1
|
Murphy MM, Colquitt GT, Ryals PS, Shin K, Kjeldsen WC, McIntyre A, Whitten SVW, Modlesky CM, Maitre NL. Synergies, Discrepancies, and Action Priorities: A Statewide Engagement Study to Strengthen Clinical Research in Cerebral Palsy. Health Expect 2025; 28:e70257. [PMID: 40275596 PMCID: PMC12022003 DOI: 10.1111/hex.70257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 02/17/2025] [Accepted: 03/25/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Cerebral palsy (CP) clinical research is fraught with challenges, in part due to health-related disparities common among people with disabilities. Perspectives of people with lived experience of CP, clinicians and researchers vary on how to address these disparities. The present initiative explores synergies and discrepancies among stakeholders (n = 212) representing these partner groups in perceived barriers and facilitators to high-quality clinical CP research and robust trainee pathways. The overarching goal is to generate priority actions to empower meaningful partner group engagement in CP research and, ultimately, improve health outcomes for people with CP. METHODS Grounded in empowerment theory, mixed methods needs assessments were conducted separately with partner groups to capture perspectives on barriers and facilitators to high-quality CP research and strong trainee pathways. Thematic analysis was applied to focus groups and interviews to identify themes and subthemes. RESULTS Discrepancies among partner groups emerged related to informational needs, community connection, ethical research and equitable representation in research, and fair compensation for lived experience partner engagement in the research process. CONCLUSIONS Ongoing opportunities for researcher action to empower partner group engagement include building shared purpose, nurturing social connection within and among groups and intentional efforts to build trust and codesign studies. PATIENT OR PUBLIC CONTRIBUTION The initiative described here was informed by caregivers of children with CP from Georgia, USA, using a community-based participatory research (CBPR) approach. CPBR is a collaborative approach, designed to give communities, which here include people with lived experience of CP, control over research processes and outcomes. Their perspectives were essential to the premise of this study and guided data interpretation, especially with regard to how their perspectives may or may not correspond to those of CP researchers and clinicians. To ensure inclusion of all perspectives, individuals with CP were also represented in these latter two engagement groups. Finally, the design, conduct, analysis and interpretation of data were informed by a researcher and a clinician-scientist, both of whom have lived experience as caregivers of children with CP.
Collapse
Affiliation(s)
| | | | | | - Katie Shin
- Emory University School of MedicineAtlantaGeorgiaUSA
| | | | | | | | | | - Nathalie L. Maitre
- Emory University School of MedicineAtlantaGeorgiaUSA
- Children's Healthcare of AtlantaAtlantaGeorgiaUSA
| |
Collapse
|
2
|
Bonezzi L, Accorinti I, Papoff FMA, Orsi M, D'Arcangelo G, Bartolini E, Battini R. Cerebral Palsy in a Rural Desert Population of Southern Algeria: A Cross-Sectional Study of Epidemiology of Comorbidities and Unmet Needs. J Child Neurol 2025:8830738251336486. [PMID: 40340658 DOI: 10.1177/08830738251336486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
BackgroundCerebral palsy is a group of nonprogressive motor disorders resulting from early brain development impairment. Its prevalence is higher in low- and middle-income countries, where health care resources are limited. Data on cerebral palsy in refugee settings remain scarce, particularly in regions marked by prolonged displacement.MethodsThis cross-sectional study examined 29 children with cerebral palsy in the Sahrawi refugee camps in Tindouf, Algeria. Detailed demographic, medical history, neurological findings, and comorbidity data were collected during outpatient visits conducted as part of a humanitarian mission.ResultsPerinatal distress was reported in 65.5% of cases. Motor impairments were significant, with only 44.8% able to walk and 20.7% lacking head control. Language delays (65.5%), feeding difficulties (65.5%), and epilepsy (52%) were highly prevalent. Diagnostic evaluations, such as magnetic resonance imaging (MRI) and electroencephalography (EEG), were scarce and inconsistent. Access to rehabilitation services was discontinuous, and pharmacologic treatments for spasticity and pain were unavailable. Environmental factors, such as sandy terrain, further complicated mobility.ConclusionCerebral palsy in the Sahrawi refugee camps reflects patterns seen in low- and middle-income countries but is exacerbated by displacement and resource scarcity. Improved access to early diagnosis, structured rehabilitation, and targeted pharmacologic therapies is urgently needed to address these unmet needs and improve outcomes for affected children.
Collapse
Affiliation(s)
- Linda Bonezzi
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- School of Medicine, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Brisbane, Australia
| | - Ilaria Accorinti
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Francesca Maria Agostina Papoff
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Maria Orsi
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Giacomo D'Arcangelo
- Scuola Normale Superiore of Pisa, Class of Science, Pisa, Italy
- Applied and Laser Spectroscopy Laboratory, Institute of Chemistry of Organometallic Compounds, Research Council, Pisa, Italy
| | - Emanuele Bartolini
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Roberta Battini
- Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| |
Collapse
|
3
|
Zhuo H, Rogne T, Liew Z. A sibling study of the prenatal and perinatal risks for cerebral palsy. Pediatr Res 2025:10.1038/s41390-025-04055-4. [PMID: 40316681 DOI: 10.1038/s41390-025-04055-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 03/21/2025] [Accepted: 03/23/2025] [Indexed: 05/04/2025]
Abstract
BACKGROUND To evaluate the associations between prenatal and perinatal factors and CP risk using a statewide sibling-comparison design. METHODS We established a cohort of over 4 million singleton births in California during 2007-2015, and we identified families with outcome-discordant siblings of 1213 CP and 1544 non-CP. We estimated odds ratio (OR) and 95% confidence interval (CI) for CP according to perinatal factors including preterm birth (PTB), small for gestational age, low Apgar score, and prenatal factors including maternal pregnancy complications (perinatal infection, gestational diabetes, preeclampsia) and lifestyle-related factors (cigarette smoking, pre-pregnancy overweight). RESULTS The perinatal factors remained strongly associated with CP using sibling design, although the point estimates were smaller for PTB (cohort OR = 4.72, 95%CI 4.42-5.04, sibling OR = 3.49, 95%CI 2.74-4.46) and low Apgar score (cohort OR = 19.62, 95%CI 17.99-21.41, sibling OR = 8.79, 95%CI 5.49-14.08). In sibling design, the associations between maternal pregnancy complications or pre-pregnancy overweight and CP risk were attenuated to null. We observed stronger effects between maternal cigarette smoking and CP in the sibling design, however sensitivity tests indicated possible bias from carryover effects. CONCLUSION Adverse perinatal factors remained strongly associated with childhood CP, while uncontrolled confounding bias required considerations for pregnancy complications and CP development. IMPACT We conducted a population-based sibling comparison study to evaluate the associations between several prenatal and perinatal factors and cerebral palsy (CP). Preterm birth, small for gestational age, and low Apgar score at birth remained strongly associated with CP using the sibling comparison design. The associations between several maternal pregnancy complications and CP were close to null in the sibling comparison design, raising the possibility of uncontrolled confounding bias in the cohort analyses. We demonstrated that a sibling comparison design can provide valuable information to triangulate research evidence for CP etiology, but a careful implementation and interpretation of findings is warranted.
Collapse
Affiliation(s)
- Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA
| | - Tormod Rogne
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA
- Department of Community Medicine and Global Health, University of Oslo, Oslo, Norway
| | - Zeyan Liew
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
| |
Collapse
|
4
|
Finch-Edmondson M, Paton MCB, Webb A, Reza Ashrafi M, Blatch-Williams RK, Cox CS, Crompton K, Griffin AR, Kim M, Kosmach S, Kurtzberg J, Nouri M, Ri Suh M, Sun J, Zarrabi M, Novak I. Cord Blood Treatment for Children With Cerebral Palsy: Individual Participant Data Meta-Analysis. Pediatrics 2025; 155:e2024068999. [PMID: 40210215 DOI: 10.1542/peds.2024-068999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 01/10/2025] [Indexed: 04/12/2025] Open
Abstract
CONTEXT Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP), with trials indicating UCB can improve gross motor function. However, heterogeneity has limited the ability to interpret findings. OBJECTIVE Assess the safety and efficacy of UCB for improving gross motor function in children with CP, including exploring cell dose effect and responder subgroups. DATA SOURCES Individual participant data from published reports and registered trials identified via systematic searches. STUDY SELECTION Studies administering UCB to individuals with CP collecting Gross Motor Function Measure (GMFM) scores. DATA EXTRACTION A 1-stage individual participant data meta-analysis was conducted in R to obtain the pooled effect of UCB and cell dose effect on GMFM using linear mixed models. Responder subgroups were also investigated. RESULTS Four hundred ninety-eight participant data records were obtained from 11 studies. Main analysis of 170 participants treated with UCB and 171 controls demonstrated UCB increased mean GMFM-66 score compared with controls by 1.36 points at 6 months (95% CI, 0.41-2.32; P = .005) and 1.42 at 12 months (95% CI, 0.31-2.52; P = .012). Mean GMFM-66 effect size increased with increasing cell dose at 3 (P < .001) and 12 months (P = .047). CP severity and baseline age were associated with GMFM-66 effect size. The rate of serious adverse events was similar between groups. LIMITATIONS Heterogeneity across variables and time points, reducing subanalysis power. CONCLUSIONS UCB is safe and provides benefit for improving gross motor function in some children with CP, with higher doses associated with increased effect size. Younger participants (aged approximately <5 years) with milder CP showed increased benefit. Findings will help design future trials with precision.
Collapse
Affiliation(s)
- Megan Finch-Edmondson
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Madison C B Paton
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Annabel Webb
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Mahmoud Reza Ashrafi
- Department of Pediatrics, Division of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Remy K Blatch-Williams
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Charles S Cox
- Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas
| | - Kylie Crompton
- Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, The University of Melbourne, Melbourne, Victoria, Australia
| | - Alexandra R Griffin
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - MinYoung Kim
- CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Steven Kosmach
- Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas
| | - Joanne Kurtzberg
- The Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, North Carolina
| | - Masoumeh Nouri
- R&D Department of Royan Stem Cell Technology, Tehran, Iran
| | - Mi Ri Suh
- CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Jessica Sun
- The Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, North Carolina
| | - Morteza Zarrabi
- Department of Regenerative Medicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Iona Novak
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| |
Collapse
|
5
|
Han JY, Gwack J, Kim JH, Park MK, Park J. Genetic Alterations in Atypical Cerebral Palsy Identified Through Chromosomal Microarray and Exome Sequencing. Int J Mol Sci 2025; 26:2929. [PMID: 40243517 PMCID: PMC11988916 DOI: 10.3390/ijms26072929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/17/2025] [Accepted: 03/19/2025] [Indexed: 04/18/2025] Open
Abstract
This study investigated the genetic causes of atypical cerebral palsy (CP) through chromosomal microarray (CMA) and exome sequencing (ES) in a cohort of 10 Korean patients to identify variants and expand the spectrum of mutations associated with atypical cerebral palsy. Whole ES and/or genome sequencing (GS) after routine karyotyping and CMA was performed to identify causative variants and expand the spectrum of mutations associated with atypical CP. In cases of atypical CP, scoliosis and/or kyphosis, ranging from mild to severe, were present in all patients. Epilepsy was a comorbidity in seven patients (70%), and intellectual disability (ID) was observed in varying degrees. This study identified three copy number variations (CNVs), including 15q11.2 microdeletion (n = 1), 17p11.2 duplication (n = 1), and 12p13.33p11.23 duplication/18p11.32 microdeletion (n = 1), and six likely pathogenic variants (LPVs) or pathogenic variants (PVs) detected in the SLC2A1, PLAA, CDC42BPB, CACNA1D, ALG12, and SACS genes (n = 6). These findings emphasize the significance of incorporating genetic testing into the diagnostic process for atypical CP to improve our understanding of its molecular basis and inform personalized treatment strategies. To further advance this research, future studies should focus on exploring genotype-phenotype correlations, assessing the functional impact of identified variants, and increasing the sample size to validate the observed patterns.
