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. Author manuscript; available in PMC: 2018 Nov 12.
Published in final edited form as: Neurorehabil Neural Repair. 2017 Nov 12;31(10-11):965–976. doi: 10.1177/1545968317739997

Less-affected hand function in children with hemiparetic unilateral cerebral palsy: A comparison study to typically developing peers

Tonya L Rich 1,✉, Jeremiah S Menk 2, Kyle D Rudser 3, Timothy Feyma 4, Bernadette Gillick 5,6
PMCID: PMC5729110  NIHMSID: NIHMS912426  PMID: 29130382

Abstract

Background

Neurorehabilitation interventions in children with unilateral cerebral palsy (UCP) target motor abilities in daily life yet deficits in hand skills persist. Limitations in the less-affected hand may impact overall bimanual hand skills.

Objective

To compare hand function, by timed motor performance on the Jebsen-Taylor Test of Hand Function (JTTHF) and grip strength of children with UCP to children with typical development (CTD), ages 8–18 years old. Exploratory analyses compared hand function measures with respect to neurophysiological outcomes measured by transcranial magnetic stimulation and between group comparisons of hemispheric motor threshold.

Methods

Baseline hand skills were evaluated in 47 children (21 UCP; 26 CTD). Single-pulse transcranial magnetic stimulation testing assessed corticospinal tract and motor threshold.

Results

The mean difference of the less-affected hand of children with UCP to the dominant hand of CTD on the JTTHF was 21.4 seconds [95% Confidence Interval = 9.32, 33.46, p=0.001]. The mean difference in grip strength was −30.8 N [−61.9, 0.31, p = 0.052]. Resting motor thresholds between groups were not significant, but age was significantly associated with RMT (p<0.001; p=0.001). Children with UCP ipsilateral pattern of motor representation demonstrated greater mean differences between hands than children with contralateral pattern of motor representation (p<0.001). All results adjusted for age and sex.

Conclusions

The less-affected hand in children with UCP underperformed the dominant hand of CTD. Limitations were greater in children with UCP ipsilateral motor pattern. Rehabilitation in the less-affected hand may be warranted. Bilateral hand function in future studies may help identify the optimal rehabilitation and neuromodulatory intervention.

Keywords: children, stroke, cerebral palsy, rehabilitation, neuroplasticity, non-invasive brain stimulation

Graphical abstract

graphic file with name nihms912426u1.jpg

Introduction

Perinatal stroke occurring in utero or at the time of birth is a common cause of unilateral cerebral palsy (UCP) with the incidence of 1 in 2,300 live births.1 Upper limb intervention for children with UCP emphasizes motor skill development and compensation primarily targeting the more-affected (or weaker) hand for functional tasks. Even though up to one-third of individuals with UCP have bilateral lesions, the function of the less-affected hand is often assumed to be within expected norms for children with typical development (CTD)2. Consequently, comparison of the more-affected hand to the less-affected hand, instead of to normative data, further conceals identification of deficits in the less-affected hand.3 Although subtle deficits in the less-affected hand are reported in the literature, these less-affected hand deficits are often masked by the complex clinical presentation of the more-affected hand in children with UCP.2,4–6 Thus, intervention targeting the less-affected hand is not often a component of the child’s rehabilitation plan of care. The presence of bilateral hand deficits, even if subtle in the less-affected hand, may limit the transfer of unimanual gains following rehabilitation to bimanual activities of daily living tasks.2

Studies suggest the pattern of motor representation of the corticospinal tract, or laterality, is one of the key factors influencing motor development after injury early in life.7,8 One method for assessment of laterality is non-invasive brain stimulation assessment. Single-pulse transcranial magnetic stimulation assessment of the corticospinal tract for an upper limb muscle occurs by stimulating a targeted region such as the hand knob of the primary motor cortex and monitoring electromyography responses. Surface electromyography from a hand muscle allows for visualization of the motor evoked potential (MEP) response. Typically, in individuals without neurological conditions, we would expect to observe a MEP response in the hand contralateral to single pulse transcranial magnetic stimulation.

Laterality after hemispheric stroke or periventricular leukomalacia diagnosed prenatally or within the first year of life can be categorized with testing both the non-lesioned and lesioned hemispheres. Laterality in UCP can be categorized by TMS assessment of both the non-lesioned and lesioned hemispheres for responses on the more-affected side of the body. If the more-affected side has MEP only from the lesioned hemisphere, the laterality pattern is contralateral; if only from the non-lesioned hemisphere, the motor pattern is ipsilateral, and if from both, the motor pattern is mixed.9,10,11

A contralateral motor pattern describes a MEP response in the more-affected hand following stimulation of the contralateral, lesioned hemisphere –the typical pattern. An ipsilateral motor pattern describes an absent MEP response in the more-affected hand following stimulation of the lesioned hemisphere and a present MEP response in the more-affected hand following stimulation of the non-lesioned hemisphere. A mixed motor pattern describes MEP responses in the more-affected hand following stimulation to either hemisphere. MEP responses can also be absent where no MEP response is detected following stimulation to either hemisphere including mapping areas outside of the hand knob of the primary motor cortex. Single-pulse transcranial magnetic stimulation testing and subsequent categorization of children with UCP may aid in identifying predictive biomarkers of motor development and response to rehabilitation interventions.11 Individualized protocols considering neurophysiological underpinnings will allow for greater intervention efficacy with the ability to precisely influence motor function in children with UCP.8,12

Pediatric, diagnosis-specific non-invasive brain stimulation protocols to guide assessment and intervention do not yet exist given the nascent field of pediatric neuromodulation. In children with UCP and typical development, data suggest that age is correlated to motor threshold of the motor cortex as assessed by transcranial magnetic stimulation.13–15 The development of interhemispheric inhibition through the establishment of the connecting fibers of the corpus callosum, as evidenced by transcranial magnetic stimulation16 and neuroimaging,17 occurs after age 5 and has served as a target for interventional non-invasive brain stimulation in children with UCP.15 Hemispheric differences may contribute to the development of bimanual coordination however studies have not fully investigated the neurophysiological development of motor skills in CTD, limiting the generalizability to children with UCP and the development of non-invasive brain stimulation protocols.

