Phenol Versus Botulinum Toxin A Injection in Ambulatory Cerebral Palsy Spastic Diplegia: A Comparative Study.

The aim of this study is to compare the treatment effectiveness of botulinum toxin type A (BTX-A) and phenol blocks in the management of lower limb spasticity and to measure improvement in gross motor functional outcome in children with cerebral palsy (CP). This is a hospital-based prospective, noncontrolled randomized study that took place in a tertiary care center. A total of 61 ambulatory children with CP spastic diplegia, aged from 4 to 10 years, were randomly divided into two groups and included in this study. Twenty-eight children with CP received BTX-A injections and 33 received phenol motor point blocks. The measures performed were as follows: outcome assessment spasticity by the Modified Ashworth scale (MAS), active range of motion (AROM) of lower limb joint by goniometer, and functional improvement by Gross Motor Function Measures (GMFM). Postinjection follow-up done at 2, 6, 12, 24, and 48 weeks. Significant improvement in reduction of spasticity, increased AROM of all joints of lower limbs, and improvement in functional outcome were observed in CP with spastic diplegia after BTX-A injections as compared with the phenol motor point block group. There was no significant side effect after BTX-A injections as compared with phenol injections. BTX-A injections showed superior treatment effects in the reduction of spasticity and improvement in AROM and functional outcome measures with spastic diplegia as compared with phenol blocks. BTX-A injections also revealed fewer clinical side effects and were well tolerated by children with CP.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Cerebral palsy (CP) is a disorder of movement and posture that is caused by damage occurring in immature brain. The world-wise incidence of CP is 2-2.5/1000 live birth.[1] Majority of children with CP have impairment of posture and movements of varying severity. They are also at increased risk for the disturbance of higher mental function, vision impairment, speech and language delay, and epilepsy.[2] Although the brain lesion in CP is static, musculoskeletal impairments and associated complications increase with time if ignored.[34] Primary motor impairments in CP directly correlate with the degree of brain insult and manifest as alteration in tone, power, movements, and balance. Secondary impairments in the form of contractures and deformities occur due to disuse. Chronic adaptation to compromised motor system manifests as tertiary impairments.[56] Spastic CP is the most common type of CP and spasticity is among the most disabling problems in a child with CP.[7] Diplegic CP spasticity primarily involves the hamstrings, adductors, and planter flexors. Progressive deformity, contractures, pain and muscle spasms, immobility, perineal hygiene, depression, obesity, bone loss, and fractures necessitate the treatment of spasticity at the earliest.[89] Management of spasticity is aimed at prevention of irreversible soft-tissue damage and tendon contractures thus abolishing secondary complications. An assortment of physical and occupational therapies, oral and intrathecal medications, surgery, botulinum toxin type A (BTX-A), and neurolytic agents like alcohol and phenol is used in the management of spasticity.[10] Treatment using phenol and BTX-A is well established.[1112] However, in studies comparing the efficacy of injection Phenol and BTX-A in the age group of 4–8 years, cases of ambulatory CP with spastic diplegia are few. Our study aimed to measure and compare the results of injection Phenol and injection BTX-A on the reduction of spasticity, improvement of the range of motion, and overall gross motor function outcome.

MATERIALS AND METHODS

After obtaining approval from the local institutional ethical committee, this prospective, noncontrolled randomized study was conducted for a period of 2 years in the Department of Physical Medicine and Rehabilitation of All India Institute of Physical Medicine and Rehabilitation tertiary care teaching hospital, Mumbai, India. After obtaining consent from parents/guardians, we included 61 ambulatory CP children with spastic diplegia of either sex between 4 and 10 years of age with spasticity of 2 or 3 on Modified Ashworth scale (MAS) and mild to moderate degree of motor affliction matching Gross Motor Functional Classification (GMFC) level 1 to 3. All patients satisfying inclusion criteria divided randomly into Phenol and BTX-A groups by using chit draw. Thirty-three children with CP (20 boys and 13 girls, mean age: 6.0 ± 1.3 years) denominated as Group 1 received 6% injection Phenol and 28 children with CP (16 boys and 12 girls, mean age: 5.8 ± 0–8 years) denominated as Group 2 received injection BTX-A. Children with compromised higher mental function, musculoskeletal deformities, limb length discrepancy, previous corrective surgeries, and other co-morbidities were excluded. Detailed history was elicited, and patients were clinically evaluated for spasticity in three muscle groups, i.e., adductors, hamstring, and gastro soleus, by MAS. Goniometer was used to assess the active range of motion (AROM), contracture, and deformity at the hip, knee, and ankle joint. Physiotherapy and occupational therapy were provided to all patients postinjection. Follow up was done at 2, 6, 12, 24, and 48 weeks postinjection. Functional assessments were done on the Gross Motor Function Measures (GMFM) score sheet. Gross motor function was assessed using the GMFM score sheet by evaluating changes in over a period of time. It is a reliable and valid measure of gross motor functions consisting of five dimensions. In the present study, we have used (1) standing and (2) walking, running, and jumping parameters. GMFM88 scale was used.

