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1 This article was downloaded by:[casa di Cura San Raffaele] On: 17 January 2007 Access Details: [subscription number ] Publisher: Informa Healthcare Informa Ltd Registered in England and Wales Registered Number: Registered office: Mortimer House, Mortimer Street, London W1T 3JH, UK Disability & Rehabilitation Publication details, including instructions for authors and subscription information: Computerized gait analysis of Botulinum Toxin treatment in children with cerebral palsy Manuela Galli a ; Veronica Cimolin a ; Enza Valente; Marcello Crivellini a ; Tamara Ialongo; Giorgio Albertini a a ManuelaGalliVeronicaCimolinEnzaMariaValenteMarcelloCrivelliniTamaraIalongoGiorgioAlbertiniDipartimento di Bioingegneria, Politecnico di Milano, MilanoIRCCS San Raffaele Pisana, Tosinvest Sanita, RomaIRCCS Istituto CSS-Mendel, RomaIstituto di Neurologia, Università Cattolica, RomaSan Raffaele Cassino, Tosinvest Sanità, Roma, Italy. First Published on: 29 November 2006 To link to this article: DOI: / URL: Full terms and conditions of use: This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Taylor and Francis 2007

2 Disability and Rehabilitation, 2006; 1 6, PrEview article RESEARCH PAPER Computerized gait analysis of Botulinum Toxin treatment in children with cerebral palsy MANUELA GALLI 1, VERONICA CIMOLIN 1, ENZA MARIA VALENTE 2,3, MARCELLO CRIVELLINI 1, TAMARA IALONGO 2,4 & GIORGIO ALBERTINI 5 1 Dipartimento di Bioingegneria, Politecnico di Milano, Milano, 2 IRCCS San Raffaele Pisana, Tosinvest Sanita, Roma, 3 IRCCS Istituto CSS-Mendel, Roma, 4 Istituto di Neurologia, Università Cattolica, Roma, and 5 San Raffaele Cassino, Tosinvest Sanità, Roma, Italy Accepted August 2006 Abstract Purpose. Intramuscular botulinum toxin A (BTA) injection is a local reversible treatment with a wide range of therapeutic applications, including temporary reduction of spasticity. The aim of this work was a quantitative, computerized objective evaluation of BTA-induced improvement of the walking functional ability in a group of children with cerebral palsy (CP). Methods. Fifteen children with CP and 20 healthy children were evaluated. All patients were equinus walkers without fixed contractures of triceps surae muscles and they were evaluated before and after about 1.5 months from BTA injections into the calf muscles. The effectiveness of treatment was evaluated by 3D computerized gait analysis. Results. Data analysis revealed a significant improvement of equinus foot and ankle range of motion during gait after BTA injection. Positive effects were evident also at the knee joint as documented by the improvement of kinetics characteristics (moment and power). Conclusions. Computerized gait analysis is a valid method for quantification of BTA effect on walking in children with CP, allowing a detailed evaluation of improvement at each joint and a quantitative evaluation of treatment outcome. Keywords: Botulinum Toxin A, cerebral palsy, equinus foot, gait analysis, gastrocnemius Introduction Intramuscular botulinum toxin type A (BTA) is a potent neurotoxin produced by Clostridium Botulinum. It binds to the presinaptic membranes of cholinergic motor neurones and, once internalized, it cleaves components of the cells exocytotic machinery, preventing the discharge of acetylcholine-containing vesicles and hence neurotransmission at the neuromuscular junction [1 3]. Consequently, injection of BTA into selected muscles produces dose-dependent chemical denervation resulting in reduced muscular activity lasting about weeks [4]. Over the past 10 years, BTA has been used to treat focal spasticity in children with cerebral palsy (CP). In literature, some studies [5 13] evaluated the effects of BTA injections into the triceps surae e/o hamstring muscle groups in children affected by CP, using gait analysis (GA). GA is a computerized analysis of gait which allows the quantifying of the limitation in gait function compared to the normal range. In particular, GA quantifies kinematics (angles, velocities, accelerations) in 3D of main joints (pelvis, hip, knee and ankle joints), kinetics (forces, moments, power) and muscles activation contemporaneously in a simple, multifactorial and non invasive way. For this reason, GA is particularly useful to quantify treatment outcomes and, in case of BTA treatment, it allows the measuring of treatmentrelated improvement and its duration. Previous studies presented both the effectiveness of the BTA for treatment of spasticity in CP patients and the key role of GA in the evaluation of its effects; in particular they showed that injections into calf muscles had effects mainly on sagittal ankle Correspondence: Prof. Manuela Galli, PhD, Bioeng. Dept, Politecnico di Milano, P.zza Leonardo da Vinci 32, Milano (IT). Tel: þ Fax: þ manuela.galli@biomed.polimi.it ISSN print/issn online ª 2006 Informa UK Ltd. DOI: /

