Effects of dose and duration of Robot-Assisted Gait Training on walking ability of children affected by cerebral palsy

Abstract

BACKGROUND:

Robot-Assisted Gait Training (RAGT) is a widespread approach for locomotion rehabilitation but information about intervention frequency and duration is still lacking.

OBJECTIVE:

To evaluate the effect of frequency and duration of a RAGT on motor outcome of children affected by Cerebral Palsy (CP).

METHODS:

Forty-four CP children (age 4–17) underwent one among four different intensive trainings with equal dose of intervention, combining Task-Oriented Physiotherapy (TOP) and RAGT: 40 sessions (4 sessions/week) over 10 weeks of sole TOP (group1) or RAGT (group2) or RAGT and TOP (2 $+$ 2 sessions/week; group3); 40 sessions in shorter period (4 weeks) of RAGT and TOP (5 $+$ 5 sessions/week; group4). Each child was assessed before, after the training and after 3 months with: Ashworth, gross motor function measure (GMFM)-88, GMFM-66, six minutes walking test and gait analysis.

RESULTS:

No differences among the 4 protocols were highlighted although both groups with exclusive physiotherapy and RAGT obtained significant improvements in GMFM-88, GMFM-E and GMFM-66 while the mixed approaches did not show significant changes.

CONCLUSION

: Single-treatment approaches seem to be more effective than mixed approaches, independently from the duration (4 or 10 weeks). RAGT seems to have similar effect with respect to the traditional TOP, at least over 10 weeks.

Keywords

Robot-Assisted Gait Training lower limb rehabilitation cerebral palsy frequency and duration of intervention

1. Introduction

Cerebral palsy (CP) is characterized by various abnormal patterns of movement and posture related to defective coordination of movement and/or regulation of muscle tone. Because CP is a neurodevelopmental condition beginning in early childhood and persisting through the lifespan, the motor disabilities interferes with normal developmental and aging processes, which alter its presentation with time [1].

Currently, the standard of care for the motor disorder in CP consists of physical therapy, followed by multiple, and often concurrent, medical and surgical interventions, most intensively in early childhood through preadolescence. The main aim of motor and functional physiotherapy in children with CP is to improve activity and participation and to maintain the status quo or minimize future deformity or disability [2]. In particular, walking ability and efficient gait is often one of the primary goal for children affected by CP: decreased locomotor function is predictive of reduced capacity for activity, participation, and social interaction for these children [3].

In addition to traditional physiotherapy treatment, gait rehabilitation by using technological devices such as robotic orthoses has been recently proposed for gait recovery in children with neurological pathologies [4, 5, 6]. Recently, the use of robot-assisted gait training (RAGT) has become rather widespread across Europe. This technology is composed of a system supporting the body weight while two active orthoses drive the patient’s legs on a treadmill. The rationale of RAGT approach is grounded on some principles of motor learning and neuroplasticity, including that the degree of improvement is often dependent on the amount of practice, the number of repetitions and the goal oriented task. Robotic devices are often integrated with virtual reality in order to increase the patients’ motivation and promote their active participation. RAGT has some potential advantages including patient safety and engagement, movement repeatability and repetitiveness, kinematic consistency of the gait pattern and operation by a single therapist. Moreover, there is some evidence that RAGT training influences cortical organization [7] and thus motor recovery and (re) learning. While this appears to be true in the adult brain, there might be an even bigger window of opportunity during childhood, thanks to their greater neuroplasticity.

Currently, evidence on the positive treatment effects in adult patients with stroke are now confirmed [8] and RAGT has become a widespread approach in the rehabilitation of locomotion also in the paediatric population. However there are controversial results in published research. Several groups reported positive effects of RAGT in the paediatric population and described improvements in standing and walking in children with CP [9] which were maintained after a period of six months [10]. Standing and walking ability, as well as endurance and hip range of motion, showed improvements due to RAGT also in children suffering from acquired brain injury [6]. In contrast, the unique randomized control trial on a group of children with CP observed no significant improvements in spatiotemporal parameters and kinematics [11]. Explanations for the controversial results of the literature might be due to different patient populations, or to different methods of enhancing active participation during training interventions [12]. Furthermore these studies are often preliminary and frequently performed without control groups.