Collapse
Affiliation(s)
- Ji Yoon Han
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
- Department of Pediatrics, Daejeon St. Mary’s Hospital, Daejeon 34943, Republic of Korea
| | - Jin Gwack
- Department of Preventive Medicine, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea;
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Jong Hun Kim
- Department of Thoracic and Cardiovascular Surgery, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea;
| | - Min Kyu Park
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheongju 28644, Republic of Korea
- Research Institute of Cheongju-Osong Advanced Clinical Trial Center, Osong 28161, Republic of Korea
| | - Joonhong Park
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
| |
Collapse
|
6
|
Letzkus L, Picavia R, Lyons G, Brandberg J, Qiu J, Kausch S, Lake D, Fairchild K. Heart rate patterns predicting cerebral palsy in preterm infants. Pediatr Res 2025; 97:1040-1046. [PMID: 37891365 PMCID: PMC12100623 DOI: 10.1038/s41390-023-02853-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND Heart rate (HR) patterns can inform on central nervous system dysfunction. We previously used highly comparative time series analysis (HCTSA) to identify HR patterns predicting mortality among patients in the neonatal intensive care unit (NICU) and now use this methodology to discover patterns predicting cerebral palsy (CP) in preterm infants. METHOD We studied NICU patients <37 weeks' gestation with archived every-2-s HR data throughout the NICU stay and with or without later diagnosis of CP (n = 57 CP and 1119 no CP). We performed HCTSA of >2000 HR metrics and identified 24 metrics analyzed on HR data from two 7-day periods: week 1 and 37 weeks' postmenstrual age (week 1, week 37). Multivariate modeling was used to optimize a parsimonious prediction model. RESULTS Week 1 HR metrics with maximum AUC for CP prediction reflected low variability, including "RobustSD" (AUC 0.826; 0.772-0.870). At week 37, high values of a novel HR metric, "LongSD3," the cubed value of the difference in HR values 100 s apart, were added to week 1 HR metrics for CP prediction. A combined birthweight + early and late HR model had AUC 0.853 (0.805-0.892). CONCLUSIONS Using HCTSA, we discovered novel HR metrics and created a parsimonious model for CP prediction in preterm NICU patients. IMPACT We discovered new heart rate characteristics predicting CP in preterm infants. Using every-2-s HR from two 7-day periods and highly comparative time series analysis, we found a measure of low variability HR week 1 after birth and a pattern of recurrent acceleration in HR at term corrected age that predicted CP. Combined clinical and early and late HR features had AUC 0.853 for CP prediction.
Collapse
Affiliation(s)
- Lisa Letzkus
- Department of Pediatrics, Neurodevelopmental and Behavioral Pediatrics, UVA Children's Hospital, University of Virginia School of Medicine, Charlottesville, VA, USA.
| | - Robin Picavia
- University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Genevieve Lyons
- Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
| | | | - Jiaxing Qiu
- University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Sherry Kausch
- University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Doug Lake
- Department of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Karen Fairchild
- Department of Pediatrics, Neonatology, UVA Children's Hospital, University of Virginia School of Medicine, Charlottesville, VA, USA
| |
Collapse
|
7
|
Zhao J, Qiu Y, Wang H. Nutritional risk screening and nutritional assessment for children with cerebral palsy: A review of the current research status and future directions. Clin Nutr ESPEN 2025; 65:382-389. [PMID: 39710170 DOI: 10.1016/j.clnesp.2024.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/11/2024] [Accepted: 12/17/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Although the primary impairment involved in Cerebral palsy (CP) is motor function, malnutrition is also common. However, there is a lack of tool recommendations for early malnutrition risk screening in children with CP, and the means of nutritional intervention for children with CP are also limited. METHODS This study systematically searched the literature about clinical nutrition related content of cerebral palsy in Pubmed, MEDLINE, Embase, and the Cochrane Library in Jan 2024 and by hand searching, and we checked reference lists and citations to identify additional studies. Search terms include cerebral palsy, children, diagnosis, prediction, malnutrition, nutritional risk screening, nutritional assessment, nutritional support. Additions are marked in red in the modified version. RESULTS The timing of diagnosis of CP has been moving forward, and some new diagnostic tools have been developed. Nutritional status is correlated with regional economic level, but there is still a malnutrition rate of nearly 30 % in developed countries. Severe restrictions in terms of gross motor function, swallowing dysfunction, feeding difficulties, cognitive impairment, and insufficient energy intake are common risk factors for malnutrition in children with CP. Z-score should be calculated in combination with measurement indicators in the assessment of physical development of children with CP. The nutritional outcomes of children with CP can be improved by various means, including diversified a Nutrition Support Team (NST) interventions. CONCLUSIONS The incidence of malnutrition in children with CP is high, which needs to be paid more attention. More effective malnutrition risk screening tools need to be developed for children with CP to guide the implementation of comprehensive and personalized nutritional interventions and improve malnutrient-related outcomes.
Collapse
Affiliation(s)
- Jixun Zhao
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China; Department of Clinical Nutrition, Guizhou Rehabilitation Hospital, Guiyang, 550019, China
| | - Yuyang Qiu
- Department of Emergency Intensive Care Unit, The Second People's Hospital of Guiyang, Guiyang, 550081, China
| | - Huiqun Wang
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China.
| |
Collapse
|
8
|
Ortega-Cruz A, Sánchez-Silverio V, Riquelme-Aguado V, Alonso-Perez JL, Abuín-Porras V, Villafañe JH. Effects of Hippotherapy and Horse-Riding Simulators on Gross Motor Function in Children with Cerebral Palsy: A Systematic Review. J Clin Med 2025; 14:283. [PMID: 39797365 PMCID: PMC11720817 DOI: 10.3390/jcm14010283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: Cerebral palsy (CP) can have a negative impact on gross motor function. Conventional hippotherapy and horse-riding simulators (HRS) have shown promising results on gross motor function in populations with neurological disorders. This review aims to update the knowledge on the effectiveness of hippotherapy on gross motor function in children with CP. Methods: A search was conducted in Academic Search Ultimate, CINAHL, Medline complete, and PEDro covering publications between 2012 and 2022. Two authors identified studies that met the inclusion criteria; a third author resolved discrepancies. Studies were included if they analyzed the effects of hippotherapy on the gross motor function of children with CP. The quality of the methodology was assessed according to the PEDro scale. Results: Of the 150 studies initially identified, 9 were included in this review. The studies showed fair (N = 3) and good (N = 6) methodological quality on the PEDro scale. The majority used conventional hippotherapy (N = 7), while a minority used HRS (N = 2). The most commonly used protocol for conventional hippotherapy was 1-2 sessions of 30-45 min per week for 8 weeks (N = 4), whereas for HRS, these protocols were varied. Seven studies on conventional hippotherapy and one study on HRS showed improvements in gross motor function. However, the hippotherapy protocols were not very standardized and the samples were neither homogeneous nor representative. Conclusions: Conventional hippotherapy and HRS appear to have evidence to support their benefits on gross motor function in children with CP. However, more clinical trials with standardized protocols and more representative samples are needed to confirm these effects.
Collapse
Affiliation(s)
- Antonio Ortega-Cruz
- Department of Physiotherapy, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain; (A.O.-C.); (J.L.A.-P.); (V.A.-P.); (J.H.V.)
| | - Víctor Sánchez-Silverio
- School of Applied Health Sciences, Pontificia Universidad Católica Madre y Maestra, Autopista Duarte Km 1 1/2, Santiago De Los Caballeros 51000, Dominican Republic;
| | - Víctor Riquelme-Aguado
- Department of Basic Health Sciences, Rey Juan Carlos University, 28933 Madrid, Spain
- Grupo de Investigación Consolidado de Bases Anatómicas, Moleculares y del Desarrollo Humano de la Universidad Rey Juan Carlos (GAMDES), 28922 Alcorcón, Spain
| | - Jose Luis Alonso-Perez
- Department of Physiotherapy, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain; (A.O.-C.); (J.L.A.-P.); (V.A.-P.); (J.H.V.)
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
| | - Vanesa Abuín-Porras
- Department of Physiotherapy, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain; (A.O.-C.); (J.L.A.-P.); (V.A.-P.); (J.H.V.)
| | - Jorge Hugo Villafañe
- Department of Physiotherapy, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain; (A.O.-C.); (J.L.A.-P.); (V.A.-P.); (J.H.V.)
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
| |
Collapse
|
9
|
Zhuo H, Ritz B, Warren JL, Pollitt KG, Liew Z. Ambient Toxic Air Contaminants in the Maternal Residential Area during Pregnancy and Cerebral Palsy in the Offspring. ENVIRONMENTAL HEALTH PERSPECTIVES 2025; 133:17008. [PMID: 39853265 PMCID: PMC11758984 DOI: 10.1289/ehp14742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 11/02/2024] [Accepted: 12/19/2024] [Indexed: 01/26/2025]
Abstract
BACKGROUND Cerebral palsy (CP) is the most common permanent neuromotor disorder diagnosed in childhood. Although most cases have unknown etiology, emerging evidence suggests environmental risk factors of CP. OBJECTIVES We investigated whether ambient toxic air contaminants (TACs) in the maternal residential area during pregnancy, specifically volatile organic compounds (VOCs) and metals, were associated with offspring CP risk in California. METHODS We conducted a case-cohort study that included CP cases (N = 906 ) and a 20% random sample of all live singleton births (N = 184,954 ) who lived within a 5 -mile (8-km) radius of air toxics monitoring stations in California during 2005-2015 as the control comparison group. CP cases were ascertained from diagnostic records of the California Department of Developmental Services. We a priori selected TACs with suspected neurotoxicity and developmental toxicity, including 14 VOCs and 6 metals. We estimated the adjusted risk ratio (RR) and 95% confidence interval (CI) for CP and the average maternal residential exposures to each TAC over the entire pregnancy using modified Poisson regression. For air contaminant mixtures, we used quantile-based g-computation to estimate the effects of mixtures of VOCs or metals. Finally, we performed a negative control exposure analysis on exposure estimates of 36-48 months after delivery to evaluate uncontrolled confounding bias. RESULTS Maternal residential exposures to six VOCs (benzene, toluene, 1,3-butadiene, acetone, acetonitrile, and methylene chloride) and four metals (antimony, lead, nickel, and vanadium) were associated with 3%-25% higher risk of CP per interquartile range increase, and the estimated mixture effects of VOCs (RR = 1.24 ; 95% CI: 1.08, 1.43) or metals (RR = 1.38 ; 95% CI: 1.20, 1.58) were stronger. The observed associations were close to null for negative control exposures (36-48 months after delivery) to mixtures of VOCs or metals and CP. DISCUSSION In California, maternal prenatal residential exposure to VOCs and metals in the outdoor air, largely attributed to mobile traffic emission sources, was associated with an increased risk of CP in offspring. https://doi.org/10.1289/EHP14742.
Collapse
Affiliation(s)
- Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
| | - Beate Ritz
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA
- Department of Neurology, School of Medicine, UCLA, Los Angeles, California, USA
| | - Joshua L. Warren
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
| | - Krystal Godri Pollitt
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
| | - Zeyan Liew
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
| |
Collapse
|
10
|
Pulay MÁ, Kornis K, Bednárikné Dörnyei G, Feketéné Szabó É, Horváth M, Matiscsák A, Nyakas C, Tenk Miklósné Zsebe A, Vissi T, Mayer Á, Túri I. Feasibility of Using Pulsed Electromagnetic Field Therapy to Improve the Dynamic Postural Balance of Children with Cerebral Palsy: A Randomized, Sham-Controlled Pilot Study. J Clin Med 2024; 14:192. [PMID: 39797275 PMCID: PMC11721189 DOI: 10.3390/jcm14010192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/26/2024] [Accepted: 12/28/2024] [Indexed: 01/13/2025] Open
Abstract
Cerebral palsy (CP) manifests with abnormal posture and impaired selective motor control, notably affecting trunk control and dynamic balance coordination, leading to inadequate postural control. Previous research has indicated the benefits of pulsed electromagnetic field (PEMF) therapy for various musculoskeletal and neurological conditions. Therefore, we conducted a randomized pilot study to assess the feasibility of our preliminary research design and examine the effect of the PEMF treatment among children with CP. Methods: Twelve children with spastic CP participated, with the study group undergoing PEMF treatment three times a week for four weeks. The treatment involved sine signal form, 20/200 Hz frequencies at an amplitude of 150 μT, initially administered for 8, 12, and 16 min per session. The control group received a sham treatment. Dynamic postural balance was evaluated using a force platform at baseline and post-intervention, and the data were analyzed. Data were processed using IBM SPSS 27 by repeated factorial analysis of variance. The significance level was α = 0.05. Results: No side effects of PEMF therapy were detected; this is important, because this intervention has not yet been applied among CP patients. The treatment group demonstrated a positive trend in fine balance coordination tests (p = 0.049); however, the small sample size and variability in control group performance suggest caution in interpreting these findings. Other test domains did not show significant differences. Conclusions: Our pilot study reveals the safety, feasibility, and potential efficacy of pulsed electromagnetic field (PEMF) therapy for children with cerebral palsy. With no observed side effects, the significant improvement in fine balance coordination suggests a promising avenue.