The purpose of this study was to understand the motor abilities of the less-affected hand in children with UCP as compared to the dominant hand of CTD. We hypothesize that the less-affected hand of children with UCP differs from the dominant hand function of CTD regarding motor function and strength. Through a post-hoc analysis, we examined the neurophysiological underpinnings contributing to differences in hand function through our analysis of laterality in children with UCP and CTD. We hypothesized that between-group motor threshold differences would exist comparing children with UCP and CTD. We also hypothesized a contralateral pattern of motor representation would be the optimal laterality type in children with UCP for the within-group analyses.

Methods

Participants

Children ages 8–18 were recruited for a cross-sectional study comparing hand function and methods for localizing the primary motor cortex (clinicaltrials.gov identifier: NCT02015338). This study included 1) children with UCP secondary to hemispheric stroke or periventricular leukomalacia diagnosed within the first year of life and confirmed by neuroimaging and 2) children with typical development. Exclusion criteria for both groups of children included a history of seizures within the last two years, contraindications for transcranial magnetic stimulation such as indwelling metal or medical devices incompatible with transcranial magnetic stimulation, co-occurring diagnoses (such as acquired brain injury, neoplasm, pregnancy), communication deficits that limit a child from answering safety questions related to the transcranial magnetic stimulation, and botulinum toxin or phenol intramuscular block within 6 months prior to study participation. Children with UCP from a clinical trial that was held concurrently during the timeframe of this study were also invited to participate. This study was approved by the University of Minnesota’s Institutional Review Board. Written consent from all legal guardians and adult participants and assent was obtained from children.

Forty-seven children participated in the study including 21 children with UCP and 26 CTD. The supplemental materials include a flow diagram for participants. One child with UCP was included for grip strength testing but excluded from JTTHF and MEP analysis secondary to inability to tolerate the complete testing session due to difficulty engaging in testing. Therefore, our results reflect 20 children with UCP for JTTHF and 21 children with UCP for grip testing. One CTD was excluded from all testing following consent secondary to arriving with a cast on the participant’s arm from a non-study related injury. In total, forty-six children (21 children with UCP and 25 CTD) were included in the final behavioral analysis. Baseline characteristics for gender, age, and group specific data such as side of hemiparesis, laterality and hand dominance are reported in Table 1.

Table 1.

Participant characteristics by group.

Contralateral Ipsilateral All UCP CTD
n (row %) 10 (62.5) 6 (37.5) 21 (44.7) 26 (55.3)
Gender, n (column %)
 Female 4 (40.0) 3 (50.0) 10 (47.6) 16 (61.5)
Age, y
 Mean (SD) 14.1 (2.4) 12.5 (3. 7) 13.5 (3.0) 13.7 (3.2)
Side of hemiparesis or Hand Dominance, n (column %)
 Right 8 (80.0) 4 (66.7) 15 (71.4) 25 (96.2)
 Left 2 (20.0) 2 (33.3) 6 (28.6) 1 (3.8)
MACS Level, n (column %)
 Level I 4 (44.4) 0 (0.0) 6 (30.0) –
 Level II 5 (55.6) 6 (100.0) 14 (70.0) –
Missing 1 0 1
More-Affected/Non-dominant Hand Jebsen Taylor Test of Hand Function, sec
Mean (SD) [NA] 151.6 (114.0) 373.2
(193.7)		 234.2 (167.5)
[1]		 38.6 (9.7) [1]
Grip Strength, N
 Mean (SD) [NA] 121.9 (70.1) 54.6 (32.4) 92.0 (65.8)
[0]		 535.5 (95.8)
[1]
%MSO
 Mean (SD) [NA] 65.0 (12.8) 57.2 (12.7)
Less-Affected/Dominant Hand
Jebsen Taylor Test of Hand Function, sec
Mean (SD) [NA] 47.3 (11.0) 66.7 (45.1) 53.2 (27.3)
[1]		 32.1 (5.5)[1]
Grip Strength, N
Mean (SD) [NA] 232.3 (61.4) 207.4
(116.1)		 217.0 (78.7)
[0]		 246.8 (105.2)
[1]
%MSO of both hemispheres
Mean (SD) [NA] 55.6 (10.4) 56.8 (15.3)
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CTD: Children with typical development, %MSO: maximum stimulator output, MACS: Manual Abilities Classification System, n: number, N: newtons, NA: not applicable, SD: standard deviation, secs: seconds, UCP: Children with unilateral cerebral palsy, y: years.

Measures

The primary objective of this analysis was to evaluate differences between groups for outcome measures of hand function in children with UCP and CTD including the 1) more-affected hand in comparison to the non-dominant hand and 2) less-affected hand in comparison to the dominant hand. Four additional within-group comparisons on hand function measures are reported for completeness. The secondary objectives included six within-group comparisons of differences in hand function and motor thresholds for CTD, and children with UCP as grouped by contralateral, and ipsilateral motor patterns and two between-group comparisons of differences in motor thresholds for CTD and children with UCP with contralateral patterns of motor representation. Hand function was measured using speed during functional tasks with the Jebsen Taylor Test of Hand Function (JTTHF)29 and gross hand strength as measured by hydraulic grip dynamometry (Jamar Dynamometer, Patterson Medical, Warrenville, IL, USA). The post-hoc objective was to examine the relationship between the performance on the JTTHF and grip strength with the presence of a MEP as elicited by transcranial magnetic stimulation.

Behavioral Measures

Clinical measures were used to characterize both populations. Children with UCP were classified by caregivers using the Manual Abilities Classification System, with high reliability, to reflect overall bimanual hand use as hand dominance cannot be inferred due to neurological injury early in life.18,19 CTD completed the 10-question Edinburgh Handedness Inventory as a measure of hand dominance.20

Participants were positioned at an adjustable-height table in a university lab setting for hand function measures with environmental distractions minimized. The JTTHF measured maximal performance of speed and dexterity of each hand for functional tasks such as writing and stacking checkers with results reported as the total time in seconds.21 Similar to other studies in children with UCP, a 120 second maximum time limit per task on the JTTHF was established to reduce frustration in children with UCP who have greater hand impairments.22–24 The JTTHF data included in the analyses represents the total time per hand with the writing subtest time subtracted. A lower time on the JTTHF indicates more efficient performance.

Grip strength was measured using a calibrated hydraulic dynamometer set to the second rung of the device following the administration guidelines recommended by the American Society of Hand Therapists.25,26 Grip strength assessment was completed using a Jamar hydraulic dynamometer and has been found to have high reliability.27,28 For children with UCP, assistance to initially position the dynamometer was provided as needed. A maximum voluntary contraction for grip strength testing was recorded in pounds and converted to newtons for 3 trials with the average of the three tests used in the analysis.

