[show abstract][hide abstract] ABSTRACT: Purpose: Hip adductor spasticity has a great impact on developing hip displacement in children with cerebral palsy (CP). Obturator nerve (ON) block is less invasive intervention rather than soft tissue surgery for reduction of hip adductor spasticity. The aim of this study is to investigate the effect of ON block on hip lateralization in low functioning children with spastic CP. Materials and Methods: The study was performed by retrospective investigation of the clinical and radiographic follow-up data of low functioning children [gross motor function classification system (GMFCS) level III to V] with spastic cerebral palsy whose hip was subluxated. Migration percentage (MP) was measured on hip radiographs and its annual change was calculated. In intervention group, ON block was done with 50% ethyl alcohol under the guidance of electrical stimulation. Results: The data of 49 legs of 25 children for intervention group and the data of 41 legs of 23 children for nonintervention group were collected. In intervention group, the MP were significantly reduced at 1st follow-up and the MPs at 2nd and last follow-up did not show significant differences from initial MP. Whereas in nonintervention group, the MPs at 1st, 2nd and last follow-up were all significantly increased compared to initial MPs. Conclusion: ON block with ethyl alcohol is useful as an early effective procedure against progressive hip displacement in these children with spastic CP.
Yonsei medical journal 01/2014; 55(1):191-6. · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). METHODS: We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. RESULTS: In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. CONCLUSION: Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.
Journal of Nuclear Medicine 06/2013; · 5.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: . Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. OBJECTIVES: . We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. METHODS: . We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). RESULTS: . In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na(+)/Cl(-)-dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. CONCLUSION: . An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.
Neurorehabilitation and neural repair 04/2013; · 4.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several cases of acute necrotizing encephalopathy (ANE) with influenza A (H1N1) have been reported to date. The prognosis of ANE associated with H1N1 is variable; some cases resulted in severe neurologic complication, whereas other cases were fatal. Reports mostly focused on the diagnosis of ANE with H1N1 infection, rather than functional recovery. We report a case of ANE with H1N1 infection in a 4-year-old Korean girl who rapidly developed fever, seizure, and altered mentality, as well as had neurologic sequelae of ataxia, intentional tremor, strabismus, and dysarthria. Brain magnetic resonance imaging showed lesions in the bilateral thalami, pons, and left basal ganglia. To our knowledge, this is the first report of ANE caused by H1N1 infection and its long-term functional recovery in Korea.
Annals of rehabilitation medicine. 04/2013; 37(2):286-290.
[show abstract][hide abstract] ABSTRACT: Isodicentric chromosome 15 [idic(15)] is a rare chromosomal abnormality that occurs due to inverted duplication of chromosome 15q. It is associated with many clinical findings such as early central hypotonia, developmental delay, cognitive dysfunction, autism spectrum disorders, and seizure. Delayed development is a common problem referred to pediatric rehabilitation clinics. A 9-month-old boy with delayed development was referred to our clinic for assessment and treatment. On chromosomal analysis, he was diagnosed as idic(15) syndrome with 47,XY,+idic(15)(q12) on karyotyping. Herein we describe his clinical manifestations and provide a brief review of the related literature.
Annals of rehabilitation medicine. 04/2013; 37(2):291-294.
[show abstract][hide abstract] ABSTRACT: Purpose: The objective of this study was to describe hand function in relation with gross motor function and subtype of spastic cerebral palsy and to investigate the relationships among gross motor function, bimanual performance, unimanual capacity and upper limb functional measures in children with spastic cerebral palsy (CP). Materials and Methods: We collected upper extremity data of 140 children with spastic CP. The Gross Motor Functional Classification System (GMFCS) was used to assess gross motor function, Manual Ability Classification System (MACS) for bimanual performance, and Modified House Functional Classification (MHC) for the best capacity of each hand. Upper limb functions were evaluated by using the Upper Limb Physician's Rating Scale and Upper Extremity Rating Scale. Results: There was a good correlation between GMFCS and MACS in children with bilateral CP, but the correlation was not strong in children with unilateral CP. No significant difference between GMFCS and MACS was found in children with bilateral CP, but children with unilateral CP scored higher on GMFCS than on MACS. A strong correlation was observed between MACS and MHC in children with bilateral CP, but not in children with unilateral CP. The upper limb functional measures in each hand were highly related with MACS and MHC in bilateral CP, but not in unilateral CP. Conclusion: Gross motor function, bimanual performance and the best capacity of each hand are closely related with each other in children with bilateral CP, but not in children with unilateral CP.
Yonsei medical journal 03/2013; 54(2):516-22. · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O₂ for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASCSC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin⁺ neurons derived from the transplanted ASCs were significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increasedBrdU⁺βIII-tubulin⁺ neurons, GFAP⁺ astrocytic density and fibroblast growth factor-2 (FGF2) level but not the level of CS-56⁺ glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Several experimental studies in stroke patients suggest that mirror therapy and various virtual reality programs facilitate motor rehabilitation. However, the underlying mechanisms for these therapeutic effects have not been previously described.Objectives
We attempted to delineate the changes in corticospinal excitability when individuals were asked to exercise their upper extremity using a real mirror and virtual mirror. Moreover, we attempted to delineate the role of visual modulation within the virtual environment that affected corticospinal excitability in healthy subjects and stroke patients. METHODS: A total of 18 healthy subjects and 18 hemiplegic patients were enrolled into the study. Motor evoked potential(MEP)s from transcranial magnetic stimulation were recorded in the flexor carpi radialis of the non-dominant or affected upper extremity using three different conditions: (A) relaxation; (B) real mirror; and (C) virtual mirror. Moreover, we compared the MEPs from the virtual mirror paradigm using continuous visual feedback or intermittent visual feedback. RESULTS: The rates of amplitude increment and latency decrement of MEPs in both groups were higher during the virtual mirror task than during the real mirror. In healthy subjects and stroke patients, the virtual mirror task with intermittent visual feedback significantly facilitated corticospinal excitability of MEPs compared with continuous visual feedback. CONCLUSION: Corticospinal excitability was facilitated to a greater extent in the virtual mirror paradigm than in the real mirror and in intermittent visual feedback than in the continuous visual feedback, in both groups. This provides neurophysiological evidence supporting the application of the virtual mirror paradigm using various visual modulation technologies to upper extremity rehabilitation in stroke patients.
Journal of NeuroEngineering and Rehabilitation 10/2012; 9(1):71. · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: In writing, linguistic (i.e., spelling) and nonlinguistic (i.e., arranging strokes or letters) functions are processed by the left and right hemispheres, respectively. The configuration of Korean alphabet, 'Hangul' invokes nonlinguistic, visuospatial functions that other writing systems use less extensively. Patients with Alzheimer's disease (AD) have bilateral involvement of temporoparietal-frontal areas that are responsible for processing language and visuospatial functions.
The aim of this study was to examine the nature of Hangul writing dysfunction, which may be associated with bilateral hemispheric impairments in AD.
A sample of 75 patients with AD and 20 healthy controls (HC) performed a Hangul writing task. Neuroimaging positron emission tomography (PET) data of 22 patients were utilized to measure the regional brain glucose metabolism associated with Hangul writing.
The writing performance of the AD group was significantly reduced and different types of errors were observed as the disease got worse. Glucose hypometabolism correlated with Hangul writing impairment was located in the right occipitotemporal lobe and left temporoparietal lobe.
The PET findings demonstrate that impairment in Hangul writing performance in Korean AD patients is closely related to a functional decline in both the right and left hemispheres. The study provides a unique contribution to the knowledge of dysgraphia in a non-alphabetical writing system as well as the underlying neuropathology of dysgraphic features in such languages.
Journal of the neurological sciences 07/2012; 320(1-2):72-8. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Resonance problems in hearing impaired (HI) individuals have been described as aspects of nasality. However, there are limitations in being able to explain the range of resonance problems. Therefore, this study suggests a perceptual rating that will effectively explain the characteristics of resonance problems in HI individuals.