Injection Phenol technique

Under aseptic precaution in the prone posture after sedation with oral midazolam (0.5 mg/kg) injection 6% Phenol was given as motor point block with the help of 27G Teflon-coated needle connected to the nerve stimulator (STIMUPLEX DIG RC). Phenol motor point injections give as per the standardized anatomical landmarks for adductors, hamstrings and gastro soleus.[14] We found that one person needs to manipulate the needle to achieve maximum muscle contraction with a minimum amount of direct electric current lasting 0.05–0.1 ms with current strength of 3–5 mA at the rate of 0.5–3 Hz and a second person needs to palpate the spastic muscle and adjust output current. This demanded good technical rapport between the operators. Once the desired nerve was identified with minimal current, after preliminary aspiration 1–4 ml of solution was injected. The immediate effects are the abolition of contractions and a reduction in the degree of spasticity.

Injection BTX-A

After sterile preparation, BTX-A (BOTOX 100 Allergan Irvine CA) was injected in prone posture after confirmation on anatomical landmark in intended muscles like adductors, hamstrings, and gastro soleus without anesthesia. Each vial of BTX-A (100 units) was diluted with 2 ml of normal saline. After preliminary aspiration, BTX-A was injected. We followed certain recommendations for BTX-A injection at dosage of 1–3 U/Kg, no more than 6 U/kg in large muscle on any single occasion, and did not exceed a maximum total dose of 12 U/kg body weight.

Following the injection, the patient remained under observation for 15–30 min and was monitored for any complications. Parents were to report whether their child suffered any side effects, such as systemic fever, local pain or tenderness, irritability, generalized weakness, localized weakness, or sphincter incontinence. Nine children had injection site tenderness, two had fever along with local injection site tenderness. Postinjection analgesia was achieved with paracetamol. All children participating in the study were assigned rehabilitation sessions consisting of stretching of hip adductor, hamstring, and gastro soleus, strengthening of hip extensors quadriceps and back muscles, and gait training daily for 30 min five times per week for a month. They were then asked to continue home-based exercises daily and were followed up at 2, 6, 12, 24 and 48 weeks postinjection.

Statistical analysis

Data are summarized in the tables and represented as mean and standard error of mean with P values. The repeated measures analysis of variance and Tukey’s multiple comparison tests were conducted to assess the statistical significance for three outcome measures, MAS score, active range of motion, and GMFM score, with pretreatment scores within groups. Pre-treatment (baseline) scores were compared to 2, 6, 12, 24, and 48 weeks follow up. Analysis was carried out using SPSS 20. P value <0.05 was considered as statistically significant.

RESULTS

Statistically significant differences were not observed between age and sex distribution, mean body weight, and mean body height in two groups. Mean body weight for Group 1 was 14.7 ± 3.8 and for Group 2 it was 14.9 ± 4.1, whereas mean body height in Group 1 was 103.7 ± 12.3 cm and for Group 2 it was 102 ± 11.6 cm. There was no significant difference between the two treatment groups for score of spasticity, range of motion, and GMFM prior to treatment. Table 1 summarizes modified Ashworth scores of three different muscles—adductor, hamstring, and gastrocnemius soleus—at different intervals (baseline, 2, 6, 12, 24, and 48 weeks). Mean Ashworth score for adductor in comparison with pretreatment score was decreased after injections Phenol and BTX-A. After injection Phenol, a significant decrease in muscle tone was observed for 6 weeks (P < 0.05) whereas in the case of injection BTX-A, significant reduction in tone lasted for up to 12 weeks (P < 0.05) as compared to pretreatment values.