Moreover, no established and well-defined therapeutic schemes involving RAGT are shared between clinics even in the same country, and every institute defines its protocol by means of experience and preliminary data. Often those protocols are used independently from the origin and the level of the impairment even though it has been recently shown that the positive effects of RAGT therapy are linearly associated with gross motor abilities [13]. This is especially true on the developmental age.

Recently, a panel made of people from the most important research groups working with RAGT has established several practical recommendations for RAGT in children with CP, such as age, motivation, and a high personalization of the treatment [14]. However, data about the frequency and the duration of the intervention for the best practice and customization for different therapeutic goals is still lacking, as clearly stated in [14]: “Best therapy intensity, duration, and frequency are topics of ongoing clinical research and still to some extend controversially”.

The aim of the present work was to investigate the effect of four rehabilitative trainings with equal dose of intervention (40 sessions) distributed over different periods (10 weeks or 4 weeks) and with different combinations of Task-Oriented Physiotherapy (TOP) and RAGT in improving motor outcome and locomotion of children affected by CP, with the hope of defining a best clinical practice.

2. Methods

2.1 Participants

Forty-four children (22 males and 22 females, ranging in age from 4 to 17 years) with a diagnosis of spastic bilateral CP [15] were enrolled in this study (demographic details are shown in Table 1). At baseline, the children were classified according to the Gross Motor Function Classification System (GMFCS) [16].

Table 1
Participants’ details at baseline

	TOP 4 sessions/week	RAGT 4 sessions/week	RAGT $+$ TOP-10w	RAGT $+$ TOP-4w
	over 10 weeks	over 10 weeks	2 $+$ 2 sessions/week	2 $+$ 2 sessions/week
			over 10 weeks	over 4 weeks
Sample size	10	12	10	12
Gender (M/F)	5/5	6/6	4/6	7/5
Age ${}^{*}$ (years)	9.3 $\pm$ 3.9	8.0 $\pm$ 3.0	6.8 $\pm$ 2.0	10.8 $\pm$ 2.7
GMFCS (I/III/III)	3/5/2	3/5/4	3/4/3	5/2/5

TOP: Intensive task-oriented physiotherapy; RAGT: Intensive robot-assisted gait training; RAGT $+$ TOP-10w: A combination of physiotherapy exercises and RAGT over 10 weeks; RAGT $+$ TOP-4w: A combination of physiotherapy exercises and RAGT over 4 weeks. ${}^{*}$ means $\pm$ standard deviation.

Inclusion criteria were: 1) ability to communicate pain, fear or discomfort, 2) ability to walk independently with or without the use of assistive devices or orthoses, 3) co-operation for assessment, 4) femur length bigger than 21 cm for an appropriate use of robotic orthoses, and 5) a regular routine in physiotherapy treatment before this study.

Children were excluded if they underwent multi-level surgery within six months before the onset of the study, or Botulinum Toxin A injections within the previous three months or if under baclofen therapy using an implanted infusion pump.

Approval for the study was obtained from the local Ethics Committee of the Institute and a written consent was signed by the parents/caregivers of each child.

2.2 Therapy device

Robot Assisted Gait Training (RAGT program) was conducted using the commercially available Lokomat ${}^{\@setsize{\scriptsize}{9.5pt}{\viiipt}{\@viiipt}\textregistered}$ pro paediatric V6 device (Hocoma, Switzerland). It consists of two orthoses that actively drive the locomotion on a treadmill, thanks to motors at hip and knee joint level. Ankles are fixed in dorsiflexion with two foot lifting belts. The exoskeleton is connected to a body weight support system that provides vertical stability. The software version used was the 6.2.2. During the treatment, the guidance force (GF), the body weight support (BWS) and the treadmill speed can be adjusted according to the ability of the patients via ad hoc software. In order to account for different patients’ anthropometric measures, the Lokomat ${}^{\@setsize{\scriptsize}{9.5pt}{\viiipt}{\@viiipt}\textregistered}$ device (Hocoma, Zurich, CH) with the paediatric or adult orthosis was used. With the femur length between 210 mm and 350 mm the paediatric module was chosen, with femur length greater than 350 mm the adult module was used.

2.3 Protocols of intervention

The enrolled children were sequentially allocated into four training groups, each receiving a training dose of 40 rehabilitation sessions (each lasting 30 minutes), with different duration (10 or 4 weeks), frequency (4 or 10 sessions/week) and types of intervention (RAGT or TOP or both). A schematic representation of the four groups and their intervention protocols is provided in Table 2 and described below:

•
Group 1 – Task-Oriented Physiotherapy (TOP): ten children underwent 40 sessions of exclusive Task-Oriented Physiotherapy, with 4 weekly sessions over 10 weeks of intervention.

For standardization of TOP, several specific exercises aimed at improving gait (sideward walking, backward walking, climbing over obstacles, changing directions during walking, going up and down the stairs), balance, and functional abilities (standing on one leg, standing during throwing and catching a ball), strengthening gluteus and quadriceps muscles, and stretching of hip flexor and hamstrings muscles were selected and were repeated with the same physical therapist.
•
Group 2 – Robot Assisted Gait Training (RAGT): twelve children were assigned to the exclusive RAGT intervention, providing 40 sessions over 10 weeks of exclusive robot assisted gait training (4 sessions/week). During each session, the children walked for 30 minutes with the BWS steady at 50% during the entire duration of the training and the GF at 100%. The gait velocity was set at 1.2 km/h at the beginning for all children and gradually increased to 1.6 km/h for younger children (10% every 5 sessions) and to 2.0 km/h for older (20% every 5 sessions). The gait velocity remained constant during a single treatment session.
•
Group 3 – Robot Assisted Gait Training $+$ Task-Oriented Physiotherapy (RAGT $+$ TOP-10w): ten children were assigned to the combined RAGT $+$ TOP group with a 10 weeks duration of the intervention (2 $+$ 2 sessions/week). The settings of each RAGT session were the same described for group 1. The TOP intervention was settled as for group 2.
•
Group 4 – Robot Assisted Gait Training $+$ Task-Oriented Physiotherapy (RAGT $+$ TOP-4w): twelve children were assigned to a combination of RAGT and TOP with different temporal distribution: forty sessions (20 $+$ 20) over 4 weeks (5 $+$ 5 sessions/week). The TOP intervention was settled as previously described for group 1. During each session of RAGT, the children walked for 30 minutes with a personalized setting of the Lokomat. In particular the physiotherapists could vary the BWS, the GF and the walking speed accordingly to the patients’ abilities, in order to maximize the intensity of the training and to keep the motivation during each session.

Table 2
Schematic representation of intervention protocols

ID Code Description TOP RAGT Personalised Duration Frequency

(weeks) (sessions/week)

Group 1 TOP Intensive task-oriented physiotherapy yes no no 10 4

Group 2 RAGT Intensive robot assisted gait training no yes no 10 4

Group 3 RAGT $+$ Task-oriented physiotherapy $+$ robot yes yes no 10 2 $+$ 2

TOP-10w assisted gait training

Group 4 RAGT $+$ Task-oriented physiotherapy $+$ personalized yes yes yes 4 5 $+$ 5

TOP-4w robot assisted gait training

TOP: Task-oriented physiotherapy; RAGT: Robot-assisted gait training.

