Cerebral Palsy

The currently accepted definition classifies Cerebral Palsy (CP) as a mere posture and movement disorder. Conversely, some authors have recently associated the presence of several motor dysfunctions exhibited by diplegic children with CP to an impairment in the perceptive system. The aim of the present study was to investigate the influence of the Perceptive Impairment (PI) on motor control and to appraise if the PI can be revealed by a reaching task. A functional reach and touch experiment was accomplished from sitting posture considering different directions and distances. Typically developing and diplegic children with CP were enrolled and, the latter, a priori divided in two subgroups considering a positive or negative diagnosis of PI. The reaching trials were quantified by means of centre of pressure analysis in terms of the overall quality of the task, and accuracy and effectiveness of postural adjustments and Anticipatory Postural Adjustments (APAs). The three groups showed statistically significant differences in terms of percentage of touched target, and of time spent and maximum distance covered to reach the target. In particular, PI caused a major difficulty in accomplishing the reaching tasks, thus a lower autonomy level in action. Overall, the PI strongly affected the anticipatory control system. Children with PI, rarely recruited APAs, each of which was characterized by small amplitude and inaccuracy in direction. The lack of effective APAs indicated how PI strongly influenced the motor control strategy. The present study demonstrates that the PI is a primary syndrome responsible for the long-term prognosis beside the motor and the postural disorders in CP. Copyright © 2010 Elsevier B.V. All rights reserved.

OBJECTIVE: To quantify dynamic spasticity, i.e. the coupling between muscle-tendon stretch velocity and muscle activity during gait, of the gastrocnemius and soleus muscles in children with spastic cerebral palsy. DESIGN: Prospective, cross-sectional study. SUBJECTS: Seventeen ambulatory children with cerebral palsy with spastic calf muscles, and 11 matched typically developing children. METHODS: The children walked at 3 different speeds. Three-dimensional kinematic and electromyographic data were collected. Muscle-tendon velocities of the gastrocnemius medialis and soleus were calculated using musculoskeletal modelling. RESULTS: In typically developing children, muscles were stretched fast in swing without subsequent muscle activity, while spastic muscles were stretched more slowly for the same walking speed, followed by an increase in muscle activity. The mean ratio between peak activity and peak stretch velocity in swing was approximately 4 times higher in spastic muscles, and increased with walking speed. In stance, the stretch of muscles in typically developing children was followed by an increase in muscle activity. Spastic muscles were stretched fast in loading response, but since muscle activity was already built up in swing, no clear dynamic spasticity effect was present. CONCLUSION: Spastic calf muscles showed increased coupling between muscle-tendon stretch velocity and muscle activity, especially during the swing phase of gait.

ABSTRACT: BACKGROUND: Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A. METHODS: A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes include: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale. DISCUSSION: The aim of this paper is to describe the methodology of a randomized controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus conventional occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided. Trial Registration ACTRN12605000002684.

Recent studies suggest that in addition to low-level motor impairments, individuals with Hemiparetic Cerebral Palsy (HCP) are characterized by anticipatory action planning deficits as well. In the present EEG study we investigated the neural and temporal dynamics of action planning in participants with right-sided HCP (n=10) and in left-handed control subjects (n=10). An anticipatory planning task was used in which participants were required to grasp and rotate a hexagonal knob over different angles (60 degrees , 120 degrees or 180 degrees ). At a behavioral level, participants with HCP were slower in their movements and often selected an inappropriate grip when grasping the object. At a neural level, individuals with HCP showed a strong reduction in the amplitude of the P2 component, likely reflecting an impaired process of action selection. In addition, a strong correlation was observed between the P2 amplitude and grasping and rotation times. The P2 component was localized to sources in the dorsal posterior cingulate cortex (dPCC), an area that is known to be involved in orienting visual body parts in space. Together these findings suggest that anticipatory planning deficits in cerebral palsy arise mainly due to an impaired process of action selection. Copyright © 2010. Published by Elsevier B.V.

OBJECTIVE: To evaluate neurodevelopment after necrotizing enterocolitis (NEC) and late bacteremia, alone and together. STUDY DESIGN: Sample included 1155 infants born at 23 to 27 weeks' gestation. NEC was classified by the modified Bell's staging criteria and grouped as medical NEC or surgical NEC. Late bacteremia was defined as a positive blood culture result after the first postnatal week. Neurodevelopment was assessed at 24 months corrected age. Multivariable models estimated the risk of developmental dysfunction and microcephaly associated with medical or surgical NEC with and without late bacteremia. RESULTS: Children who had surgical NEC unaccompanied by late bacteremia were at increased risk of psychomotor developmental indexes <70 (OR = 2.7 [1.2, 6.4]), and children who had both surgical NEC and late bacteremia were at increased risk of diparetic cerebral palsy (OR = 8.4 [1.9, 39]) and microcephaly (OR = 9.3 [2.2, 40]). In contrast, children who had medical NEC with or without late bacteremia were not at increased risk of any developmental dysfunction. CONCLUSION: The risk of neurodevelopmental dysfunction and microcephaly is increased in children who had surgical NEC, especially if they also had late bacteremia. These observations support the hypothesis that bowel injury might initiate systemic inflammation potentially affecting the developing brain. (J Pediatr 2010;157:***). Copyright © 2010 Mosby, Inc. All rights reserved.

