Predictors of Response to an Intensive Bimanual Intervention in Children With Cerebral Palsy
Phase: NA
Conditions: Cerebral Palsy
Sponsor: Laval University

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Project Number: 2020-1961 
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Predictors of Response to an Intensive Bimanual Intervention  
in Children Living with Cerebral Palsy 
 
 
 
 
 
 
Principal investigator:  
MERCIER, Catherine 
 
 
 
 
Researcher, CIRRIS 
 
 
 
 
Professor, Université Laval 
 
 
 
 
525 boul. Hamel 
 
 
 
 
Québec, QC 
 
 
 
 
G1V 2P3 
 
 
 
 
catherine.mercier@rea.ulaval.ca 
 
 
 
 
418-529-9141 ext. 6701 
 
 
 
 
 
 
 
Co-investigators:  
 
FLAMAND, Véronique (CIRRIS, U. Laval) 
 
 
 
 
ROBERT, Maxime (CIRRIS, U. Laval) 
 
 
 
 
CAMPEAU-LECOURS, Alexandre (CIRRIS, U. Laval) 
CROTEAU, Émilie (CIUSSS Capitale-Nationale) 
 
 
 
 
 
 
 
 
 
 
 
 

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1. Introduction 
 
Cerebral palsy (CP) is a group of permanent disorders that affect movement and posture 
development, leading to activity limitations due to damage occurring in the developing brain of 
the fetus or infant (Cans C., 2000; Oskoui et al., 2013; Rosenbaum et al., 2007). With 2 to 3 
children affected per 1,000 live births, CP is the most common disability in childhood. Motor 
disorders related to CP are often accompanied by sensory, cognitive, perceptive, communication, 
and behavioural disorders. The most predominant type of CP is hemiparesis: a more pronounced 
motor impairment on one side of the body. Although motor deficits predominantly affect one of 
the upper limbs, bimanual coordination deficits are also observed. These bimanual coordination 
deficits are often more profound than expected based on the deficits of the most affected upper 
limb (Gordon et al., 2013). Since most activities of daily living (ADL) require the use of both hands 
in a coordinated manner, deficits in bilateral coordination have a direct impact on ADL. 
 
Seeking to improve upper limb function, several studies have assessed intensive rehabilitation 
approaches that are based on motor learning principles and performed in a group context (Novak 
et al., 2013). Moreover, one study shows that task-oriented training that requires a high number of 
repetitions and a progression in task requirements improves motor control and manual function 
(Gordon et al., 2013). The two most studied approaches – constraint-induced therapy and intensive 
bimanual therapy – show comparable short- and long-term (6 months) outcomes in terms of 
unimanual and bimanual skills (Gordon et al., 2011). However, results also suggest that bimanual 
therapy provides larger gains in terms of performance and satisfaction in functional activities 
(subjectively measured with the Canadian Occupational Performance Measure), potentially 
because this approach focuses on bimanual activities with the spontaneous use of the most affected 
arm (de Brito Brandão et al., 2012; Gordon et al., 2011). That said, while self-reported measures 
provide relevant information about subjects’ own perception of their abilities, these measures are 
subject to many biases (i.e., social desirability) (Waddell & Lang, 2018). Changes in spontaneous 
use of the most affected limb in activities of daily living that follow interventions are rarely 
examined objectively, so the link between improvements measured through clinical evaluations or 
laboratory tests and any spontaneous use of the most affected limb remains to be definitively 
established. This issue is of particular importance considering the Developmental Disregard 
theory, which suggests that the more affected side is often overlooked during child development 
since a child learns to prioritize using their healthy side (Taub et al., 2006; Zielinski et al., 2014). 
As a result, the benefits an intervention may have on motor performance can be different when we 
compare on-demand tasks and spontaneous use in ADL. Based on this theory, improving 
spontaneous use of the most affected limb might provide better long-term gains than improving 
motor performance. The development of small wireless motion sensors (accelerometry) now 
makes it possible to quantify the relative use of each upper limb. A recent study has validated the 
use of such sensors (ActiGraph) to assess spontaneous movements of upper limbs in ADL in 
children with hemiplegic cerebral palsy (Dawe et al., 2019) ). These advances pave the way for a 
quantitative characterization of the impact of intensive bimanual therapy in children’s daily living. 
 

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Another important challenge that researchers and clinicians presently face in implementing 
interventions is the heterogeneity of the population of children living with cerebral palsy, and the 
variability observed in response to interventions. The heterogeneous nature of brain damage that 
results in cerebral palsy may be a crucial factor in explaining variability in response to treatment. 
However, biomarkers derived from magnetic resonance imaging (MRI) – such as the timing when 
the lesion occurred, as well as its extent and precise location – only moderately predict effects on 
sensorimotor functions  (Feys et al., 2010; Holmefur et al., 2013). One of the reasons for this is 
that the brain is still highly plastic at this stage of development, which allows for significant “re-
wiring” that may deviate from what is observed in typically developing children. Characterizing 
this re-wiring could be useful at a clinical level: the identification of specific biomarkers may help 
clinicians customize interventions according to individual characteristics (Jaspers et al., 2015) . 
For example, it has been shown that brain damage can interfere with the phenomenon of 
withdrawal of ipsilateral corticospinal projections normally occurring during development, 
especially if it occurs between the 24th and 34th week of gestation (Staudt et al., 2004) . As a result, 
some children will demonstrate ipsilateral control of the most affected hand (or mixed control, 
rather than contralateral control). The presence of ipsilateral control, as demonstrated for example 
in transcranial magnetic stimulation (TMS), is typically associated with poorer motor function 
(Holmström et al., 2010; Mackey et al., 2014; Staudt, 2002; van der Aa et al., 2013) . The structural 
integrity of the corticospinal pathway between the injured hemisphere and the most affected hand, 
based on diffusion tensor imaging (DTI) measurements, has also been reported to be associated 
with motor function (Bleyenheuft et al., 2007; Friel et al., 2014; Glenn et al., 2007; Gupta et al., 
2017; Holmström et al., 2011; Hung et al., 2019; Kuczynski, Dukelow, et al., 2018; Mackey et al., 
2014; Marneweck et al., 2018; Nemanich et al., 2019; Smorenburg et al., 2017). 
 