Collapse
Affiliation(s)
- Márk Ágoston Pulay
- Pető András Faculty, Semmelweis University, 1125 Budapest, Hungary
- Department of Ergonomics and Psychology, Faculty of Economic and Social Sciences, Budapest University of Technology and Economics, 1111 Budapest, Hungary
| | - Krisztina Kornis
- Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | | | | | - Mónika Horváth
- Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | - Attila Matiscsák
- Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | - Csaba Nyakas
- Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | | | - Tímea Vissi
- Pető András Faculty, Semmelweis University, 1125 Budapest, Hungary
| | - Ágnes Mayer
- Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | - Ibolya Túri
- Pető András Faculty, Semmelweis University, 1125 Budapest, Hungary
| |
Collapse
|
11
|
Prasad J, Van Steenwinckel J, Gunn AJ, Bennet L, Korzeniewski SJ, Gressens P, Dean JM. Chronic Inflammation Offers Hints About Viable Therapeutic Targets for Preeclampsia and Potentially Related Offspring Sequelae. Int J Mol Sci 2024; 25:12999. [PMID: 39684715 PMCID: PMC11640791 DOI: 10.3390/ijms252312999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
The combination of hypertension with systemic inflammation during pregnancy is a hallmark of preeclampsia, but both processes also convey dynamic information about its antecedents and correlates (e.g., fetal growth restriction) and potentially related offspring sequelae. Causal inferences are further complicated by the increasingly frequent overlap of preeclampsia, fetal growth restriction, and multiple indicators of acute and chronic inflammation, with decreased gestational length and its correlates (e.g., social vulnerability). This complexity prompted our group to summarize information from mechanistic studies, integrated with key clinical evidence, to discuss the possibility that sustained or intermittent systemic inflammation-related phenomena offer hints about viable therapeutic targets, not only for the prevention of preeclampsia, but also the neurobehavioral and other developmental deficits that appear to be overrepresented in surviving offspring. Importantly, we feel that carefully designed hypothesis-driven observational studies are necessary if we are to translate the mechanistic evidence into child health benefits, namely because multiple pregnancy disorders might contribute to heightened risks of neuroinflammation, arrested brain development, or dysconnectivity in survivors who exhibit developmental problems later in life.
Collapse
Affiliation(s)
- Jaya Prasad
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand; (J.P.); (A.J.G.); (L.B.); (J.M.D.)
| | | | - Alistair J. Gunn
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand; (J.P.); (A.J.G.); (L.B.); (J.M.D.)
| | - Laura Bennet
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand; (J.P.); (A.J.G.); (L.B.); (J.M.D.)
| | - Steven J. Korzeniewski
- C.S. Mott Center for Human Growth and Development, Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48202, USA
| | - Pierre Gressens
- Inserm, Neurodiderot, Université de Paris, 75019 Paris, France;
- Centre for the Developing Brain, Division of Imaging Sciences and Department of Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London SE1 7EH, UK
| | - Justin M. Dean
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand; (J.P.); (A.J.G.); (L.B.); (J.M.D.)
| |
Collapse
|
12
|
Suresh V, Gupta S, Khulbe Y, Shamim MA, Jain V, Jayan M, Waleed MS, Joe N, Sanker V, Gandhi AP, Alam A, Singh Malhotra H, Garg RK, Gulati S, Roy P, Bardhan M. Identification of Putative Biomarkers in Cerebral Palsy: A Meta-Analysis and Meta-Regression. Pediatr Neurol 2024; 161:43-54. [PMID: 39265434 DOI: 10.1016/j.pediatrneurol.2024.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/16/2024] [Accepted: 07/26/2024] [Indexed: 09/14/2024]
Abstract
BACKGROUND Cerebral palsy (CP) is a neurological disorder that impairs motor abilities. Identifying maternal biomarker derangements can facilitate further evaluation for early diagnosis, potentially leading to improved clinical outcomes. This study investigates the association between maternal biomarker derangements and CP development during the antenatal period. METHODS A systematic search was conducted in MEDLINE, EMBASE, and Cochrane databases, following MOOSE guidelines. Data on participants exceeding biomarker thresholds (95th and 5th percentiles) were extracted for combined odds ratio estimation. Geometric mean differences, reported as multiples of the median (MoMs), were used to analyze changes in marker levels. Trimesterwise subgroup analysis and metaregression assessed the impact of variables on outcomes. RESULTS Five observational studies (1552 cases, 484,985 controls) revealed lower maternal pregnancy-associated plasma protein A levels were associated with CP (pooled odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.22 to 2.09; I = 0%), with a -0.04 MoM geometric mean difference. Lower maternal beta-human chorionic gonadotropin (HCG) levels in first and second trimesters indicated a pooled OR = 1.18 (95% CI = 0.85 to 1.63; I = 57%). Sensitivity analysis showed an OR = 1.40 (95% CI = 1.08 to 1.82; I = 0%), with a -0.07 MoM geometric mean difference. Metaregression identified primigravida status as negatively influencing beta-HCG levels. Elevated nuchal translucency values and CP presented a pooled OR = 1.06 (95% CI = 0.77 to 1.44; I = 0%). CONCLUSION Lower maternal pregnancy-associated plasma protein A levels during the first trimester and lower beta-HCG levels in the first and second trimesters are associated with CP development in children. Future research should validate the predictive utility of these biomarkers and explore novel ones through large-scale cohort studies.
Collapse
Affiliation(s)
- Vinay Suresh
- King George's Medical University, Lucknow, India
| | - Shiva Gupta
- King George's Medical University, Lucknow, India
| | | | - Muhammad Aaqib Shamim
- Department of Pharmacology, All India Institute of Medical Sciences - Jodhpur, Jodhpur, India
| | - Vaibhav Jain
- Davao Medical School Foundation, Davao City, Philippines
| | - Malavika Jayan
- Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
| | | | - Neha Joe
- St. John's Medical College, Bengaluru, Karnataka, India
| | - Vivek Sanker
- Department of Neurosurgery, Trivandrum Medical College, Thiruvananthapuram, Kerala, India
| | - Aravind P Gandhi
- Assistant Professor, Department of Community Medicine, ESIC Medical College & Hospital, Hyderabad, India
| | - Areesha Alam
- Department of Pediatrics, King George's Medical University, Lucknow, India
| | - Hardeep Singh Malhotra
- Department of Neurology, King George's Medical University, Lucknow, India; Research Cell and Development, King George's Medical University, Lucknow, India
| | - Ravindra K Garg
- Department of Neurology, King George's Medical University, Lucknow, India; Head of Department, Department of Neurology, King George's Medical University, Lucknow, India
| | - Sheffali Gulati
- Child Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Priyanka Roy
- Directorate of Factories, Department of Labour, Kolkata, Government of West Bengal, India
| | - Mainak Bardhan
- Neuro Medical-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
| |
Collapse
|
13
|
Thys L, Beysen D, Ceulemans B, Kenis S, Dielman C, Roelens F, Reyniers E, Mateiu L, Janssens K, Meuwissen M. The Genetic Puzzle of Cerebral Palsy: Results of a Monocentric Study. Pediatr Neurol 2024; 161:1-8. [PMID: 39213953 DOI: 10.1016/j.pediatrneurol.2024.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 06/03/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Cerebral palsy (CP) is the most frequent cause of motor impairment in children. Although perinatal asphyxia was long considered to be the leading cause of CP, recent studies demonstrate its causation in only around one in 10 individuals with CP. Instead, genetic causes are increasingly demonstrated. We systematically performed clinical phenotyping and genetic investigations in a monocentric CP cohort, aiming to gain insight into the contribution of genetic variants in CP and its different subtypes. METHODS Chromosomal microarray and/or trio exome sequencing were systematically performed in 337 individuals with CP between September 2017 and August 2022. Deep phenotyping was performed through clinical multidisciplinary evaluation and review of medical files. RESULTS Genetic analyses resulted in an overall diagnostic yield of 38.3% (129 of 337). In cases with one or more comorbidities (intellectual disability, epilepsy, autism spectrum disorder), the yield increased to almost 50%. Functional enrichment analysis showed over-representation of the following pathways: genetic imprinting, DNA modification, liposaccharide metabolic process, neuron projection guidance, and axon development. CONCLUSIONS Genetic analyses in our CP cohort, the largest monocentric study to date, demonstrated a diagnostic yield of 38.3%, highlighting the importance of genetic testing in CP. The diagnosis of a genetic disorder is essential for prognosis and clinical follow-up, as well as for family counseling. Pathway analysis points to dysregulation of general developmental and metabolic processes as well as neuronal development and function. Unraveling the role of these pathways in CP pathogenesis is instrumental for the identification of CP candidate genes as well as potential therapeutic targets.
Collapse
Affiliation(s)
- Liene Thys
- Department of Pediatric Neurology, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Diane Beysen
- Department of Pediatric Neurology, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Berten Ceulemans
- Department of Pediatric Neurology, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Sandra Kenis
- Department of Pediatric Neurology, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Charlotte Dielman
- Department of Pediatrics, Queen Paola Children's Hospital, Wilrijk, Belgium
| | - Filip Roelens
- Department of Pediatrics, AZ Delta Hospital, Roeselare, Belgium
| | - Edwin Reyniers
- Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Ligia Mateiu
- Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Katrien Janssens
- Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium
| | - Marije Meuwissen
- Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem/Wilrijk, Belgium.
| |
Collapse
|
14
|
Wilson YA, Garrity N, Smithers-Sheedy H, Goldsmith S, Karim T, Henry G, Paget S, Kyriagis M, Badawi N, Baynam G, Gecz J, McIntyre S. Clinically Relevant Genes Identified in Cerebral Palsy Cohorts Following Evaluation of the Clinical Description and Phenotype: A Systematic Review. J Child Neurol 2024; 39:500-509. [PMID: 39246294 DOI: 10.1177/08830738241277231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
A growing number of genes have been identified in individuals with cerebral palsy (CP); however, many of these studies have poor compliance with the cerebral palsy clinical description. This systematic review aimed to assess the quality of the cerebral palsy clinical description/phenotype in cerebral palsy genetic studies published between 2010 and 2024 and report clinically relevant genes based on the quality of the cerebral palsy phenotype. An expert panel developed 6 criteria to review the reported cerebral palsy phenotype/description for each included study. Clinically relevant genes were extracted from each study and stratified into 2 tiers based on the quality. Eighteen studies were included. There was high confidence in the reported cerebral palsy description/phenotype from 8 studies. Of the initial 373 clinically relevant genes, 85 were tier II genes. Individual cerebral palsy motor disorder and phenotype data were absent for 349 of these individuals, limiting further analysis. The tier I gene list was composed of 6 genes: ATL1, COL4A1, GNAO1, KIF1A, SPAST, and TUBA1A. Bilateral spasticity was the most common motor disorder reported in individuals with variants in all 6 genes, and most individuals had accompanying conditions. Prioritizing the accurate reporting of motor and nonmotor phenotypes is crucial for future cerebral palsy genetic studies to further understand the underlying neurobiology.
