Gait classification for growing children with Duchenne muscular dystrophy.

Classifying gait patterns into homogeneous groups could enhance communication among healthcare providers, clinical decision making and clinical trial designs in boys with Duchenne muscular dystrophy (DMD). Sutherland's classification has been developed 40 years ago. Ever since, the state-of-the-art medical care has improved and boys with DMD are now longer ambulatory. Therefore, the gait classification requires an update. The overall aim was to develop an up-to-date, valid DMD gait classification. A total of 137 three-dimensional gait analysis sessions were collected in 30 boys with DMD, aged 4.6-17 years. Three classes were distinguished, which only partly aligned with increasing severity of gait deviations. Apart from the mildly affected pattern, two more severely affected gait patterns were found, namely the tiptoeing pattern and the flexion pattern with distinct anterior pelvic tilt and posterior trunk leaning, which showed most severe deviations at the ankle or at the proximal segments/joints, respectively. The agreement between Sutherland's and the current classification was low, suggesting that gait pathology with the current state-of-the-art medical care has changed. However, overlap between classes, especially between the two more affected classes, highlights the complexity of the continuous gait changes. Therefore, caution is required when classifying individual boys with DMD into classes.

The influence of ankle-foot orthoses on gait pathology in children with cerebral palsy: A retrospective study.

BACKGROUND: Ankle-foot orthoses (AFOs) are frequently prescribed in children with cerebral palsy (CP) to improve their gait. Due to the heterogeneous nature of CP and contradictions among previous studies, it is important to evaluate the AFO-specific effects, as well as explore their effects on different gait patterns. RESEARCH QUESTIONS: a) What are the prevalence and specific features of AFOs in children with CP? b) How do AFOs affect gait pathology in children with CP? c) What are the pattern-specific effects of AFOs in children with CP? METHODS: A group of 170 patients with CP underwent a three-dimensional gait analysis with and without AFOs (either carbon fiber, rigid, flexible or hinged). The gait profile score, the gait variable scores of the hip, knee and ankle joints, non-dimensional step length and walking speed were used as outcome measures. The AFO-specific effects on the kinematic and kinetic waveforms were investigated using statistical non-parametric mapping (SnPM). Effects were considered relevant when the minimal clinically important difference (MCID) or the standard errors of measurement, for the parameters or the waveforms respectively, were exceeded. RESULTS: Rigid AFOs were prescribed for more than 80 % of the children. Significant beneficial effects were observed for non-dimensional step length and walking speed. Most changes in gait indices were not considered relevant. The SnPM-analyses on the total group and specific gait patterns revealed that walking with AFOs improved the kinematic and kinetic waveforms. These effects were relevant, and were most obvious for crouch, apparent equinus and the total group. SIGNIFICANCE: The use of AFOs improves gait, whether we inspect a total -and thus heterogeneous- group or focus on specific gait patterns. However, focussing on specific parameters (i.e. general gait indices) does not provide a full picture of the AFO-effects.

The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy.

Children with spastic cerebral palsy (SCP) are often treated with intramuscular Botulinum Neurotoxin type-A (BoNT-A). Recent studies demonstrated BoNT-A-induced muscle atrophy and variable effects on gait pathology. This group-matched controlled study in children with SCP compared changes in muscle morphology 8-10 weeks post-BoNT-A treatment (n = 25, median age 6.4 years, GMFCS level I/II/III (14/9/2)) to morphological changes of an untreated control group (n = 20, median age 7.6 years, GMFCS level I/II/III (14/5/1)). Additionally, the effects on gait and spasticity were assessed in all treated children and a subgroup (n = 14), respectively. BoNT-A treatment was applied following an established integrated approach. Gastrocnemius and semitendinosus volume and echogenicity intensity were assessed by 3D-freehand ultrasound, spasticity was quantified through electromyography during passive muscle stretches at different velocities. Ankle and knee kinematics were evaluated by 3D-gait analysis. Medial gastrocnemius (p = 0.018, -5.2%) and semitendinosus muscle volume (p = 0.030, -16.2%) reduced post-BoNT-A, but not in the untreated control group, while echogenicity intensity did not change. Spasticity reduced and ankle gait kinematics significantly improved, combined with limited effects on knee kinematics. This study demonstrated that BoNT-A reduces spasticity and partly improves pathological gait but reduces muscle volume 8-10 weeks post-injections. Close post-BoNT-A follow-up and well-considered treatment selection is advised before BoNT-A application in SCP.

