DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
Scientific Posters SP1 Living arrangements, occupation, and use of personal assistance in young Swedes with cerebral palsy 1 € A ALRIKSSON-SCHMIDT 1 , G H AGGLUND , E RODBY BOUSQUET 2 , L WESTBOM 3 1 Orthopedics, Sk ane University Hospital Lund, Lund, Sweden; 2Centre for Clinical Research, Uppsala University, Central Hospital V€a ster as, V€a ster as, Sweden; 3Department of Paediatrics, Lund University, Sk ane University Hospital, Lund, Sweden
Background/Objectives: The majority of children living with cerebral palsy (CP) in Sweden are participating in a nationwide multidisciplinary follow-up program/registry called CPUP. However, there is a dearth of data on adults with CP after they leave the pediatric healthcare system. CPUP has recently started to enroll adults with CP. In this study, we investigated type of living arrangements, occupation status, and use of personal assistance in young Swedish adults with CP. Design: Descriptive population based cross-sectional registry study. Participants and Setting: Hundred and two participants (63 males) with a median age of 21 years (19 to 23) living in southern Sweden were included. All were part of a 2-year pilot project (2009 to 2010) designed to provide information and guidance before CPUP officially extended the inclusion criteria to also cover adults with CP. Methods: Participants were examined by a physical and an occupational therapist. The assessment lasted approximately 1.5 hours. Data on gross motor function (Gross Motor Function Classification System (GMFCS) levels 1-V), hand function (Manual Ability Classification System (MACS) levels I-V), living arrangements (“independent living”, “living with parents”, or “special service housing”), occupation status (“employed”, “student”, “daily activity”, or “unemployed”) and use of personal assistance (“yes” or “no”) were collected. Caregivers or personal assistants answered as proxies if needed. Data were analyzed in relation to GMFCS and MACS. Results: Fifty-eight “lived with parents”, 29 reported “independent living”, and 15 reported “special service housing”. Living arrangements differed among GMFCS levels (p5mm and invariable femoral head deformity. The method of hip reconstruction was chosen at the preference of the surgeon and influenced by the child’s health. Outcome measures were MP and acetabular index (AI). All children had a minimum follow up of 2 years after surgery. Generalized estimating equation was used to account for any known and unknown correlations between hips from bilateral cases. Results: Median (range) age at time of surgery was 10 (3 – 16) years. Six children were GMFCS 3, fourteen were GMFCS 4 and thirty-seven were GMFCS 5. Thirty hips underwent VDRO alone and 46 hips had VDRO plus Dega. In the VDRO group the pre-Op mean MP was 62° (Std Dev 25) and 36° (Std Dev 15) at 2 years post-OP. In the VDRO+Dega group the pre-OP MP was 63° (Std Dev 19) and 21° (Std Dev 14) at 2 years post-OP. At 2 years post-OP 14 hips (47%) were stable in the VDRO group, 35 (76%) were stable in the VDRO+Dega group. The odds of being stable at 2 years post-OP were almost four times higher in hips undergoing VDRO+Dega than VDRO alone (Odds ratio=3.9, 95% confi-
dence interval=1.5 to 10.1, P=0.005). The mean AI in the VDRO group changed from 29° to 23° immediately after surgery, where it remained at 2 years follow up. In the VDRO+Dega group the mean AI changed from 30° to 16° immediately post-Op and to 18° at 2 years. Conclusions: An acetabuloplasty/Dega osteotomy in addition to a VDRO increases hip stability significantly in children with cerebral palsy, GMFCS 3-5 and hip instability, and is likely to reduce the risk of long term dislocation and/or bony deformities associated with pain. There was no meaningful change of the AI in the VDRO-only group which could be attributed to acetabular development over time. References: Robin J, Graham HK, Baker R, Selber P, Simpson P, Symons S, Thomason P. A classification system for hip disease in cerebral palsy. Dev Med Child Neurol. 2009;51:183-192.