Collapse
Affiliation(s)
- Yana A Wilson
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
- Children's Hospital Westmead Clinical School, Discipline of Child & Adolescent Health, University of Sydney, Sydney, New South Wales, Australia
| | - Natasha Garrity
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Hayley Smithers-Sheedy
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Shona Goldsmith
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Tasneem Karim
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Georgina Henry
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Simon Paget
- Child Population and Translational Health Research, Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Maria Kyriagis
- Rehab2Kids, Sydney Children's Hospital, Sydney, New South Wales, Australia
| | - Nadia Badawi
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
- Grace Centre for Newborn Intensive Care, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Gareth Baynam
- Western Australian Register of Developmental Anomalies, King Edward Memorial Hospital, Perth, Western Australia, Australia
- Rare Care Centre, Perth Children's Hospital, Perth, Western Australia, Australia
- Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| | - Jozef Gecz
- Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Sarah McIntyre
- Cerebral Palsy Alliance Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| |
Collapse
|
15
|
Patel DR, Bovid KM, Rausch R, Ergun-Longmire B, Goetting M, Merrick J. Cerebral palsy in children: A clinical practice review. Curr Probl Pediatr Adolesc Health Care 2024; 54:101673. [PMID: 39168782 DOI: 10.1016/j.cppeds.2024.101673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Abstract
Cerebral palsy is a disorder characterized by abnormal tone, posture, and movement. In clinical practice, it is often useful to approach cerebral palsy based on the predominant motor system findings - spastic hemiplegia, spastic diplegia, spastic quadriplegia, extrapyramidal or dyskinetic, and ataxic. The prevalence of cerebral palsy is between 1.5 and 3 per 1,000 live births with higher percentage of cases in low to middle income countries and geographic regions. Pre-term birth and low birthweight are recognized as the most frequent risk factors for cerebral palsy; other risk factors include hypoxic-ischemic encephalopathy, maternal infections, and multiple gestation. In most cases of cerebral palsy, the initial injury to the brain occurs during early fetal brain development. Intracerebral hemorrhage and periventricular leukomalacia are the main pathologic findings found in preterm infants who develop spastic cerebral palsy. The diagnosis of cerebral palsy is primarily based on clinical findings. Early recognition of infants at risk for cerebral palsy as well as those with cerebral palsy is possible based on a combination of clinical history, use of standardized neuromotor assessment and findings on magnetic resonance imaging; however, in clinical practice, cerebral palsy is more reliably diagnosed by 2 years of age. Magnetic resonance imaging scan is indicated to delineate the extent of brain lesions and to identify congenital brain malformations. Genetic testing and tests for inborn errors of metabolism are indicated to identify specific disorders, especially treatable disorders. Because cerebral palsy is associated with multiple associated and secondary medical conditions, its management requires a sustained and consistent collaboration among multiple disciplines and specialties. With appropriate support, most children with cerebral palsy grow up to be adults with good functional abilities.
Collapse
Affiliation(s)
- Dilip R Patel
- Neurodevelopmental Disabilities. Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States.
| | - Karen M Bovid
- Neurodevelopmental Disabilities. Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States; Department of Orthopedic Surgery and Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States
| | - Rebecca Rausch
- Neurodevelopmental Disabilities. Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States
| | - Berrin Ergun-Longmire
- Neurodevelopmental Disabilities. Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States
| | - Mark Goetting
- Department of Pediatric and Adolescent Medicine, Department of Medicine, Western Michigan University Homer Stryker MD School of Medicine, United States
| | - Joav Merrick
- National Institute of Child Health and Human Development, Israel; Professor of Pediatrics, Division of Pediatrics, Hadassah Hebrew University Medical Center, Kentucky; Children's Hospital, University of Kentucky, Lexington, United States; Professor of Public Health, Center for Healthy Development, School of Public Health, Georgia State University, Atlanta, United States
| |
Collapse
|
16
|
Eken MM, Langerak NG, du Toit J, Saywood M, Lamberts RP. Physical Health and Socioeconomic Status in Ambulatory Adults With Bilateral Spastic Cerebral Palsy. Rehabil Res Pract 2024; 2024:8368191. [PMID: 39502305 PMCID: PMC11537745 DOI: 10.1155/2024/8368191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 09/18/2024] [Accepted: 09/24/2024] [Indexed: 11/08/2024] Open
Abstract
Socioeconomic status (SES) tends to influence an individual's access to health care. It is commonly assumed that a poorer SES is associated with a weaker physical health status, especially in disadvantaged populations such as people with cerebral palsy (CP). However, to our knowledge, no study has looked at this assumption. Therefore, the aim of this study was to describe and compare the physical health status of ambulant adults with bilateral CP with different SES backgrounds. In addition, the physical health status of the ambulatory adults with CP was compared to well-matched, typically developing adults. Twenty-eight ambulatory adults with CP (gross motor functional classification system Level I/II/III: n = 11/12/5; SES low/middle/high: n = 10/9/9), and 28 matched typically developing adults were recruited for this study. No differences were observed between adults with CP from different SES backgrounds. Differences in physical health status between typically developing adults and ambulatory adults with CP in all SES backgrounds were found in passive range of motion (p < 0.05), muscle strength (p < 0.001), selectivity (p < 0.001), and muscle tone (p < 0.001) and balance (p < 0.05). The main finding of this study is that physical health status did not differ between ambulatory adults with CP from different SES backgrounds. This finding shows that SES does not always directly impact physical health status in ambulatory adults with CP and highlights the importance of an individual approach. Future research should determine the impact of SES on nonambulatory adults with CP.
Collapse
Affiliation(s)
- Maaike M. Eken
- Division of Orthopaedic Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
- Division of Sport and Exercise Medicine, Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
| | - Nelleke G. Langerak
- Neuroscience Institute and Division of Neurosurgery, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- Department of Research, Sint Maartenskliniek, Nijmegen, The Netherlands
| | - Jacques du Toit
- Division of Orthopaedic Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
| | - Melanie Saywood
- Orthopaedic, Sports and Rehabilitation Center, Linksfield Hospital, Johannesburg, South Africa
| | - Robert P. Lamberts
- Division of Orthopaedic Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
- Division of Movement Science and Exercise Therapy (MSET), Department of Exercise, Sport and Lifestyle Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| |
Collapse
|
17
|
Sanches E, Ho D, van de Looij Y, Aebi Toulotte A, Baud L, Bouteldja F, Barraud Q, Araneda R, Bleyenheuft Y, Brochard S, Kathe C, Courtine G, Sizonenko S. Early intensive rehabilitation reverses locomotor disruption, decrease brain inflammation and induces neuroplasticity following experimental Cerebral Palsy. Brain Behav Immun 2024; 121:303-316. [PMID: 39098438 DOI: 10.1016/j.bbi.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/17/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND Cerebral Palsy (CP) is a major cause of motor and cognitive disability in children due to injury to the developing brain. Early intensive sensorimotor rehabilitation has been shown to change brain structure and reduce CP symptoms severity. We combined environmental enrichment (EE) and treadmill training (TT) to observe the effects of a one-week program of sensorimotor stimulation (EETT) in animals exposed to a CP model and explored possible mechanisms involved in the functional recovery. METHODS Pregnant Wistar rats were injected with Lipopolysaccharide (LPS - 200 µg/kg) intraperitoneally at embryonic days 18 and 19. At P0, pups of both sexes were exposed to 20' anoxia at 37 °C. From P2 to P21, hindlimbs were restricted for 16 h/day during the dark cycle. EETT lasted from P21 to P27. TT - 15 min/day at 7 cm/s. EE - 7 days in enriched cages with sensorimotor stimulus. Functional 3D kinematic gait analysis and locomotion were analyzed. At P28, brains were collected for ex-vivo MRI and histological assessment. Neurotrophins and key proteins involved in CNS function were assessed by western blotting. RESULTS CP model caused gross and skilled locomotor disruption and altered CNS neurochemistry. EETT reversed locomotor dysfunction with minor effects over gait kinematics. EETT also decreased brain inflammation and glial activation, preserved myelination, upregulated BDNF signaling and modulated the expression of proteins involved in excitatory synaptic function in the brain and spinal cord. CONCLUSIONS Using this translational approach based on intensive sensorimotor rehabilitation, we highlight pathways engaged in the early developmental processes improving neurological recovery observed in CP.
Collapse
Affiliation(s)
- Eduardo Sanches
- Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland
| | - Dini Ho
- Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland
| | - Yohan van de Looij
- Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland; Center for Biomedical Imaging (CIBM), Animal Imaging Technology Section, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Audrey Aebi Toulotte
- Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland
| | - Laetitia Baud
- Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Farha Bouteldja
- Department of Fundamental Neurosciences, University of Lausanne (Unil), Switzerland
| | - Quentin Barraud
- Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Rodrigo Araneda
- Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium; Exercise and Rehabilitation Science Institute, Faculty of Rehabilitation Science, Universidad Andres Bello, Santiago, Chile
| | - Yannick Bleyenheuft
- Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
| | - Sylvain Brochard
- Physical and Medical Rehabilitation Department, CHRU Brest, Brest, France; Paediatric Physical and Medical Rehabilitation Department, Fondation ILDYS, Brest, France; University of Western Brittany, Laboratory of Medical Information Processing, Inserm U1101, Brest, France
| | - Claudia Kathe
- Department of Fundamental Neurosciences, University of Lausanne (Unil), Switzerland
| | - Grégoire Courtine
- Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Stéphane Sizonenko
- Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland.
| |
Collapse
|
18
|
Lyu J, Zhang X, Xiong S, Wu H, Han J, Xie Y, Qiu F, Yang Z, Huang C. Different care mode alter composition and function of gut microbiota in cerebral palsy children. Front Pediatr 2024; 12:1440190. [PMID: 39239470 PMCID: PMC11374594 DOI: 10.3389/fped.2024.1440190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 07/26/2024] [Indexed: 09/07/2024] Open
Abstract
Introduction Specialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota. Methods Fecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed. Results There was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P < 0.05), and a significant decrease in the abundance of opportunistic pathogens Prevotella, Clostridium cluster IV, Oscillibacter, and Fusobacterium (P < 0.05). Additionally, lipid metabolism, carbohydrate metabolism, transcription, cellular processes and signaling, and membrane transport were significantly upregulated in the observation group. Lipid metabolism was positively correlated with Bacteroides and Lachnospiracea incertae sedis, indicating a positive impact of the family-centered care mode on bacterial metabolism processes. Discussion This study highlights that the family-centered care mode had a positive impact on the composition and function of the gut microbiota. The study provides valuable insights into the relationship between care mode and gut microbiota, which can inspire the development of interventions for cerebral palsy.
Collapse
Affiliation(s)
- Jinli Lyu
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Xiaowei Zhang
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Shenghua Xiong
- Department of Pediatrics, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, China
| | - Hui Wu
- Department of Pediatrics, Hexian Memorial Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Jing Han
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Yongjie Xie
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Feifeng Qiu
- Department of Critical Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Zhenyu Yang
- Department of Microbial Research, WeHealthGene Institute, Joint Laboratory of Micro-Ecology and Children's Health, Shenzhen Children's Hospital, Shenzhen WeHealthGene Co., Ltd., Shenzhen, China
| | - Congfu Huang
- Department of Pediatrics, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, China
| |
Collapse
|
19
|
Mayston MJ, Saloojee GM, Foley SE. ボバースフレームワーク:をむのにするシステマチックサイエンスのアプローチ. Dev Med Child Neurol 2024; 66:e112-e119. [PMID: 38239103 DOI: 10.1111/dmcn.15851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/05/2024]
Abstract
要旨現在、発達領域で推奨されているボバース臨床推論フレームワーク(Bobath Clinical Reasoning Framework: BCRF)によるボバース実践を、システム科学のレンズによって概念化し、小児期発症の障害に関連する様々な変数の相互関係・相関依存に対する全人的観点を提供する。BCRFはICFの各領域間の関係性を理解し、それぞれがどのように影響を与え、どのように影響を受けるのかを理解する助けとなる臨床推論の詳細なフレームワークである。BCRFは介入計画へとつながる観察に基づく学際的なシステムであり、実践的な推論のアプローチである。BCRFにより脳性麻痺(Cerebral Palsy: CP)などの障害における複雑な状況を全人的に理解し、神経学的障害がある人々の生涯にわたるマネジメントおよびハビリテーションの基盤を持つことができる。BCRFが用いる臨床推論は、個々人およびその社会的環境、とくに家族単位で見られる重要な文脈的要因を重視している。定型発達・非定型発達、病態生理(感覚運動・認知・行動)、神経科学の相互関連性、および、心身機能・身体構造レベルの構成要素がどのように活動・参加レベルに影響を与えるのか、BCRFはその理解に根差している。BCRFにとって不可欠なシステム科学system science※1)のモデルはCPの複雑性を理解および対応を進める有用な方法であり、何よりも大切な目標とはあらゆる文脈であらゆる個々人の生きた経験を最適化することである。.