Muscle synergy structure and gait patterns in children with spastic cerebral palsy.

AIM: To determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP). METHOD: In this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns. RESULTS: Synergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high. INTERPRETATION: The similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.

Structural Brain Lesions and Gait Pathology in Children With Spastic Cerebral Palsy.

The interaction between brain damage and motor function is not yet fully understood in children with spastic cerebral palsy (CP). Therefore, a semi-quantitative MRI (sqMRI) scale was used to explore whether identified brain lesions related to functional abilities and gait pathology in this population. A retrospective cohort of ambulatory children with spastic CP was selected [N = 104; 52 bilateral (bCP) and 52 unilateral (uCP)]. Extent and location-specific scores were defined according to the sqMRI scale guidelines. The gross motor function classification system (GMFCS), the gait profile score (GPS), GPSs per motion plane, gait variable scores (GVS) and multiple-joint (MJ) gait patterns were related to brain lesion scores. In all groups, the global total brain scores correlated to the GPS (total: r s = 0.404, p ≤ 0.001; bCP: r s = 0.335, p ≤ 0.05; uCP: r s = 0.493, p ≤ 0.001). The global total hemispheric scores correlated to the GMFCS (total: r s = 0.392, p ≤ 0.001; bCP: r s = 0.316, p ≤ 0.05; uCP: r s = 0.331, p ≤ 0.05). The laterality scores of the hemispheres in the total group correlated negatively to the GMFCS level (r s = -0.523, p ≤ 0.001) and the GVS-knee sagittal (r s = -0.311, p ≤ 0.01). Lesion location, for the total group demonstrated positive correlations between parietal lobe involvement and the GPS (r s = 0.321, p ≤ 0.001) and between periventricular layer damage and the GMFCS (r s = 0.348, p ≤ 0.001). Involvement of the anterior part of the corpus callosum (CC) was associated with the GVS-hip sagittal in all groups (total: r pb = 0.495, p ≤ 0.001; bCP: r pb = 0.357, p ≤ 0.05; uCP: r pb = 0.641, p ≤ 0.001). The global total hemispheric and laterality of the hemispheres scores differentiated between the minor and both the extension (p ≤ 0.001 and p ≤ 0.001) and flexion (p = 0.016 and p = 0.013, respectively) MJ patterns in the total group. Maximal periventricular involvement and CC intactness were associated with extension patterns (p ≤ 0.05 and p ≤ 0.001, respectively). Current findings demonstrated relationships between brain structure and motor function as well as pathological gait, in this cohort of children with CP. These results might facilitate the timely identification of gait pathology and, ultimately, guide individualized treatment planning of gait impairments in children with CP.

Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

Physics-based simulations of walking have the theoretical potential to support clinical decision-making by predicting the functional outcome of treatments in terms of walking performance. Yet before using such simulations in clinical practice, their ability to identify the main treatment targets in specific patients needs to be demonstrated. In this study, we generated predictive simulations of walking with a medical imaging based neuro-musculoskeletal model of a child with cerebral palsy presenting crouch gait. We explored the influence of altered muscle-tendon properties, reduced neuromuscular control complexity, and spasticity on gait dysfunction in terms of joint kinematics, kinetics, muscle activity, and metabolic cost of transport. We modeled altered muscle-tendon properties by personalizing Hill-type muscle-tendon parameters based on data collected during functional movements, simpler neuromuscular control by reducing the number of independent muscle synergies, and spasticity through delayed muscle activity feedback from muscle force and force rate. Our simulations revealed that, in the presence of aberrant musculoskeletal geometries, altered muscle-tendon properties rather than reduced neuromuscular control complexity and spasticity were the primary cause of the crouch gait pattern observed for this child, which is in agreement with the clinical examination. These results suggest that muscle-tendon properties should be the primary target of interventions aiming to restore an upright gait pattern for this child. This suggestion is in line with the gait analysis following muscle-tendon property and bone deformity corrections. Future work should extend this single case analysis to more patients in order to validate the ability of our physics-based simulations to capture the gait patterns of individual patients pre- and post-treatment. Such validation would open the door for identifying targeted treatment strategies with the aim of designing optimized interventions for neuro-musculoskeletal disorders.