Table 1

Mean and standard error mean for modified Ashworth score of adductor, hamstring, and gastrocnemius soleus at each measurement point

After BTX-A injection, a decrease in the mean Ashworth score for hamstring was significant for up to 24 weeks whereas after injection Phenol, a reduction in spasticity was significant for 6 weeks. Similar reduction in muscle tone was seen after injection Phenol and injection BTX-A in gastrocnemius soleus except that the duration of reduction of mean Ashworth score lasted till 6 weeks after injection Phenol and the effect of injection BTX-A lasted till 24 weeks (P < 0.05). Postinjection in the phenol and BTX-A groups, there was significant increase in active hip abduction. In the BTX-A group, improvement in active hip abduction lasted for 24 weeks when compared to the Phenol group which lasted for 6 weeks (P < 0.05) only [Figure 1A]. Our study revealed that there is significant improvement in active knee range of motion after injection Phenol and injection BTX-A. It remained improved statistically for 12 weeks in the Phenol group when compared to 24 weeks in the BTX-A group [Figure 1B]. Active dorsiflexion was improved significantly after BTX-A injection (P < 0.05) and to a certain extent after phenol injection, but these improvements were not statistically significant [Figure 2A]. Improvement in GMFM score was highly significant after injection BTX-A as compared to injection Phenol. In the BTX-A group, improvement in GMFM score remained statistically significant for 24 weeks (P < 0.05) and in the Phenol group it was for 6 weeks only [Figure 2B].

Figure 1

Changes in active abduction (A) and active knee range of motion (B) after injection Phenol and injection BTX-A

Figure 2

Postinjection Phenol and BTX-A changes in active dorsiflexion (A) and (B) gross motor function