SP6 Abnormal expression of GADD45b and epigenomic abnormalities in skeletal muscle from children with spastic cerebral palsy 1,2
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DT BARNES , K ROBINSON , F MILLER , R AKINS 1 Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA; 2Biological Sciences, University of Delaware, Newark, DE, USA
Background/Objectives: Cerebral palsy (CP) is a static encephalopathy resulting from injury to the developing brain. CP has been associated with hypertonia, gait abnormalities, decreased coordination, and weakness. Previous data suggest that abnormalities exist in the peripheral nervous system of patients with spastic CP including abnormal structure in neuromuscular junctions (NMJs). Preliminary studies of gene expression in laser-dissected muscle samples from patients with CP indicated that a large number of genes may be differentially expressed at NMJs. Expression of the Growth Arrest and DNA Damage Inducible 45b (GADD45b) mRNA was found to be significantly depressed (~15 fold) in samples from CP patients. In the current study, we explore the expression of GADD45b protein and begin to elucidate the potential downstream effects of altered GADD45b and its role in demethylating brain derived neurotrophic factor (BDNF). We hypothesize that GADD45b protein is decreased in CP patients, and that a shift in epigenomic patterning in post-synaptic myonuclei is associated with abnormal NMJs and altered GADD45b expression. Design: Case/control study of surgical biopsy tissue. Participants and Setting: After IRB approval and informed consent/assent, children with diagnosis of spastic cerebral palsy or idiopathic scoliosis were enrolled. Samples of spinalis muscle were acquired during posterior spinal fusion surgery. Methods: Samples were snap frozen in liquid-nitrogen chilled isopentane. Synaptic myonuclei were collected using laser capture micro-dissection of cryosectioned material, and mRNA was purified from pooled samples. Levels of 84 candidate genes were analyzed using qPCR. Fluorescence microscopic assessments using anti-GADD45b and anti-slow myosin (A4.951) were performed. Western blotting was performed to quantify GADD45b expression in muscle tissues. In ongoing studies,
nuclei isolated from fresh muscle tissue were collected and synaptic nuclei are being separated from extra-synaptic nuclei, and differences in epigenetic patterning are being determined for both CP and idiopathic scoliosis samples. Results: GADD45b mRNA expression was significantly downregulated (~159 by qPCR) in muscle samples from children with CP. GADD45b protein was elevated in type I fibers of control patients with idiopathic scoliosis relative to neighboring type II fibers. This relative distinction was not apparent in the CP muscle. Quantitatively, patients with CP had a significantly lower mean ratio of signal in type I versus type II fibers by fluorescence microscopy. Preliminary GADD45b quantification indicates that Western blot results have shown no trend in GADD45b protein levels. Conclusions: Children with CP have alterations in synaptic gene expression and GADD45b protein distribution in skeletal muscle fibers. These changes may be important indicators of underlying peripheral dysfunction in CP patients and may prove to be clinically useful in the assessment and treatment of CP.
SP7 Dietary intake and undernutrition in preschool children with cerebral palsy: comparison between high- and low-resource countries K BENFER 1,2 , KA WEIR 1,3 , KL BELL 1,4 , R WARE 5 , PS DAVIES 4 , RN BOYD 1 1 Queensland Cerebral Palsy and Rehabilitation Research Centre, University of Queensland, Herston, QLD, Australia; 2Centre for the Rehabilitation of the Paralysed, Savar, Bangladesh; 3Speech Pathology, Royal Children’s Hospital, Herston, QLD, Australia; 4Children’s Nutrition Research Centre, QCMRI, The University of Queensland, Herston, QLD, Australia; 5School of Population Health, The University of Queensland, Herston, QLD, Australia
Background/Objectives: Undernutrition is common in children with cerebral palsy (CP) and is associated with decreased dietary intake, based largely on studies in high-resource countries. There has been no direct analysis of how patterns of dietary intake and undernutrition differ between high- and low-resource countries. Objective: To determine the energy intake and prevalence of undernutrition in preschool children with CP in Bangladesh compared to Australian children. Design: Cross sectional, comparison of two cohorts.
Figure 1: Energy intake by body size for the Australia and Bangladesh Cohorts.