Transcranial Magnetic Stimulation Measures

Motor cortex localization techniques and safety results are described elsewhere.29,30 Briefly, the hand knob region of the primary motor cortex was visually identified on a template brain and targeted as the starting location for motor hotspot searching. Children recruited for this study were co-registered to template magnetic resonance data with stereotactic neuronavigation (Brainsight™ Rogue Research, Quebec, Canada) (43 of 47 participants). Children recruited for this study with concurrent participation in a clinical trial (4 of 46 participants) completed the same co-registration procedures however were assessed with their individual anatomical magnetic resonance imaging data. In all children, hotspot searching commenced at 50% of the maximum stimulator output using a Magstim 200 stimulator with a 70-mm figure-of-eight coil (Magstim Company Ltd, Dyfed, United Kingdom). Surface electromyography from the first dorsal interosseous muscle of the contralateral hand was recorded for each hemisphere assessed.

Each hemisphere was assessed individually for a motor evoked potential starting at the hand knob and expanding the region assessed as needed to locate a response. Once a consistent MEP with an amplitude of 50 μV in 3 of 5 trials was observed using electromyography at the first dorsal interosseous, the maximum stimulator output was then decreased by 1% to identify the exact motor threshold of the motor hotspot. When the motor threshold was identified, further motor hotspot searching was performed using 1% less than the identified motor threshold to search the locations 1 cm anterior, posterior, medial, and lateral of the originally identified location. This process was repeated until the location with the lowest maximum stimulator output that produced a consistent MEP was identified. In children with UCP, if a MEP was observed in the hand contralateral to stimulation when assessing both hemispheres (active or resting motor threshold), contralateral motor pattern was described as “contralateral motor pattern”. Children with an active motor threshold on either hemisphere were excluded from analyses specific to motor threshold but were included in the behavioral analysis of motor patterns and function.

If a consistent motor evoked potential response from surface electromyography was not observed, testing continued in the same location and the intensity was increased by 5% of the maximum stimulator output. In children with UCP, the presence of a motor evoked potential from the non-lesioned hemisphere only was described as “ipsilateral motor pattern”. A “mixed” motor pattern incorporating bilateral surface electromyography recording was not assessed in this study.

Children recruited for this study were tested up to 100% maximum stimulator output (43 of 47 participants). For evaluative-only studies, we have found that children tolerate up to 100% maximum stimulator output for neurophysiological testing. Children with UCP recruited for this study and who were concurrently enrolled in a clinical trial were tested up to 85% maximum stimulator output (4 of 21 participants with UCP). For interventional studies, we have chosen to assess children up to 85% maximum stimulator output. The change in upper limit for testing is based on our experience testing a child in the context of a multi-day intervention study and maximizing tolerance for testing and interventional procedures. Following behavioral and transcranial magnetic stimulation testing, all children completed safety and study satisfaction measures.

Statistical Analysis

Descriptive statistics including means and standard deviations were used for continuous variables and counts and percentages were computed for categorical variables by laterality and group (children with UCP compared to CTD). The primary analysis for the outcomes JTTHF and grip strength, included four generalized linear models (GLM) that were fit using a Gaussian distribution with an identity link to evaluate the difference between groups by more-affected hand versus non-dominant hand and less-affected hand versus dominant hand separately. Age and sex were included in the models to adjust for their potential impact, with the association between age and the outcomes assumed to be linear. Thus, the parameter estimate for age is interpreted as the increase or decrease in the outcome for a one year difference in age adjusted for sex and group. Because of the potential for heteroscedasticity, robust standard errors were computed for the parameter estimates using generalized estimating equations with an independent correlation structure. Parameter estimates and 95% confidence intervals are presented. P-values were computed using a Wald Statistic. Four paired t-tests were conducted to compare between hand differences within each group of children (CTD and UCP) to summarize differences that were anticipated. In addition, one secondary analysis was conducted in the CTD for resting motor thresholds, five secondary paired t-tests were conducted in children with UCP, and two additional GLM were fit using a Gaussian distribution with an identity link to evaluate between hemisphere differences between the lesioned hemisphere in children with UCP and the non-dominant hemisphere in CTD and, the non-lesioned hemisphere in children with UCP and the dominant hemisphere in CTD. The secondary paired t-tests in the children with UCP were computed by contralateral and ipsilateral motor patterns for the JTTHF, grip strength, and resting motor thresholds (in contralateral motor pattern subgroup only). A p-value less than 0.05 was defined as statistically significant for the main effects from the generalized linear models and the paired t-tests. No adjustments were made for multiple comparisons due to the a priori belief that the possibility of making a Type 1 error was offset by the importance of identifying potential associations in this exploratory study on this topic.31–33 We present confidence intervals to show the precision of our estimates in this early phase study. All analyses were completed using R Statistical Software, Version 3.3.0 within R-Studio, Version 0.99.902.

Results

To summarize the results, the less-affected hand of children with UCP demonstrated greater time on the JTTHF as compared to the dominant hand of a CTD. Further, children with ipsilateral motor pattern demonstrated greater mean differences between hands as compared to children with contralateral motor pattern. The resting motor threshold between groups was not significant. We expand on the results below.

For neurophysiological testing, 5 children were excluded from analysis due to the following reasons: stereotactic neuronavigation equipment malfunction (n=3), missing data (n=1), or unable to tolerate full testing sessions (n=1). Two children with UCP with active motor thresholds were excluded from analyses specific to resting motor threshold comparisons but were included in the behavioral analysis based on motor pattern and function (n=2). Final neurophysiological analysis included 18 children with UCP and 21 CTD.

Hand Function Measures

Baseline hand function is displayed in Figure 1 (total time in seconds on the JTTHF) and Figure 2 (average grip strength in newtons). CTD and laterality subgroups of children with UCP are differentiated by symbols. Unadjusted summary statistics for both CTD and children with UCP are presented in Table 2.

Figure 1.

Figure 1

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Plot of Jebsen Taylor Test of Hand Function total time with writing task subtracted by age and handedness. Age is reported in years (y) whereas time is reported in seconds (s). Children with unilateral cerebral palsy (UCP) are represented by laterality groups (contralateral, ipsilateral, and absent motor evoked potential (MEP) responses bilaterally) for the more-affected (or weaker) and less-affected (or stronger) hand. Children with typical development (CTD) are represented by a cross for the dominant and non-dominant hand.