3 2 M. Galli et al. kinematics and kinetics, demonstrating the BTA efficacy for the treatment of equinus foot, while those into hamstring muscle exhibited their effectiveness generally on the knee joint. However, their limits are that they focused mainly on the joint with kinematics related to the treated muscle (i.e., ankle joint if the treated muscle was the calf muscle) while other joints, not directly related to the treated muscle, were neglected, such as the hip joint, or poorly investigated, the knee joint. The evaluation of biomechanical strategy on proximal joints, such as the hip joint, has been revealed to be significant from a clinical viewpoint, because it could highlight possible compensatory patterns due to the treatment on distal joints. The main effect of inoculation into the gastrocnemius muscle group is the reduction of equinus foot deformity. The new foot position during gait which is directly connected to the reduction of calf muscle spasticity could produce a new biomechanical strategy, not only at distal but also at proximal joints. The aim of the current study was to quantify with GA the effects of the treatment on overall gait ability, highlighting the effects of treatment not only at the joint interested by the treatment but also at all joints involved in gait. Methods Fifteen children (7 with diparesis and 8 with hemiparesis) with CP and dynamic calf contracture, selected for BTA treatment and able to walk independently, were included in this study. The following criteria were met for subject selection, diagnosis of CP, problems with pure dynamic equinus due to increased spasticity in the calf muscle without other muscle involvement, no fixed contractures in the lower limbs, no prior orthopaedic surgery in the lower extremities and no previous injections of BTA. All patients were independent ambulators without the assistance of aids. A control group of 20 healthy children was included. All the subjects were volunteers and their parents gave their informed consent to the children s participation in the study. This study was approved by the ethics committee of IRCCS San Raffaele, Tosinvest Sanità, in Rome, Italy. BTA was injected into the calf muscle of the patients; two sites of injection (medial and lateral gastrocnemius muscle) were used with an initial dose of 2 6 U/kg body weight per muscle (BOTOX@, Allergan Inc.). Hemiparetic subjects had the total dosage injected into one leg, while diparetic children had the dosage split evenly between the two legs. In the case of asymmetric subjects, the clinician chose to treat the more severely affected side only. The patients after the BTA injections were treated with a rehabilitation programme based on cognitive training on motor control. The rehabilitation sections were applied at least 3 days for each week. A clinical team made up of a paediatric orthopaedic surgeon, a paediatric neurologist and a physical therapist examined each child. Each patient was evaluated before the injection (pre: mean months) and after the injection in one post treatment session (post: mean 1.5 þ 0.5 months). The complete evaluation consisted of three components: Clinical examination, videotaping and three-dimensional GA. GA was performed in the Gait Analysis Laboratory at IRCCS San Raffaele in Rome, Italy. Three-dimensional GA was conducted using the following equipment:. A 12-camera optoelectronic system with passive markers (ELITE2002, BTS S.p.A., Milan, Italy [14]) working at a sampling rate of 100 Hz, to measure the kinematic of movement;. Two force platforms (Kistler, CH), to obtain the kinetic data of movement (i.e., ground reaction forces);. Two TV camera Video system (BTS S.p.A., Milan, Italy) synchronized with the optoelectronic and force platform systems for videorecording. To evaluate the kinematics of each body segment, markers were positioned as described by Davis et al. [15]. In particular the kinematics of the pelvis was defined by three markers positioned respectively on right and left anterior superior iliac spines and on the sacrum, the thigh was defined by three markers positioned on the hip joint on the femoral condyle and in the middle of the thigh, the leg by three markers positioned on tibial condyle on the malleolus and on the middle of the tibial and the foot was defined by three markers positioned on external malleolus, V8 metatarsal joint and on the heel. Starting from the 3-D coordinates of the three markers fixed with each segment (pelvis, thigh, leg and foot), a rigid frame was computed; the Euler angles between two frames are the flex-extension, abdo-adduction and intra-extra rotation of principal joint (hip, knee, ankle joints) [15]. The subjects, after marker placement, were asked to walk barefoot at their own natural pace (selfselected speed) along a 10-m walkway containing the force platforms at the mid-point. Six trials were collected for each child in order to guarantee reproducibility of results. Kinetic data reduction was based on Euler s equations of motion [15]. All graphs obtained from GA were normalized as % of gait cycle. By the analysis of these graphs, some parameters were defined and analysed before and

