Potentials of Ultrahigh-Field MRI for the Study of Somatosensory Reorganization in Congenital Hemiplegia.

Reorganization of somatosensory function influences the clinical recovery of subjects with congenital unilateral brain lesions. Ultrahigh-field (UHF) functional MRI (fMRI) with the use of a 7 T magnet has the potential to contribute fundamentally to the current knowledge of such plasticity mechanisms. The purpose of this study was to obtain preliminary information on the possible advantages of the study of somatosensory reorganization at UHF fMRI. We enrolled 6 young adults (mean age 25 ± 6 years) with congenital unilateral brain lesions (4 in the left hemisphere and 2 in the right hemisphere; 4 with perilesional motor reorganization and 2 with contralesional motor reorganization) and 7 healthy age-matched controls. Nondominant hand sensory assessment included stereognosis and 2-point discrimination. Task-dependent fMRI was performed to elicit a somatosensory activation by using a safe and quantitative device developed ad hoc to deliver a reproducible gentle tactile stimulus to the distal phalanx of thumb and index fingers. Group analysis was performed in the control group. Individual analyses in the native space were performed with data of hemiplegic subjects. The gentle tactile stimulus showed great accuracy in determining somatosensory cortex activation. Single-subject gentle tactile stimulus showed an S1 activation in the postcentral gyrus and an S2 activation in the inferior parietal insular cortex. A correlation emerged between an index of S1 reorganization (distance between expected and reorganized S1) and sensory deficit (p < 0.05) in subjects with hemiplegia, with higher distance related to a more severe sensory deficit. Increase in spatial resolution at 7 T allows a better localization of reorganized tactile function validated by its correlation with clinical measures. Our results support the S1 early-determination hypothesis and support the central role of topography of reorganized S1 compared to a less relevant S1-M1 integration.

REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia.

OBJECTIVES: Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. METHODS AND ANALYSIS: 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. ETHICS AND DISSEMINATION: Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results.

Corticopontocerebellar Connectivity Disruption in Congenital Hemiplegia.

BACKGROUND: Crossed cerebellar diaschisis is the disruption of functional connectivity between cerebrum and cerebellum after hemispheric unilateral brain lesions. In adults and to a lesser extent in children, crossed cerebellar diaschisis has been largely investigated by functional connectivity and demonstrated to influence paretic hand function. OBJECTIVE: We aim to demonstrate a disruption in structural corticopontocerebellar (CPC) connectivity in children with congenital brain lesions and examine its correlation with paretic hand motor function. METHODS: Thirty-six children (Manual Ability Classification System: I, n = 21; II, n = 15) with unilateral brain lesions and 18 controls were analyzed in a case-control study, and diffusion magnetic resonance imaging data were acquired at 3T. High angular resolution diffusion imaging probabilistic tractography was employed for the region of interest-based reconstruction of CPC tracts. To identify statistical differences in structural cerebrocerebellar connectivity between case and control groups, an asymmetry index based on the number of streamlines of CPC tracts was used. In the case group, the correlation between asymmetry index and hand function measures was also determined. RESULTS: Projections through the middle cerebellar peduncle to the contralateral cerebral cortex showed greater asymmetry in children with congenital unilateral brain lesion compared to controls (P = .03), thus indicating a disruption of structural cerebrocerebellar connectivity. The degree of asymmetry index showed a correlation (P < .03; r = -0.31) with impaired hand abilities in bimanual tasks. CONCLUSIONS: Disruption of structural cerebrocerebellar connectivity is present in patients with congenital unilateral brain injury and might be related to impaired hand function in bimanual skills, with potential implication in tailoring early intervention strategies.

Mastery motivation as a predictor of occupational performance following upper limb intervention for school-aged children with congenital hemiplegia.