Figure 2.

Figure 2

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Plot of mean grip strength by age and handedness. Age is reported in years (y) whereas grip strength is reported in newtons (N). Children with unilateral cerebral palsy (UCP) are represented by laterality groups (contralateral, ipsilateral, missing motor evoked potential (MEP) data, and absent motor evoked potential responses bilaterally) for the more-affected (or weaker) and less-affected (or stronger) hand. Children with typical development (CTD) are represented by a cross for the dominant and non-dominant hand.

Table 2.

Between group comparison of performance and strength of children with unilateral cerebral palsy compared to children with typical development

Estimate Lower 95% CI Upper 95% CI P-value
More affected hand versus non-dominant hand
 Jebsen Taylor Test of Hand Function, secs
  UCP versus CTD 194.8 121.3 268.3 <0.001
  One year increase in age −7.7 −18.1 2.7 0.147
  Females versus Males −0.64 −66.5 65.2 0.985
 Grip strength, N
  UCP versus CTD −140.9 −180.0 −101.8 <0.001
  One year increase in age 16.8 11.8 21.7 <0.001
  Females versus Males −24.3 −62.1 13.5 0.208
 %MSO*
  UCP versus CTD 6.9 −1.5 15.3 0.106
  One year increase in age −2.5 −3.8 −1.2 <0.001
  Females versus Males −3.7 −10.7 3.4 0.306
Less affected hand versus dominant hand
 Jebsen Taylor Test of Hand Function, secs
  UCP versus CTD 21.4 9.3 33.5 0.001
  One year increase in age −1.7 −3.5 0.07 0.060
  Females versus Males 2.7 −7.0 12.4 0.589
 Grip strength, N
  UCP versus CTD −30.8 −61.9 0.31 0.052
  One year increase in age 23.5 18.9 28.1 <0.001
  Females versus Males −37.0 −68.5 −5.4 0.022
 %MSO*
  UCP versus CTD −1.3 −7.9 5.4 0.713
  One year increase in age −2.6 −4.2 −1.1 <0.001
  Females versus Males −0.06 −7.1 7.0 0.986
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CI: Confidence Interval, CTD: Children with typical development, MSO: maximum stimulator output, N: newtons, secs: seconds, UCP: Children with unilateral cerebral palsy. The Jebsen Taylor Test of Hand Function and Grip Strength analyses included 21 children with UCP and 26 CTD.

%MSO* Because of missing data in six children with UCP, the analysis for %MSO included 15 children with UCP and 21 children with CTD.

Between-Group Results

Between-group comparisons evaluating the more-affected hand of children with UCP to the non-dominant hand of CTD resulted in statistically significant group differences as expected. Holding age and sex constant in the generalized linear model, we observed a decrease in performance for the more-affected hand in participants with UCP compared to the non-dominant hand of CTD. UCP participants required an additional 195 seconds (p<0.001). Similar results were observed for grip strength testing. The more-affected hand of children with UCP had a mean grip strength of −140.9 N [−180.0, −101.8] (p<0.001) less compared to the non-dominant hand of CTD adjusted for age and sex in the generalized linear model.

We observed significant between-group differences when evaluating the less-affected hand of children with UCP to the dominant-hand of CTD using the JTTHF, but not when comparing grip strength. Using the less-affected hand, participants with UCP took 21.4 seconds [9.32 – 33.5] longer to complete the JTTHF (p=0.001) compared to the dominant hand of CTD while adjusting for age and sex in the generalized linear model. Children with UCP had a grip strength 30.8 newtons [−61.9, 0.31], (p = 0.052) less for their less-affected hand compared to the dominant hand of CTD while adjusting for age and sex in the generalized linear model. Regardless of the pattern of motor representation, the less-affected hand of children with UCP differed from the dominant hand of CTD on grip strength however this result was not statistically significant. Table 2 summarizes the parameter estimates from the between-group comparisons from the six generalized linear models, including the estimates for age and sex.

Within-Group and Laterality Results

Children with UCP were grouped by motor patterns and included: contralateral (n=12), ipsilateral (n=6), and absent on both hemispheres (n=1). Of the children identified with an ipsilateral pattern, three children were enrolled in a concurrent clinical trial where the maximum stimulator output was 85%. In comparison, all CTD displayed an MEP from both hemispheres with contralateral pattern to each hand with testing (n=21). In 17 of 18 children with UCP, an MEP was present on the non-lesioned hemisphere with a MEP response measured from the contralateral less-affected hand.

For children with UCP and contralateral motor pattern, the mean time on the JTTHF for the less-affected hand was 47.3 seconds. For children with UCP and ipsilateral motor pattern, the mean time on the JTTHF for the less-affected hand was 66.7 seconds and greater limitations in grip strength in either hand were observed as compared to children with contralateral motor pattern. Regardless of the patterns of motor representation, the less-affected hand of children with UCP differed from the dominant hand of CTD (Table 3). In comparison to children with UCP, CTD’s dominant hand performance on the JTTHF had a mean score of 32.1 seconds compared to 53.2 seconds in the children with UCP.

Table 3.

Unadjusted paired analyses for within-group comparisons
More-affected/non-dominant versus less-affected/dominant Mean Difference Lower 95% CI Upper 95% CI P-value
Jebsen Taylor Test of Hand Function, secs
 UCP All 241.3 159.0 323.6 <0.001
 UCP Contralateral 102.2 40.5 163.9 0.004
 UCP Ipsilateral 306.5 106.1 506.9 0.011
 CTD 26.2 19.6 32.8 <0.001
Grip strength, N
 UCP All −125.0 −161.1 −88.9 <0.001
 UCP Contralateral −110.4 −156.7 −64.1 <0.001
 UCP Ipsilateral −152.8 −266.9 −38.6 0.018
 CTD −14.3 −24.7 −3.9 0.009
%MSO
 UCP- Contralateral reorganization only 9.4 3.9 14.9 0.004
 CTD 0.4 −2.5 3.4 0.765
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CI: Confidence Interval, CTD: Children with typical development, N:newtons, %MSO: maximum stimulator output, secs: seconds, UCP: Children with unilateral cerebral palsy.