Are spasticity, weakness, selectivity, and passive range of motion related to gait deviations in children with spastic cerebral palsy? A statistical parametric mapping study.

This study aimed to identify the relationships between clinical impairments and gait deviations in children with cerebral palsy (CP). A retrospective convenience sample of 367 children with CP was selected (3-18 years old) and divided in two groups based on clinical symptomatology [unilateral (uCP) / bilateral CP (bCP), (n = 167/200)]. All children underwent a three-dimensional gait analysis and a standardized clinical examination. Gait was inspected on a vector level (all sagittal motions combined), and an individual joint level (pelvis, hip, knee and ankle joint motions). Statistical non-parametric mapping was applied to identify specific parts of the gait cycle displaying relationships between the gait deviations of both groups and the impairment scores of spasticity, weakness, selectivity, and passive range of motion. Impairment scores were summarized in two ways: a) composite impairment scores (e.g. combined spasticity of all assessed muscles acting around the hip, knee and ankle joints) and b) joint specific impairment scores (e.g. spasticity of the muscles acting around the knee joint). Results showed that the vector and most of the individual motions were related to the composite scores. Direct and carry-over relationships were found between certain individual motions and joint impairment scores (around the same or neighboring joints, respectively). All correlations were more prominent for children with bCP compared to uCP, especially regarding the relationships of gait deviations with weakness and reduced selectivity. In conclusion, this study enabled the mapping of relationships between clinical impairments and gait deviations in children with CP, by identifying specific parts of the gait cycle that are related to each of these impairments. These results provide a comprehensive description of these relationships, while simultaneously highlighting the differences between the two CP groups. Integration of these findings could lead to a better understanding of the pathophysiology of gait deviations and, eventually, support individualized treatment planning.

SimCP: A Simulation Platform to Predict Gait Performance Following Orthopedic Intervention in Children With Cerebral Palsy.

Gait deficits in cerebral palsy (CP) are often treated with a single-event multi-level surgery (SEMLS). Selecting the treatment options (combination of bony and soft tissue corrections) for a specific patient is a complex endeavor and very often treatment outcome is not satisfying. A deterioration in 22.8% of the parameters describing gait performance has been reported and there is need for additional surgery in 11% of the patients. Computational simulations based on musculoskeletal models that allow clinicians to test the effects of different treatment options before surgery have the potential to drastically improve treatment outcome. However, to date, no such simulation and modeling method is available. Two important challenges are the development of methods to include patient-specific neuromechanical impairments into the models and to simulate the effect of different surgical procedures on post-operative gait performance. Therefore, we developed the SimCP framework that allows the evaluation of the effect of different simulated surgeries on gait performance of a specific patient and includes a graphical user interface (GUI) that enables performing virtual surgery on the models. We demonstrated the potential of our framework for two case studies. Models reflecting the patient-specific musculoskeletal geometry and muscle properties are generated based solely on data collected before the treatment. The patient's motor control is described based on muscle synergies derived from pre-operative EMG. The GUI is then used to modify the musculoskeletal properties according to the surgical plan. Since SEMLS does not affect motor control, the same motor control model is used to define gait performance pre- and post-operative. We use the capability gap (CG), i.e., the difference between the joint moments needed to perform healthy walking and the joint moments the personalized model can generate, to quantify gait performance. In both cases, the CG was smaller post- then pre-operative and this was in accordance with the measured change in gait kinematics after treatment.