OBJECTIVE: To examine adverse birth events on the development of cerebral palsy in California. STUDY DESIGN: A retrospective population-based study of children with cerebral palsy (as of Nov. 30, 2006), matched to their maternal/infant delivery records (Jan. 1, 1991 to Dec. 31, 2001) was performed. Demographic data and intrapartum events were examined. Six adverse birth-related events were chosen. Children without cerebral palsy were controls. RESULTS: There were 7242 children who had cerebral palsy (59% term) and 31.3% had 1 or more of the 6 adverse intrapartum events (12.9% in controls P < .0001). This held for both term (28.3% vs 12.7% controls) and preterm (36.8% vs 15.9%, controls) neonates (both P < .0001). Maternal (15.1% vs 6.6%) and neonatal (0.9% vs 0.1%) infection were increased in cerebral palsy cases (P < .0001). CONCLUSION: Almost one-third of children with cerebral palsy had at least 1 adverse birth-related event. Higher rates in the preterm group may partially explain the higher rates of cerebral palsy in this group. Copyright © 2010 Mosby, Inc. All rights reserved.

Among autologous somatic stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) are the most widely used worldwide to repair not only mesenchymal tissues (bone, cartilage) but also many other kinds of tissues, including heart, skin, and liver. Autologous BMSCs are thought to be safe because of the absence of immunological reaction and disease transmission. However, it is possible that they will form tumours during long-term follow-up. In 1988, we transplanted autologous BMSCs to repair articular cartilage, which was the first such trial ever reported. Subsequently we performed this procedure in about 40 patients. Demonstration that neither partial infections nor tumours appeared in these patients provided strong evidence for the safety of autologous BMSC transplantation. Thus, in this study we checked these patients for tumour development and infections. Between January 1998 and November 2008, 41 patients received 45 transplantations. We checked their records until their last visit. We telephoned or mailed the patients who had not visited the clinics recently to establish whether there were any abnormalities in the operated joints. Neither tumours nor infections were observed between 5 and 137 (mean 75) months of follow-up. Autologous BMSC transplantation is a safe procedure and will be widely used around the world. Copyright (c) 2010 John Wiley & Sons, Ltd.

PURPOSE: The aim of this study was to determine the prevalence of glaucomatous optic nerve atrophy among a working population in Germany by secondary evaluation of a study conducted to estimate the prevalence of retinal microangiopathic abnormalities by telemedical examination of the retina. PATIENTS AND METHODS: From August 2002 until January 2004 the retina and optic nerve head were examined in 19,294 Caucasians using a non-mydriatic fundus camera (Kowa, nonmyd-alpha 45), which produces colour images with 45 degrees. The images of the retina and optic nerve head were evaluated telemedically by glaucoma specialists in respect to optic nerve pathologies and microangiopathic abnormalities by a standardised procedure. Glaucomatous optic nerve atrophy was diagnosed when specific glaucomatous morphological alterations of the optic nerve head were present. A complete medical history including reported elevated intraocular pressure (IOP) and blood pressure was obtained. RESULTS: The intra-observer and inter-observer reliability were 0.884 and 0.740, respectively. Cronbach’s alpha for two evaluation cycles each of two observers was 0.870. The prevalences of glaucomatous optic nerve atrophy in the different age groups were 0.07 % (45 – 49 years), 0.40 % (50 – 54 years), 0.45 % (55 – 59 years) and 0.82 % (60 – 64 years). Age could be established as an important risk factor for glaucomatous optic nerve atrophy, while no influence of gender or family history was found. CONCLUSION: Telemedical evaluation of colour images of the retina and optic nerve acquired by a non-mydriatic fundus camera allows a fast and efficient screening of many subjects with medium reliability. © Georg Thieme Verlag KG Stuttgart · New York.

Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1 ( ep )-Ap3b1 ( pe ), exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lyst ( bg-J )-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF beta1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and alpha-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS.

BACKGROUND: AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC. METHODS: A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records. RESULTS: AML MRC patients showed a lower complete remission (CR) rate (44.7% vs. 64.9%, P=0.002) and shorter OS (297 vs. 561 days, P=0.004) and EFS (229 vs. 374 days, P=0.004) than AML NOS patients. Patients with MLD among AML MRC also showed a lower CR rate (37.7%, P=0.001) and shorter OS (351 days, P=0.036) and EFS (242 days, P=0.076) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and CR between patients with and without MLD. CONCLUSIONS: AML MRC patients showed a lower CR rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML.