankle joint 13; 12.7% 1.09 ± 1.11 In the study, we found that 55.9% of patients had painful spasticity after stroke, equivalent to the proportion of patients in Wissel Jửrg et al’s study [8]. In Luong Tuan Khanh’s study, 64 patients with pain after stroke, experienced a 46.9% of pain due to spasticity, lower than our study. It was explained that the time after stroke in our study was on average 31.1 months meanwhile it was 28.09 months in Luong Tuan Khanh’s study, the longer the time of stroke is, the more increasing the spasticity level and pain rate [1]. John W Dunne et al (1995) had a 77.5% of stroke rate (31/40 patients), which was higher than our study, because the pain after stroke was only assessed in the upper limbs [3]. In this research, we found that post-stroke spasticity occurred in the flexor muscles of upper limb and the Journal of military pharmaco-medicine n o 3-2019 123 extensor muscles of lower limb, which are the most common after stroke. This result was similar to Wissel Jửrg’s finding (2010) [8]. Upper limbs, adduction muscles of the shoulder joint (51.9%) and elbow joint (48.0%) accounted for a high rate of muscle spasticity. In the lower extremities, flexor muscles of the knee joint (44.1%) were characterized by painful muscle spasticity, which were common muscle groups suffering from spasticity after stroke, according to Yelnik (2007). VAS pain score was 2.35 ± 1.22, with typical pain at the adduction muscles of shoulder joint (2.98 ± 1.34), flexor muscles of elbow joint (2.67 ± 1.51), flexor muscles of knee joint (2.06 ± 1.28); pain was moderate (average pain score VAS < 5 points); the results were similar to John W Dunne et al’s findings where the pain due to spasticity after stroke was 2.5 VAS [3]. Pain in the spasticity group is one of the indications for the patient to receive specialized treatment such as medication and blocking. Table 3: Assessment of the decreasing of pain level in VAS time before and after injection of botulinum type A (n = 57). VAS Muscle groups At admission (aa) ( X ±SD) One month p (aa-1) ( X ± SD) Three months p (aa-3) ( X ± SD) Six months p (aa-6) ( X ± SD) 2.35 ± 1.22 0.97 ± 0.11 (p < 0.05) 1.00 ± 0.31 (p < 0.05) 1.89 ± 0.7 (p > 0.05) Pain in at least one position Pain relief 87.7% (50) Time to start pain relief 7.5 ± 5.7 days Shoulder adduction (n = 53) 2.98 ± 1.34 0.80 ± 0.12 (p < 0.05) 1.04 ± 0.36 (p < 0.05) 1.82 ± 0.27 (p > 0.05) Elbow flexion (n = 49) 2.67 ± 1.51 1.11 ± 0.54 (p < 0.05) 1.25 ± 0.42 (p < 0.05) 2.31 ± 0.40 (p > 0.05) Wrist flexion (n = 45) 1.98 ± 1.37 1.09 ± 0.25 (p < 0.05) 1.12 ± 0.31 (p < 0.05) 2.18 ± 0.11 (p > 0.05) Knee extension (n = 27) 2.06 ± 1.28 0.89 ± 0.37 (p < 0.05) 1.09 ± 0.48 (p < 0.05) 1.89 ± 0.33 (p > 0.05) Ankle flexion (n = 13) 1.90 ± 1.11 1.05 ± 0.21 (p < 0.05) 1.19 ± 0.31 (p < 0.05) 1.79 ± 0.22 (p > 0.05) Our findings showed that the decreasing of pain level occupied 87.7% of patients (50/57). The mean duration of pain relief ranged from 7.5 ± 5.7 days. Our study was similar to John W Dunne’s finding with a 90.3% of reduction in pain (28/31 patients) [3]; according to Wissel Jửrg (2000), the decreasing pain levels achieved in 90% of patients and a clear reduction in pain was found in 6.8 ± 5.2 days [9]. Seven patients in our study showed a reduction of pain after botulinum A and 3 patients had a post- stroke duration of over 43 months, and four patients had a muscle spasticity with a 3-point Ashworth score. The placement Journal of military pharmaco-medicine n o 3-2019 124 with no decreasing pain were seen in the muscles of the shoulder and the knee, where many mass muscles participate in a movement. To improve the level of pain associated with spasticity, muscle spasticity groups were injected with botulinum A at 1 and 3 months, there was a statistically signigficant reduction in pain (p < 0.05). At 6 months, pain level was significantly lower than at admission but the difference was not statistically significant (p > 0.05), it was the time when botulinum was about to expire. Our research results were similar to Luong Tuan Khanh’s [1], John W Dunne’s [3]. Yelnik et al carried a randomized, double-blind, placebo-controlled study of patients with shoulder pain due to spasticity after stroke who received botulinum A injections into the muscles spasticity, showed that pain reduced more than the control group, which had statistically significant with p < 0.05 [7]. The cause of pain in muscle contraction is not fully understood. There are now many theories that explain spasticity and pain. One of the theories is that the long- term and abnormal contraction of the muscle acts on the artery wall, excessive oxygen consumption gradually leads to coercive muscle spasticity in the absence of oxygen, resulting in the release of inflammatory and painful mediators such as bradykinin, prostaglandins (PGE2), potassium in blood in the muscle and tendon site; pain can be a long-term muscle spasm that causes joint deformities, arthritis pain. Pain is also a stimulant to increase the degree of contraction of the muscles, which is a pathological twist that promote each other in the course of the disease. Injection of botulinum toxin A cuts neuromuscular transmission to soften the muscles, cuting off the adverse cycle and alleviates pain. The results have been well documented and proven in the treatment of postmenopausal stroke and skull brain injury [8]. Table 4: Side effects (n = 102). Side effects Painful spasticity (n = 57); n; % Painless spasticity (n = 45); n; % p Bleeding at the injection site 11; 19.3% 09; 20.0% > 0.05 Pain at the injection site 34; 59.6 % 30; 66.7% > 0.05 Swine flu syndrome 03; 5.3% 02; 4.4% > 0.05 Dry mouth 02; 3.5 % 02; 4.4% > 0.05 In our study, side effects of botulinum type A in patients with post-stroke spasticity included pain at the injection site with 59.6%, bleeding at the injection site with 19.3%; there was no difference between the two groups about adverse effects (p > 0.05). These unwanted effects usually disappear after 3 days of injection. The rate of adverse effects in the study was similar to that in other researches, according to John W Dunne, the rate of patients with pain after injection with botulinum A was 61.3% [3]. Journal of military pharmaco-medicine n o 3-2019 125 CONCLUSION Through a study of 102 patients with muscle spasticity after stroke in Stroke Department, 103 Military Hospital, we drew the following conclusions: - The incidence of pain due to spasticity in patients with post-stroke muscle spasticity was 55.9%; mean intensity of pain with pain score VAS was 2.35 ± 1.22; severe spasticity was present in the adduction muscles of the shoulder joint with 51.9%, and flexor muscles of knee joint with 48.0%. - After injecting botulinum in group A: pain due to muscle spasticity at 1 month, 3 months decreased significantly compared to the time of hospitalization (p < 0.05); at 6-month post-injection, the pain level increased at 1 and 3 months (VAS: 1.89 ± 0.7), but still lower than at admission. - Side effects of injection of botulinum A in pain treatment: pain at the injection site with 59.6%, bleeding at the injection site with 19.3%, the side effects disappeared after 3 days. REFERENCES 1. 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