Systematic review on gait classifications in children with cerebral palsy: An update.

BACKGROUND: Gait classification systems (GCSs) aim to aid clinicians and researchers in categorizing the gait of pathological populations, with the intent to improve the communication between them, to support treatment planning and enable the evaluation of patients over time. Throughout the years, various GCSs have been defined for children with cerebral palsy (CP), which were first summarized in a systematic review published in 2007. RESEARCH QUESTION: The current systematic review aimed to: a) identify GCSs that have been more recently developed, b) appraise their methodological quality and c) specify the most commonly used multiple joint gait patterns for children with CP reported in literature. METHODS: Four databases (Medline, EMBASE, CINAHL, Web of Science) were searched until July 2017. Several forms of validity and the reliability of these studies were assessed according to the principles of the consensus-based standards for the selection of health measurement instruments checklist or criteria defined in the original review. All published GCSs were also scrutinized in order to identify multiple joint patterns that have reached a predefined level of consensus. RESULTS: Thirty-six studies were considered in this review, 15 of them being GCSs that were not included in the original review. The validity, reliability and clinical applicability of all GCSs was reported, including 3 studies from the original review. Six multiple joint patterns for children with CP reached a consensus in literature. CONCLUSION: Since the previous review, obvious progress has been made in the field of GCSs for CP, resulting in improved methodological quality of the majority of published GCSs. This encouraged the applicability of GCSs in clinical or research settings. The six reliable, valid and commonly used multiple joint patterns, emerging from this systematic review, may aid clinical and research applications and create a common language among healthcare providers.

Combining muscle morphology and neuromotor symptoms to explain abnormal gait at the ankle joint level in cerebral palsy.

BACKGROUND: Individuals with spastic cerebral palsy (CP) have neuromotor symptoms contributing towards their gait patterns. However, the role of altered muscle morphology alongside these symptoms is yet to be fully investigated. RESEARCH QUESTION: To what extent can medial gastrocnemius and tibialis anterior volume and echo-intensity, plantar/dorsiflexion strength and selective motor control, plantarflexion spasticity and passive ankle dorsiflexion explain abnormal ankle gait. METHOD: In thirty children and adolescents with spastic CP (8.6 ± 3.4 y/mo) and ten typically developing peers (9.9 ± 2.4 y/mo), normalised muscle volume and echo-intensity were estimated. Both cohorts also underwent three-dimensional gait analysis, whilst for participants with spastic CP, plantar/dorsi-flexion strength and selective motor control, plantarflexion spasticity and maximum ankle dorsiflexion were also measured. The combined contribution of these parameters towards five clinically meaningful features of gait were evaluated, using backwards multiple regression analyses. RESULTS: With respect to the typically developing cohort, the participants with spastic CP had deficits in normalised medial gastrocnemius and tibialis anterior volume of 40% and 33%, and increased echo-intensity values of 19% and 16%, respectively. The backwards multiple regression analyses revealed that the combination of reduced ankle dorsiflexion, muscle volume, plantarflexion strength and dorsiflexion selective motor control could account for 12-62% of the variance in the chosen features of gait. SIGNIFICANCE: The combination of altered muscle morphology and neuromotor symptoms partly explained abnormal gait at the ankle in children with spastic CP. Both should be considered as important measures for informed treatment decision-making, but further work is required to better unravel the complex pathophysiology.

Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

OBJECTIVES: Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions. METHODS: DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined. RESULTS: The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes. CONCLUSIONS: Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome.

Does expert knowledge improve automatic probabilistic classification of gait joint motion patterns in children with cerebral palsy?