2.4 Outcome measures

ID	Code	Description	TOP	RAGT	Personalised	Duration	Frequency
						(weeks)	(sessions/week)
Group 1	TOP	Intensive task-oriented physiotherapy	yes	no	no	10	4
Group 2	RAGT	Intensive robot assisted gait training	no	yes	no	10	4
Group 3	RAGT $+$	Task-oriented physiotherapy $+$ robot	yes	yes	no	10	2 $+$ 2
	TOP-10w	assisted gait training
Group 4	RAGT $+$	Task-oriented physiotherapy $+$ personalized	yes	yes	yes	4	5 $+$ 5
	TOP-4w	robot assisted gait training

The children’s performance during locomotion was assessed before the training (baseline, T0), at the end of the training (T1, after 4 or 10 weeks accordingly to the intervention protocol) and three months after the end of the treatment (T2), allowing an evaluation of both short and long terms variations.

After the baseline classification (gender, age and GMFCS), a GMFM-certified therapist assessed the gross motor ability by applying the Gross Motor Function Measure-88 (GMFM-88) and considered ability in standing (dimension D) and walking (dimension E). GMFM-66 scores were derived from GMFM-88, by using the Gross Motor Ability Estimator software [17]. Minimum Clinically Important Difference (MCID) for variations of GMFM dimension D, E and GMFM-66 were gathered from [18].

An evaluation of the spasticity was provided by the Ashworth scale, which scores the degree of muscular tone between 0 (lack of spasticity) and 4 (severe rigidity).

Gait endurance was assessed by the 6-Minute Walk Test (6MWT) [19], during which the children were instructed to cover as much distance as possible within a 6-minute period.

Functional assessment included 3D-Gait Analysis (3DGA). The Movement Analysis Laboratory of the Institute is equipped with an optoelectronic system of 8-infrared cameras working at 100 Hz (Elite, Bts, Italy) and two force plates (Kistler, Switzerland). The children were asked to walk barefoot or to wear their usual orthoses and footwear, to utilize their regular walking aids and to walk at their preferred speed for at least 10 times on a walkway. Each child’s walking condition was recorded during the baseline evaluation in order to replicate it in the following assessments. For each child the most representative trial was selected and spatio-temporal and kinematic parameters were calculated. Walking speed, step length, stride length, step width and cadence (all normalized over height), duration of stance phase (expressed as percentage of the gait cycle) and measure of stride length, step length and duration of stance symmetry (computed as ratio between right and left values [20]) were measured. Range of Motion (ROM) on sagittal plane of pelvis, hip, knee, ankle for both the legs was collected.

When the children were assessed through GMFM, 6minWT and 3DGA, they were allowed to wear their usual footwear/orthoses and to use their own walking aids. The information about orthoses and assistive devices were recorded by the therapist during the baseline evaluation in order to have the same condition in the following assessments.

2.5 Data analysis and statistical analysis

The normality of the data distribution was verified using the Shapiro-Wilk test. As the outcome measures were mostly not normally distributed, median values and interquartile (IQ) were computed.

At baseline, the homogeneity of every group was evaluated by means of the Chi-square test. The differences among groups due to classification parameters (i.e. age, gender, GMFCS) were assessed by means of the non-parametric Kruskall-Wallis test (post-hoc with Bonferroni-Holm corrected Mann-Whitney U-test) before further evaluations.

In accordance with the non-normal distributions of the majority of the dataset, the effect of training over time for each protocol was assessed using the non parametric Friedman test, with the Bonferroni-Holm corrected Wilcoxon test as post-hoc, more conservative than its parametric version. The variations pre and post intervention were compared to the Minimum Clinical Important Difference (MCID), when available [18].

A comparison of the different protocols of intervention is provided. Differences among the 4 protocols were considered through the Kruskall-Wallis test, with the Bonferroni-Holm corrected Mann-Whitney U-test as post-hoc.

The level of significance was set at 0.05 for all statistical comparisons. All computations were performed with Matlab R2014b and SPSS version 21.0; SPSS, Chicago, IL.