Nasalance scores were obtained from 32 subjects in each of HI and normal hearing (NH) groups using a nasometer. The subjects were categorized into groups based on normal and abnormal nasalance ranges. The abnormal nasalance range group was further divided into hyper-, hypo-, and mixed-nasal groups. Nasalance scores were based the individuals performance in a series of passage and syllable tasks. The perceptual rating was evaluated using a newly introduced tool, 'vertical focus of resonance' (VFR), which focuses on the resonance energy in the frontal, throat, pharyngeal and nasal locations.
The NH group demonstrated a significantly lower nasalance score in the oral coupling and passage tasks than the HI group. Based on the results of nasalance correlation analysis, the HI group showed highly significant correlations between syllable and passage tasks, as contrasted with the NH group. There were significant differences in VFR between the nasalance types in both the NH and the HI groups.
The HI hyper-nasal group showed tendencies of velopharyngeal opening, as opposed to the HI hypo-nasal group which showed tendencies of velopharyngeal closure. The HI mixed-nasal group showed inappropriate coordination of velopharyngeal function. In the HI group, the results of VFR showed that the air flow and the resonance energy were not released from the cavity of resonance. The suggested VFR tool explains the focusing characteristics of resonance energy within a continuation of speech sound regardless of the phonetic environment. Therefore, VFR may be a useful tool in explaining the deviant resonance patterns of HI individuals.
Clinical and Experimental Otorhinolaryngology 03/2012; 5(1):1-9. · 0.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim was to investigate the factors affecting the self-esteem and social competence of children with attention deficit hyperactivity disorder.
Many studies have reported parenting variables such as parenting attitude and sense of competence have been suggested as significant determinants of socio-emotional development of children with attention deficit hyperactivity disorder. In South Korean society, the traditional culture of Confucianism is a strong influence on parenting practices and children's behaviour. However, there have been few studies that examined the relative significance of the parenting and other associated factors for self-esteem and social competence in children with attention deficit hyperactivity disorder in Korea living in a strict parenting environment.
This study was designed as a cross-sectional and descriptive survey.
The subjects were 124 pairs of mothers and their children with attention deficit hyperactivity disorder, recruited from local paediatric psychiatric clinics in South Korea. Data collection was conducted through the use of questionnaires.
Affectionate parenting attitude and co-morbid condition of the child were the most important predictors of self-esteem. Rejecting parenting attitude was the most important predictor of social competence.
Higher levels of affectionate parenting attitude of mothers and non-co-morbid status of children both contributed unique variance to the overall prediction of higher self-esteem of children. Higher levels of rejecting parenting attitude of mothers contributed unique variance to the overall prediction of lower social competence in children with attention deficit hyperactivity disorder.
Parenting attitude is the most important factor to contribute to the healthy socio-emotional development in children with attention deficit hyperactivity disorder. Health care providers need to develop and apply a parenting skills improvement program to improve positive parenting attitudes, which will benefit self-esteem and social competence in children with attention deficit hyperactivity disorder.
Journal of Clinical Nursing 02/2012; 21(13-14):1932-42. · 1.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objectives: To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. Design: A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Setting: Human gait analysis laboratory. Subjects: Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Interventions: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Main measures: Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Results: Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). Conclusions: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.
[show abstract][hide abstract] ABSTRACT: To determine reliability and clinical use of two methods of migration index (MI) in CP patients with or without hip dysplasia.
The materials included radiographs of 200 hips of children with cerebral palsy. Conventional anteroposterior radiographs of the pelvis were taken with the child in the supine position with standardized methods. Two rehabilitation doctors measured the migration index using two methods. In the classic method, the lateral margin of the acetabular roof was used as a landmark and in the modified method the lateral margin of the sourcil was used as a landmark. Each rater measured the migration index at three separate times with a time interval of at least one week. Intraclass correlation (ICC) was used to test the inter- and intra-rater reliability.
MI shows excellent intra-rater reliability in both the classic and modified methods, but the inter-rater reliability was higher in the classic method than in the modified method. When categorized according to the sourcil classification, inter-rater reliability was higher in the normal sourcil type and lower in the dysplastic sourcil types.
Generally, the classic method showed higher reliability than the modified method, even though the reliability of the MI measurement was relatively high with both methods.