BACKGROUND: This study aimed to improve the automatic probabilistic classification of joint motion gait patterns in children with cerebral palsy by using the expert knowledge available via a recently developed Delphi-consensus study. To this end, this study applied both Naïve Bayes and Logistic Regression classification with varying degrees of usage of the expert knowledge (expert-defined and discretized features). A database of 356 patients and 1719 gait trials was used to validate the classification performance of eleven joint motions. HYPOTHESES: Two main hypotheses stated that: (1) Joint motion patterns in children with CP, obtained through a Delphi-consensus study, can be automatically classified following a probabilistic approach, with an accuracy similar to clinical expert classification, and (2) The inclusion of clinical expert knowledge in the selection of relevant gait features and the discretization of continuous features increases the performance of automatic probabilistic joint motion classification. FINDINGS: This study provided objective evidence supporting the first hypothesis. Automatic probabilistic gait classification using the expert knowledge available from the Delphi-consensus study resulted in accuracy (91%) similar to that obtained with two expert raters (90%), and higher accuracy than that obtained with non-expert raters (78%). Regarding the second hypothesis, this study demonstrated that the use of more advanced machine learning techniques such as automatic feature selection and discretization instead of expert-defined and discretized features can result in slightly higher joint motion classification performance. However, the increase in performance is limited and does not outweigh the additional computational cost and the higher risk of loss of clinical interpretability, which threatens the clinical acceptance and applicability.

Prevalence of Joint Gait Patterns Defined by a Delphi Consensus Study Is Related to Gross Motor Function, Topographical Classification, Weakness, and Spasticity, in Children with Cerebral Palsy.

During a Delphi consensus study, a new joint gait classification system was developed for children with cerebral palsy (CP). This system, whose reliability and content validity have previously been established, identified 49 distinct joint patterns. The present study aims to provide a first insight toward the construct validity and clinical relevance of this classification system. The retrospective sample of convenience consisted of 286 patients with spastic CP (3-18 years old, GMFCS levels I-III, 166 with bilateral CP). Kinematic and kinetic trials from three-dimensional gait analysis were classified according to the definitions of the Delphi study, and one classified trial was randomly selected for each included limb (n = 446). Muscle weakness and spasticity were assessed for different muscle groups acting around the hip, knee, and ankle. Subsequently, Pearson Chi square tests, Cramer's V, and adjusted standardized residuals were calculated to explore the strength and direction of the associations between the joint patterns, and the different patient-specific characteristics (i.e., age, GMFCS level, and topographical classification) or clinical symptoms (muscle weakness and spasticity). Patient-specific characteristics showed several significant associations with the patterns of different joints, but the strength of most identified associations was weak. Apart from the knee during stance phase and the pelvis in the sagittal plane, the results systematically showed that the patterns with "minor gait deviations" were the most frequently observed. These minor deviations were found significantly more often in limbs with a lower level of spasticity and good muscle strength. Several other pathological joint patterns were moderately associated with weakness or spasticity, including but not limited to "outtoeing" for weakness and "intoeing" for spasticity. For the joints in the sagittal plane, significantly stronger associations were found with muscle weakness and spasticity, possibly because most of the evaluated muscles in this study mainly perform sagittal plane motions. Remarkably, the hip patterns in the coronal plane did not associate significantly with any of the investigated variables. Although further validation is warranted, this study contributes to the construct validity of the joint patterns of the Delphi consensus study, by demonstrating their ability to distinguish between clinically relevant subgroups in CP.

Inter- and intrarater clinician agreement on joint motion patterns during gait in children with cerebral palsy.

AIM: This study aimed to quantify the inter- and intrarater clinician agreement on joint motion patterns in children with spastic cerebral palsy (CP), which were recently specified by a Delphi consensus study. It also examined whether experience with three-dimensional gait analysis (3DGA) is a prerequisite for using the patterns. METHOD: The experimental group consisted of 82 patients with CP (57 males, 25 females; uni-/bilateral CP [n=27/55]; Gross Motor Function Classification System levels I to III; mean age 9y 5mo [range 4y-18y]). Thirty-two clinicians were split into 'experienced' and 'inexperienced' rater groups. Each rater was asked to classify 3DGA reports of 27 or 28 patients twice. Inter- and intrarater agreement on 49 joint motion patterns was estimated using percentage of agreement and kappa statistics. RESULTS: Twenty-eight raters completed both classification rounds. Intrarater agreement was 'substantial' to 'almost perfect' for all joints (0.64<ĸ<0.91). Interrater agreement reached similar results (0.63<ĸ<0.86), except for the knee patterns during stance (ĸ=0.49, 'moderate agreement'). Experienced raters performed significantly better on patterns of the knee during stance and ankle during swing. INTERPRETATION: Apart from some specific knee patterns during stance and ankle patterns during swing, the results suggested that clinicians could use predefined joint motion patterns in CP with good confidence, even in case of limited experience with 3DGA.