4 Gait analysis of BTA treatment in CP children 3 after the injections (like time/distance parameters, angles joint values in specific gait cycle instant, joint range of motion, peak values in joint power graphs) in order to evaluate the effects of BTA treatment into the calf muscle. In particular the following parameters were evaluated for kinematics of the gait:. Walking velocity (m/sec);. Duration of the stance and swing phase (as % of the gait);. The angle between the foot (defined from the coordinates of markers placed on malleolus and on 5th metatarsal head) and the ground on sagittal plane, not obtained directly by GA and called b angle (Figure 1);. The values of plantarflexion of ankle joint (AIC), the angle of flexion of knee joint (KIC) and the angle of flexion of hip joint (HIC) at the contact of the foot with the ground (i.e., Initial Contact or IC);. The values of maximal dorsiflexion of the ankle (A-Max) the maximal flexion of the knee (K-Max) during the gait cycle;. The values of minimal plantarflexion of the ankle (A-Min), the values of minimal flexion of the knee (K-Min) and the angle of minimal extension of the hip (H-Min) during the gait cycle;. The range of motion of ankle joint (A-ROM) of the knee joint (K-ROM) and hip joint (H-ROM) and the range of motion of pelvis in sagittal plane (PT-ROM) during the gait cycle. For the evaluation of joint kinetics we evaluated:. The ankle joint power in sagittal plane considering in particular the maximum value of absorbed power during loading response and mid-stance (maximum value of negative ankle power during loading response and mid-stance) (A1) representing the ability to absorb the impact of the foot to the ground and the maximum value of generated ankle power during terminal stance (maximum value of positive ankle power during terminal stance) (A2) representing the push off ability of the foot during walking;. The knee joint power in sagittal plane considering in particular the maximum value of generated power during stance phase (maximum value of positive knee power during stance phase) (K2) and the maximum value of absorbed power during terminal stance phase (maximum value of negative knee power during terminal stance phase) (K3);. The hip joint power in sagittal plane considering in particular the maximum value of generated hip power in the first phase of stance (maximum value of positive hip power in the first phase of stance) (H1). All the parameters were evaluated for each trial and then the mean value and SD were considered. Parametric and non-parametric tests were applied for statistical analysis to compare healthy and pathological states. Null hypotheses were rejected when probabilities were below 0.05 (p ). Figure 1. b Angle: Angle between the foot and the ground on sagittal plane; it derives from the coordinates of markers placed on malleolus and 5th metatarsal head. Results The mean ages of subjects evaluated in the present study are years (range: 5 11 years) as for children affected by CP and years (range: 5 14 years) as for healthy children. In accordance with other studies, no side effects or complications, either local or generalized, following BTA injection, were found [6,7,16]. In Tables I and II, the mean values (+ standard deviation) of all GA parameters considered in this

5 4 M. Galli et al. Table I. Kinematic parameters (mean and standard deviation) of pre- and post-treatment sessions for CP group and for the control group (*p value ). CP group Control Pre Post group Spatio-temporal parameters Velocity (m/sec) 0.62 (0.09) 0.66 (0.39) 1.07 (0.21) %stance (%gait cycle) (3.63) (3.39) (2.34) Ankle Dorsi-Plantarflexion (degrees) b (5.23) (5.49)* 9.14 (5.29) AIC (4.76) (4.81) (5.14) A-Max 7.91 (4.53) (3.17)* (4.86) A-Min (4.71) (6.97) (6.79) A-ROM (4.17) (5.05)* (6.63) Knee Flex-Extension (degrees) KIC (6.96) (6.29)* 8.54 (5.55) K-Min 3.80 (4.97) 3.12 (6.98) 2.01 (4.36) K-Max (6.58) (7.47)* (5.52) K-ROM (8.12) (7.65)* (6.64) Hip Flex-Extension (degrees) HIC (6.21) (6.03)* (3.99) H-Min 9.39 (8.27) (8.18) (4.51) H-ROM (7.03) (9.04)* (4.47) Pelvic Tilt (degrees) ROM 3.51 (2.04) 3.28 (1.41) 1.75 (0.96) Table II. Kinetic parameters (mean and standard deviation) of pre- and post-treatment session for the CP group and for the control group (*p value ). CP group Control Pre Post group Ankle power (W/kg) A (0.39) (0.37)* (0.29) A (0.41) 1.29 (0.63) 3.75 (1.89) Knee power (W/kg) K (0.33) 0.88 (0.56)* 0.53 (0.36) K (0.72) (1.27) (0.62) Hip power (W/kg) H (0.69) 2.21 (1.08)* 0.84 (0.40) study for the CP group and for control group were reported. In particular, Table I summarizes the results of kinematics, and Table II of kinetics. About time/distance parameters, there were improvements in velocity and in % stance in most subjects but the improvement was not statistically significant. Statistically significant improvements were found in kinematics and kinetics behaviour. Ankle joint Before BTA, all pathological limbs showed an excessive b angle value, in line with equinus foot deformity. After treatment, a more physiological position of the foot in respect to the ground characterized the gait of the treated patients. The changes in b angle value were statistically significant. Of particular interest for the ankle joint was the statistically significant improvement in the dorsiflexion angle represented by the A-Max and by the A-ROM parameter. The reduction of the activation of gastrocnemius permits the tibialis anterior to work better and to produce a good kinematics during walking. With regard to the kinetics, the maximum of generated ankle power (A2 index), that is representative of the push off ability, did not change, while the peak of absorbed ankle power (A1 index), representative of the absorption power during the impact