Despite established relationships between neuroanatomical or neurophysiological markers and 
motor function of the most affected upper limb, few studies have been able to establish links 
between these markers and the response to specific interventions (Robert et al., 2021; Rocca et al., 
2013) . Several reasons may explain these inconsistent results: On the one hand, there are inherent 
limitations of neuroimaging approaches that target specific structures (e.g., corticospinal pathway, 
corpus callosum, etc.). The use of multiple metrics in one study could help us understand the 
complexity of brain reorganization (e.g., the importance of the integrity of the corticospinal 
pathway between the affected hemisphere and the most affected hand may depend on the presence 
of a predominantly ipsilateral or contralateral reorganisation of the corticospinal pathway). On the 
other hand, these results are usually related to changes in complex functional tasks, which require 
many brain structures and processes. Although the goal of rehabilitation is ultimately to improve 
motor function in the context of ADL, the standardized assessment of mediating variables 
(intermediate between two other variables and less complex than the use of the upper limb in ADL) 
that focused on a specific function, can be an interesting way to bridge the gap between 
neuroanatomical/neurophysiological variables and complex motor functions. The use of more 
precise assessments of uni- and bilateral sensorimotor control, as made possible by the 
development of robotic upper limb assessment systems, could clarify the relationship between 
neuroanatomical/neurophysiological variables and clinical improvements. This approach could 
lead to a better understanding of the variability observed in response to interventions, and 
ultimately to predicting the effectiveness of interventions based on key biomarkers. 
 

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2. Objectives and hypothesis 
 
• Main objective of the study 
To understand the impacts of an intensive bimanual therapy on uni- and bimanual motor functions 
and on the spontaneous use of the most affected arm, by clarifying what are the underlying 
neurophysiological mechanisms involved. 
 
• Specific objective 1 
To describe changes that occur in motor function (uni- and bimanual) and in the spontaneous use 
of the most affected limb following intensive bimanual therapy. 
 
Hypothesis 1.1: Improvements of uni- and bilateral motor function will be observed both 
following the intervention and at 6 months follow-up.  
 
Hypothesis 1.2: Improvements of spontaneous use of the most affected limb will be observed 
both following the intervention and at 6 months follow-up. 
 
• Specific objective 2 
To assess the relationship between uni- and bilateral motor changes, spontaneous use of the most 
affected limb, and self-reported changes. Potential covariables (for example proprioception) will 
also be evaluated. 
 
Hypothesis 2.1: Immediately after the intervention, improvements of bilateral motor 
function will be observed using clinical and robotic assessments. These evaluations will 
better predict changes in the spontaneous use of the most affected limb in the context of ADL 
than evaluations of unilateral motor function do.  
 
Hypothesis 2.2: The long-lasting effect of the intervention (6-month follow up vs. post-
intervention evaluation) will be predicted by improvements during the intervention (post vs. 
pre-evaluation).  
 
Hypothesis 2.3: At the 6-month follow-up, changes in spontaneous use of the most affected 
limb will be moderately associated with self-reported changes. 
 
• Specific objective 3 
To explore predictive value of neuroimaging variables evaluated in pre-intervention on motor 
function changes (uni- and bilateral). 
 
Hypothesis 3: The integrity of the corpus callosum will be a predictor of changes in bilateral 
performance, with a lower integrity being associated with smaller gains. 
 
 
 

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• Specific objective 4 
To compare the changes observed during a first exposure to intensive bimanual therapy with 
changes observed during a subsequent exposure. 
 
Hypothesis 4: The beneficial effects of a subsequent exposure to the bimanual therapy will be 
identical to those observed during the first exposure (i.e., no ceiling effect will be observed). 
 
3. Methodology 
 
• 
Research design 
The experimental design is presented in Figure 1. All participants will receive an intensive 
bimanual therapy of a total of 60 hours over a two-week period. Evaluations will be performed 
before, immediately after, and 6 months after the intervention. All participants will be invited to 
repeat the intensive bimanual therapy camp on subsequent years if they wish to, if they meet the 
inclusion criteria. 
 
 
 
 
 
Figure 1. Experimental design 
 
• 
Participants  
Thirty children living with cerebral palsy will be recruited over a 5-year period for a first 
participation in an intensive bimanual therapy camp. Several recruitment approaches will be used, 
including clinical programs, websites, and social media. 
 
Selection criteria: 
(1) being aged between 6 and 17 years old;  
(2) having a diagnosis of cerebral palsy or spastic hemiparesis encephalopathy; 
(3) having sensorimotor deficits of one or both upper limbs (spastic hemiparesis with a 
dominance on one side of the body; Manual Ability Classification System (MACS) level 1, 
2 or 3); 
(4) having the cognitive capacity to understand and perform tasks in the study. 
 
Exclusion criteria: 
(1) presenting other significant health problems that may interfere with requested tasks or with 
clinical interventions;  
(2) having had a Botox injection in one or both upper limb(s) with the 4 months prior to the 
bimanual therapy intervention;  
(3) presenting uncorrected visual deficits. 

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N.B. Having a ferromagnetic implant is not an exclusion criterion; any such participants will be 
eligible but will not be required to perform the MRI.  
 
Participants recruited for specific objective 4 
Children who have already participated in this bimanual therapy once will be eligible to participate 
in the therapy again, assuming they still meet the inclusion criteria.  
 
• 
Summary of the intervention 
Children will participate in an intensive bimanual therapy session of 6 hours of therapy per day, 5 
days a week, for a period of two weeks (so the intervention’s total duration is of 60 hours of 
bimanual therapy). The camp will be held every year at the PEPS at Université Laval, in Quebec 
City, Canada. Each child will be paired with the same therapy worker throughout the camp (1:1 
ratio). The therapy workers will be students in health programs (occupational therapy, 
physiotherapy, and kinesiology) or graduate students in clinical research at Université Laval. A 
mandatory training will be offered to all students in order to ensure that the strategies used for 
bimanual activities are standardised; safety protocols and data collection will be also addressed 
during the training. At least one occupational therapist will always be present on-site to supervise 
the student therapy workers and the activities (i.e., board games, arts and crafts, basic cooking, 
etc.). Detailed information related to how intensive bimanual therapy is developed and conducted 
can be found in (Charles & Gordon, 2006). 
 