AIM: To determine the extent to which children's mastery motivation predicts occupational performance outcomes following upper limb intervention (ULI). METHOD: In this cohort study, participants received 45 hours of ULI, either in an intensive group-based or distributed individualized model. The Dimensions of Mastery Questionnaire (DMQ) measured mastery motivation at baseline. Occupational performance outcomes were assessed at baseline and 13 weeks' post-intervention using the Canadian Occupational Performance Measure (COPM). Multivariable models determined the contribution of mastery motivation to COPM outcome irrespective of group membership. RESULTS: Forty-two children with congenital hemiplegia (29 males, 13 females; mean age 7y 8mo [SD 2y 2mo]; range 5y 1mo-12y 8mo; Manual Ability Classification System [MACS] I=20 and II=22; predominant motor type unilateral spastic n=41) participated in the study. Significant gains were seen in COPM performance and satisfaction scores (p<0.001) post-intervention with no between group differences. Children who had greater persistence with object-oriented tasks (p=0.02) and better manual ability (p=0.03) achieved higher COPM performance scores at 13 weeks. Children's persistence on object-oriented tasks was the strongest predictor of COPM satisfaction (p=0.01). INTERPRETATION: Children's persistence with object-oriented tasks as well as manual abilities needs to be considered when undertaking ULI. Predetermining children's motivational predispositions can assist clinicians to tailor therapy sessions individually based on children's strengths, contributing to effective engagement in ULI.

Early intervention after perinatal stroke: opportunities and challenges.

Perinatal stroke is the most common cause of hemiplegic cerebral palsy. No standardized early intervention exists despite evidence for a critical time window for activity-dependent plasticity to mould corticospinal tract development in the first few years of life. Intervention during this unique period of plasticity could mitigate the consequences of perinatal stroke to an extent not possible with later intervention, by preserving the normal pattern of development of descending motor pathways. This article outlines the broad range of approaches currently under investigation. Despite significant progress in this area, improved early detection and outcome prediction remain important goals.

Numerical abilities in children with congenital hemiplegia: an investigation of the role of finger use in number processing.

In this study, we assessed basic and more complex non-symbolic and symbolic numerical task abilities in children with hemiplegia and obtained a detailed picture of their strengths and weaknesses in the numerical domain. Those children, who experience difficulties in finger gnosia and spontaneous use of fingers in counting, exhibit difficulties in finger pattern recognition and symbolic numerical tasks. However, their non-symbolic numerical abilities and arithmetic skills are preserved. These original results are discussed in light of the "manumerical cognition" hypothesis, which postulates that the use of fingers in numerical activities during childhood shapes our comprehension of numbers.

Mastery motivation in children with congenital hemiplegia: individual and environmental associations.

AIM: The aim of this study was to examine the relationship between mastery motivation and individual and environmental characteristics in school-aged children with congenital hemiplegia. METHOD: Forty-eight child-caregiver dyads (children's mean age 7y 11mo, SD 2y 4mo; 33 males, 15 females; Manual Ability Classification System [MACS] level I, n=25, and level II, n=23; predominant motor type spastic hemiplegia, n=47) were recruited to this cross-sectional study. Children were assessed using the Melbourne Assessment of Unilateral Upper Limb Function (MUUL) and the Assisting Hand Assessment. Caregivers completed the Dimensions of Mastery Questionnaire, the Parenting Scale, and a demographic questionnaire. RESULTS: Consistent and positive parental disciplinary practices were associated with higher total motivation (p=0.006) and instrumental aspect scores (p=0.009). Children with siblings and from single-parent families experienced greater negative reactions to failure (p=0.006). Children from two-parent families (p=0.018) and with better bimanual performance (p=0.015) demonstrated greater object-oriented persistence. Age, sex, limitations in manual ability (MACS), and movement and body function of the impaired limb (MUUL) did not contribute significantly to mastery motivation. INTERPRETATION: Inconsistent, excessively lax, and verbose parenting practices may discourage children from persevering with challenging tasks. Functional parenting styles, positive discipline practices, and autonomy-supportive strategies for task engagement should be encouraged when intervening with children with cerebral palsy. Parents should be supported to engage in these practices in all aspects of daily activities.

The Dimensions of Mastery Questionnaire in school-aged children with congenital hemiplegia: test-retest reproducibility and parent-child concordance.

AIM: To examine internal consistency, test-retest reproducibility, and parent-child concordance of the Dimensions of Mastery Questionnaire 17.0 (DMQ) in school-aged children with congenital hemiplegia. METHOD: Forty-two children (8.24 ± 2.38 years, Manual Ability Classification System (MACS) I = 23, MACS II = 19) and their parents completed the DMQ, and a subset on two occasions 2-30 days apart (n = 27). Cronbach's alpha (α), intraclass correlation coefficients (ICCs), standard error of measurement (SEM), and 95% limits of agreement were calculated. RESULTS: Internal consistency for child self-report was variable (α = 0.57-0.90). Cronbach's alphas for parent proxy report were good (α = 0.69-0.86). Test-retest reproducibility for instrumental aspect (ICC = 0.86) and total motivation (ICC = 0.84) were excellent with subscales ranging from 0.70 to 0.91. The SEM for total motivation was 0.23 points. Parent-child concordance was poor across all scores (ICC = -0.04 to 0.42) with a large SEM (0.50-0.91). INTERPRETATION: The DMQ parent report has good test-retest reproducibility for subscales, instrumental, and total motivation scores in school-aged children with congenital hemiplegia. Parent-child concordance was low highlighting differences in individual and contextual perspectives.