Scientific Posters 5
Participants and Setting: Hundred and eighty children with CP aged 18 to 36 months, 81 children born in Bangladesh (mean age=27.6mo, 50 males, GMFCS I–II=23.5%, III=30.9%, IV– V=45.7%) and 99 children born in Queensland, Australia (mean age=27.1mo, 65 males, GMFCS I-II=56.2%, III=17.7%, IV-V=26.2%). Methods: Parents reported on their child’s dietary intake using a 1 day (Bangladesh, BD) and 3 day (Australia, AU) weighed record. Records were analyzed for energy intake using Foodworks dietary analysis software. Gross motor skills were classified using the Gross Motor Function Classification System (GMFCS) combined based on ambulatory status for analysis (GMFCS I-II, III, IV-V). (i) Mean energy intake between AU and BD cohorts was compared by GMFCS with t tests. Linear regression was used to determine differences in energy intake between cohorts based on body weight. (ii) Z-scores for weight for age, height for age and weight for height (WHZ) were calculated using the World Health Organization reference data. The proportion of each cohort with WHZ
Scientific Posters SP1 Living arrangements, occupation, and use of personal assistance in young Swedes with cerebral palsy 1 € A ALRIKSSON-SCHMIDT 1 , G H AGGLUND , E RODBY BOUSQUET 2 , L WESTBOM 3 1 Orthopedics, Sk ane University Hospital Lund, Lund, Sweden; 2Centre for Clinical Research, Uppsala University, Central Hospital V€a ster as, V€a ster as, Sweden; 3Department of Paediatrics, Lund University, Sk ane University Hospital, Lund, Sweden
Background/Objectives: The majority of children living with cerebral palsy (CP) in Sweden are participating in a nationwide multidisciplinary follow-up program/registry called CPUP. However, there is a dearth of data on adults with CP after they leave the pediatric healthcare system. CPUP has recently started to enroll adults with CP. In this study, we investigated type of living arrangements, occupation status, and use of personal assistance in young Swedish adults with CP. Design: Descriptive population based cross-sectional registry study. Participants and Setting: Hundred and two participants (63 males) with a median age of 21 years (19 to 23) living in southern Sweden were included. All were part of a 2-year pilot project (2009 to 2010) designed to provide information and guidance before CPUP officially extended the inclusion criteria to also cover adults with CP. Methods: Participants were examined by a physical and an occupational therapist. The assessment lasted approximately 1.5 hours. Data on gross motor function (Gross Motor Function Classification System (GMFCS) levels 1-V), hand function (Manual Ability Classification System (MACS) levels I-V), living arrangements (“independent living”, “living with parents”, or “special service housing”), occupation status (“employed”, “student”, “daily activity”, or “unemployed”) and use of personal assistance (“yes” or “no”) were collected. Caregivers or personal assistants answered as proxies if needed. Data were analyzed in relation to GMFCS and MACS. Results: Fifty-eight “lived with parents”, 29 reported “independent living”, and 15 reported “special service housing”. Living arrangements differed among GMFCS levels (p5mm and invariable femoral head deformity. The method of hip reconstruction was chosen at the preference of the surgeon and influenced by the child’s health. Outcome measures were MP and acetabular index (AI). All children had a minimum follow up of 2 years after surgery. Generalized estimating equation was used to account for any known and unknown correlations between hips from bilateral cases. Results: Median (range) age at time of surgery was 10 (3 – 16) years. Six children were GMFCS 3, fourteen were GMFCS 4 and thirty-seven were GMFCS 5. Thirty hips underwent VDRO alone and 46 hips had VDRO plus Dega. In the VDRO group the pre-Op mean MP was 62° (Std Dev 25) and 36° (Std Dev 15) at 2 years post-OP. In the VDRO+Dega group the pre-OP MP was 63° (Std Dev 19) and 21° (Std Dev 14) at 2 years post-OP. At 2 years post-OP 14 hips (47%) were stable in the VDRO group, 35 (76%) were stable in the VDRO+Dega group. The odds of being stable at 2 years post-OP were almost four times higher in hips undergoing VDRO+Dega than VDRO alone (Odds ratio=3.9, 95% confi-
dence interval=1.5 to 10.1, P=0.005). The mean AI in the VDRO group changed from 29° to 23° immediately after surgery, where it remained at 2 years follow up. In the VDRO+Dega group the mean AI changed from 30° to 16° immediately post-Op and to 18° at 2 years. Conclusions: An acetabuloplasty/Dega osteotomy in addition to a VDRO increases hip stability significantly in children with cerebral palsy, GMFCS 3-5 and hip instability, and is likely to reduce the risk of long term dislocation and/or bony deformities associated with pain. There was no meaningful change of the AI in the VDRO-only group which could be attributed to acetabular development over time. References: Robin J, Graham HK, Baker R, Selber P, Simpson P, Symons S, Thomason P. A classification system for hip disease in cerebral palsy. Dev Med Child Neurol. 2009;51:183-192.