• 
Evaluations 
There will be three periods of evaluation (pre-intervention, post-intervention, and 6-month follow-
up).  
 
Table 1. Summary and planning of the evaluation 
Evaluations 
Pre-
intervention 
During the 
intervention 
Post-
intervention 
6-month 
follow-up 
Neurophysiological 
evaluation 
MRI/DTI* 
✔ 
 
 
 
Robotic evaluation 
KINARM 
✔ 
 
✔ 
✔ 
Spontaneous use 
Accelerometry  
✔ 
✔ 
✔ 
✔ 
Clinical evaluation 
TPDT  
✔ 
 
✔ 
✔ 
JTTHF 
✔ 
 
✔ 
✔ 
BBT 
✔ 
 
✔ 
✔ 
AHA 
✔ 
 
✔ 
✔ 
TACT 
✔ 
 
✔ 
✔ 
MVPT-R 
✔ 
 
✔ 
✔ 
Self-assessments 
CHEQ 
✔ 
 
✔ 
✔ 
COPM 
✔ 
 
✔ 
✔ 
MRI: Magnetic Resonance Imaging; DTI: Diffusion Tensor Imaging; JTTHF: Jebsen Taylor Test of Hand Function; 
BBT: Box and Block Test; AHA: Assisting Hand Assessment; TACT: Two-Arm Coordination Test; MVPT-R: Motor-
Free Visual Perception Test–Revised; CHEQ: Children’s Hand-use Experience Questionnaire; COPM: Canadian 
Occupational Performance Measure. *MRI will be performed only in the first participation in the bimanual therapy. 

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Neuroimaging evaluation 
Each child will undergo a magnetic resonance imaging (MRI) test prior to the pre-intervention, 
with the exception of children presenting a contraindication to MRI and/or children who have 
already participated in the therapy camp once (Objective 4) and so have already provided MRI test 
results. 
 
The diffusion tensor imaging (DTI) technique will be used for the pre-evaluation MRI. That will 
make it possible to assess the integrity of several neuroanatomical structures (i.e., corpus callosum, 
corticospinal pathways, etc.). The tractography of neuroanatomical pathways will be reconstructed 
using the Continuous Tracking method (Mori et al., 1999)  In order to assess the integrity of 
neuroanatomical motor structures (e.g., corpus callosum, ascending and descending sensorimotor 
pathways) (Robert et al., 2021), the diffusion analysis will be done using the TractoFlow 
processing pipeline (Garyfallidis et al., 2014; Theaud et al., 2020).  
 
Robotic evaluation 
Four standardized sensorimotor tasks will be performed using a Kinarm Exoskeleton Lab (Kinarm, 
Kingston, ON Canada) in a randomized order for a total duration of approximately 45 minutes 
(including installation and calibration). This system allows for the execution of upper limb tasks 
on the horizontal plane while recording upper limb kinematics and tracking eye movements. The 
metrological properties of these tasks have been assessed in adults and children with hemiparesis 
(see the description of each task). 
 
In the unilateral task Visually Guided Reaching, the child must point at 4 targets as quickly and 
accurately as possible. The targets are spread out over a radius of 10 cm from the starting target, 
and are presented in a pseudo-random order (for total of 32 reaching movements) (Coderre et al., 
n.d.; Kuczynski, Dukelow, et al., 2018; Kuczynski, Kirton, et al., 2018). The two upper limbs will 
be evaluated successively.  
 
In the bilateral task Object Hit, balls move from the distal part of the screen to the proximal part 
(i.e., towards the child) in different medial-lateral positions (Tyryshkin et al., 2014). Child must 
hit the balls with the hand of their choice, with each successful contact generating haptic feedback. 
Three hundred balls are presented at a speed that gradually increases as the task progresses.  
 
In the bilateral task Ball on the Bar, a virtual bar is put into the hands of the subject, and a virtual 
ball is placed on the bar (R Lowrey, 2014). Four targets are successively presented to the child, 
whose objective is to move the ball into each target as quickly and accurately as possible. The task 
has 3 levels of one minute’s duration. At levels 2 and 3, the ball can “roll” and fall off the bar, 
which requires precise bilateral control.  
 
In the proprioception task Arm-Position Matching, the child’s sense of upper limb position is 
evaluated (Dukelow et al., 2010; Kuczynski, Dukelow, et al., 2018; Kuczynski et al., 2017). The 
Kinarm moves one of the more affected upper limb passively to a predetermined position. The 
child must then move their contralateral limb to match the position of the limb in the other hemi-
space without any visual feedback. Four different positions are tested for a total of 7 times each.  

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Spontaneous use 
Inertial control units (ActiGraph GT9X-BT Link, ActiGraph, Florida, FL; 3.5 cm 3.5 cm 1 cm, 14 
g) worn on both wrists (Velcro bracelets from the company) will be used to assess spontaneous 
use of the most affected arm, with respect to the use of the less affected arm. The validity of this 
type of sensor is good (agreement >81%) based on results of studies that compared accelerometer 
data to video observations in children living with cerebral palsy (Beani et al., 2019; Dawe et al., 
2019)  . In our case, sensors will be worn for 4 weekends (before, during, immediately after, and 
6 months after the intervention) as well as for two days (one per week) during the intervention. 
While data will be measured during the interventions, the majority of data will be collected 
exclusively on weekends in an effort to minimize differences between school attendance and 
holiday periods. The ActiGraph data will be collected in 3 axes at 100 Hz, and then analyzed as 
vectors with the ActiLife v.6.13.4 software (ActiGraph, Pensacola, FL). Unilateral and bilateral 
functions will be quantified by summing up the activities detected at the upper limbs, which makes 
it possible to obtain use ratios for each limb. 
 