Chiari type 1 malformation and periventricular nodular heterotopia in a 6-year-old boy with congenital hemiplegia: a case report.

A 6-year-old boy presented with weakness of the right upper and lower limbs, noted since infancy. Magnetic resonance imaging of the brain revealed periventricular nodular heterotopia lining the trigone and occipital horns of bilateral lateral ventricles along with herniation of the cerebellar tonsils below the foramen magnum suggestive of Chiari type 1 malformation. The association of periventricular nodular heterotopia with Chiari type 1 malformation has not been described earlier in children.

Brain reorganization following intervention in children with congenital hemiplegia: a systematic review.

Noninvasive rehabilitation strategies for children with unilateral cerebral palsy are routinely used to improve hand motor function, activity, and participation. Nevertheless, the studies exploring their effects on brain structure and function are very scarce. Recently, structural neuroplasticity was demonstrated in adult poststroke patients, in response to neurorehabilitation. Our purpose is to review current evidence on the effects of noninvasive intervention strategies on brain structure or function, in children with unilateral cerebral palsy. The main literature databases were searched up to October 2013. We included studies where the effects of upper limb training were evaluated at neurofunctional and/or neurostructural levels. Only seven studies met our selection criteria; selected studies were case series, six using the intervention of the constraint-induced movement therapy (CIMT) and one used virtual reality therapy (VR). CIMT and VR seem to produce measurable neuroplastic changes in sensorimotor cortex associated with enhancement of motor skills in the affected limb. However, the level of evidence is limited, due to methodological weaknesses and small sample sizes of available studies. Well-designed and larger experimental studies, in particular RCTs, are needed to strengthen the generalizability of the findings and to better understand the mechanism of intervention-related brain plasticity in children with brain injury.

COMBIT: protocol of a randomised comparison trial of COMbined modified constraint induced movement therapy and bimanual intensive training with distributed model of standard upper limb rehabilitation in children with congenital hemiplegia.

INTRODUCTION: Children with congenital hemiplegia often present with limitations in using their impaired upper limb which impacts on independence in activities of daily living, societal participation and quality of life. Traditional therapy has adopted a bimanual training approach (BIM) and more recently, modified constraint induced movement therapy (mCIMT) has emerged as a promising unimanual approach. Evidence of enhanced neuroplasticity following mCIMT suggests that the sequential application of mCIMT followed by bimanual training may optimise outcomes (Hybrid CIMT). It remains unclear whether more intensely delivered group based interventions (hCIMT) are superior to distributed models of individualised therapy. This study aims to determine the optimal density of upper limb training for children with congenital hemiplegia. METHODS AND ANALYSES: A total of 50 children (25 in each group) with congenital hemiplegia will be recruited to participate in this randomized comparison trial. Children will be matched in pairs at baseline and randomly allocated to receive an intensive block group hybrid model of combined mCIMT followed by intensive bimanual training delivered in a day camp model (COMBiT; total dose 45 hours direct, 10 hours of indirect therapy), or a distributed model of standard occupational therapy and physiotherapy care (SC) over 12 weeks (total 45 hours direct and indirect therapy). Outcomes will be assessed at 13 weeks after commencement, and retention of effects tested at 26 weeks. The primary outcomes will be bimanual coordination and unimanual upper-limb capacity. Secondary outcomes will be participation and quality of life. Advanced brain imaging will assess neurovascular changes in response to treatment. Analysis will follow standard principles for RCTs, using two-group comparisons on all participants on an intention-to-treat basis. Comparisons will be between treatment groups using generalized linear models. TRIAL REGISTRATION: ACTRN12613000181707.

Brain structure and executive functions in children with cerebral palsy: a systematic review.

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures.

Dynamic equinus with hindfoot valgus in children with hemiplegia.