Collapse
Affiliation(s)
| | - Gillian M Saloojee
- Department of Physiotherapy, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sarah E Foley
- Kids Plus Foundation, Deakin University, Melbourne, VIC, Australia
| |
Collapse
|
20
|
Marinelli T, Yi JX, O'Shea TM, Joseph RM, Hooper SR, Kuban KCK, Sakai C, Msall ME, Fry R, Singh R. Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years. J Pediatr 2024; 271:114037. [PMID: 38580191 PMCID: PMC11239312 DOI: 10.1016/j.jpeds.2024.114037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/26/2024] [Accepted: 03/26/2024] [Indexed: 04/07/2024]
Abstract
OBJECTIVE To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.
Collapse
Affiliation(s)
- Timothy Marinelli
- Department of Pediatrics, Tufts University School of Medicine, Boston, MA
| | - Joe X Yi
- Frank Porter Graham Child Development Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - T Michael O'Shea
- Frank Porter Graham Child Development Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Robert M Joseph
- Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA
| | - Stephen R Hooper
- Frank Porter Graham Child Development Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Karl C K Kuban
- Department of Pediatrics and Neurology, Boston Medical Center, Boston, MA
| | - Christina Sakai
- Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA
| | - Michael E Msall
- Department of Pediatrics, Kennedy Research Center and Comer Children's Hospital, The University of Chicago Pritzker School of Medicine, Chicago, IL
| | - Rebecca Fry
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC
| | - Rachana Singh
- Department of Pediatrics, Tufts University School of Medicine, Boston, MA.
| |
Collapse
|
21
|
Mayston MJ, Saloojee GM, Foley SE. Le cadre de raisonnement clinique Bobath: un modèle de science des systèmes pour aborder la complexité des troubles neurodéveloppementaux, y compris la paralysie cérébrale. Dev Med Child Neurol 2024; 66:e84-e92. [PMID: 38351502 DOI: 10.1111/dmcn.15866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/22/2024]
Abstract
RésuméLa pratique Bobath actuelle telle qu'elle est recommandée dans le cadre du Bobath Clinical Reasoning Framework (BCRF) se base sur une application clinique de la science des systèmes. Elle offre une perspective holistique des relations entre les variables qui sont associées à l'apparition d'un handicap chez l'enfant. Le BCRF est un cadre de raisonnement clinique qui peut aider à comprendre les relations entre les domaines de la Classification Internationale du Fonctionnement, du Handicap et de la Santé. C'est un système d'observation transdisciplinaire de raisonnement pratique qui vise à proposer un plan d'intervention. Plus généralement, le BCRF permet une compréhension holistique de la complexité des situations associées à des troubles tels que la paralysie cérébrale et indique des choix d'adaptation et de prise en charge tout au long de la vie des personnes vivant avec des troubles neurologiques. Ce raisonnement clinique se base sur les facteurs contextuels importants de l'individu et de son environnement social, principalement la cellule familiale, et sur une compréhension des relations entre le développement typique et atypique, la physiopathologie (sensorimotrice, cognitive, comportementale) et les neurosciences, ainsi que sur l'impact des fonctions et des structures corporelles sur les activités et la participation. Le modèle de la science des systèmes du BCRF permet d'aborder la complexité de la paralysie cérébrale, avec l'objectif global d'optimiser l'expérience vécue par chaque individu dans chaque contexte.
Collapse
Affiliation(s)
- Margaret J Mayston
- Division des biosciences, University College London, Londres, Royaume-Uni
| | - Gillian M Saloojee
- Département de physiothérapie, Faculté des sciences de la santé, Université des Pays-Bas, Londres, Royaume-Uni. des sciences de la santé, Université du Witwatersrand, Johannesburg, Afrique du Sud
| | - Sarah E Foley
- Kids Plus Foundation, Deakin University, Melbourne, VIC, Australie
| |
Collapse
|
22
|
Mayston MJ, Saloojee GM, Foley SE. El marco de razonamiento clínico de Bobath: Un modelo de ciencia de sistemas para abordar la complejidad de los trastornos del neurodesarrollo incluida la parálisis cerebral. Dev Med Child Neurol 2024; 66:e120-e129. [PMID: 38113324 DOI: 10.1111/dmcn.15812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 07/31/2023] [Indexed: 12/21/2023]
Abstract
ResumenLa actual práctica de desarrollo Bobath recomendada dentro del Marco de Razonamiento Clínico Bobath (BCRF) puede conceptualizarse utilizando la visión de la ciencia de los sistemas. Proporciona, así, una perspectiva holística de la interrelación e interconexión de las variables asociadas con la discapacidad aparecida durante la infancia. El BCRF se define como un marco exhaustivo de razonamiento clínico que puede aplicarse para ayudar a comprender las relaciones entre los dominios de la Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud, cómo se puede influir en esos dominios y cómo influyen entre sí. El BCRF es un sistema de observación transdisciplinario y de razonamiento práctico que da lugar a un plan de intervención. Esto proporciona una comprensión holística de la complexidad de las situaciones asociadas a trastornos como la parálisis cerebral (PC) y la base para la gestión y habilitación a lo largo de la vida de personas que viven con trastornos neurológicos. El razonamiento clínico utilizado por el BCRF se basa en los importantes factores contextuales del individuo y su entorno social, principalmente la unidad familiar. Se basa en la comprensión de las interrelaciones entre el desarrollo típico y atípico, la fisiopatología (sensoriomotora, cognitiva, conductual) y la neurociencia, así como el impacto de funciones y estructuras corporales sobre la actividad y la participación. El modelo de ciencia de sistemas del BCRF es una forma útil de comprender y responder a la complejidad de la parálisis cerebral, con el objetivo global de optimizar la experiencia vivida de todo individuo en cualquier contexto.
Collapse
Affiliation(s)
| | - Gillian M Saloojee
- Department of Physiotherapy, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sarah E Foley
- Kids Plus Foundation, Deakin University, Melbourne, VIC, Australia
| |
Collapse
|
23
|
Tillberg E, Persson JKE. Hemiplegic (unilateral) cerebral palsy in northern Stockholm: Intellectual disability and epilepsy. Seizure 2024; 120:110-115. [PMID: 38941801 DOI: 10.1016/j.seizure.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 06/30/2024] Open
Abstract
PURPOSE The purpose of this study was to describe intellectual disability and its association with epilepsy and brain imaging, in a population-based group of children with hemiplegic (unilateral) cerebral palsy, previously investigated and published in 2020. MATERIALS AND METHODS Forty-seven children of school age in northern Stockholm, fulfilling the Surveillance of Cerebral Palsy in Europe-criteria of hemiplegic (unilateral spastic) cerebral palsy, were invited to participate in the study. Twenty-one children consented to participate. A WISC (Wechsler Intelligence Scale for Children)-test was performed by an experienced psychologist. RESULTS In the study population of twenty-one children, 57 % (n 12) displayed uneven cognitive profiles, 38 % (n 8) intellectual disability and 62 % (n 13) had a normal IQ. 43 % (n 9) developed epilepsy. Children with extensive brain lesions had more severe intellectual disability. CONCLUSIONS In this study intellectual disability and/or epilepsy were associated with the type and extent of the underlying brain lesion. Intellectual disability and uneven cognitive profiles were common. We therefore recommend individual cognitive assessment to ensure an optimal school start.
Collapse
Affiliation(s)
- Elsa Tillberg
- Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
| | - Jonas K E Persson
- Department of Clinical Neurophysiology, Karolinska University Hospital, Eugeniavägen 11 SE-171 76 Stockholm, Sweden
| |
Collapse
|
24
|
Mayston MJ, Saloojee GM, Foley SE. O Quadro de Raciocínio Clínico Bobath: Uma abordagem de ciência de sistemas para a complexidade das condições do neurodesenvolvimento, incluindo a paralisia cerebral. Dev Med Child Neurol 2024; 66:e102-e111. [PMID: 38303632 DOI: 10.1111/dmcn.15877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Esta revisão descreve um modelo de prática pediátrica recomendada do Bobath, o Quadro de Raciocínio Clínico Bobath (QRCB), e explica como esse conhecimento contribui para a área de habilitação em distúrbios pediátricos. A ciência de sistemas proporciona uma nova maneira de concetualizar a paralisia cerebral como uma condição complexa. Ela foi aplicada ao QRCB para ilustrar uma perspetiva holística sobre a inter-relação e interconexão das variáveis associadas à PC. O modelo de ciência de sistemas adotado pelo QRCB é uma forma promissora de construir uma estrutura abrangente que engloba a complexidade da PC e possibilitará pesquisas mais robustas.
Collapse
Affiliation(s)
- Margaret J Mayston
- Divisão de Ciências Biológicas, University College London, Londres, Reino Unido
| | - Gillian M Saloojee
- Departamento de Fisioterapia, Faculdade de Ciências da Saúde, University of the Witwatersrand, Joanesburgo, África do Sul
| | - Sarah E Foley
- Kids Plus Foundation, Deakin University, Melbourne, VIC, Austrália
| |
Collapse
|
25
|
Mayston MJ, Saloojee GM, Foley SE. Bobath Klinik Gerekçelendirme Çerçevesi: Serebral palsi dahil nörogelişimsel durumların karmaşıklığında sistemler bilimi yaklaşımı. Dev Med Child Neurol 2024; 66:e93-e101. [PMID: 38343079 DOI: 10.1111/dmcn.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/05/2024]
Abstract
ÖzetBobath Klinik Gerekçelendirme Çerçevesi (BKGÇ) içerisindeki önerilen güncel gelişimsel Bobath uygulaması sistemler bilimi merceği kullanılarak kavramsallaştırılabilir ve bunu çocukluk çağı engelliliği ile ilişkilendirilen değişkenlerin birbirine bağlılığı ve etkileşimine bütüncül bir bakış açısıyla sağlar. BKGÇ, İşlevsellik, Yetiyitimi ve Sağlığın Uluslararası Sınıflandırması (ICF)’nın alt boyutları arasındaki ilişkiyi ve bu alt boyutların birbirini nasıl etkilediğini anlamak için uygulanabilen derinlemesine bir klinik gerekçelendirme çerçevesi olarak tanımlanmaktadır. BKGÇ, bir tedavi planı ile sonuçlanan klinik gerekçelendirme ve transdisipliner gözlemsel bir sistemdir. Bu sistem ise, serebral palsi (SP) gibi bozuklukların karmaşıklığını anlamak için bütüncül bir anlayış sunar ve nörolojik bozukluğu olan bireylerin yaşam boyu tedavisi ve rehabilitasyonu için temel oluşturur. BKGÇ tarafından kullanılan klinik gerekçelendirme, başta aile birimi olmak üzere bireyin ve sosyal çevresinin önemli bağlamsal faktörlerine dayanmaktadır. Tipik ve atipik gelişim, patofizyoloji (sensorimotor, bilişsel, davranışsal) ve sinirbilim arasındaki karşılıklı ilişkilerin ve bu vücut yapı ve fonksiyonlarının aktivite ve katılım üzerindeki etkisinin anlaşılmasına dayanır. BKGÇ'nin ayrılmaz bir parçası olan sistemler bilimi modeli, SP'nin karmaşıklığını anlamak ve buna yanıt vermek için yararlı bir yoldur; kapsayıcı hedef, herhangi bir bağlamda herhangi bir bireyin yaşadığı deneyimi optimize etmektir.