3. Results

According to the Chi-square test, TOP, RAGT $+$ TOP-10w and RAGT were uniformly distributed in terms of age, gender and GMFCS; RAGT $+$ TOP-4w was uniformly distributed in terms of gender and GMFCS but not in terms of age ( $p=$ 0.008). The non-parametric Kruskall-Wallis test showed that there were no differences among the groups at baseline in terms of gender and GMFCS, while RAGT $+$ TOP-4w significantly differed in terms of age at T0 with respect to the other groups.

Table 3
Outcome measured at T0, T1 and T2

	T0		T1		T2		MCID	Friedman
								T0 vs T1	T0 vs T2	T1 vs T2
TOP (4 TOP sessions/weeks $\times$ 10 weeks)
GMFM-88	88.9	(11.8)	90.2	(12.5)	91.0	(11.3)	NA	*
								0.033	0.024	0.030
GMFM-D	85.0	(13.8)	90.0	(12.3)	90.0	(16.8)	$++$	NS
GMFM-E	70.7	(36.3)	73.9	(34.5)	75.0	(35.3)	$++$	*
								0.022	0.018	0.140
GMFM-66	66.4	(13.4)	68.2	(11.9)	69.2	(9.7)	$++$	*
								0.030	0.039	0.074
6MWT	378.2	(182.6)	381.7	(159.3)	364.1	(179.8)	NA	NS
RAGT (4 RAGT sessions/weeks $\times$ 10 weeks)
GMFM-88	89.5	(8.0)	90.5	(11.5)	90.5	(9.5)	NA	*
								0.034	0.033	0.589
GMFM-D	82.0	(11.0)	85.0	(13.8)	85.0	(13.8)	$++$	NS
GMFM-E	65.0	(26.8)	68.5	(34.5)	67.0	(34.0)	$++$	*
								0.024	0.049	0.310
GMFM-66	68.5	(8.8)	68.9	(8.6)	69.8	(12.2)	$-$	*
								0.042	0.036	0.123
6MWT	324.4	(110.2)	345.0	(92.4)	346.5	(84.3)	NA	NS
RAGT $+$ TOP-10w (2 RAGT $+$ 2 TOP sessions/weeks $\times$ 10 weeks)
GMFM-88	88.5	(11.5)	91.0	(7.8)	90.5	(9.8)	NA	NS
GMFM-D	83.5	(15.8)	91.0	(10.3)	91.0	(16.5)	$++$	NS
GMFM-E	69.0	(42.8)	71.0	(41.8)	64.0	(33.8)	$+$	NS
GMFM-66	66.0	(12.1)	67.0	(12.7)	69.2	(10.4)	$+$	NS
6MWT	285.2	(219.2)	300.9	(201.9)	309.0	(214.9)	NA	NS
RAGT $+$ TOP-4w (5 RAGT $+$ 5 TOP sessions/weeks $\times$ 4 weeks)
GMFM-88	87.5	(7.3)	88.0	(6.3)	87.0	(4.0)	NA	NS
GMFM-D	83.5	(14.8)	89.5	(13.8)	90.0	(13.0)	$++$	NS
GMFM-E	58.0	(19.5)	58.0	(20.0)	58.0	(16.5)	$-$	NS
GMFM-66	66.2	(6.3)	67.1	(6.2)	68.1	(6.3)	$+$	NS
6MWT	222.1	(237.6)	208.5	(252.7)	225.0	(193.7)	NA	NS

Gross Motor abilities, 6minWT for TOP, RAGT, RAGT $+$ TOP-10w and RAGT $+$ TOP-4w groups. Median (interquartile) values are shown. Comparison with minimum clinically significant values between T0 and T1 is reported as $-$ : Low effect size, $+$ : Medium effect size or $++$ : Large effect size, NA: Data not available. Statistically significant differences between T0, T1 and T2 were computed (Friedman test) and reported as *. Wilcoxon test corrected with Bonferroni-Holm was also computed as post-hoc comparison and p-values are reported. Significance ( $p<$ 0.05) is indicated with bold values, NS: Not significant.