Clinical evaluation 
The Two-Point Discrimination Test (TPDT) at a distance of 3 mm is the most sensitive test there 
is to determine tactile threshold in children with spastic hemiplegia (Krumlinde-Sundholm & 
Eliasson, 2002). Only the pulp of the fingers will be evaluated, starting with the less-affected 
hand. A successful trial will be considered to be 5 consecutive successes out of 10 attempts, since 
children often need more testing to understand what they are seeking to detect as sensation 
(Krumlinde-Sundholm & Eliasson, 2002) . If a child is not able to distinguish between 2 static 
points spaced at 3 mm distance (the standard for the tactile threshold), the test will be repeated 
with a distance of 7 mm between the 2 static points. This test is valid and accurate in children 
living with cerebral palsy (Bolanos et al., 1989). 
 
The Jebsen Taylor Test of Hand Function (JTTHF) is used to evaluate the unimanual function. 
This test consists of 7 standardized tasks, performed first with the non-dominant hand and then 
with the dominant hand (Jebsen et al., 1969). In this project, only the first 6 tasks will be used. For 
each task, the score is the time required to complete the task, in seconds (a maximum of 120 
seconds is allocated per task). The total score is the sum of time for all six tasks. Test fidelity is 
good in children with stable manual impairment (range of intraclass correlation coefficients (ICC) 
is between 0.88-0.97 for the dominant hand and 0.95-0.99 for the non-dominant hand, depending 
on the task) (Taylor et al., 1973). No learning effect has been detected (Jebsen et al., 1969). 
 
The Box and Blocks Test (BBT) is a standardized, validated test that measures manual dexterity. 
In this test, the child must take one block at a time with one hand, then transfer it to the other side 
of the box (across a middle line) (Mulcahey et al., 2012). The score is the number of blocks moved 
in 60 seconds. Normative values for children with typical development are available, and the CCI 
is 0.85 for test-retest fidelity, and 0.99 for inter-evaluator fidelity (Platz et al., 2005). 
 
The Assisting Hand Assessment (AHA) (Krumlinde-Sundholm et al., 2007) evaluates how 
effectively the most affected limb assists the dominant hand in bimanual tasks. This test consists 
of standardized tasks with toys that are used during a semi-structured game session. The test is 
video-recorded, and the video is analyzed and scored later. The AHA was designed and validated 

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specifically to measure bimanual performance in children with hemiparesis (cerebral palsy of the 
spastic hemiparesis type, or with brachial plexus resulting in unilateral damage to the upper limb). 
The AHA has excellent fidelity (ICC 0.97 for inter-evaluator and ICC 0.99 for intra-evaluator) and 
sensitivity to change (Holmefur et al., n.d.; Krumlinde-Sundholm et al., 2007). The game session 
takes 15-20 minutes. Results are scored in logit-based AHA-units (maximum score 100). The 
evaluator must be certified to administer, score, and analyze this evaluation.  
 
The Two-Arm Coordination Test (TACT) evaluates the constrained bilateral use of both upper 
limbs, using an electronic tracking device (eight tests; four clockwise and four counter-clockwise). 
This device has been validated with people living with cerebral palsy (Riquelme et al., 2019). The 
variables are time and number of errors. 
 
The Motor-Free Visual Perception Test–Revised (MVPT-R) is a visual perception test that 
assesses consistency of form, spatial orientation, discrimination, memory, and visual closure. This 
test was validated with people living with cerebral palsy (Tsai et al., 2009). 
 
Self-assessments 
Questionnaires related to daily-living activities will be completed both pre- and post-intervention, 
as well as at the follow-up 6 months later.  
 
The Children’s Hand-use Experience Questionnaire (CHEQ) consists of 29 questions designed 
to evaluate how the most-affected upper limb is used in ADL (Sköld et al., 2011). The 
questionnaire presents a list of everyday life activities that are usually carried out with both hands; 
the child and the parents rate the time required to accomplish the task, the effectiveness of the 
child’s grip, and how hampered they felt in the task. A web version of the questionnaire is available 
and has been validated (test-retest fidelity for all 3 scales: CCI 0.88- 0.91) in children with spastic 
hemiparesis cerebral palsy (Amer et al., 2016). 
 
The Canadian Occupational Performance Measure (COPM) will be administered both pre- and 
post-intervention, as well as at the 6-month follow-up. Pre-intervention COPM will make it 
possible to identify bilateral activities that the child wants to improve (Law et al., 1990)  and the 
child and their parents will establish current performance and satisfaction scores for these 
activities. After the intervention, they will again establish performance and satisfaction scores for 
the activities initially identified (a 2-point change is considered clinically significant with this 
measure) (Verkerk et al., 2006). COPM is a well-established measurement tool, valid, faithful and 
responsive to changes. This tool measures the functional changes perceived by the client and 
provides an indication of how the clinical setting have been transferred to daily life (Carswell et 
al., 2004). 
 
• 
Statistical analysis 
For objectives 1, 2 and 4, in addition to descriptive statistics (mean or median), a general (or 
generalized if the assumptions of normality are not met), linear mixed model (GLMM) with 
maximum likelihood estimates will be used. GLMM provides flexibility to examine the effect of 
categorical and continuous independent variables (and their interactions) within and across related 
observation groups, and robustness to missing data. In this study, data are sampled in a multi-stage 

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manner (children are nested within recruitment cohorts), and ignoring this clustering will lead to 
the violation of the independence of the residuals and the underestimation of the parameters of the 
statistical model(McNeish & Stapleton, 2016). However, GLMM requires large sample size. Due 
to financial costs (2-week intervention across five years with one therapy worker per child) and 
recruitment difficulties, it is not possible to go beyond 30 participants. Therefore, a bootstrap 
method (i.e., a statistical procedure that resamples a single dataset to create many simulated 
samples) will be applied to meet the assumptions of GLMM.  
Objective 1&4 – Participants and Cohorts will be set as random effects, Time (pre- post- 6-months) 
and Exposition (first year, second year, etc.) and their interaction will be set as fixed effects.  
Objective 2 – Participants and Cohorts will be set as random effects, Time (pre- post- and 6-
months), uni- and bi-lateral Motor functions and their interaction as fixed effects.  
Objective 3 - Correlational analyses (Pearson or Spearman) will be performed between corpus 
callosum integrity (measured by MRI/DTI) and changes in variable of bilateral motor tasks 
(measured by robotic evaluation). 
Given that children will be aged from 6 to 17, the potential effect of age on the different variables 
will be explored to determine the relevance of including age as a covariate in some analyses. 
However, it has been proved recently that age is not associated with different measures obtained 
by DTI in youth with cerebral palsy, contrary to what is observed in youth with a typical 
development (Papadelis, Kaye et al. 2019). Moreover, when normative data is available, tests 
results will be converted to z-score to minimize the impact of age and sex. 
P-values will be corrected for multiple testing using the Benjamini and Hochberg False Discovery 
Rate. 
 