Collapse
Affiliation(s)
- Margaret J Mayston
- Biyobilimler Bölümü, Londra College Üniversitesi, Londra, Birleşik Krallık
| | - Gillian M Saloojee
- Fizyoterapi Bölümü, Sağlık Bilimleri Fakültesi, Witwatersrand Üniversitesi, Johannesburg, Güney Afrika
| | - Sarah E Foley
- Kids Plus Vakfı, Deakin Üniversitesi, Melbourne, VIC, Avustralya
| |
Collapse
|
26
|
Saranti A, Dragoumi P, Papavasiliou A, Zafeiriou D. Current approach to cerebral palsy. Eur J Paediatr Neurol 2024; 51:49-57. [PMID: 38824721 DOI: 10.1016/j.ejpn.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 05/26/2024] [Accepted: 05/28/2024] [Indexed: 06/04/2024]
Abstract
This teaching review aims to provide an overview of the current approach to children with cerebral palsy (CP), retrieving the best available evidence and summarizing existing knowledge in the field of CP in children. We also highlight areas where more research is needed and novel strategies for diagnosing and treating cerebral palsy. CP includes a group of permanent disorders of movement and posture that cause activity limitation. Multiple risk factors, occurring preconceptionally, prenatally, perinatally, or postneonatally, are involved in the pathogenesis of CP, with the prenatal ones accounting for 80-90 % of cases. Due to its heterogeneity, CP has various classifications, but usually is classified based on clinical findings and motor impairment. Standardized function classification systems have been developed to address inconsistencies in previous classifications. The combination of clinical assessment and validated predictive tools is recommended for an early diagnosis, which is important for early intervention and prevention of secondary impairments. The therapeutic regimen in CP involves prevention and management of the motor and associated problems. It includes the enhancement of motor performance, the enrichment of cognition and communication skills, the prevention of secondary impairments, and the support of parents and caregivers. The care of CP children demands a multidisciplinary approach focused on improving motor skills, reducing comorbidities, enhancing the quality of life, and prolonging survival.
Collapse
Affiliation(s)
- Anna Saranti
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece
| | - Pinelopi Dragoumi
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece
| | | | - Dimitrios Zafeiriou
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece.
| |
Collapse
|
27
|
Zhang Y, Hu Y, Talarico R, Qiu X, Schwartz J, Fell DB, Oskoui M, Lavigne E, Messerlian C. Prenatal Exposure to Ambient Air Pollution and Cerebral Palsy. JAMA Netw Open 2024; 7:e2420717. [PMID: 38980674 PMCID: PMC11234239 DOI: 10.1001/jamanetworkopen.2024.20717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 04/25/2024] [Indexed: 07/10/2024] Open
Abstract
Importance Air pollution is associated with structural brain changes, disruption of neurogenesis, and neurodevelopmental disorders. The association between prenatal exposure to ambient air pollution and risk of cerebral palsy (CP), which is the most common motor disability in childhood, has not been thoroughly investigated. Objective To evaluate the associations between prenatal residential exposure to ambient air pollution and risk of CP among children born at term gestation in a population cohort in Ontario, Canada. Design, Setting, and Participants Population-based cohort study in Ontario, Canada using linked, province-wide health administrative databases. Participants were singleton full term births (≥37 gestational weeks) born in Ontario hospitals between April 1, 2002, and March 31, 2017. Data were analyzed from January to December 2022. Exposures Weekly average concentrations of ambient fine particulate matter with a diameter 2.5 μm (PM2.5) or smaller, nitrogen dioxide (NO2), and ozone (O3) during pregnancy assigned by maternal residence reported at delivery from satellite-based estimates and ground-level monitoring data. Main outcome and measures CP cases were ascertained by a single inpatient hospitalization diagnosis or at least 2 outpatient diagnoses for children from birth to age 18 years. Results The present study included 1 587 935 mother-child pairs who reached term gestation, among whom 3170 (0.2%) children were diagnosed with CP. The study population had a mean (SD) maternal age of 30.1 (5.6) years and 811 745 infants (51.1%) were male. A per IQR increase (2.7 μg/m3) in prenatal ambient PM2.5 concentration was associated with a cumulative hazard ratio (CHR) of 1.12 (95% CI, 1.03-1.21) for CP. The CHR in male infants (1.14; 95% CI, 1.02-1.26) was higher compared with the CHR in female infants (1.08; 95% CI, 0.96-1.22). No specific window of susceptibility was found for prenatal PM2.5 exposure and CP in the study population. No associations or windows of susceptibility were found for prenatal NO2 or O3 exposure and CP risk. Conclusions and relevance In this large cohort study of singleton full term births in Canada, prenatal ambient PM2.5 exposure was associated with an increased risk of CP in offspring. Further studies are needed to explore this association and its potential biological pathways, which could advance the identification of environmental risk factors of CP in early life.
Collapse
Affiliation(s)
- Yu Zhang
- Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts
| | - Yuhong Hu
- Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts
| | - Robert Talarico
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
| | - Xinye Qiu
- Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts
| | - Joel Schwartz
- Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Deshayne B. Fell
- School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
- ICES, Ottawa, Ontario, Canada
- Now with Pfizer, Kirkland, Quebec, Canada
| | - Maryam Oskoui
- Department of Pediatrics, McGill University, Montreal, Quebec, Canada
- Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
| | - Eric Lavigne
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
- ICES, Ottawa, Ontario, Canada
| | - Carmen Messerlian
- Department of Environmental Health, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
- Massachusetts General Hospital Fertility Center, Department of Obstetrics and Gynecology, Boston
| |
Collapse
|
28
|
Micheletti S, Galli J, Vezzoli M, Scaglioni V, Agostini S, Calza S, Merabet LB, Fazzi E. Academic skills in children with cerebral palsy and specific learning disorders. Dev Med Child Neurol 2024; 66:778-792. [PMID: 37990438 DOI: 10.1111/dmcn.15808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 09/02/2023] [Accepted: 10/17/2023] [Indexed: 11/23/2023]
Abstract
AIM To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment. METHOD A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses. RESULTS About 59% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups. INTERPRETATION Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal. WHAT THIS PAPER ADDS Reading, writing, and mathematics disorders in cerebral palsy have specific clinical characteristics. Their underlying mechanisms differ from those described in specific learning disorders. Working memory impairment can be considered a hallmark of learning disorders in children with cerebral palsy.
Collapse
Affiliation(s)
- Serena Micheletti
- Unit of Child Neurology and Psychiatry, ASST Spedali Civili of Brescia, Brescia, Italy
| | - Jessica Galli
- Unit of Child Neurology and Psychiatry, ASST Spedali Civili of Brescia, Brescia, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Marika Vezzoli
- Unit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Vera Scaglioni
- Unit of Child Neurology and Psychiatry, ASST Spedali Civili of Brescia, Brescia, Italy
| | - Stefania Agostini
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Stefano Calza
- Unit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Lotfi B Merabet
- Laboratory for Visual Neuroplasticity, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
| | - Elisa Fazzi
- Unit of Child Neurology and Psychiatry, ASST Spedali Civili of Brescia, Brescia, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| |
Collapse
|
29
|
Shepherd ES, Goldsmith S, Doyle LW, Middleton P, Marret S, Rouse DJ, Pryde P, Wolf HT, Crowther CA. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024; 5:CD004661. [PMID: 38726883 PMCID: PMC11082932 DOI: 10.1002/14651858.cd004661.pub4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/13/2024]
Abstract
BACKGROUND Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.
Collapse
Affiliation(s)
- Emily S Shepherd
- SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Shona Goldsmith
- Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Lex W Doyle
- Department of Obstetrics, Gynaecology and Newborn Health, The University of Melbourne, Melbourne, Australia
| | - Philippa Middleton
- SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Stéphane Marret
- INSERM Unit 1245, Team 4, Rouen School of Medicine, Normandy University, Rouen, France
- Department of Neonatal Pediatrics, Intensive Care, and Neuropediatrics, Rouen University Hospital, Rouen, France
| | - Dwight J Rouse
- Women & Infants Hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Peter Pryde
- Department of Anesthesiology, The University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Hanne T Wolf
- Department of Gynaecology and Obstetrics, Hvidovre University Hospital, Hvidovre, Denmark
| | | |
Collapse
|
30
|
Mayston MJ, Saloojee GM, Foley SE. The Bobath Clinical Reasoning Framework: A systems science approach to the complexity of neurodevelopmental conditions, including cerebral palsy. Dev Med Child Neurol 2024; 66:564-572. [PMID: 37653669 DOI: 10.1111/dmcn.15748] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 05/04/2023] [Accepted: 07/31/2023] [Indexed: 09/02/2023]
Abstract
The current recommended developmental Bobath practice within the Bobath Clinical Reasoning Framework (BCRF) can be conceptualized using the lens of systems science, thereby providing a holistic perspective on the interrelatedness and interconnectedness of the variables associated with childhood-onset disability. The BCRF is defined as an in-depth clinical reasoning framework that can be applied to help understand the relationships between the domains of the International Classification of Functioning, Disability and Health, how those domains can be influenced, and how they impact each other. The BCRF is a transdisciplinary observational system and practical reasoning approach that results in an intervention plan. This provides a holistic understanding of the complexity of situations associated with disorders such as cerebral palsy (CP) and the basis for the lifelong management and habilitation of people living with neurological disorders. The clinical reasoning used by the BCRF draws on the important contextual factors of the individual and their social environment, primarily the family unit. It is rooted in an understanding of the interrelationships between typical and atypical development, pathophysiology (sensorimotor, cognitive, behavioural), and neuroscience, and the impact of these body structure and function constructs on activity and participation. The systems science model integral to the BCRF is a useful way forward in understanding and responding to the complexity of CP, the overarching goal being to optimize the lived experience of any individual in any context.
Collapse
Affiliation(s)
| | - Gillian M Saloojee
- Department of Physiotherapy, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sarah E Foley
- Kids Plus Foundation, Deakin University, Melbourne, VIC, Australia
| |
Collapse
|
31
|
Moll I, Marcellis RGJ, Fleuren SM, Coenen MLP, Senden RHJ, Willems PJB, Speth LAWM, Witlox MA, Meijer K, Vermeulen RJ. Functional electrical stimulation during walking in children with unilateral spastic cerebral palsy: A randomized cross-over trial. Dev Med Child Neurol 2024; 66:598-609. [PMID: 37823431 DOI: 10.1111/dmcn.15779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 09/03/2023] [Accepted: 09/07/2023] [Indexed: 10/13/2023]
Abstract
AIM To study if functional electrical stimulation (FES) of the peroneal nerve, which activates dorsiflexion, can improve body functions, activities, and participation and could be an effective alternative treatment in individuals with unilateral spastic cerebral palsy (CP). METHOD A randomized cross-over trial was performed in 25 children with unilateral spastic CP (classified in Gross Motor Function Classification System levels I and II) aged 4 to 18 years (median age at inclusion 9 years 8 months, interquartile range = 7 years-13 years 8 months), 15 patients were male. The study consisted of two 12-week blocks of treatment, that is, conventional treatment (ankle foot orthosis [AFO] or adapted shoes) and FES, separated by a 6-week washout period. Outcome measures included the Goal Attainment Scale (GAS), the Cerebral Palsy Quality of Life questionnaire, and a three-dimensional gait analysis. RESULTS Eighteen patients completed the trial. The proportion of GAS goals achieved was not significantly higher in the FES versus the conventional treatment phase (goal 1 p = 0.065; goal 2 p = 1.00). When walking while stimulated with FES, ankle dorsiflexion during mid-swing decreased over time (p = 0.006, average decrease of 4.8° with FES), with a preserved increased ankle range of motion compared to conventional treatment (p < 0.001, mean range of motion with FES +10.1° compared to AFO). No changes were found in the standard physical examination or regarding satisfaction with orthoses and feelings about the ability to dress yourself. In four patients, FES therapy failed; in 12 patients FES therapy continued after the trial. INTERPRETATION FES is not significantly worse than AFO; however, patient selection is critical, and a testing period and thorough follow-up are needed.