The effect of the different protocols over time is shown in Table 3.

Patients trained with TOP (group 1) and RAGT (group 2) protocols showed improvements in GMFM-88, GMFM-E and GMFM-66 between T0 and T1 and maintained at T2. In these groups, a non-significant improvement was observed in 6MWT and a numerically large but statistically non-significant effect size was obtained for GMFM-D.

Patients who underwent RAGT $+$ TOP-10w and RAGT $+$ TOP-4w protocols did not obtain any significant changes, although non-significant improving trends were observed for all the variables after the RAGT $+$ TOP-10w protocol, where changes had a medium or a large effect size. In contrast, only GMFM-D had a non-significant large effect size improvement after RAGT $+$ TOP-4w protocols while the others parameters almost unchanged or even worsen (i.e. 6MWT).

The 3DGA did not show any significant variation for any of the four protocols under analysis.

No differences among the 4 protocols were found accordingly to the Kruskall-Wallis test.

4. Discussion

RAGT could play an important role in motor recovery of children with CP and help define the best rehabilitative program. Though most studies are still empirical, an increasing amount of structured and evidence-based studies are coming [21]. The effectiveness of integrated interventions and of periods of higher frequency intervention in children with CP is documented [22]. The evaluation of RAGT effectiveness must therefore account for the variables of rehabilitation protocols, that is the content of the intervention, the treatment dose, the duration and the frequency.

In this work, four different training paradigms were investigated with the aim of defining an evidence-based best clinical practice in terms of approach (physiotherapy-based VS robotic-based), frequency (sessions per week), and duration of the treatment.

An equal dose of 40 sessions, each lasting 30 minutes, of lower-limb training was delivered to 44 children affected by bilateral CP. The approach varied among physiotherapy-based only (TOP), robotic-based only (RAGT) and mixed interventions (RAGT $+$ TOP); the duration varied between 4 and 10 weeks, with a frequency of 4 or 10 sessions per week (see Table 2).

The physiotherapy-based rehabilitation was organized with several specific standardised exercises and aimed at improving gait, balance and functional abilities. The physiotherapist assisted the patient during active and passive movement: the intervention was standardised as described above, quite replicable and with high physical burden for the operator. The robotic intervention assisted the patients during walking and guaranteed high repeatability of the gesture in a safe environment with limited physical burden for the operator; the active participation was stimulated thanks to the augmented visual feedback during the training [23, 24].

Previous studies investigated the effectiveness on CP children of twelve sessions of RAGT, each lasting 30–60 minutes and distributed over 3 weeks [9, 10, 13, 25, 26]. They consistently showed significant improvements in terms of walking ability, as assessed by GMFM66–E, while no significant improvement in walking endurance was measured by 6MWT [25]. Four of these studies also showed significant improvement in standing ability (GMFM66-D) [9, 10, 13, 25] as observed also in [4]. None of these studies considered a comparison with a control group.

Higher training-doses were also studied considering a training of 15–20 sessions lasting 45 minutes each [6, 11, 26]. Meyer Heim and colleagues showed that the 15 inpatients with neurological diseases (9 CP and 7 with other disorders) had significant improvements in terms of standing ability, walking ability and endurance during walking (GMFM66-D, GMFM66-E and 6MWT). However, considering the inpatient CP subgroup ( $N=$ 9), a significant improvement was only achieved in GMFM-E [26]. Druzbicki and collaborators performed an RCT on 52 CP children (unfortunately with a significant drop-out of 33%). The children underwent gait analysis before and after the training, studying possible changes in terms of motor strategy. The results did not show any differences either in temporal-spatial or in kinematics parameters among the group performing RAGT and the one involved in treadmill training [11]. Beretta et al. performed a study on 23 acquired brain injury children treated either with RAGT or with physiotherapy. The RAGT group obtained significant improvements in terms of GMFM-D, GMFM-E and 6MWT, while the control group had improvement in GMFM-D only. However, deepening the analysis, this group of patients was composed by 10 patients in acute or sub-acute phase of the disease, which is recognized to be the period of wider recovery. Thus, these results should be carefully compared with results obtained by CP children [6].