• 
Limitations of the methodology 
The main limitation of the study will be its limited sample size: It is expected that the sample will 
be heterogeneous in terms of age and clinical criteria. This is a common limitation for studies in 
this area. A multimodal approach to assess intra-participant changes will be used to minimize the 
impact of these limitations.  
 
Another limitation is the restricted time for accelerometry measurements (2 days for each time 
point). One-week periods are generally preferred in studies conducted in adults. The choice was 
made here to restrict measurements to weekends in order to reduce biases related to ADL 
differences between schooldays and holidays (especially for the 6-month follow-up). This option 
was also selected to yield greater acceptability among the children (since they must wear the 
devices for four separate periods totalling 8 days of time).  
 
The use of GLMM with a small sample size is another limitation. However, a bootstrap technique 
will be used. This method does not create any data and the estimated parameters might not reflect 
with precision the parameters of the population, which is not a major issue in this project.   
 
Finally, it is important to underscore that the goal of this study is not to determine the effectiveness 
of intensive bimanual interventions: this has already been established by previous studies (Novak 
et al., 2013; O’Connor et al., 2016; Peters et al., 2019; Shierk et al., 2016), which is why no control 
group was included here. 
 
 

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Bibliography 
 
Amer, A., Eliasson, A.-C., Peny-Dahlstrand, M., & Hermansson, L. (2016). Validity and test-
retest reliability of Children’s Hand-use Experience Questionnaire in children with unilateral 
cerebral palsy. Developmental Medicine and Child Neurology, 58(7), 743–749. 
https://doi.org/10.1111/dmcn.12991 
Beani, E., Maselli, M., Sicola, E., Perazza, S., Cecchi, F., Dario, P., Braito, I., Boyd, R., Cioni, 
G., & Sgandurra, G. (2019). Actigraph assessment for measuring upper limb activity in 
unilateral cerebral palsy. Journal of Neuroengineering and Rehabilitation, 16(1), 30. 
https://doi.org/10.1186/s12984-019-0499-7 
Bleyenheuft, Y., Grandin, C. B., Cosnard, G., Olivier, E., & Thonnard, J.-L. (2007). Corticospinal 
dysgenesis and upper-limb deficits in congenital hemiplegia: a diffusion tensor imaging 
study. Pediatrics, 120(6), e1502-11. https://doi.org/10.1542/peds.2007-0394 
Bolanos, A. A., Bleck, E. E., Firestone, P., & Young, L. (1989). Comparison of stereognosis and 
two-point discrimination testing of the hands of children with cerebral palsy. Developmental 
Medicine and Child Neurology, 31(3), 371–376. https://doi.org/10.1111/j.1469-
8749.1989.tb04006.x 
Cans C. (2000). Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy 
surveys and registers. Surveillance of Cerebral Palsy in Europe (SCPE). Developmental 
Medicine and Child Neurology, 42(12), 816–824. 
https://doi.org/10.1017/s0012162200001511 
Carswell, A., McColl, M. A., Baptiste, S., Law, M., Polatajko, H., & Pollock, N. (2004). The 
Canadian Occupational Performance Measure: a research and clinical literature review. 
Canadian Journal of Occupational Therapy. Revue Canadienne d’ergotherapie, 71(4), 
210–222. https://doi.org/10.1177/000841740407100406 
Charles, J., & Gordon, A. M. (2006). Development of hand-arm bimanual intensive training 
(HABIT) for improving bimanual coordination in children with hemiplegic cerebral palsy. 
Developmental Medicine and Child Neurology, 48(11), 931–936. 
https://doi.org/10.1017/S0012162206002039 
Coderre, A. M., Zeid, A. A., Dukelow, S. P., Demmer, M. J., Moore, K. D., Demers, M. J., 
Bretzke, H., Herter, T. M., Glasgow, J. I., Norman, K. E., Bagg, S. D., & Scott, S. H. (n.d.). 
Assessment of upper-limb sensorimotor function of subacute stroke patients using visually 
guided reaching. Neurorehabilitation and Neural Repair, 24(6), 528–541. 
https://doi.org/10.1177/1545968309356091 
Dawe, J., Yang, J. F., Fehlings, D., Likitlersuang, J., Rumney, P., Zariffa, J., & Musselman, K. E. 
(2019). Validating Accelerometry as a Measure of Arm Movement for Children With 
Hemiplegic Cerebral Palsy. Physical Therapy, 99(6), 721–729. 
https://doi.org/10.1093/ptj/pzz022 
de Brito Brandão, M., Gordon, A. M., & Mancini, M. C. (2012). Functional impact of constraint 
therapy and bimanual training in children with cerebral palsy: a randomized controlled trial. 
The American Journal of Occupational Therapy : Official Publication of the American 
Occupational Therapy Association, 66(6), 672–681. 
https://doi.org/10.5014/ajot.2012.004622 