In children with hemiplegia, it is important to distinguish between equinus with hindfoot varus (equinovarus) or valgus (equinovalgus). Premature onset of medial gastrocnemius (GM) EMG in individuals with equinus is well documented. Premature onset of Peroneus longus (PL) EMG has been described in neurologically impaired adults with equinovalgus, but not in children. Our aim was to record the onset of PL and GM activity on the hemiplegic side of children with equinovalgus deformity. Fifteen children GMFCS 1 (3.8 yrs ± 2) with hemiplegia had a goniometric assessment of passive ankle range of motion and assessment of ankle function from video and surface EMG recording during gait. The clinical and video observations were used to determine the equinovalgus, as defined by Wren, at initial contact (IC). The premature onset of muscle activity was normalised as a swing (SW) percentage prior to IC of the following stance (ST). A paired T-test compared the onset of muscle activity between PL and GM. The ankle passive dorsiflexion was 13° ± 12° (hemiplegic side) versus 18° ± 10° (non-involved side) (p<0.05). For the non-involved limb, the onset of GM activity was at 14% of the gait cycle (midstance), the onset of PL activity was at 19% (p<0.05). For the hemiplegic limb with equinovalgus, there was a premature onset activity of PL (-24%) and GM(-8%) (p<0.001). On the non involved side, the onset of PL activity occurred, as in adults, after the onset of GM activity, during ST. On the hemiplegic side, there was no triceps surae contracture and the onset of PL activity occurred prior to the onset of GM activity, during terminal SW. This study confirmed the overactivity of PL in hemiplegic children with equinovalgus.

The effect of intensive bimanual training on coordination of the hands in children with congenital hemiplegia.

Recent studies have suggested efficacy of intensive bimanual training in improving the quality and quantity of affected hand use in children with hemiplegia. However, it is not known whether such training affects the coordination of the two hands. In the present study, 20 children with congenital hemiplegia (age 4-10 years; MACS levels I-II) were randomly assigned to either an intensive bimanual training (Hand-Arm Bimanual Intensive Therapy: HABIT) group, or a control group consisting of equally intensive unimanual treatment (Constraint-Induced Movement Therapy, CIMT) for 6h per day for 15 days (90h). To assess their bimanual coordination, children were asked to open a drawer with one hand and manipulate its contents with the other hand. 3-D movement kinematics were recorded and subsequently analyzed by a blind evaluator. The role of the two hands was varied. Following treatment, superior improvement in bimanual coordination was found for the bimanual training group as indicated by greater movement overlap (the percentage of time with both hands engaged in the task p = 0.047) and better goal synchronization (reduced time differences between the two hands completing the task goals, p = 0.005). The results suggest that bimanual training improves the spatial-temporal control of the two hands, and are in agreement with the principle of practice specificity.

Randomized trial of constraint-induced movement therapy and bimanual training on activity outcomes for children with congenital hemiplegia.

AIM: To determine if constraint-induced movement therapy (CIMT) is more effective than bimanual training (BIM) in improving upper limb activity outcomes for children with congenital hemiplegia in a matched-pairs randomized trial. METHOD: Sixty-three children (mean age 10.2, SD 2.7, range 5-16 y; 33 males, 30 females), 16 in Manual Ability Classification System level I, 46 level II, and 1 level III and 16 in Gross Motor Function Classification level I, 47 level II) were randomly allocated to either CIMT or BIM group day camps (60 hours over 10 days). The Melbourne Assessment of Unilateral Upper Limb Function assessed unimanual capacity of the impaired limb and Assisting Hand Assessment evaluated bimanual coordination at baseline, 3 and 26 weeks, scored by blinded raters. RESULTS: After concealed random allocation, there was no baseline difference between groups. CIMT had superior outcomes compared with BIM for unimanual capacity at 26 weeks (estimated mean difference [EMD] 4.4, 95% confidence interval [CI] 2.2-6.7; p < 0.001). There was no other significant difference between groups post-intervention. Both groups demonstrated significant improvements in bimanual performance at 3 weeks, with gains maintained by BIM at 26 weeks (EMD 2.3; 95% CI 0.6-4.0; p = 0.008). Interpretation Overall, there were only small differences between the two training approaches. CIMT yielded greater changes in unimanual capacity of the impaired upper limb compared with BIM. Results generally reflect specificity of practice, with CIMT improving unimanual capacity and BIM improving bimanual performance. Considerable inter-individual variation in response to either intervention was evident. Future research should consider serial sequencing unimanual then BIM approaches to optimize upper limb outcomes for children with congenital hemiplegia.

Participation outcomes in a randomized trial of 2 models of upper-limb rehabilitation for children with congenital hemiplegia.