Annals of rehabilitation medicine. 02/2012; 36(1):33-8.
[show abstract][hide abstract] ABSTRACT: The neural tracts responsible for gross motor dysfunction in children with spastic cerebral palsy (CP) caused by periventricular leukomalacia remain unknown. This study investigated both sensory and motor tracts using diffusion tensor tractography (DTT).
Brain MRIs with diffusion tensor imaging (DTI) performed on 19 children (ten boys and nine girls) with bilateral spastic CP were analyzed. DTT was reconstructed from DTI. Participants were classified according to gross motor function measured with Gross Motor Function Classification System (GMFCS). Those with GMFCS levels I-III comprised the high-functioning group (n = 11), and those with GMFCS levels IV-V comprised the low-functioning group (n = 8). We compared DTT-based metrics, such as fractional anisotropy, apparent diffusion coefficient, and fiber number and volume, between the groups.
In the corticospinal tract, the volume and number of fibers were significantly higher in the high-functioning group (p < 0.001), whereas the fractional anisotropy and apparent diffusion coefficient of the corticospinal tract did not differ significantly between the groups. In the somotosensory tract and posterior thalamic radiation, none of the DTT parameters differed significantly between the groups.
Children with bilateral spastic CP with differing levels of gross motor function have corresponding differences detectable on DTT in their corticospinal tracts but not in their somatosensory tracts and posterior thalamic radiations. In addition, the number and volume of fibers, but not fractional anisotropy values or apparent diffusion coefficients, are lower in the corticospinal tracts in children with low gross motor function than in those with high gross motor function.
[show abstract][hide abstract] ABSTRACT: The aims of this study were to clarify the intramuscular branching patterns and arborizing area of hip adductor muscles with reference to surface landmarks on the thigh and to thus suggest effective and safe injection points for botulinum neurotoxin (BoNT).
Ten gracilis and 10 adductor longus specimens were subjected to Sihler staining to reveal intramuscular nerve arborization patterns, and findings were matched with and referred to surface landmarks. Using these results, we determined the optimal location for BoNT injection in hip adductors in relation to the long axis of the femur.
The corrected, most dense areas of innervation in adductor longus and gracilis were typically 30-50% and 40-50% from the anterior superior iliac spine (ASIS) along the vertical line of the femur, respectively.
The most effective and safest point for BoNT injection into adductor muscles appears to be between 35% and 50% from ASIS, where neuromuscular junctions are most densely distributed.
[show abstract][hide abstract] ABSTRACT: Dystonia is a symptom defined by involuntary and irregular contractions of the muscles, which cause movement disorders and postural problems. Deep brain stimulation (DBS) in globus pallidus interna (GPi) is a good option for controlling dystonia. DBS has already been shown to have significant effects on primary dystonia as well as Parkinson's disease. Dystonia is very difficult to manage, as seen in cerebral palsy (CP) mixed with spasticity. As CP patients grow, their musculoskeletal problems may require orthopedic surgery. However, the outcome of orthopedic surgery is not usually suitable due to dystonia. Therefore, we attempted to control dystonia through DBS initially and perform orthopedic surgery to correct musculoskeletal deformities after treatment of dystonia. Herein, we report a case that showed remarkable improvement in terms of the dystonia rating scale and gait pattern after combined therapy of DBS and orthopedic surgery.
Annals of rehabilitation medicine. 10/2011; 35(5):742-6.