CÉR-S en réadaptation et intégration sociale  
 
Project Number: 2020-1961 
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12
Dukelow, S. P., Herter, T. M., Moore, K. D., Demers, M. J., Glasgow, J. I., Bagg, S. D., Norman, 
K. E., & Scott, S. H. (2010). Quantitative assessment of limb position sense following 
stroke. Neurorehabilitation and Neural Repair, 24(2), 178–187. 
https://doi.org/10.1177/1545968309345267 
Feys, H., Eyssen, M., Jaspers, E., Klingels, K., Desloovere, K., Molenaers, G., & de Cock, P. 
(2010). Relation between neuroradiological findings and upper limb function in hemiplegic 
cerebral palsy. European Journal of Paediatric Neurology : EJPN : Official Journal of the 
European Paediatric Neurology Society, 14(2), 169–177. 
https://doi.org/10.1016/j.ejpn.2009.01.004 
Friel, K. M., Kuo, H.-C., Carmel, J. B., Rowny, S. B., & Gordon, A. M. (2014). Improvements in 
hand function after intensive bimanual training are not associated with corticospinal tract 
dysgenesis in children with unilateral cerebral palsy. Experimental Brain Research, 232(6), 
2001–2009. https://doi.org/10.1007/s00221-014-3889-x 
Garyfallidis, E., Brett, M., Amirbekian, B., Rokem, A., van der Walt, S., Descoteaux, M., Nimmo-
Smith, I., & Dipy Contributors. (2014). Dipy, a library for the analysis of diffusion MRI data. 
Frontiers in Neuroinformatics, 8, 8. https://doi.org/10.3389/fninf.2014.00008 
Glenn, O. A., Ludeman, N. A., Berman, J. I., Wu, Y. W., Lu, Y., Bartha, A. I., Vigneron, D. B., 
Chung, S. W., Ferriero, D. M., Barkovich, A. J., & Henry, R. G. (2007). Diffusion tensor MR 
imaging tractography of the pyramidal tracts correlates with clinical motor function in 
children with congenital hemiparesis. AJNR. American Journal of Neuroradiology, 28(9), 
1796–1802. https://doi.org/10.3174/ajnr.A0676 
Gordon, A. M., Bleyenheuft, Y., & Steenbergen, B. (2013). Pathophysiology of impaired hand 
function in children with unilateral cerebral palsy. Developmental Medicine and Child 
Neurology, 55 Suppl 4, 32–37. https://doi.org/10.1111/dmcn.12304 
Gordon, A. M., Hung, Y.-C., Brandao, M., Ferre, C. L., Kuo, H.-C., Friel, K., Petra, E., Chinnan, 
A., & Charles, J. R. (2011). Bimanual training and constraint-induced movement therapy in 
children with hemiplegic cerebral palsy: a randomized trial. Neurorehabilitation and Neural 
Repair, 25(8), 692–702. https://doi.org/10.1177/1545968311402508 
Gupta, D., Barachant, A., Gordon, A. M., Ferre, C., Kuo, H.-C., Carmel, J. B., & Friel, K. M. 
(2017). Effect of sensory and motor connectivity on hand function in pediatric hemiplegia. 
Annals of Neurology, 82(5), 766–780. https://doi.org/10.1002/ana.25080 
Holmefur, M., Kits, A., Bergström, J., Krumlinde-Sundholm, L., Flodmark, O., Forssberg, H., & 
Eliasson, A.-C. (2013). Neuroradiology can predict the development of hand function in 
children with unilateral cerebral palsy. Neurorehabilitation and Neural Repair, 27(1), 72–78. 
https://doi.org/10.1177/1545968312446950 
Holmefur, M., Krumlinde-Sundholm, L., & Eliasson, A.-C. (n.d.). Interrater and intrarater 
reliability of the Assisting Hand Assessment. The American Journal of Occupational 
Therapy : Official Publication of the American Occupational Therapy Association, 61(1), 
79–84. https://doi.org/10.5014/ajot.61.1.79 
Holmström, L., Lennartsson, F., Eliasson, A.-C., Flodmark, O., Clark, C., Tedroff, K., Forssberg, 
H., & Vollmer, B. (2011). Diffusion MRI in corticofugal fibers correlates with hand function in 
unilateral cerebral palsy. Neurology, 77(8), 775–783. 
https://doi.org/10.1212/WNL.0b013e31822b0040 