Statistical Parametric Mapping to Identify Differences between Consensus-Based Joint Patterns during Gait in Children with Cerebral Palsy.

Experts recently identified 49 joint motion patterns in children with cerebral palsy during a Delphi consensus study. Pattern definitions were therefore the result of subjective expert opinion. The present study aims to provide objective, quantitative data supporting the identification of these consensus-based patterns. To do so, statistical parametric mapping was used to compare the mean kinematic waveforms of 154 trials of typically developing children (n = 56) to the mean kinematic waveforms of 1719 trials of children with cerebral palsy (n = 356), which were classified following the classification rules of the Delphi study. Three hypotheses stated that: (a) joint motion patterns with 'no or minor gait deviations' (n = 11 patterns) do not differ significantly from the gait pattern of typically developing children; (b) all other pathological joint motion patterns (n = 38 patterns) differ from typically developing gait and the locations of difference within the gait cycle, highlighted by statistical parametric mapping, concur with the consensus-based classification rules. (c) all joint motion patterns at the level of each joint (n = 49 patterns) differ from each other during at least one phase of the gait cycle. Results showed that: (a) ten patterns with 'no or minor gait deviations' differed somewhat unexpectedly from typically developing gait, but these differences were generally small (≤3°); (b) all other joint motion patterns (n = 38) differed from typically developing gait and the significant locations within the gait cycle that were indicated by the statistical analyses, coincided well with the classification rules; (c) joint motion patterns at the level of each joint significantly differed from each other, apart from two sagittal plane pelvic patterns. In addition to these results, for several joints, statistical analyses indicated other significant areas during the gait cycle that were not included in the pattern definitions of the consensus study. Based on these findings, suggestions to improve pattern definitions were made.

Literature Review and Comparison of Two Statistical Methods to Evaluate the Effect of Botulinum Toxin Treatment on Gait in Children with Cerebral Palsy.

AIM: This study aimed at comparing two statistical approaches to analyze the effect of Botulinum Toxin A (BTX-A) treatment on gait in children with a diagnosis of spastic cerebral palsy (CP), based on three-dimensional gait analysis (3DGA) data. Through a literature review, the available expert knowledge on gait changes after BTX-A treatment in children with CP is summarized. METHODS: Part 1--Intervention studies on BTX-A treatment in children with CP between 4-18 years that used 3DGA data as an outcome measure and were written in English, were identified through a broad systematic literature search. Reported kinematic and kinetic gait features were extracted from the identified studies. Part 2--A retrospective sample of 53 children with CP (6.1 ± 2.3years, GMFCS I-III) received 3DGA before and after multilevel BTX-A injections. The effect of BTX-A on gait was interpreted by comparing the results of paired samples t-tests on the kinematic gait features that were identified from literature to the results of statistical parametric mapping analysis on the kinematic waveforms of the lower limb joints. RESULTS: Part 1-53 kinematic and 33 kinetic features were described in literature. Overall, there is no consensus on which features should be evaluated after BTX-A treatment as 49 features were reported only once or twice. Part 2--Post-BTX-A, both statistical approaches found increased ankle dorsiflexion throughout the gait cycle. Statistical parametric mapping analyses additionally found increased knee extension during terminal stance. In turn, feature analyses found increased outtoeing during stance after BTX-A. CONCLUSION: This study confirms that BTX-A injections are a valuable treatment option to improve gait function in children with CP. However, different statistical approaches may lead to different interpretations of treatment outcome. We suggest that a clear, definite hypothesis should be stated a priori and a commensurate statistical approach should accompany this hypothesis.