on the ground, reached after-treatment values close to those of the control group. This improvement may be related to a better activity of tibialis anterior that after the treatment it is able to better control the position of the foot on the ground and consequently to reduce the impact of the foot. Knee joint Before treatment, the patients were characterized by a more flexed knee flexion at initial contact (KIC index) respect to the control group. This significantly improved after treatment; the maximal flexion ability (K-max index) also improved and consequently the Range of Motion (K-ROM index). In fact it was expected that reduction of gastrocnemius contraction would improve the kinematics of the knee. Knee joint power (K2 index) increases probably in order to amplify the push-off ability that was reduced for the effect of the temporary paralysis related to the BTA on the gastrocnemius. Hip joint Improvement of hip excursion during gait cycle (H-ROM index) was particularly significant as all patients were characterized by a more flexed hip during the whole gait cycle. Discussion and conclusion The aim of this study was the evaluation with GA of the effects of BTA injection in calf muscle as a conservative treatment of equinus foot in CP children. A number of studies had previously demonstrated a quantitative effectiveness of the treatment. However, the limit of such studies resides in that they only investigated effects on knee and ankle joints. Conversely, we focused on all the joints

6 Gait analysis of BTA treatment in CP children 5 of lower limb including the hip, and on kinematic and kinetic data obtained by GA. The obtained results support the clinical relevance of this study, which showed in a complete way the effects on gait of BTA inoculation for the correction of dynamic equinus foot in CP, underlying the role of GA to evaluate the treatment in an objective, noninvasive way. First, the treatment had positive effects on ankle and knee joints, showing an improvement of angles of these joints at initial contact. This is representative of a better mechanical position of lower limbs for weight acceptance. Secondly, ankle and knee range of motion increased, showing a better movement during the gait cycle. BTA treatment reduced the dominance of the ankle plantarflexors over the antagonist muscles and tibialis anterior was not contrasted by the abnormal gastrocnemius activity any more. It is important to stress that, in most subjects, changes were not only present at distal joints directly associated to gastrocnemius muscle, but also at proximal joints, as the hip, which always showed an improvement in range of motion. Although an improvement in foot position was evident after BTA, we observed an improvement of absorbed power on ankle joint at the beginning of stance phase. It is possible that, before treatment, the antagonist tibialis anterior was not able to perform a good control due to gastrocnemius contraction, and therefore the initial contact occurred roughly. After treatment, the reduced contraction of gastrocnemius permitted the tibialis anterior to work more physiologically and consequently to better control foot positioning to the ground with a reduction of absorbed power. The peak of generated power at ankle joint at terminal stance (A2 index) was also analysed. Before BTA injection, spasticity of triceps surae caused a reduced value of this index, because this muscle complex is not able to strongly contract during terminal stance. After treatment, no significant changes of this index were detected. This result was not unexpected and it is strictly connected to the nature of BTA, which produces a temporary paralysis of the treated muscle. At the hip joint there is a worsening of positive power during the first phase of stance, presenting a larger and longer period of positive power during early stance and higher value of its peak (H1 index) than before the treatment. This result is connected not only with the increased hip flexion at initial contact as affirmed previously, but also with the reduced ankle power during terminal stance (A2 index): the low levels of ankle work resulted in greater amounts of work being done by muscle groups of the hip, in this case by hip extensors [17]. On the basis of these results, it is evident that BTA injection may be considered an effective treatment of dynamic contractures in CP subjects. Future experiments are needed to confirm these data and several important issues must be considered. First, it would be interesting to adopt other indices in order to deepen the investigation of BTA effects. Then, it would be important to determine the time span required for successful treatment; the periods of most rapid growth are likely to be the critical times for injections. Injections in additional muscles other than the gastrocnemius are essential for appropriate management and further studies are needed to determine the safest and most effective manner to accomplish this. It will be interesting to evaluate, including long-term results beyond the first month. Studies need to be carried out to compare the results of BTA injection treatments with other treatment methods using GA. References 1. Ahnert-Hilger G, Bigalke H. 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