CÉR-S en réadaptation et intégration sociale  
 
Project Number: 2020-1961 
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13
Holmström, L., Vollmer, B., Tedroff, K., Islam, M., Persson, J. K. E., Kits, A., Forssberg, H., & 
Eliasson, A.-C. (2010). Hand function in relation to brain lesions and corticomotor-
projection pattern in children with unilateral cerebral palsy. Developmental Medicine and 
Child Neurology, 52(2), 145–152. https://doi.org/10.1111/j.1469-8749.2009.03496.x 
Hung, Y.-C., Robert, M. T., Friel, K. M., & Gordon, A. M. (2019). Relationship Between Integrity 
of the Corpus Callosum and Bimanual Coordination in Children With Unilateral Spastic 
Cerebral Palsy. Frontiers in Human Neuroscience, 13, 334. 
https://doi.org/10.3389/fnhum.2019.00334 
Jaspers, E., Byblow, W. D., Feys, H., & Wenderoth, N. (2015). The Corticospinal Tract: A 
Biomarker to Categorize Upper Limb Functional Potential in Unilateral Cerebral Palsy. 
Frontiers in Pediatrics, 3, 112. https://doi.org/10.3389/fped.2015.00112 
Jebsen, R. H., Taylor, N., Trieschmann, R. B., Trotter, M. J., & Howard, L. A. (1969). An 
objective and standardized test of hand function. Archives of Physical Medicine and 
Rehabilitation, 50(6), 311–319. 
Krumlinde-Sundholm, L., & Eliasson, A.-C. (2002). Comparing tests of tactile sensibility: aspects 
relevant to testing children with spastic hemiplegia. Developmental Medicine and Child 
Neurology, 44(9), 604–612. https://doi.org/10.1017/s001216220100264x 
Krumlinde-Sundholm, L., Holmefur, M., Kottorp, A., & Eliasson, A.-C. (2007). The Assisting 
Hand Assessment: current evidence of validity, reliability, and responsiveness to change. 
Developmental Medicine and Child Neurology, 49(4), 259–264. 
https://doi.org/10.1111/j.1469-8749.2007.00259.x 
Kuczynski, A. M., Carlson, H. L., Lebel, C., Hodge, J. A., Dukelow, S. P., Semrau, J. A., & 
Kirton, A. (2017). Sensory tractography and robot-quantified proprioception in hemiparetic 
children with perinatal stroke. Human Brain Mapping, 38(5), 2424–2440. 
https://doi.org/10.1002/hbm.23530 
Kuczynski, A. M., Dukelow, S. P., Hodge, J. A., Carlson, H. L., Lebel, C., Semrau, J. A., & 
Kirton, A. (2018). Corticospinal tract diffusion properties and robotic visually guided 
reaching in children with hemiparetic cerebral palsy. Human Brain Mapping, 39(3), 1130–
1144. https://doi.org/10.1002/hbm.23904 
Kuczynski, A. M., Kirton, A., Semrau, J. A., & Dukelow, S. P. (2018). Bilateral reaching deficits 
after unilateral perinatal ischemic stroke: a population-based case-control study. Journal of 
NeuroEngineering and Rehabilitation, 15(1), 77. https://doi.org/10.1186/s12984-018-0420-
9 
Law, M., Baptiste, S., McColl, M., Opzoomer, A., Polatajko, H., & Pollock, N. (1990). The 
Canadian occupational performance measure: an outcome measure for occupational 
therapy. Canadian Journal of Occupational Therapy. Revue Canadienne d’ergotherapie, 
57(2), 82–87. https://doi.org/10.1177/000841749005700207 
Mackey, A., Stinear, C., Stott, S., & Byblow, W. D. (2014). Upper limb function and cortical 
organization in youth with unilateral cerebral palsy. Frontiers in Neurology, 5, 117. 
https://doi.org/10.3389/fneur.2014.00117 
Marneweck, M., Kuo, H.-C., Smorenburg, A. R. P., Ferre, C. L., Flamand, V. H., Gupta, D., 
Carmel, J. B., Bleyenheuft, Y., Gordon, A. M., & Friel, K. M. (2018). The Relationship 
Between Hand Function and Overlapping Motor Representations of the Hands in the 

CÉR-S en réadaptation et intégration sociale  
 
Project Number: 2020-1961 
2022.03.31 
14
Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy. Neurorehabilitation and 
Neural Repair, 32(1), 62–72. https://doi.org/10.1177/1545968317745991 
McNeish, D. M., & Stapleton, L. M. (2016). The Effect of Small Sample Size on Two-Level 
Model Estimates: A Review and Illustration. Educational Psychology Review, 28(2), 295–
314. https://doi.org/10.1007/s10648-014-9287-x 
Mori, S., Crain, B. J., Chacko, V. P., & van Zijl, P. C. (1999). Three-dimensional tracking of 
axonal projections in the brain by magnetic resonance imaging. Annals of Neurology, 
45(2), 265–269. https://doi.org/10.1002/1531-8249(199902)45:2<265::aid-ana21>3.0.co;2-
3 
Mulcahey, M. J., Kozin, S., Merenda, L., Gaughan, J., Tian, F., Gogola, G., James, M. A., & Ni, 
P. (2012). Evaluation of the box and blocks test, stereognosis and item banks of activity 
and upper extremity function in youths with brachial plexus birth palsy. Journal of Pediatric 
Orthopedics, 32 Suppl 2, S114-22. https://doi.org/10.1097/BPO.0b013e3182595423 
Nemanich, S. T., Mueller, B. A., & Gillick, B. T. (2019). Neurite orientation dispersion and 
density imaging quantifies corticospinal tract microstructural organization in children with 
unilateral cerebral palsy. Human Brain Mapping, 40(17), 4888–4900. 
https://doi.org/10.1002/hbm.24744 
Novak, I., McIntyre, S., Morgan, C., Campbell, L., Dark, L., Morton, N., Stumbles, E., Wilson, S.-
A., & Goldsmith, S. (2013). A systematic review of interventions for children with cerebral 
palsy: state of the evidence. Developmental Medicine and Child Neurology, 55(10), 885–
910. https://doi.org/10.1111/dmcn.12246 
O’Connor, B., Kerr, C., Shields, N., & Imms, C. (2016). A systematic review of evidence-based 
assessment practices by allied health practitioners for children with cerebral palsy. 
Developmental Medicine and Child Neurology, 58(4), 332–347. 
https://doi.org/10.1111/dmcn.12973 
Oskoui, M., Coutinho, F., Dykeman, J., Jetté, N., & Pringsheim, T. (2013). An update on the 
prevalence of cerebral palsy: a systematic review and meta-analysis. Developmental 
Medicine and Child Neurology, 55(6), 509–519. https://doi.org/10.1111/dmcn.12080 
Peters, C., Chang, A., Morales, A., Barnes, K., & Allegretti, A. (2019). An integrative review of 
assessments used in occupational therapy interventions for children with cerebral palsy. 
Cadernos Brasileiros de Terapia Ocupacional, 27(1), 168–185. 
https://doi.org/10.4322/2526-8910.ctoAR1856 
Platz, T., Pinkowski, C., van Wijck, F., Kim, I.-H., di Bella, P., & Johnson, G. (2005). Reliability 
and validity of arm function assessment with standardized guidelines for the Fugl-Meyer 
Test, Action Research Arm Test and Box and Block Test: a multicentre study. Clinical 
Rehabilitation, 19(4), 404–411. https://doi.org/10.1191/0269215505cr832oa 
R Lowrey, C. (2014). A Novel Robotic Task for Assessing Impairments in Bimanual 
Coordination Post-Stroke. International Journal of Physical Medicine & Rehabilitation, 
s3(01). https://doi.org/10.4172/2329-9096.S3-002 
Riquelme, I., Arnould, C., Hatem, S. M., & Bleyenheuft, Y. (2019). The Two-Arm Coordination 
Test: Maturation of Bimanual Coordination in Typically Developing Children and Deficits in 
Children with Unilateral Cerebral Palsy. Developmental Neurorehabilitation, 22(5), 312–
320. https://doi.org/10.1080/17518423.2018.1498552 