SP6 Abnormal expression of GADD45b and epigenomic abnormalities in skeletal muscle from children with spastic cerebral palsy 1,2
1
1
1
DT BARNES , K ROBINSON , F MILLER , R AKINS 1 Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA; 2Biological Sciences, University of Delaware, Newark, DE, USA
Background/Objectives: Cerebral palsy (CP) is a static encephalopathy resulting from injury to the developing brain. CP has been associated with hypertonia, gait abnormalities, decreased coordination, and weakness. Previous data suggest that abnormalities exist in the peripheral nervous system of patients with spastic CP including abnormal structure in neuromuscular junctions (NMJs). Preliminary studies of gene expression in laser-dissected muscle samples from patients with CP indicated that a large number of genes may be differentially expressed at NMJs. Expression of the Growth Arrest and DNA Damage Inducible 45b (GADD45b) mRNA was found to be significantly depressed (~15 fold) in samples from CP patients. In the current study, we explore the expression of GADD45b protein and begin to elucidate the potential downstream effects of altered GADD45b and its role in demethylating brain derived neurotrophic factor (BDNF). We hypothesize that GADD45b protein is decreased in CP patients, and that a shift in epigenomic patterning in post-synaptic myonuclei is associated with abnormal NMJs and altered GADD45b expression. Design: Case/control study of surgical biopsy tissue. Participants and Setting: After IRB approval and informed consent/assent, children with diagnosis of spastic cerebral palsy or idiopathic scoliosis were enrolled. Samples of spinalis muscle were acquired during posterior spinal fusion surgery. Methods: Samples were snap frozen in liquid-nitrogen chilled isopentane. Synaptic myonuclei were collected using laser capture micro-dissection of cryosectioned material, and mRNA was purified from pooled samples. Levels of 84 candidate genes were analyzed using qPCR. Fluorescence microscopic assessments using anti-GADD45b and anti-slow myosin (A4.951) were performed. Western blotting was performed to quantify GADD45b expression in muscle tissues. In ongoing studies,
nuclei isolated from fresh muscle tissue were collected and synaptic nuclei are being separated from extra-synaptic nuclei, and differences in epigenetic patterning are being determined for both CP and idiopathic scoliosis samples. Results: GADD45b mRNA expression was significantly downregulated (~159 by qPCR) in muscle samples from children with CP. GADD45b protein was elevated in type I fibers of control patients with idiopathic scoliosis relative to neighboring type II fibers. This relative distinction was not apparent in the CP muscle. Quantitatively, patients with CP had a significantly lower mean ratio of signal in type I versus type II fibers by fluorescence microscopy. Preliminary GADD45b quantification indicates that Western blot results have shown no trend in GADD45b protein levels. Conclusions: Children with CP have alterations in synaptic gene expression and GADD45b protein distribution in skeletal muscle fibers. These changes may be important indicators of underlying peripheral dysfunction in CP patients and may prove to be clinically useful in the assessment and treatment of CP.
SP7 Dietary intake and undernutrition in preschool children with cerebral palsy: comparison between high- and low-resource countries K BENFER 1,2 , KA WEIR 1,3 , KL BELL 1,4 , R WARE 5 , PS DAVIES 4 , RN BOYD 1 1 Queensland Cerebral Palsy and Rehabilitation Research Centre, University of Queensland, Herston, QLD, Australia; 2Centre for the Rehabilitation of the Paralysed, Savar, Bangladesh; 3Speech Pathology, Royal Children’s Hospital, Herston, QLD, Australia; 4Children’s Nutrition Research Centre, QCMRI, The University of Queensland, Herston, QLD, Australia; 5School of Population Health, The University of Queensland, Herston, QLD, Australia
Background/Objectives: Undernutrition is common in children with cerebral palsy (CP) and is associated with decreased dietary intake, based largely on studies in high-resource countries. There has been no direct analysis of how patterns of dietary intake and undernutrition differ between high- and low-resource countries. Objective: To determine the energy intake and prevalence of undernutrition in preschool children with CP in Bangladesh compared to Australian children. Design: Cross sectional, comparison of two cohorts.
Figure 1: Energy intake by body size for the Australia and Bangladesh Cohorts.
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Participants and Setting: Hundred and eighty children with CP aged 18 to 36 months, 81 children born in Bangladesh (mean age=27.6mo, 50 males, GMFCS I–II=23.5%, III=30.9%, IV– V=45.7%) and 99 children born in Queensland, Australia (mean age=27.1mo, 65 males, GMFCS I-II=56.2%, III=17.7%, IV-V=26.2%). Methods: Parents reported on their child’s dietary intake using a 1 day (Bangladesh, BD) and 3 day (Australia, AU) weighed record. Records were analyzed for energy intake using Foodworks dietary analysis software. Gross motor skills were classified using the Gross Motor Function Classification System (GMFCS) combined based on ambulatory status for analysis (GMFCS I-II, III, IV-V). (i) Mean energy intake between AU and BD cohorts was compared by GMFCS with t tests. Linear regression was used to determine differences in energy intake between cohorts based on body weight. (ii) Z-scores for weight for age, height for age and weight for height (WHZ) were calculated using the World Health Organization reference data. The proportion of each cohort with WHZ