[show abstract][hide abstract] ABSTRACT: The aims of this study were to investigate the nature and extent of upper limb deformities via the use of various classifications, and to analyze the relationship between upper limb deformities and gross motor or upper limb functionality levels. Upper extremity data were collected from 234 children with spastic cerebral palsy (CP) who were admitted to the university hospital for intensive rehabilitation. Upper limb deformities were classified according to the Zancolli classification for finger and wrist extension ability, the Gshwind and Tonkin classification for supination ability, and the House classification for thumb-in-palm deformity. Digital deformity was also classified. Upper limb function was assessed using the Upper Extremity Rating Scale (UERS) and the Upper Limb Physician's Rating Scale (ULPRS). Gross motor function was assessed using the Gross Motor Functional Classification System (GMFCS). Among the 234 children observed, 70.5% had a limitation in forearm supination, and 62.8% had problems with wrist and finger extension in at least one limb. Thumb-in-palm deformity of at least one hand was found in 47.0% of patients. Swan neck deformity was the most common finger deformity. Upper limb functional measures, the ULPRS and the UERS, significantly correlated with the degree of upper limb deformity, as assessed by the Gschwind and Tonkin, Zancolli, and House classifications. Further, the degree of upper limb deformity was significantly related to the GMFCS level in children with bilateral CP, but not in children with unilateral CP. Limitation of forearm supination was the most common upper limb deformity in children with spastic CP. The degree of upper limb deformity significantly affected upper limb function in these children.
Research in developmental disabilities 08/2011; 32(6):2389-97. · 4.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the reliability of inspection-based classification of sagittal gait patterns in children with bilateral spastic cerebral palsy (CP).
Video clip recordings of gait patterns and sagittal kinematic data obtained by a computerized motion analysis system from 91 patients with bilateral spastic CP were reviewed. The abnormal gait patterns were classified into 4 groups using the method described by Rodda et al. Visual observation-based classification (visual classification) was compared with classification by 3D analysis-based methods (3D classification). The reliabilities of visual classifications made by an experienced physician and a trainee physician were analyzed.
The consistency of inspection-based gait classification using kinematic data analysis was demonstrated by an experienced physician (Kappa coefficient (k)=0.67, p<0.001). However, the consistency was low for the trainee physician (k=0.37, p<0.001). Group III (apparent equinus) was commonly confused with group IV (crouch gait) by the trainee physician, resulting in lower agreement for those two evaluation groups than for other patterns. Video observation showed low reliability in comparisons made between the experienced and the trainee physician (k=0.37, p<0.001).
There was substantial agreement of gait classification between video observation and kinematic data analysis by the experienced physician, but not by the trainee physician. Low reliability was also demonstrated for inspection-based gait classification.
Annals of rehabilitation medicine. 06/2011; 35(3):354-60.
[show abstract][hide abstract] ABSTRACT: Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.
[show abstract][hide abstract] ABSTRACT: Constraint-induced movement therapy (CIMT) has emerged as a promising therapeutic strategy for improving affected upper limb function in children with hemiplegic cerebral palsy (CP). However, little is known about the changes in the brain that are induced by CIMT. This study was designed to investigate these changes and behavioural performance after CIMT intervention in mice with neonatal hypoxic-ischemic brain injury.
We utilized the neonatal hypoxic-ischemic brain injury model established in mice pups. Three weeks after the injury, the mice were randomly assigned to the following three groups: the control group (n = 15), the enriched-environment group (n = 17), and the CIMT with an enriched-environment group (CIMT-EE, n = 15). 5-bromo-2-deoxyuridine (BrdU) was injected daily to label proliferating cells during the 2 weeks of intervention.
The CIMT-EE group showed better fall rate in the horizontal ladder rung walking test (mean 5.4%, SD 3.6%) than either the control (mean 14.3%, SD 7.3%; p = 0.001) or enriched-environment (mean 12.4%, SD 7.7%; p = 0.010) groups 2 weeks after the end of intervention. The CIMT-EE group also showed more neurogenesis (mean 7069 cells/mm³, SD 4017 cells/mm³) than either the control group (mean 1555 cells/mm³, SD 1422 cells/mm³; p < 0.001) or enriched-environment group (mean 2994 cells/mm³, SD 3498 cells/mm³; p = 0.001) in the subventricular zone. In the striatum, neurogenesis in the CIMT-EE group (mean 534 cells/mm³, SD 441 cells/mm³) was greater than in the control group (mean 95 cells/mm³, SD 133 cells/mm³; p = 0.001).
There was CIMT-EE enhanced neurogenesis in the brain along with functional benefits in mice after early hypoxic-ischemic brain injury. This is the first study to demonstrate the effects of CIMT on neurogenesis and functional recovery after experimental injury to an immature brain.