Collapse
Affiliation(s)
- Irene Moll
- School of Mental Health and Neurosciences, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
- Department of Nutrition and Movement Sciences, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
- Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Rik G J Marcellis
- Department of Physiotherapy, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Sabine M Fleuren
- Department of Physiotherapy, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Marcel L P Coenen
- Adelante, Center of Expertise in Rehabilitation and Audiology, the Netherlands
| | - Rachel H J Senden
- Department of Physiotherapy, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Paul J B Willems
- Department of Nutrition and Movement Sciences, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | | | - M Adhiambo Witlox
- Department of Orthopedics, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Kenneth Meijer
- Department of Nutrition and Movement Sciences, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - R Jeroen Vermeulen
- School of Mental Health and Neurosciences, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
- Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands
| |
Collapse
|
32
|
Wang Y, Xu Y, Zhou C, Cheng Y, Qiao N, Shang Q, Xia L, Song J, Gao C, Qiao Y, Zhang X, Li M, Ma C, Fan Y, Peng X, Wu S, Lv N, Li B, Sun Y, Zhang B, Li T, Li H, Zhang J, Su Y, Li Q, Yuan J, Liu L, Moreno-De-Luca A, MacLennan AH, Gecz J, Zhu D, Wang X, Zhu C, Xing Q. Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy. Nat Med 2024; 30:1395-1405. [PMID: 38693247 DOI: 10.1038/s41591-024-02912-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 03/06/2024] [Indexed: 05/03/2024]
Abstract
Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.
Collapse
Affiliation(s)
- Yangong Wang
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
| | - Yiran Xu
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Chongchen Zhou
- Rehabilitation Department, Henan Key Laboratory of Child Genetics and Metabolism, Children's Hospital of Zhengzhou University, Zhengzhou, China
| | - Ye Cheng
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
- Shanghai Center for Women and Children's Health, Shanghai, China
| | - Niu Qiao
- State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine (Shanghai), and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Qing Shang
- Rehabilitation Department, Henan Key Laboratory of Child Genetics and Metabolism, Children's Hospital of Zhengzhou University, Zhengzhou, China
| | - Lei Xia
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Juan Song
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Chao Gao
- Rehabilitation Department, Henan Key Laboratory of Child Genetics and Metabolism, Children's Hospital of Zhengzhou University, Zhengzhou, China
| | - Yimeng Qiao
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Xiaoli Zhang
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Ming Li
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Caiyun Ma
- Rehabilitation Department, Henan Key Laboratory of Child Genetics and Metabolism, Children's Hospital of Zhengzhou University, Zhengzhou, China
| | - Yangyi Fan
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
| | - Xirui Peng
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Silin Wu
- Department of Neurosurgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, China
| | - Nan Lv
- Rehabilitation Department, Henan Key Laboratory of Child Genetics and Metabolism, Children's Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingbing Li
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Yanyan Sun
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Bohao Zhang
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Tongchuan Li
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Hongwei Li
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Jin Zhang
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
- Shanghai Center for Women and Children's Health, Shanghai, China
| | - Yu Su
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
| | - Qiaoli Li
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
| | - Junying Yuan
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Lei Liu
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China
| | - Andres Moreno-De-Luca
- Department of Radiology, Neuroradiology Section, Kingston Health Sciences Centre, Queen's University Faculty of Health Sciences, Kingston, Ontario, Canada
| | - Alastair H MacLennan
- Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
| | - Jozef Gecz
- Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
| | - Dengna Zhu
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Xiaoyang Wang
- Centre for Perinatal Medicine and Health, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Changlian Zhu
- Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China.
| | - Qinghe Xing
- Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China.
- Shanghai Center for Women and Children's Health, Shanghai, China.
| |
Collapse
|
33
|
Yuan J, Cui M, Liang Q, Zhu D, Liu J, Hu J, Ma S, Li D, Wang J, Wang X, Ma D, Himmelmann K, Wang X, Xu Y, Zhu C. Cerebral Palsy Heterogeneity: Clinical Characteristics and Diagnostic Significance from a Large-Sample Analysis. Neuroepidemiology 2024; 58:470-480. [PMID: 38636464 PMCID: PMC11633901 DOI: 10.1159/000539002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 04/08/2024] [Indexed: 04/20/2024] Open
Abstract
INTRODUCTION Cerebral palsy (CP) is a nonprogressive movement disorder resulting from a prenatal or perinatal brain injury that benefits from early diagnosis and intervention. The timing of early CP diagnosis remains controversial, necessitating analysis of clinical features in a substantial cohort. METHODS We retrospectively reviewed medical records from a university hospital, focusing on children aged ≥24 months or followed up for ≥24 months and adhering to the International Classification of Diseases-10 for diagnosis and subtyping. RESULTS Among the 2012 confirmed CP cases, 68.84% were male and 51.44% had spastic diplegia. Based on the Gross Motor Function Classification System (GMFCS), 62.38% were in levels I and II and 19.88% were in levels IV and V. Hemiplegic and diplegic subtypes predominantly fell into levels I and II, while quadriplegic and mixed types were mainly levels IV and V. White matter injuries appeared in 46.58% of cranial MRI findings, while maldevelopment was rare (7.05%). Intellectual disability co-occurred in 43.44% of the CP cases, with hemiplegia having the lowest co-occurrence (20.28%, 58/286) and mixed types having the highest co-occurrence (73.85%, 48/65). Additionally, 51.67% (697/1,349) of the children with CP aged ≥48 months had comorbidities. CONCLUSIONS This study underscores white matter injury as the primary CP pathology and identifies intellectual disability as a common comorbidity. Although CP can be identified in infants under 1 year old, precision in diagnosis improves with development. These insights inform early detection and tailored interventions, emphasizing their crucial role in CP management.
Collapse
Affiliation(s)
- Junying Yuan
- Henan Pediatric Clinical Research Center and Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou, China
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Menglin Cui
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qiongqiong Liang
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dengna Zhu
- Henan Pediatric Clinical Research Center and Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou, China
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jie Liu
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiefeng Hu
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shijie Ma
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dong Li
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Wang
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuejie Wang
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Deyou Ma
- Cerebral Palsy Rehabilitation Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kate Himmelmann
- Pediatric Neurology, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Xiaoyang Wang
- Henan Pediatric Clinical Research Center and Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou, China
- Centre of Perinatal Medicine and Health, Institute of Clinical Science, University of Gothenburg, Gothenburg, Sweden
| | - Yiran Xu
- Henan Pediatric Clinical Research Center and Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou, China
| | - Changlian Zhu
- Henan Pediatric Clinical Research Center and Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou, China
- Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
34
|
Khan Z, Noohu MM, Parveen S, Usmani M, Khan F, Alsobhi MG, Manzar MD, Sehgal CA. Effect of Mirror Therapy on Upper Limb Function in Children and Adolescents with Hemiplegic Cerebral Palsy: A Systematic Review and Meta-Analysis. Dev Neurorehabil 2024; 27:106-115. [PMID: 38712882 DOI: 10.1080/17518423.2024.2349676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2024]
Abstract
BACKGROUND This review aimed to explore the effect of mirror therapy (MT) on upper limb function in children and adolescents with hemiplegic cerebral palsy (HCP). METHODS MEDLINE, CENTRAL, Scopus, PEDro, and Web of Science were systematically searched. PEDro scale was used for the quality assessment of included trials. Risk of Bias assessment was done using Cochrane Risk-of-bias tool version 2. Meta-analysis was performed on four of the seven studies included. RESULTS & CONCLUSION The majority of the trials included in this review found MT efficacious in improving motor function in HCP. Quantitative analysis of the included trials using QUEST scores for evaluation of quality of upper extremity function revealed positive but non-significant difference between the groups (MD = -0.12; 95% CI = -2.57,2.33; Z = 0.09, p = .92). Pooled analysis of the included trials using BBT, however, favored control (MD = 4.98; 95% CI = 2.32,7.63; Z = 3.67, p = .0002).
Collapse
Affiliation(s)
- Zubina Khan
- Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India
| | - Majumi M Noohu
- Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India
| | - Sarah Parveen
- Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India
| | - Maria Usmani
- Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India
| | - Fayaz Khan
- Department of Physical Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mashael Ghazi Alsobhi
- Department of Physical Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Md Dilshad Manzar
- Department of Nursing, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia
| | - Chhavi Arora Sehgal
- Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India
| |
Collapse
|
35
|
Kilic MA, Yildiz EP, Kurekci F, Coskun O, Cura M, Avci R, Genc HM. Association of epilepsy with neuroimaging patterns in children with cerebral palsy. Acta Neurol Belg 2024; 124:567-572. [PMID: 37777694 DOI: 10.1007/s13760-023-02385-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 09/07/2023] [Indexed: 10/02/2023]
Abstract
OBJECTIVES In this study, we examined whether epilepsy and drug-resistant epilepsy are associated with neuroimaging findings in children with cerebral palsy (CP). METHODS Magnetic resonance imaging classification system (MRICS) proposed by Surveillance of Cerebral Palsy in Europe (SCPE) was used for classification of different MRI patterns in patients with cerebral palsy. We reviewed the brain MRI scans and medical records of children with CP who were followed-up in our clinic between 2019 and 2023. Patients were divided into three categories: CP without epilepsy, CP with controlled epilepsy and CP with DRE. MRI patterns were grouped as maldevelopments, predominant white matter injury, predominant gray matter injury, miscellaneous (delayed myelination, cerebral atrophy, cerebellar atrophy, brainstem lesions and calcifications, lesions that were not classified under any other group) and normal according to MRICS of the SCPE. RESULTS There were 325 CP patients. The most common MRI patterns were predominant white matter injury (47.6%) and gray matter injury (23.8%). There was a 1.5-fold reduction in the risk of epilepsy in patients with predominant white matter injury (OR = 1.54, 95% CI 1.23-1.94). In contrast, children in the miscellaneous group had significantly higher risks of epilepsy (p < 0.001), and we were able to determine that miscellaneous findings increased the risk by 1.8 times (OR = 1.77, 95% CI 1.47-2.12). CONCLUSION In conclusion, more than half of the children with CP had epilepsy, 40.7% of whom had DRE. On MRI, miscellaneous findings may indicate a poor prognosis for epilepsy, while predominant white matter injury may indicate a good outcome. Children with CP, especially those with miscellaneous findings on MRI, should be closely monitored for epilepsy development.
Collapse
Affiliation(s)
- Mehmet Akif Kilic
- Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
| | - Edibe Pembegul Yildiz
- Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Fulya Kurekci
- Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Orhan Coskun
- Department of Pediatric Neurology, Gaziosmanpasa Training and Research Hospital, Istanbul, Turkey
| | - Meryem Cura
- Department of Pediatrics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Ridvan Avci
- Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Hulya Maras Genc
- Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| |
Collapse
|
36
|
Maimin D, Mentz A, Thomas M, Van Heerden TM, Horn A. The Etiologic Risk Factors for Cerebral Palsy at an Orthopedic Surgery Clinic in South Africa. Pediatr Neurol 2024; 153:175-178. [PMID: 38412782 DOI: 10.1016/j.pediatrneurol.2024.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 01/07/2024] [Accepted: 01/25/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Cerebral palsy (CP) is a group of disorders that affect movement and posture caused by injury to the developing brain. Although prematurity and low birth weight are common causes in developed countries, birth asphyxia, kernicterus, and infections have been identified as predominant etiologies in Africa. There is, however, very little information on the etiology of CP in South Africa. We aimed to determine the etiology, severity, and topographic distribution of CP in children undergoing orthopedic surgery at our tertiary pediatric unit. METHOD A retrospective folder review was performed for patients with CP who underwent orthopedic surgery from July 2018 to June 2022. Data were collected on perinatal circumstances, etiologic risk factors for developing CP, severity of disability as classified by the Gross Motor Function Classification Scale (GMFCS), and topographic distribution. Descriptive analysis was performed. RESULTS A total of 202 patients were included in the analysis. Prematurity (gestational age less than 37 weeks) was noted in 41.6% of the cohort and was the most common risk factor. Hypoxic-ischemic encephalopathy (30.7%), postnatal infections (13.4%), congenital brain malformations (10.4%), and cerebral infections were the next most common etiologic risk factors. Forty-eight percent of patients were classified as GMFCS IV or V. There was a predominance of bilateral (69.5%) compared with unilateral (21.3%) subtypes. CONCLUSION Most patients undergoing orthopedic surgery for musculoskeletal sequelae of CP had GMFCS levels of IV or V and were bilateral subtypes, emphasizing the need for intervention at a primary care level to decrease the incidence of this frequently preventable condition.