Within-group comparisons examined the differences between hands with the JTTHF and grip strength. Comparing children with UCP grouped by laterality for between-hand differences on the JTTHF, we observed a mean difference between the more-affected hand and less-affected hand of 102.2 seconds (p=0.004) for the 12 children with contralateral reorganization and 306.5 seconds (p=0.011) for the 6 children with ipsilateral reorganization. CTD’s non-dominant hand versus dominant hand difference was 6.5 seconds (p<0.001). Comparing grip strength between hands for children with UCP, we observed a mean difference between the more-affected hand and less-affected hand of −110.4 N (p<0.001) for children with contralateral reorganization and – 152.8 N (p=0.018) for children with ipsilateral reorganization. In CTD, grip strength of the non-dominant compared to the dominant hand was −14.3 N (p=0.009). The estimates of the mean difference within-group, 95% confidence intervals, and p-values are presented in Table 3.

Transcranial Magnetic Stimulation Measures

Between-Group Results

Between-group comparisons of motor thresholds were not significant comparing the lesioned hemisphere of children with UCP, contralateral motor pattern only, to the non-dominant hemisphere of CTD (p=0.137) and the non-lesioned hemisphere of children with UCP (contralateral motor pattern only) to dominant hemisphere of CTD (p= 0.568). Age was significant as relates to motor thresholds in the Generalized Linear Model adjusted for group and sex (both p<0.001). Figure 3 displays the individual resting motor thresholds by hemisphere providing a visual comparison between groups of children with UCP and CTD.

Figure 3.

Figure 3

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Plot of resting motor threshold comparing lesioned hemisphere (children with unilateral cerebral palsy (UCP)) to non-dominant hemisphere (children with typical development (CTD)) and non-lesioned hemisphere (UCP) to dominant hemisphere (CTD) by group. Resting motor threshold is reported in the percentage of maximum stimulator output (% MSO). Age is reported in years (y). Symbols denote children with UCP by laterality groups (contralateral and ipsilateral) and CTD.

Within-Group Results

Within-group differences were observed for the average resting motor threshold of each hemisphere for the children with UCP (contralateral motor pattern only), but not CTD (Table 3). Comparing hemispheres, the average resting motor threshold had a mean difference of 9.4% maximum stimulator output (p = 0.004) for the children with UCP (contralateral motor pattern only). The average resting motor threshold in the lesioned hemisphere was 65.00% maximum stimulator output (n=10) and the non-lesioned hemisphere was 56.25% maximum stimulator output (n=16). In comparison, between hemisphere differences in the average resting motor threshold in CTD’s was 0.4 % maximum stimulator output (p=0.765). The non-dominant hemisphere of CTD had an average resting motor threshold of 57.24% (n=21) and the dominant hemisphere of CTD had an average motor threshold of 56.81% (n=21).

Discussion

Hand Function Measures

As expected, the more-affected hand of children with UCP demonstrated deficits in timed motor performance and strength. Significant differences in the JTTHF of the less-affected hand of children with UCP as compared to the dominant hand of CTD were observed. Our observations are consistent with previous reports of deficits including kinematic differences (reliance on feedback strategies instead of feedforward programming during reaching towards a target34 and impairments in movement duration and time to peak hand speed during reaching35) and grip (subtle changes in the grip-lift movement36, gross manual dexterity37, and grip strength37,38). Deficits in timed motor performance may be a target for intervention clinically and in research and warrants pursuit of a larger trial.23,37

The mean of the differences between hands observed within both groups revealed CTD have performance and strength similarities between the hands in contrast to children with UCP who display large differences between hands. In our study, CTD displayed relatively small differences between hands for grip strength and time motor performance (Table 3). We observed a large mean difference between hands for grip strength and timed motor performance comparing hands within children with UCP stratified by patterns of motor representation (Table 3).

Previous investigations have reported the differences between hands in grip strength is unrelated to bimanual hand function in children with UCP.23 However, bimanual hand function is one component of effective hand use for daily tasks. Strength deficits between sides could direct selection of rehabilitation techniques. For example, if the difference between hands in grip strength parallels the expected differences in CTD, bimanual therapy may be indicated to facilitate bimanual hand use. Conversely, if the difference between hands in grip strength exceeds the expected differences in CTD, constraint-induced movement therapy may be more appropriate to facilitate the use and strength of the more-affected hand.41,42 There is no current consensus on the optimal therapy for individuals with UCP (bimanual vs. CIMT). Optimal clinical decision making incorporates the multifaceted components of general limb usage and may take into consideration differences in strength.

Transcranial Magnetic Stimulation Measures

When evaluating the children with UCP motor performance on the JTTHF and grip strength based on patterns of motor representation, there are significant differences in the more-affected hand baseline abilities between the motor pattern groups consistent with previous reports.9,10 The mean time on the JTTHF and grip strength differed for children based on the motor pattern warranting additional investigation to determine the discriminative sensitivity of our behavioral measures. Other data suggest the patterns of motor representation is not indicative of responsiveness to intervention.12,24 Further examination of the neurophysiological relationship between baseline motor pattern and the components of intervention is critical for the design of individualized interventions in the future.

This study did not include investigation of the “mixed” re-organization pattern meaning a MEP is observed in the more-affected hand following transcranial magnetic stimulation to both the non-lesioned and lesioned hemispheres. Therefore, it is possible that children within the contralateral group may in fact have a “mixed” pattern impacting their abilities on the JTTHF. For children with ipsilateral and mixed motor patterns, decreases in function of the less-affected hand may be attributed to a shared non-lesioned hemisphere that controls the more-affected and less-affected hand. Our data showing differences based on re-organization pattern contribute to the neurophysiological underpinnings of motor performance.40

Our between-group analysis of motor threshold data did not detect a statistically significant difference between children with UCP and CTD. Others have reported significant motor threshold differences between diagnostic groups of children with Tourette’s Syndrome43 and typical development and in children born early preterm birth (≤32 weeks gestational age) as compared to late preterm (33–36 weeks’ gestation age) and term-born (37–41 weeks gestational age) groups44. Pitcher et al. (2012) proposed that the lower cortical excitability as reflected by a higher resting motor threshold in children with early preterm birth may reflect weaker connectivity between the primary and secondary motor areas. Future studies will contribute to our understanding of motor thresholds and its impact on motor development in CTD and children with UCP.

