Application of Botulinum Toxin in Treatment of Spasticity and Functional Improvements for Children Suffering from Cerebral Palsy

Abstract

Application of Botulin toxin type A in children with cerebral palsy is represent targeted antispasm treatment for relaxation of spastic muscles. Goal: The goal of this study was to determine the significance of the application of Botulin toxin in the treatment of spasticity and functional progress of children suffering from cerebral palsy. Material and methods: At the Department of Developmental diagnosis, habilitation and rehabilitation of children in the Pediatric Clinic, Clinical Center of Sarajevo University study included 20 patients aged 4-18 years. Data were obtained by examining the patient's records. Selected patients are diagnosed with cerebral palsy and were treated with Botulin toxin. The study was retrospective, and data are presented in tables and charts using descriptive statistics. As a measurement scale, we used the "gross motor function measurement"-GMFM, based on which the children were scored by the " Gross Motor Function Classification System"-the GMFCS. Results: Of 20 children, 11 or 55% were boys and 9 or 45% of girls. The largest number of children in the sample had 9 ± 4.03 years (5 or 25%), with an average age of 9 years (range: 4-18 years). 80% of children suffering from cerebral palsy for the first time received botulin toxin at the age of 2-6 years, 40% of children had 2 applications of Botulin toxin, and for 45% of children the time interval between repeated applications was from 3-6 months. Measuring gross motor function before and after botulin toxin application registered significant functional improvement. Conclusion: Botulin toxin is beneficial in the treatment of spasticity in children suffering from cerebral palsy.

Application of Botulinum Toxin in Treatment of Spasticity and Functional Improvements for Children Suffering from Cerebral Palsy

ORIGINAL PAPER

Application of Botulinum Toxin in Treatment of Spasticity and Functional Improvements for Children Suffering from Cerebral Palsy

Ajsa Meholjic, Dijana MadjarPediatric Clinic, Clinical Centre of Sarajevo University, Patriotske Lige 81, 71000 Sarajevo, Bosnia and Herzegovina

Application of Botulin toxin type A in children with cerebral palsy is represent targeted antispasm treatment for relaxation of spastic muscles. Goal: The goal of this study was to determine the signicance of

the application of Botulin toxin in the treatment of spasticity and functional progress of children suering from cerebral palsy. Material and methods:

At the Department of Developmental diagnosis, habilitation and rehabilitation of children in the Pediatric Clinic, Clinical Center of Sarajevo University study included 20 patients aged 4-18 years. Data were obtained by examining the patients records. Selected patients are diagnosed with cerebral palsy and were treated with Botulin toxin. The study was retrospective, and data are presented in tables and charts using descriptive statistics. As a measurement scale, we used the gross motor function measurementGMFM, based on which the children were scored by the Gross Motor Function Classication Systemthe GMFCS. Results: Of 20 children, 11 or 55% were boys and 9 or 45% of girls. The largest number of children in the sample had 9 4.03 years (5 or 25%), with an average age of 9 years (range: 4-18 years). 80% of children suering from cerebral palsy for the rst time received botulin toxin at the age of 2-6 years, 40% of children had 2 applications of Botulin toxin, and for 45% of children the time interval between repeated applications was from 3-6 months. Measuring gross motor function before and after botulin toxin application registered signicant functional improvement. Conclusion:

Botulin toxin is benecial in the treatment of spasticity in children suering from cerebral palsy. Key words: spasticity, Botulin toxin, Gross Motor

Function Classication System

Corresponding author: Ajsa Meholjic, MD, PhD. Pediatric Clinic, Clinical Centre of Sarajevo University, Patriotske Lige 81, 71000 Sarajevo, BiH

1. INTRODUCTION

Cerebral palsy is a set of symptoms that arise as a result of abnormal brain development or brain damage at an early age. These symptoms are motor decits, non-physiological increase or decrease and the distribution of mus-

cle tone, sensory and sensitivity disturbance, mental decit, speech disturbances, neurovegetative disturbances, etc. As a result of damage to the pyramidal path develops muscle spasticity (1,2).