In our study groups, we detected improvements of GMFM in those CP patients who underwent exclusively TOP or RAGT (group 1 and 2). In particular the GMFM-88, GMFM-E (walking, running, jumping ability) and GMFM-66 slightly but significantly improved over time (i.e., 1.5%, 4.5% and 2.7% for sole TOP and 3.4%, 5.4%. and 0.5% for sole RAGT), as previously described [9, 10, 13, 25, 26], while a non-significant trend of improvement was obtained for GMFM-D (5.9% and 3.7% for TOP and RAGT, respectively) and 6MWT (0.9% and 6.4% for TOP and RAGT, respectively). These confirm what already described both as to GMFM-D [26] and 6MWT [10, 25, 26]. The improvements in terms of gross motor abilities were above the Minimum Clinical Important Difference values (MCID) for both protocols, except for the GMFM-66 obtained by the group with sole RAGT [18].

The improvement over time showed a carry-over effect in the following 3 months. Borggraefe and colleagues described a long lasting effect even if therapy was conducted via a less rigorous protocol, since their patients were allowed to perform conventional physical therapy and in some cases RAGT once a month during the period immediately after the end of the training [10]. The results of the present study support the persistence of improvements achieved both with RAGT and TOP, putatively to be attributed to neuroplasticity.

It should be noted that the absolute and relative improvements achieved by our patients are lower than those elsewhere described as to GMFM-66 and 6MWT, the only two variables already investigated by previous studies [10, 25, 26]. We put forward two possible hypotheses: firstly a ceiling effect could have limited our patients’ improvements; at baseline our patients were already proficient (e.g. 6MWT mean values 303 $\pm$ 66 m) with respect to those involved in previous studies (e.g. 6MWT reported by Meyer Heim was 152 $\pm$ 124 m, by Borggraefe and colleagues was 187 $\pm$ 142 m). The only ones described in literature with similar performance at baseline (6MWT reported by Schroeder and colleagues was 281 $\pm$ 165 m) displayed similar improvement after training (Schroeder and colleagues obtained an improvement of 2.8% while our improvements were of 0.9% for TOP, 6.4% for RAGT and 5.5% for RAGT $+$ TOP-10w) [25]. A second possible explanation is that some patients of ours underwent training with RAGT in previous years: repetition of RAGT is recognized as a factor that correlates negatively with GMFM improvement [25]. In a following study an exclusion criteria could limit the study to patients who are novel to RAGT.

The patients who underwent the mixed interventions (RAGT $+$ TOP for 4 or 10 weeks) failed to show significant variations over time independently from the duration and the frequency of the intervention. Some trends of improvement of all outcome measures in group 3 and of GMFM-88, GMFM-E and GMFM-66 in group 4 were evidenced. Considering the MCID for ambulant children with CP [18], the improvements in terms of gross motor abilities where above the MCID values for all the parameters of both groups but for GMFM-E showed by group 4. This last protocol differed from the others for two aspects: firstly a customization of robotic parameters was used. This aspect should not have been responsible of reduced improvement as it has already been considered advantageous by other research promoting active participation [9, 13, 14, 21]. More relevantly, in this group higher frequency was coupled with shorter duration: this might have prevented the patients to implement a sufficient reinforcement needed to consolidate the walking-related tasks, thus producing lower improvements detected by the outcome measures.

The 3D Gait Analysis parameters did not vary over time by any of the protocols, consistently with previous data by Druzbiki and colleagues [11], who failed to report changes in spatial-temporal and kinematics parameters during 20 sessions of training.