Within-group threshold differences observed in children with CTD were comparable to the ranges previously reported by Garvey et al. (2003) who used a similar methodology, however, threshold differences based on the dominant hemisphere differed.11 In our study, 14 of 21 CTD displayed a dominant hemisphere threshold was lower than the non-dominant hemisphere. This finding is inconsistent with previously reported findings wherein the dominant hemisphere displayed a lower MEP threshold in all 31 CTD.11 The ratio of hemispheric threshold differences may be a consideration for the individualization of non-invasive brain stimulation paradigms in children with UCP with bilateral MEP. The use of a common data set in reporting transcranial magnetic stimulation testing parameters will allow for greater pooling of data and comparison of populations in future studies.

For clinical application, we observed deficits in speed and strength of the less-affected hand in children with UCP as compared to the dominant hand of typically developing peers. Therefore, assessment of the less-affected hand should be incorporated into clinical and research protocols. Inclusion of the less-affected hand in skill development may optimize the more-affected hand as a functional assist.

In the construct of neuromodulatory/cortical excitability research protocols, we observed similar motor thresholds in our study between-groups of children with UCP and CTD. We found that age was a significant factor in thresholds and would recommend incorporation of this into future study designs (e.g. single or paired-pulse protocols).

Limitations

Our use of transcranial magnetic stimulation provides a preliminary categorization of the children’s pattern of motor representation. However, the presence or absence of an MEP may not be a sensitive enough neurophysiological marker to distinguish levels of performance and function. Perhaps other neurophysiologically-based testing paradigms such as motor mapping could provide greater ability to discriminate functional groups and predict functional recovery in children with UCP. The presence of neurophysiological responses and the child’s functional performance was explored in this sample of children with UCP and typical development however conclusions regarding the ability to predict hand function based on patterns of motor representation are limited. Of the three children who were assessed up to 85% maximum stimulator output, we cannot fully rule out that these three children would have an MEP if tested up to 100% maximum stimulator output. Conclusions are limited due to sample size and the inability to a priori stratify our UCP sample (based on the Manual Abilities Classification System levels, or corticospinal tract re-organization pattern). Breaks were provided as needed to minimize the influence of testing fatigue. An expanded neurophysiological assessment in future studies, including additional measures of cortical excitability such as motor mapping and MEP amplitude could provide additional insight into the neurophysiological contributions to the children’s motor performance. Analysis methods including the ratio of lesioned versus non-lesioned resting motor threshold or MEP amplitude may yield a more sensitive measure. Further study of these measures and analyses in children with and without UCP is warranted.

The potential exists that in our study, the children with UCP categorized as having contralateral motor pattern may indeed have bilateral motor pattern (meaning the contralesional hemisphere is contributing to movement of the more-affected hand). Others with similar methodologies and equipment have reported the presence of bilateral motor pattern in approximately 30% of pediatric UCP samples.45 Based on these reports, one could infer that a portion of the 12 children with contralateral motor pattern in our sample have bilateral motor pattern although this is speculation and was not tested. Future studies incorporating bilateral electromyography to quantify the percentage of motor evoked potentials and average amplitude elicited with stimulation to each hemisphere would aid in discerning the subtypes based on motor patterns.

Conclusions

In this study, deficits in timed motor performance and grip strength were noted in the less-affected hand of children with UCP as compared to CTD. The data suggests that the less-affected hand does not function the same as a dominant hand of a typically developing peer. Collectively, this information leads us to implications for intervention in the less-affected hand. The results of this study may be useful when considering the scope of clinical assessments and greater consideration of the less-affected hand function while goal setting during rehabilitation clinical exams is warranted.

Future larger studies may consider stratifying samples based on neurophysiological reorganization pattern. The findings of this study with respect to differences between hands and hemispheric motor thresholds may influence future study design of novel rehabilitation interventions. Reporting the quantification of the differences in hand function and hemispheric neurophysiology may allow for discernment of clinical trial results and aid in translating the findings to clinical populations. The reporting of these differences will contribute to the prediction of responders in neurorehabilitation interventions.

Acknowledgments

This work was supported by the National Institutes of Health (K01-1K01HD078484-01A1); KL2RR033182, KL2TR000113); the National Center for Advancing Translational Science Award (UL1TR000114). We thank the following graduate students: Shannon Groth DPT, Katelyn Kubat DPT, Kaitlyn Lorsbach DPT, Josa Martin DPT, Stephanie Mathiowetz DPT, Carly McQuillan DPT, Joshua Meuwissen DPT, Timothy Miller DPT, Stephanie Morse DPT, Karen Myhrman, DPT, and Andrea Tobias DPT. Finally, and most importantly, we are grateful for the children and families who participated in this study.

Footnotes

The authors have no conflicts to disclose.

Contributor Information

Tonya L. Rich, Department of Physical Medicine and Rehabilitation, Program in Rehabilitation Science, University of Minnesota, 420 Delaware Street SE, MMC 388, Minneapolis, MN 55455, United States of America.

Jeremiah S. Menk, Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, 717 Delaware Street SE, MMC 1932D, Minneapolis, MN 55414, United States of America.

Kyle D. Rudser, Division of Biostatistics, School of Public Health, Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, 717 Delaware Street SE, MMC 1932D, Minneapolis, MN 55414, United States of America.

Timothy Feyma, Gillette Children’s Specialty Healthcare, 200 E. University Avenue, St. Paul, MN 55101, United States of America.

Bernadette Gillick, Department of Physical Medicine and Rehabilitation, Program in Rehabilitation Science, University of Minnesota; Department of Physical Medicine and Rehabilitation, Program in Physical Therapy, University of Minnesota, 420 Delaware Street SE, MMC 388, Minneapolis, MN 55455, United States of America.