To decrease the muscle spasm, as one

aspect of treatment is the application Botulin toxin (BT), which is best applied to children suering from cerebral palsy at the age of 2-6 years, which have dynamic contractures that aect the function of the limbs (3)? Clinical signs of improvement are visible within the rst two weeks after the injection of botulin toxin into the muscles. The dose may be repeated before the symptoms completely disappear prior injection, but not more frequently than every 2 months (4,5). Contraindications for the application are: hypersensitivity to some component of the product, the generalized disturbance of muscle activity (e.g. myasthenia gravis), concomitant administration of amino-glycoside antibiotics, the presence of infection at the site or around the injection site, and bleeding disorder (6,7).

The main criterion for inclusion of Botulin toxin is localized hypertonic muscles and the absence of static contracture, and indications are: on the feetdynamic equinus, equinovarus, equinovalgus, dynamic restriction of movement in the knees, adduction position of the hips, scissors like position of the legs or the handspermanent position of thumb in the palm of the hand, the dominant palmar exion with ulnar deviation or only the dominant palmar exion (8,9).

2. GOAL

The goal of this study was to determine the efficacy of the treatment of spasticity in children suering from cerebral

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Application of Botulinum Toxin in Treatment of Spasticity and Functional Improvements for Children Suffering from Cerebral Palsy

palsy by application of botulin toxin in spastic muscles of the lower limbs.

3. MATERIAL AND METHODOLOGY

The study included children who were diagnosed with cerebral palsy treated at the Department of Developmental diagnosis, habilitation and rehabilitation of children at the Pediatric Clinic of Clinical Center, Sarajevo University who had received botulin toxin in spastic muscles of the lower extremities. Research data were obtained by examining the history of the disease of observed groups of patients. The total number of observed is a group of 20 patients. Patients were aged 4-18 years. The study was retrospective and all the data are presented in tables and charts using descriptive statistics and through the absolute number of cases, percentage and arithmetic mean with standard deviation.

4. RESULTS

The largest number of children in the sample had 94.03 years (5 or 25%), with an average age of 9 years (range: 4-18 years). In 10 children (50%) is registered a spastic tetraparesis. 80% of

children suering from cerebral palsy has received Botulin toxin for the rst time at the age of 2-6 years. The largest number of children (40%) had 2 appli-

cations of botulin toxin into the muscles of the lower limbs. Before application of the Botulin toxin 50% of children suering from cerebral palsy was clas-

sied as stage IV in GMFCS.

After application of Botulin toxin noticed is improvement or change to a lower level of GMFCS in 50%, of children suering from cerebral palsy.

After application of BT is evident that the measurement of gross muscle forces all respondents, except one change from high to lower levels of GMFCS. The correlation coefficient of GMFCS before and after application of Botulin toxin shows a high statistical signicance, Rho=-0.981, p<0.01.

5. DISCUSSION

Using Botulin toxin, which leads to local haemodenervation, achieved is reduction in tome of spastic muscles in children with cerebral palsy. It is of great importance for the course of treatment because it allows better mobility of joints, prevents contracture, facilitates the work of physiotherapists in the implementation of the development of medical gymnastics and postpones or even makes unnecessary the corrective surgical procedures.

At the Department of Developmental diagnosis, habilitation and rehabilitation of children at the Pediatric Clinic of the Clinical Center, University of Sarajevo, the total number of children with spastic cerebral palsy who received in the period since 2006 until 2010 botulin were 20, of which 9 (45%) were girls and 11 (55%) boys. In 20 children, aged 4-18 years Botulin toxin was injected intramuscularly into the muscles of the lower limbs, as follows: mm. adductores Magni, longi et brevi and mm. gastrocnemio. Analyzing the distribution of CP in studied children, we can see that 10 or 50% had spastic tetraparesis with dominant diaparesis, 7 children or 35% had spastic diaparesis, 2 children or 10% hemiparesis and 1 child or 5% triparesis with dominant spasmodic diaparesis. 16 or 80% of children for the rst time received botulin toxin at the age of 2-6 years, and the remaining 4 or 20%, at age 7-15 years, mean age 5.75 years. Reference literature favors early treatment with botulin toxin before the age of 4 years if we want to improve and facilitate walking, or a child can be treated by the same in any age, for better care and spastic pain relief. Analyzing the application of botulin toxin, we found that 6 or 30% of chil-