DISCUSSION

Spasticity is one of the most disabling symptoms in CP, which can cause pain and progressive muscle shortening and ultimately accentuate disability. The main goals of treatment are to alleviate the deforming force which is a result of spasticity, to improve function, and to prevent secondary complications due to spasticity. Issue of spasticity can be resolved with physical modalities, oral medications, BTX-A, chemical neurolytic agents like phenol and alcohol, and surgical methods. Physical modalities commonly used are prolonged stretching, serial casting, icing and brushing, orthotics, biofeedback, and electrical stimulation. These physical methods are labor intensive and often provide only transient relief. The advantage of oral medications is that they can be used to reduce generalized spasticity but most of these medications are expensive. Side effects are common when these drugs are administered for long periods. A number of surgical procedures can be undertaken for reducing spasticity and these procedures are also expensive. Chemical neurolytic agents like ethyl alcohol and phenol are options for decreasing localized spasticity. Phenol above 3% concentration selectively denatures the proteins and injures cells by precipitation and dehydration of protoplasm. It is easily available but its disadvantages include skin irritation, permanent peripheral nerve palsy, and painful muscle necrosis. Neuromuscular junction–blocking agents like botulinum toxin exert a paralytic effect by rapidly and strongly binding to presynaptic cholinergic nerve terminals. The toxin’s effect on motor function is observed within a few days following injection and lasts between 3 and 4 months.[15] Several studies related to the effects of injection Phenol and injection BTX-A showed that both are useful in the treatment of spasticity of the lower limb in CP. Kirazli et al.[16] compared the effect of injection Phenol and injection BTX-A in poststroke spastic foot. They found that injection BTX-A showed superior results in reductions of mean tone and improvement in dorsiflexion of foot and walking velocity at 2 and 4 weeks as compared to Phenol injection. Although our study was conducted on spastic CP instead of poststroke patients, the BTX-A group showed significant reduction in mean modified Ashworth score of gastrocnemius soleus for a longer duration (i.e., for 24 weeks) compared to the Phenol group (6 weeks only). Chua and Kong[17] conducted a noncomparative study of alcoholic neurolysis of tibial nerve to find out the clinical and functional outcome in spastic ankle foot. They found that decrease in muscle tone, increased passive ankle range of motion, and decreased clonus of plantar flexor, improved gait and easy use of orthosis. We conducted a comparative study of injection Phenol motor point block and injection BTX-A. The BTX-A group expressed a significant reduction in muscle tone as adductor (12 weeks, P < 0.05), hamstring (24 weeks, P < 0.05), and gastrocnemius soleus (24 weeks, P < 0.05), increased active dorsiflexion of foot (12 weeks, P < 0.05), and significant improvement in gross motor functional outcome (24 weeks, P < 0.05). The Phenol group showed decreased muscle tone as adductor (6 weeks, P < 0.05), hamstring (6 weeks, P < 0.05), and gastrocnemius soleus (6 weeks, P < 0.05), increased active dorsiflexion of foot (6 weeks, P < 0.05), and significant improvement in gross motor functional outcome (6 weeks, P < 0.05). The main drawback of our study was that we did not conduct posttreatment gait analysis. Helweg-Larsen and Jacobsen[18] performed 150 Phenol block both peripheral and motor point block, and they found that the mean duration of spasticity reduction was 2.2 months. In another study, Copp and Keenan[19] performed 50 peripheral nerve block and 33 motor point block with Phenol and showed a reduction in spasticity for 3–4 weeks. In the present study, we conducted 162 motor point blocks with 6% phenol and assessed on the three outcome measures. Mean duration of spasticity reduction for adductors, hamstrings and gastro soleus lasted for six weeks. The improvement in GMFM-88 also persisted till 6 weeks. Alice et al. only compared short-term effectiveness of BTX-A versus Phenol blocks in managing lower limb spasticity in children with spastic diplegia. They found that the BTX-A group was superior in terms of spasticity reduction and there was improvement in walking velocity and cadence at 8 weeks.[20] However, there were no data available on results beyond 8 weeks. In our study we assessed spasticity, active range, and functional outcome for 48 weeks. We observed that BTX-A injection was superior in terms of spasticity reduction, active range of motion, and gross motor function measure. Yadav et al.[21] performed Phenol peripheral nerve block in 116 patients of spastic CP with impaired perineal care and ambulation. They found reduction in spasticity and improvement in perineal care lasted from 3 to 18 months, with an average of 13 months. In the present study, we performed phenol motor point block to minimize sensory deficit due to phenol blockade of peripheral mixed nerve and in addition we used gross motor functional measure to assess functional outcome. There were no significant side effects, but a decrease in adductor spasticity and motor functional improvement persisted for 6 weeks. Wong[22] found significant improvements in hip abduction (mean change = 13.5°) and ankle dorsiflexion (mean change = 3.5°) after BTX-A injection into the adductor and gastrosoleus muscles, respectively. In the present study, after BTX-A injection into the adductor, hamstrings, and gastrocnemius soleus, we observed an improvement in active hip abduction (mean change = 22.5°), active knee ROM (mean change = 107.7°), and active dorsiflexion (mean change = 9.25°). In the Phenol group, we observed an improvement in active hip abduction (mean change = 18.4°), active knee ROM (mean change = 99.63°), and active dorsiflexion (mean change = 6.5°). BTX-A group showed superior result in improvement of active ROM of lower limb joints compared to the Phenol group. Ece Unlu et al. injected BTX-A in 71 patients with CP and they were followed up for 24 weeks. They found a decrease in Ashworth scores significantly at the 3-month but not at the 6-month evaluation. The GMFM total goal scores improved significantly at the 3- and 6-month evaluations.[23] In the present study, 28 patients were followed up for 48 weeks, and our study revealed that after BTX-A injection GMFM total goal score was significant (P < 0.05) from 2 to 24 weeks. Unlike the other studies, multiple parameters like Modified Ashworth scale, active range of motion, and GMFM total goal score were used and the follow up was for a longer duration. The main limitation of our study was that there was no control group and we did not conduct postinjection video gait analysis in the gait lab. Studies on the comparative effects of injection Phenol motor point block and injection BTX-A in CP are limited, making our study a unique one. This study highlights the fact that with appropriate use of injection Phenol and injection BTX-A, the treating physiatrist can achieve functional improvement in CP with spastic diplegia. This study provides treatment options for physiatrist for proper rehabilitation of patients with CP and reduces the plight of troubled parents and caregivers.

SUMMARY AND CONCLUSION

Spasticity is a velocity-dependent increase in tonic stretch reflex. It is one of the most disabling aspects of CP. This needs to be treated if it interferes with the activities of daily living, self-care, or when it causes discomfort or pain. Although BTX-A is effective in the treatment of spasticity, neurolytic block with 6% phenol, when adequately indicated, is a tool that provides excellent cost–benefit relation, high margin of safety, and infrequent complications, especially when administered by a well-qualified physiatrist. In this study, a comparison of the efficacy of injection Phenol and injection BTX-A on spasticity, range of motion, and gross motor functional outcome was carried out. We found that the effect of injection BTX-A on spasticity reduction in adductors, hamstrings, and gastrosoleus was long lasting and more effective as compared to injection Phenol. Phenol is a relatively safe and cost-effective method to reduce spasticity and to improve functions in patients with CP. The effect with phenol was short lived when compared to BTX-A; injection Phenol was painful which lead to poor follow up in few patients. BTX-A is an effective method to reduce spasticity than chemical neurolysis by Phenol, but BTX-A is expensive when compared to injection Phenol. Thus, this study shows that injection Phenol is a relatively safe and cheap option to manage spasticity in an economically poor setting and reduces financial burden of the family.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.