References

  • 1.Raju TNK, Nelson KB, Ferriero D, Lynch JK. Ischemic perinatal stroke: Summary of a workshop sponsored by the national institute of child health and human development and the national institute of neurological disorders and stroke. Pediatrics. 2007;120(3):609–616. doi: 10.1542/peds.2007-0336. [DOI] [PubMed] [Google Scholar]
  • 2.Okumura A, Kato T, Kuno K, Hayakawa F, Watanabe K. MRI findings in patients with spastic cerebral palsy. II: Correlation with type of cerebral palsy. Dev Med Child Neurol. 1997;39(6):369–372. [PubMed] [Google Scholar]
  • 3.Gordon AM, Duff SV. Fingertip forces during object manipulation in children with hemiplegic cerebral palsy. I: Anticipatory scaling. Dev Med Child Neurol. 1999;41(3):166–175. doi: 10.1017/s0012162299000353. [DOI] [PubMed] [Google Scholar]
  • 4.Annett M. Laterality of childhood hemiplegia and the growth of speech and intelligence. Cortex. 1973;9(1):4–39. doi: 10.1016/s0010-9452(73)80014-0. [DOI] [PubMed] [Google Scholar]
  • 5.Kiessling LS, Denckla MB, Carlton M. Evidence for differential hemispheric function in children with hemiplegic cerebral palsy. Dev Med Child Neurol. 1983;25(6):727–734. doi: 10.1111/j.1469-8749.1983.tb13840.x. [DOI] [PubMed] [Google Scholar]
  • 6.Brown JV, Schumacher U, Rohlmann A, Ettlinger G, Schmidt RC, Skreczek W. Aimed movements to visual targets in hemiplegic and normal children: Is the “good” hand of children with infantile hemiplegia also normal? Neuropsychologia. 1989;27(3):283–302. doi: 10.1016/0028-3932(89)90019-5. [DOI] [PubMed] [Google Scholar]
  • 7.Klingels K, Jaspers E, Staudt M, et al. Do mirror movements relate to hand function and timing of the brain lesion in children with unilateral cerebral palsy? Dev Med Child Neurol. 2015 doi: 10.1111/dmcn.12977. [DOI] [PubMed] [Google Scholar]
  • 8.Schertz M, Shiran SI, Myers V, et al. Imaging predictors of improvement from a motor learning-based intervention for children with unilateral cerebral palsy. Neurorehabil Neural Repair. 2015 doi: 10.1177/1545968315613446. [DOI] [PubMed] [Google Scholar]
  • 9.Carr LJ. Development and reorganization of descending motor pathways in children with hemiplegic cerebral palsy. Acta Paediatr Suppl. 1996;416:53–57. doi: 10.1111/j.1651-2227.1996.tb14278.x. [DOI] [PubMed] [Google Scholar]
  • 10.Holmström L, Vollmer B, Tedroff K, et al. Hand function in relation to brain lesions and corticomotor-projection pattern in children with unilateral cerebral palsy. Dev Med Child Neurol. 2010;52(2):145–152. doi: 10.1111/j.1469-8749.2009.03496.x. [DOI] [PubMed] [Google Scholar]
  • 11.Jaspers E, Byblow WD, Feys H, Wenderoth N. The corticospinal tract: A biomarker to categorize upper limb functional potential in unilateral cerebral palsy. Front Pediatr. 2015;3:112–112. doi: 10.3389/fped.2015.00112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Friel KM, Kuo H, Carmel JB, Rowny SB, Gordon AM. Improvements in hand function after intensive bimanual training are not associated with corticospinal tract dysgenesis in children with unilateral cerebral palsy. Exp Brain Res. 2014;232(6):2001–2009. doi: 10.1007/s00221-014-3889-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Moll GH, Heinrich H, Wischer S, Tergau F, Paulus W, Rothenberger A. Motor system excitability in healthy children: Developmental aspects from transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol Suppl. 1999;51:243–249. [PubMed] [Google Scholar]
  • 14.Garvey MA, Ziemann U, Bartko JJ, Denckla MB, Barker CA, Wassermann EM. Cortical correlates of neuromotor development in healthy children. Clin Neurophysiol. 2003;114(9):1662–1670. doi: 10.1016/S1388-2457(03)00130-5. [DOI] [PubMed] [Google Scholar]
  • 15.Kirton A, Deveber G, Gunraj C, Chen R. Cortical excitability and interhemispheric inhibition after subcortical pediatric stroke: Plastic organization and effects of rTMS. Clin Neurophysiol. 2010;121(11):1922–1929. doi: 10.1016/j.clinph.2010.04.021. [DOI] [PubMed] [Google Scholar]
  • 16.Heinen F, Glocker FX, Fietzek U, Meyer BU, Lucking CH, Korinthenberg R. Absence of transcallosal inhibition following focal magnetic stimulation in preschool children. Ann Neurol. 1998;43(5):608–612. doi: 10.1002/ana.410430508. [DOI] [PubMed] [Google Scholar]
  • 17.Kwon HG, Son SM, Jang SH. Development of the transcallosal motor fiber from the corticospinal tract in the human brain: Diffusion tensor imaging study. Front Hum Neurosci. 2014;8:153–153. doi: 10.3389/fnhum.2014.00153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Eliasson AC, Krumlinde-Sundholm L, Rosblad B, et al. The manual ability classification system (MACS) for children with cerebral palsy: Scale development and evidence of validity and reliability. Dev Med Child Neurol. 2006;48(7):549–554. doi: 10.1017/S0012162206001162. [DOI] [PubMed] [Google Scholar]
  • 19.Morris C, Kurinczuk JJ, Fitzpatrick R, Rosenbaum PL. Reliability of the manual ability classification system for children with cerebral palsy. Dev Med Child Neurol. 2006;48(12):950–953. doi: 10.1017/S001216220600209X. [DOI] [PubMed] [Google Scholar]
  • 20.Oldfield RC. The assessment and analysis of handedness: The edinburgh inventory. Neuropsychologia. 1971;9(1):97–113. doi: 10.1016/0028-3932(71)90067-4. [DOI] [PubMed] [Google Scholar]
  • 21.Taylor N, Sand PL, Jebsen RH. Evaluation of hand function in children. Arch Phys Med Rehabil. 1973;54(3):129–35. [PubMed] [Google Scholar]
  • 22.Gordon AM, Charles J, Wolf SL. Efficacy of constraint-induced movement therapy on involved upper-extremity use in children with hemiplegic cerebral palsy is not age-dependent. Pediatrics. 2006;117(3):e363–e373. doi: 10.1542/peds.2005-1009. [DOI] [PubMed] [Google Scholar]
  • 23.Sakzewski L, Ziviani J, Boyd R. The relationship between unimanual capacity and bimanual performance in children with congenital hemiplegia. Dev Med Child Neurol. 2010;52(9):811–816. doi: 10.1111/j.1469-8749.2009.03588.x. [DOI] [PubMed] [Google Scholar]