CÉR-S en réadaptation et intégration sociale  
 
Project Number: 2020-1961 
2022.03.31 
15
Robert, M. T., Gutterman, J., Ferre, C. L., Chin, K., Brandao, M. B., Gordon, A. M., & Friel, K. 
(2021). Corpus Callosum Integrity Relates to Improvement of Upper-Extremity Function 
Following Intensive Rehabilitation in Children With Unilateral Spastic Cerebral Palsy. 
Neurorehabilitation and Neural Repair, 35(6), 534–544. 
https://doi.org/10.1177/15459683211011220 
Rocca, M. A., Turconi, A. C., Strazzer, S., Absinta, M., Valsasina, P., Beretta, E., Copetti, M., 
Cazzagon, M., Falini, A., & Filippi, M. (2013). MRI predicts efficacy of constraint-induced 
movement therapy in children with brain injury. Neurotherapeutics : The Journal of the 
American Society for Experimental NeuroTherapeutics, 10(3), 511–519. 
https://doi.org/10.1007/s13311-013-0189-2 
Rosenbaum, P., Paneth, N., Leviton, A., Goldstein, M., Bax, M., Damiano, D., Dan, B., & 
Jacobsson, B. (2007). A report: the definition and classification of cerebral palsy April 2006. 
Developmental Medicine and Child Neurology. Supplement, 109, 8–14. 
Shierk, A., Lake, A., & Haas, T. (2016). Review of Therapeutic Interventions for the Upper Limb 
Classified by Manual Ability in Children with Cerebral Palsy. Seminars in Plastic Surgery, 
30(1), 14–23. https://doi.org/10.1055/s-0035-1571256 
Sköld, A., Hermansson, L. N., Krumlinde-Sundholm, L., & Eliasson, A.-C. (2011). Development 
and evidence of validity for the Children’s Hand-use Experience Questionnaire (CHEQ). 
Developmental Medicine and Child Neurology, 53(5), 436–442. 
https://doi.org/10.1111/j.1469-8749.2010.03896.x 
Smorenburg, A. R. P., Gordon, A. M., Kuo, H.-C., Ferre, C. L., Brandao, M., Bleyenheuft, Y., 
Carmel, J. B., & Friel, K. M. (2017). Does Corticospinal Tract Connectivity Influence the 
Response to Intensive Bimanual Therapy in Children With Unilateral Cerebral Palsy? 
Neurorehabilitation and Neural Repair, 31(3), 250–260. 
https://doi.org/10.1177/1545968316675427 
Staudt, M. (2002). Two types of ipsilateral reorganization in congenital hemiparesis: A TMS and 
fMRI study. Brain, 125(10), 2222–2237. https://doi.org/10.1093/brain/awf227 
Staudt, M., Gerloff, C., Grodd, W., Holthausen, H., Niemann, G., & Krägeloh-Mann, I. (2004). 
Reorganization in congenital hemiparesis acquired at different gestational ages. Annals of 
Neurology, 56(6), 854–863. https://doi.org/10.1002/ana.20297 
Taub, E., Uswatte, G., Mark, V. W., & Morris, D. M. M. (2006). The learned nonuse 
phenomenon: implications for rehabilitation. Europa Medicophysica, 42(3), 241–256. 
Taylor, N., Sand, P. L., & Jebsen, R. H. (1973). Evaluation of hand function in children. Archives 
of Physical Medicine and Rehabilitation, 54(3), 129–135. 
Theaud, G., Houde, J.-C., Boré, A., Rheault, F., Morency, F., & Descoteaux, M. (2020). 
TractoFlow: A robust, efficient and reproducible diffusion MRI pipeline leveraging Nextflow 
& Singularity. NeuroImage, 218, 116889. 
https://doi.org/10.1016/j.neuroimage.2020.116889 
Tsai, L., Lin, K., Liao, H., & Hsieh, C. (2009). Reliability of two visual-perceptual tests for 
children with cerebral palsy. The American Journal of Occupational Therapy : Official 
Publication of the American Occupational Therapy Association, 63(4), 473–480. 
https://doi.org/10.5014/ajot.63.4.473 
Tyryshkin, K., Coderre, A. M., Glasgow, J. I., Herter, T. M., Bagg, S. D., Dukelow, S. P., & Scott, 
S. H. (2014). A robotic object hitting task to quantify sensorimotor impairments in 

CÉR-S en réadaptation et intégration sociale  
 
Project Number: 2020-1961 
2022.03.31 
16
participants with stroke. Journal of Neuroengineering and Rehabilitation, 11, 47. 
https://doi.org/10.1186/1743-0003-11-47 
van der Aa, N. E., Verhage, C. H., Groenendaal, F., Vermeulen, R. J., de Bode, S., van 
Nieuwenhuizen, O., & de Vries, L. S. (2013). Neonatal neuroimaging predicts recruitment 
of contralesional corticospinal tracts following perinatal brain injury. Developmental 
Medicine and Child Neurology, 55(8), 707–712. https://doi.org/10.1111/dmcn.12160 
Verkerk, G. J. Q., Wolf, M. J. M. A. G., Louwers, A. M., Meester-Delver, A., & Nollet, F. (2006). 
The reproducibility and validity of the Canadian Occupational Performance Measure in 
parents of children with disabilities. Clinical Rehabilitation, 20(11), 980–988. 
https://doi.org/10.1177/0269215506070703 
Waddell, K. J., & Lang, C. E. (2018). Comparison of Self-Report Versus Sensor-Based Methods 
for Measuring the Amount of Upper Limb Activity Outside the Clinic. Archives of Physical 
Medicine and Rehabilitation, 99(9), 1913–1916. https://doi.org/10.1016/j.apmr.2017.12.025 
Zielinski, I. M., Jongsma, M. L. A., Baas, C. M., Aarts, P. B. M., & Steenbergen, B. (2014). 
Unravelling developmental disregard in children with unilateral cerebral palsy by measuring 
event-related potentials during a simple and complex task. BMC Neurology, 14, 6. 
https://doi.org/10.1186/1471-2377-14-6