Age N %

2- 6 years 16 80.0

7- 15 years 4 20.0

Total 20 100.0

Mean 5.75

Std. deviation 3.626

Minimum 2

Maximum 15

Number of BT applications N %1 6 30.0 2 8 40.0

3 3 15.0

4 2 10.0

5 1 5.0

Total 20 100.0

Table 5. Number of Botulin toxin applications

Age (in years) N %

4 2 10.0 5 2 10.0 6 1 5.07 3 15.08 2 10.0 9 5 25.0 10 1 5.0 15 2 10.0 16 1 5.0 18 1 5.0 Total 20 100.0

Mean 9.00

Standard deviation 4.026

Minimum 4

Maximum 18

Table 2. The gender representation

GMFCS before BTapplication N %

II 4 20.0

III 3 15.0

IV 10 50.0

V 3 15.0

Total 20 100.0

Table 6. Gross Motor Function Classification System (GMFCS) before application of Botulin toxin

GMFCS after BTapplication N %

I 4 20.0

II 3 15.0

III 10 50.0

IV 2 10.0

V 1 5.0

Total 20 100.0

Table 7. Gross Motor Function Classification System (GMFCS) following application of Botulin toxin

Table 1. The age of children suffering from cerebral palsy who had received Botulin toxin

N %

Male 11 55.0

Female 9 45.0

Total 20 100.0

Table 3 Clinical type of cerebral palsy

Cerebral palsy type N %

Diaparesis spastica 7 35.0

Hemipresis cer. lat. dex. 2 10.0

Tetraparesis spastica ppDiaparesis spastica 10 50.0

Triparesis spastica ppDiaparesis spastica 1 5.0

Total 20 100.0

Table 4. Age when the child first received Botulin toxin

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Application of Botulinum Toxin in Treatment of Spasticity and Functional Improvements for Children Suffering from Cerebral Palsy

GMFCS after application

dren suering from cerebral palsy and improve the their mobility, provide better position the individual parts of the body in the supine, sitting or standing position, allowing the possibility of learning new and better pattern of movement, extend the time until surgery and reduces pain in spastic muscle.

REFERENCES

1. Rameckers EA, Duysens J, Speth LA, Vles HJ, Smits-Engelsman BC.Eect of addition of botulin toxin-A to standardized therapy for dynamic manual skills measured with kinematic aiming tasks in children with spastic hemiplegia. J Rehabil Med, 2010 Apr;42(4):332-8.

2. Kaishou Xu, Tiebin Yan, Jianning Mai.A randomized controlled trial to compare two botulin toxin injection techniques on the functional improvement of the leg of children with cerebral palsy.Clin Rehabil, 2009 Sep;23(9):800-11.

3. Hu GC, Chuang YC, Liu JP, Chien KL, Chen YM, Chen YF. Botulinu toxin (Dysport) treatment of the spastic gastrocnemius muscle in children with cerebral palsy: a randomized trial comparing two injection volumes.Clin Rehabil, 2009 Jan;23(1):64-71.

4. Rameckers EA, Speth LA, Duysens J, Vles JS, Smits-Engelsman BC. Botulin toxin-a in children with congenital spastic hemiplegia does not improve upper extremity motor-related function over rehabilitation alone: a randomized controlled trial. Neurorehabil Neural Repair, 2009 Mar-Apr;23(3):218-25. Epub 2008 Dec 23.

5. Bach-Rojecky L, Relja M, Filipovi B, Lackovi Z. Botulin toxin type A and cholinergic system. Lijec Vjesn, 2007 Dec;129(12):407-14.

6. Sawek J. Botulin toxin type A in the treatment of spasticity in cerebral palsy: theoretical and practical foundations of eective therapy. Ortop Traumatol Rehabil, 2001;3(4):541-6.

7. Rameckers EA, Speth LA, Duysens J, Vles JS, Smits-Engelsman BC. Kinematic aiming task: measuring functional changes in hand and arm movements after botulin toxin-A injections in children with spastic hemiplegia. Am J Phys Med Rehabil, 2007 Jul;86(7):538-47.

8. Singhi P, Ray M. Botulin toxin in children with cerebral palsy. Indian J Pediatr, 2004 Dec;71(12):1087-91.

9. Hurvitz EA, Conti GE, Brown SH. Changes in movement characteristics of the spastic upper extremity after botulin toxin injection. Arch Phys Med Rehabil, 2003 Mar;84(3):444-54.