No improvements of spasticity were detected, but a ceiling effect should be considered. Indeed, enrolled patients were mainly characterized by none or mild spasticity (80% with Ashworth scale equal to 0 or 1).

In conclusion, while some studies widely investigate the effect of RAGT on adult population (e.g. stroke [27]), only few investigate developmental age, despite the widespread diffusion of RAGT in clinical practice on both adults and children. Thus an evidence-based well-defined protocol is a crucial issue. The present paper contributes to increase the knowledge on the role of duration, frequency and type of therapeutic intervention on CP children, being of help to set guidelines for the intervention protocol.

First of all, as to the type of intervention, a more focused training as in the “not mixed” protocols (only physiotherapy or only robotic training) seems to be more effective. Unexpectedly the training with and without the robotic device lead to similar improvements. The mixed form of intervention probably failed to provide a sufficient amount of both types of treatment (RAGT and physiotherapy). We do not have a definite explanation for this data: we cannot exclude a role for the processes underlying RAGT and physiotherapy, which were probably not sufficiently repeated and consolidated in the period. Thus the stability of the type of proposed therapy is the first crucial variable.

The second crucial element is duration: providing an intervention with longer duration, both task oriented physiotherapy (TOP) and gait training assisted by a robot (RAGT and RAGT $+$ TOP-10w) convey improvements in terms of gross motor abilities, statistically significant only in the exclusive type of intervention.

Therefore, the improvements seem to consolidate over time with longer-lasting (10 weeks) and more focused (not mixed) interventions.

Our data confirm the effectiveness of a robotic training. Limited to such intensive interventions, the duration of the treatment and the stability of the context are the crucial variables. As formerly stated, brain plasticity is intensified by exercise and the effect of motor learning depends on the intensity and regularity of activity. Trying to pursue similar goals in different contexts (mixed intervention) seemed to activate different pathways and the given time (4 or maximum 10 weeks) turned out to be not sufficient. More studies are needed to explore the outcome with longer mixed interventions, which could provide more active participation and repetition. Conversely, the focused intervention (one context, highly repetitive) seems to be more effective over 10 weeks.

The present study has several limitations. The first is the small sizes of our groups that reduce the statistical power. Furthermore, the patients’ allocation was not-randomized, weakening the study design. The inclusion criteria did not include the number of RAGT training previously performed, producing an heterogeneous group with possible ceiling effect on outcome measures.

Despite these limitations, the present study goes beyond the current state of the art being, the only study with both a follow up evaluation and a control group, and further exploring the effect of different duration, frequency and type of intervention on the motor outcome of children with CP.

Future studies may investigate the role of active participation: in our work it has not been maximized and its impact on functional abilities and participation has not been monitored. Indeed, in this work the version of the Lokomat software was not provided by the recently developed exergames, that aims at achieving the serious goal and eliciting game experience and active participation. Moreover, to support the possible central benefit elicited by RAGT training, neuroplasticity may be investigated through imaging techniques (functional magnetic resonance imaging or transcranial magnetic stimulation).

Conflict of interest

The authors have no conflict of interest to report.

Footnotes

Acknowledgments

Authors would like to thank the patients who underwent the clinical trial and the physiotherapists who performed the training with the patients. Authors would also like to thank Carolyn Schafer for the proofreading.

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Effects of dose and duration of Robot-Assisted Gait Training on walking ability of children affected by cerebral palsy

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION

Keywords

1. Introduction

2. Methods

2.1 Participants

Table 1 Participants’ details at baseline

2.3 Protocols of intervention

2.5 Data analysis and statistical analysis

3. Results

Table 3 Outcome measured at T0, T1 and T2

Conflict of interest

Footnotes

Acknowledgments

References

Table 1
Participants’ details at baseline

Table 3
Outcome measured at T0, T1 and T2