OBJECTIVE: To determine if constraint-induced movement therapy (CIMT) is more effective than bimanual training to improve occupational performance and participation in children with congenital hemiplegia. DESIGN: Single-blind randomized comparison trial with evaluations at baseline, 3, and 26 weeks. SETTING: Community facilities in 2 Australian states. PARTICIPANTS: Referred sample of children (N=64; mean age ± SD, 10.2±2.7y, 52% boys) were matched for age, sex, side of hemiplegia, and upper-limb function and were randomized to CIMT or bimanual training. After random allocation, 100% of CIMT and 94% of the bimanual training group completed the intervention. INTERVENTIONS: Each intervention was delivered in day camps (total 60 h over 10d) using a circus theme with goal-directed training. Children receiving CIMT wore a tailor-made glove during the camp. MAIN OUTCOME MEASURES: The primary outcome was the Canadian Occupational Performance Measure (COPM). Secondary measures included the Assessment of Life Habits (LIFE-H), Children's Assessment of Participation and Enjoyment, and School Function Assessment. RESULTS: There were no between-group differences at baseline. Both groups made significant changes for COPM performance at 3 weeks (estimated mean difference =2.9; 95% confidence interval [CI], 2.3-3.6; P<.001 for CIMT; estimated mean difference=2.8; 95% CI, 2.2-3.4; P<.001 for bimanual training) that were maintained at 26 weeks. Significant gains were made in the personal care LIFE-H domain following CIMT (estimated mean difference=0.5; 95% CI, 0.1-0.9; P=.01) and bimanual training (estimated mean difference=0.6; 95% CI, 0.2-1.1; P=.006). CONCLUSIONS: There were minimal differences between the 2 training approaches. Goal-directed, activity-based, upper-limb training, addressed through either CIMT or bimanual training achieved gains in occupational performance. Changes in participation on specific domains of participation assessments appear to correspond with identified goals.

Tactile spatial resolution in unilateral brain lesions and its correlation with digital dexterity.

OBJECTIVE: To test the tactile spatial resolution in chronic unilateral brain lesions. Additionally, since sensory deficits are thought to have an impact on motor deficits, this study investigated the correlation between tactile spatial resolution and finger dexterity. DESIGN: Descriptive cross-sectional study. PATIENTS: Twenty-two patients with unilateral brain lesions (12 children with congenital hemiplegia and 10 patients after stroke). METHODS: Tactile spatial resolution was measured with a grating orientation task, and finger dexterity with the Purdue Pegboard Test. RESULTS: Major tactile spatial resolution deficits were measured on the paretic hand and preserved abilities on the non-paretic hand, both in children with congenital hemiplegia and in patients after stroke. No correlation was found between the deficits of tactile spatial resolution and digital dexterity in the paretic hand (r = 0.126; p = 0.572). CONCLUSION: The specific location of tactile spatial resolution deficits on the hand contralateral to the lesion was surprising when one considers the left hemispheric dominance of tactile spatial resolution in healthy subjects. The absence of correlation between tactile spatial resolution and dexterity deficits suggest that these abilities are not related, suggesting that they should be considered separately and equally integrated into the rehabilitation of unilateral brain lesions.

Motor imagery ability in children with congenital hemiplegia: effect of lesion side and functional level.

In addition to motor execution problems, children with hemiplegia have motor planning deficits, which may stem from poor motor imagery ability. This study aimed to provide a greater understanding of motor imagery ability in children with hemiplegia using the hand rotation task. Three groups of children, aged 8-12 years, participated: right hemiplegia (R-HEMI; N=21), left hemiplegia (L-HEMI; N=19) and comparisons (N=21). All groups conformed to biomechanical limitations of the task, supporting the use of motor imagery, and all showed the expected response-time trade-off for angle. The general slowing of responses in the HEMI groups did not reach significance compared to their peers. The L-HEMI group were less accurate than the comparison group while the R-HEMI group were more variable in their performance. These results appeared to be linked to functional level. Using the Vineland Adaptive Behavior Composite, children were classified as low or normal functioning - of the seven classified as low function, six were in the L-HEMI group. Accuracy was lower in the low function subgroup, but this failed to reach significance with an adjusted critical value. However, there was a strong correlation between function level and mean accuracy. This indicates that motor imagery performance may be more closely linked to function level than to the neural hemisphere that has been damaged in cases of congenital hemiplegia. Function level may be linked to the site or extent of neural damage or the level of cortical reorganisation experienced and more attention should be paid to neural factors in future research.