10. Camargo CH, Teive HA, Zonta M, Silva GC, Oliveira MR, Roriz MM, Brandi IV, Becker N, Scola RH, Werneck LC. Botulin toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy. Arq Neuropsiquiatr, 2009 Mar;67(1):62-8.

11. Pea-Segura JL, Marco-Olloqui M, Cabrerizo de Diago R, Prez-Delgado R, Garca-Oguiza A, Lafuente-Hidalgo M, Sebastin-Torres B, Rebage V, Lpez-Pisn J. Early care and botulin toxin. Our experience in the 21 st century. Rev Neurol. 2008;47 Suppl 1:S25-33.

Total

I II III IV V

II N 4 0 0 0 0 4

% 100.0 0.0 0.0 0.0 0.0 20,0

III N 0 3 0 0 0 3

% 0.0 100.0 0.0 0.0 0.0 15,0

IV N 0 0 10 0 0 10

% 0.0 0.0 100.0 0.0 0.0 50,0

V N 0 0 0 2 1 3

% 0.0 0.0 0.0 100.0 100.0 15,0

Total N 4 3 10 2 1 20

% 100,0 100.0 100.0 100.0 100.0 100.0

Table 8. The correlation coefficient of GMFCS before and after Botulin toxin application. Pearson Rho = -0.981, p = 0.0001

GMFCS before application

dren had 1 application, 8 or 40% of children 2 applications of BT, 3 or 15% of children 3 applications of BT, 2 or 10% of children 4 BT applications and one child or 5% had 5 applications of Botulin toxin. The literature does not indicate that the maximum number of applications of BT that patient can receive, but is recommended for each subsequent application of BT to be administered 3 months after the previous. The dose may be repeated even before the symptoms of prior injection completely disappear, but not more frequently than every 2 months. To estimate the severity of cerebral palsy used is ve degrees classication system for gross motor function in cerebral palsy (Gross Motor Function Classication System GMFCS I-V). Before the BT application, for the treated children was determined a GMFCS level, and found that 10 or 50% of children belong to stage IV, 4 or 20% of children belonging to stage II, 3 or 15% of children to stage III and 3 or 15% of children belongs to the GMFCS stage V. After the application Botulin toxin, children suffering from cerebral palsy were clinically re-examined with Gross Motor Function Measure-GMFM and re-determined a degree of GMFCS. These results indicate that 10 or 50% of children now belonged to the third stage, 4 or 20% of children belonging to stage I, 3 or 15% of children belonging to stage II, 2 or 10% in stage IV and 1 or 5% of children belonging to GMFCS stage V. Noted is the decrease in GMFCS level after application of botulin toxin and all the children, except one child moved into a lower category. Only one child remained in the stage V. Statistical analysis of the correlation coeffi-

cient of GMFCS before and after application of Botulin toxin shows a high statistical signicance (Rho=-0.981, p<0.01). Lack of response to the application of botulin toxin rarely occurs but may occur as a result of wrong BT injection, lower applied doses, achievement of the maximum eect only after the second or third application, present static contractions or due to the development of antibodies.

Camargo and colleagues investigated the safety and efficacy of botulin toxin in treating spasticity in 20 children with spasmodic diplegia as a form of cerebral palsy. All patients received injections into the muscles of the lower limbs, and 15 patients in the adductors of the thighs. The total dose ranges 70-140 U (99.75 +/- 16.26 U), or 7.45 +/-2.06 U/ Kg per patient. After the applications have been recognized signicant improvements in gait in patients with a signicant increase in ankle exibility. They concluded that botulin toxin is safe and eective in the treatment of spasticity in children suering from cerebral paralysis, but that the functional changes are temporary (10). Pena-Segura and colleagues investigated the eect of botulin toxin in 702 children with cerebral palsy with positive results in reducing muscle spasms in the limbs in 70% of children (11). Based on our research and investigations of numerous authors, it is evident that botulin toxin signicantly reduces muscle spasm in children with cerebral palsy.

6. CONCLUSION

Botulin toxin is eective in the conservative treatment of spasticity in chil-

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