  • 24.Islam M, Nordstrand L, Holmström L, Kits A, Forssberg H, Eliasson A. Is outcome of constraint-induced movement therapy in unilateral cerebral palsy dependent on corticomotor projection pattern and brain lesion characteristics? Dev Med Child Neurol. 2014;56(3):252–258. doi: 10.1111/dmcn.12353. [DOI] [PubMed] [Google Scholar]
  • 25.Mathiowetz V, Wiemer DM, Federman SM. Grip and pinch strength: Norms for 6- to 19- year-olds. Am J Occup Ther. 1986;40(10):705–11. doi: 10.5014/ajot.40.10.705. [DOI] [PubMed] [Google Scholar]
  • 26.Fess E. Grip strength. In: American Society of Hand Therapists, editor. Clinical Assessment Recommendations. 2nd. Chicago: 1992. pp. 41–45. [Google Scholar]
  • 27.van den Beld WA, van der Sanden GA, Sengers RC, Verbeek AL, Gabreëls FJ. Validity and reproducibility of the jamar dynamometer in children aged 4–11 years. Disabil Rehabil. 2006;28(21):1303–1309. doi: 10.1080/09638280600631047. [DOI] [PubMed] [Google Scholar]
  • 28.Klingels K, De Cock P, Molenaers G, et al. Upper limb motor and sensory impairments in children with hemiplegic cerebral palsy. can they be measured reliably? Disabil Rehabil. 2010;32(5):409–416. doi: 10.3109/09638280903171469. [DOI] [PubMed] [Google Scholar]
  • 29.Rich TL, Menk JS, Rudser KD, et al. Determining electrode placement for transcranial direct current stimulation: A comparison of electroencephalogram versus transcranial magnetic stimulation guided methods. Clin EEG Neurosci. 2017 doi: 10.1177/1550059417709177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Gillick BT, Feyma T, Menk J, et al. Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: Randomized controlled preliminary study. Phys Ther. 2015;95(3):337–349. doi: 10.2522/ptj.20130565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Pocock SJ. Clinical trials with multiple outcomes: A statistical perspective on their design, analysis, and interpretation. Control Clin Trials. 1997;18(6):530–45. doi: 10.1016/s0197-2456(97)00008-1. [DOI] [PubMed] [Google Scholar]
  • 32.Vasilopoulos T, Morey TE, Dhatariya K, Rice MJ. Limitations of significance testing in clinical research: A review of multiple comparison corrections and effect size calculations with correlated measures. Anesth Analg. 2016;122(3):825–830. doi: 10.1213/ANE.0000000000001107. [DOI] [PubMed] [Google Scholar]
  • 33.Nakagawa S. A farewell to bonferroni: The problems of low statistical power and publication bias. Behavioral Ecology. 2004;15(6):1044–1045. doi: 10.1093/beheco/arh107. [DOI] [Google Scholar]
  • 34.Rigoldi C, Molteni E, Rozbaczylo C, et al. Movement analysis and EEG recordings in children with hemiplegic cerebral palsy. Exp Brain Res. 2012;223(4):517–524. doi: 10.1007/s00221-012-3278-2. [DOI] [PubMed] [Google Scholar]
  • 35.Steenbergen B, Meulenbroek RGJ. Deviations in upper-limb function of the less-affected side in congenital hemiparesis. Neuropsychologia. 2006;44(12):2296–2307. doi: 10.1016/j.neuropsychologia.2006.05.016. [DOI] [PubMed] [Google Scholar]
  • 36.Gordon A, Charles J, Duff S. Fingertip forces during object manipulation in children with hemiplegic cerebral palsy. II: Bilateral coordination. Pediatr Phys Ther. 2000;12(4):195–196. [PubMed] [Google Scholar]
  • 37.Tomhave WA, Van Heest AE, Bagley A, James MA. Affected and contralateral hand strength and dexterity measures in children with hemiplegic cerebral palsy. J Hand Surg Am. 2015;40(5):900–907. doi: 10.1016/j.jhsa.2014.12.039. [DOI] [PubMed] [Google Scholar]
  • 38.Arnould C, Penta M, Thonnard J. Hand impairments and their relationship with manual ability in children with cerebral palsy. J Rehabil Med. 2007;39(9):708–714. doi: 10.2340/16151977-0111. [DOI] [PubMed] [Google Scholar]
  • 39.Hepping AM, Ploegmakers JJW, Geertzen JHB, Bulstra SK, Stevens M. The influence of hand preference on grip strength in children and adolescents; A cross-sectional study of 2284 children and adolescents. PloS One. 2015;10(11):e0143476–e0143476. doi: 10.1371/journal.pone.0143476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Juenger H, Kuhnke N, Braun C, et al. Two types of exercise-induced neuroplasticity in congenital hemiparesis: A transcranial magnetic stimulation, functional MRI, and magnetoencephalography study. Dev Med Child Neurol. 2013;55(10):941–951. doi: 10.1111/dmcn.12209. [DOI] [PubMed] [Google Scholar]
  • 41.Sakzewski L, Ziviani J, Abbott DF, Macdonell RAL, Jackson GD, Boyd RN. Randomized trial of constraint-induced movement therapy and bimanual training on activity outcomes for children with congenital hemiplegia. Dev Med Child Neurol. 2011;53(4):313–320. doi: 10.1111/j.1469-8749.2010.03859.x. [DOI] [PubMed] [Google Scholar]
  • 42.Gordon AM, Hung Y, Brandao M, et al. Bimanual training and constraint-induced movement therapy in children with hemiplegic cerebral palsy: A randomized trial. Neurorehabil Neural Repair. 2011;25(8):692–702. doi: 10.1177/1545968311402508. [DOI] [PubMed] [Google Scholar]
  • 43.Pépés SE, Draper A, Jackson GM, Jackson SR. Effects of age on motor excitability measures from children and adolescents with tourette syndrome. Dev Cogn Neurosci. 2016;19:78–86. doi: 10.1016/j.dcn.2016.02.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Pitcher JB, Schneider LA, Burns NR, et al. Reduced corticomotor excitability and motor skills development in children born preterm. J Physiol. 2012;590(22):5827–5844. doi: 10.1113/jphysiol.2012.239269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Friel KM, Kuo H, Fuller J, et al. Skilled bimanual training drives motor cortex plasticity in children with unilateral cerebral palsy. Neurorehabil Neural Repair. 2016 doi: 10.1177/1545968315625838. [DOI] [PMC free article] [PubMed] [Google Scholar]

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