Collapse
Affiliation(s)
- Dane Maimin
- Orthopaedic Research Unit, Division of Orthopaedic Surgery, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
| | - Anlume Mentz
- Medical Student, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Michaela Thomas
- Medical Student, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Tao-Mae Van Heerden
- Medical Student, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Anria Horn
- Orthopaedic Research Unit, Division of Orthopaedic Surgery, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| |
Collapse
|
37
|
Dukkipati SS, Walker SJ, Trevarrow MP, Busboom MT, Schlieker KL, Kurz MJ. Linking corticospinal tract activation and upper-limb motor control in adults with cerebral palsy. Dev Med Child Neurol 2024; 66:523-530. [PMID: 37679938 PMCID: PMC10918041 DOI: 10.1111/dmcn.15750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 08/05/2023] [Accepted: 08/09/2023] [Indexed: 09/09/2023]
Abstract
AIM To quantify the cervicomedullary motor evoked potentials (CMEPs) at the cervical spinal level in adults with cerebral palsy (CP) and determine if altered CMEPs are linked with upper-extremity motor function in this population. METHOD This cross-sectional study consisted of a cohort of adults with CP (n = 15; mean age = 33 years 5 months [SD = 11 years 8 months]); Manual Ability Classification System levels I-IV) and neurotypical controls (n = 18; mean age = 30 years 10 months [SD = 10 years 4 months]), who were recruited to participate at an academic medical center. Adults with CP and typical adults (controls) were stimulated at the cervicomedullary junction to assess CMEPs at the cervical spinal cord level. Upper-extremity motor function was quantified using the Box and Blocks and Purdue Pegboard tests, self-reported upper-extremity function (UEF), and assessments of selective motor control. RESULTS At higher stimulation levels, the contralateral CMEP responses of adults with CP were different from typical adults (p = 0.032). Reduced CMEP was correlated with reduced upper-limb function, including worse performance on the Box and Blocks (rho = 0.625, p = 0.025) and Purdue Pegboard tests (rho = 0.701, p = 0.010), lower self-reported UEF (rho = 0.761, p = 0.009), and overall selective motor control (rho = 0.731, p = 0.007). INTERPRETATION Changes in the activation of spinal motoneurons through corticospinal pathways may have an important role in the altered upper-extremity motor function of individuals with CP.
Collapse
Affiliation(s)
- Saihari S Dukkipati
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
| | - Sarah J Walker
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
| | - Michael P Trevarrow
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
| | - Morgan T Busboom
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
| | - Katie L Schlieker
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
| | - Max J Kurz
- Institute for Human Neuroscience, Boys Town National Research Hospital, Omaha, NE, USA
- Department of Pharmacology & Neuroscience, Creighton University, Omaha, NE, USA
| |
Collapse
|
38
|
Xu J, Yan S, Xia C, Xue J, Yu W, Yan Y, Yin Z. Comparison and discussion of behavior and pathology of four kinds of cerebral palsy disease models. Int J Dev Neurosci 2024; 84:143-153. [PMID: 38323913 DOI: 10.1002/jdn.10315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 12/26/2023] [Accepted: 01/05/2024] [Indexed: 02/08/2024] Open
Abstract
Explore the differences in behavioral and pathological manifestations of rat models of cerebral palsy made by different methods and discuss what types of studies these models are suitable for. Behavioral evaluation and pathological section observation were used to observe and evaluate the model. Conclusion: except for the absence of data of bilateral common carotid artery ligation rats, the other three methods could all achieve a successful cerebral palsy disease model for both behavioral and pathological. For researchers, the selection of intraperitoneal infection model in pregnant rats or unilateral ischemia and hypoxia model in infant rats is sufficient to meet the experimental needs, whereas the selection of the combined method for modeling does not show enough advantages, which not only causes the waste of financial and human resources but also increases the possibility of experimental error made by intervention factors.
Collapse
Affiliation(s)
- Jinyan Xu
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Siyang Yan
- Guangxi Medical University, Nanning, China
| | - Chen Xia
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jianyi Xue
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Wentao Yu
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yuanjie Yan
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Zhenjin Yin
- Hebei University of Chinese Medicine, Shijiazhuang, China
| |
Collapse
|
39
|
Boyalı O, Kabatas S, Civelek E, Ozdemir O, Bahar-Ozdemir Y, Kaplan N, Savrunlu EC, Karaöz E. Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy. World J Clin Cases 2024; 12:1585-1596. [PMID: 38576742 PMCID: PMC10989435 DOI: 10.12998/wjcc.v12.i9.1585] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/11/2024] [Accepted: 02/28/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Cerebral palsy (CP) describes a group of disorders affecting movement, balance, and posture. Disturbances in motor functions constitute the main body of CP symptoms. These symptoms surface in early childhood and patients are affected for the rest of their lives. Currently, treatment involves various pharmacotherapies for different types of CP, including antiepileptics for epilepsy and Botox A for focal spasticity. However, none of these methods can provide full symptom relief. This has prompted researchers to look for new treatment modalities, one of which is mesenchymal stem cell therapy (MSCT). Despite being a promising tool and offering a wide array of possibilities, mesenchymal stem cells (MSCs) still need to be investigated for their efficacy and safety. AIM To analyze the efficacy and safety of MSCT in CP patients. METHODS Our sample consists of four CP patients who cannot stand or walk without external support. All of these cases received allogeneic MSCT six times as 1 × 106/kg intrathecally, intravenously, and intramuscularly using umbilical cord-derived MSCs (UC-MSC). We monitored and assessed the patients pre- and post-treatment using the Wee Functional Independence Measure (WeeFIM), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification Scale (MACS) instruments. We utilized the Modified Ashworth Scale (MAS) to measure spasticity. RESULTS We found significant improvements in MAS scores after the intervention on both sides. Two months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; four months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; 12 months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046. However, there was no significant difference in motor functions based on WeeFIM results (P > 0.05). GMFCS and MACS scores differed significantly at 12 months after the intervention (P = 0.046, P = 0.046). Finally, there was no significant change in cognitive functions (P > 0.05). CONCLUSION In light of our findings, we believe that UC-MSC therapy has a positive effect on spasticity, and it partially improves motor functions.
Collapse
Affiliation(s)
- Osman Boyalı
- Department of Neurosurgery, University of Health Sciences Turkey, Gaziosmanpaşa Training and Research Hospital, Istanbul 34360, Turkey
| | - Serdar Kabatas
- Department of Neurosurgery, University of Health Sciences Turkey, Gaziosmanpaşa Training and Research Hospital, Istanbul 34360, Turkey
- Center for Stem Cell & Gene Therapy Research and Practice, University of Health Sciences Turkey, Istanbul 34360, Turkey
| | - Erdinç Civelek
- Department of Neurosurgery, University of Health Sciences Turkey, Gaziosmanpaşa Training and Research Hospital, Istanbul 34360, Turkey
| | - Omer Ozdemir
- Department of Neurosurgery, University of Health Sciences Turkey, Gaziosmanpaşa Training and Research Hospital, Istanbul 34360, Turkey
| | - Yeliz Bahar-Ozdemir
- Department of Physical Medicine and Rehabilitation, Health Sciences University Sultan Abdulhamid Han Training and Research Hospital, Istanbul 34668, Turkey
| | - Necati Kaplan
- Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Tekirdağ 59860, Turkey
| | - Eyüp Can Savrunlu
- Department of Neurosurgery, Nevşehir State Hospital, Nevşehir 50300, Turkey
| | - Erdal Karaöz
- Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Liv Hospital, Istanbul 34340, Turkey
- Department of Histology and Embryology, Istinye University, Faculty of Medicine, İstanbul 34010, Turkey
- Center for Stem Cell and Tissue Engineering Research and Practice, Istinye University, Istanbul 34340, Turkey
| |
Collapse
|
40
|
Cheng Y, Xu Y, Li H, Qiao Y, Wang Y, Su Y, Zhang J, Wang X, Song L, Ding J, Wang D, Zhu C, Xing Q. Genetic variants in the HLA region contribute to the risk of cerebral palsy. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167008. [PMID: 38163449 DOI: 10.1016/j.bbadis.2023.167008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 12/22/2023] [Accepted: 12/22/2023] [Indexed: 01/03/2024]
Abstract
Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 × 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 × 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.
Collapse
Affiliation(s)
- Ye Cheng
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China; Shanghai Center for Women and Children's Health, Shanghai 200062, China
| | - Yiran Xu
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou 450052, China
| | - Hongwei Li
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou 450052, China
| | - Yimeng Qiao
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou 450052, China
| | - Yangong Wang
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Yu Su
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Jin Zhang
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Xiaoyang Wang
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou 450052, China; Centre of Perinatal Medicine and Health, Institute of Clinical Science, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Lili Song
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Jian Ding
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Dan Wang
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China
| | - Changlian Zhu
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou 450052, China; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg 40530, Sweden.
| | - Qinghe Xing
- Children's Hospital of Fudan University, and Institutes of Biomedical Sciences of Fudan University, Shanghai 201102, China; Shanghai Center for Women and Children's Health, Shanghai 200062, China.
| |
Collapse
|
41
|
Thacher JD, Högfeldt H, Vilhelmsson A, Lindh C, Rylander L. Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples. J Pediatr 2024; 269:113959. [PMID: 38369234 DOI: 10.1016/j.jpeds.2024.113959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 02/06/2024] [Accepted: 02/13/2024] [Indexed: 02/20/2024]
Abstract
OBJECTIVE To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring. STUDY DESIGN We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term. RESULTS Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP. CONCLUSIONS The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.
Collapse
Affiliation(s)
- Jesse D Thacher
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
| | - Hannah Högfeldt
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Andreas Vilhelmsson
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Christian Lindh
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Lars Rylander
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| |
Collapse
|
42
|
Shrinivasan R, Wyatt-Johnson SK, Brutkiewicz RR. The MR1/MAIT cell axis in CNS diseases. Brain Behav Immun 2024; 116:321-328. [PMID: 38157945 PMCID: PMC10842441 DOI: 10.1016/j.bbi.2023.12.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 12/14/2023] [Accepted: 12/21/2023] [Indexed: 01/03/2024] Open
Abstract
Mucosal-associated invariant T (MAIT) cells are a subpopulation of innate-like T cells that can be found throughout the body, predominantly in mucosal sites, the lungs and in the peripheral blood. MAIT cells recognize microbial-derived vitamin B (e.g., riboflavin) metabolite antigens that are presented by the major histocompatibility complex class I-like protein, MR1, found on a variety of cell types in the periphery and the CNS. Since their original discovery, MAIT cells have been studied predominantly in their roles in diseases in the periphery; however, it was not until the early 2000s that these cells were first examined for their contributions to disorders of the CNS, with the bulk of the work being done within the past few years. Currently, the MR1/MAIT cell axis has been investigated in only a few neurological diseases including, multiple sclerosis and experimental autoimmune encephalomyelitis, brain cancer/tumors, ischemia, cerebral palsy, general aging and, most recently, Alzheimer's disease. Each of these diseases demonstrates a role for this under-studied innate immune axis in its neuropathology. Together, they highlight the importance of studying the MR1/MAIT cell axis in CNS disorders. Here, we review the contributions of the MR1/MAIT cell axis in the progression or remission of these neurological diseases. This work has shed some light in terms of potentially exploiting the MR1/MAIT cell axis in novel therapeutic applications.
Collapse
Affiliation(s)
- Rashmi Shrinivasan
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Season K Wyatt-Johnson
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Randy R Brutkiewicz
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
| |
Collapse
|
43
|
Gill JS, Nguyen MX, Hull M, van der Heijden ME, Nguyen K, Thomas SP, Sillitoe RV. Function and dysfunction of the dystonia network: an exploration of neural circuits that underlie the acquired and isolated dystonias. DYSTONIA 2023; 2:11805. [PMID: 38273865 PMCID: PMC10810232 DOI: 10.3389/dyst.2023.11805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through an examination of cerebral palsy, in which early brain injury may lead to dystonic/dyskinetic forms of the movement disorder. The discussion of acquired etiologies then continues with an evaluation of the literature covering dystonia resulting from focal lesions followed by the isolated focal dystonias, both idiopathic and task dependent. Next, how the dystonia network responds to therapeutic interventions, from the "geste antagoniste" or "sensory trick" to botulinum toxin and deep brain stimulation, is covered with an eye towards finding similarities in network responses with effective treatment. Finally, an examination of how focal network disruptions in mouse models has informed our understanding of the circuits involved in dystonia is provided. Together, this article aims to offer a synthesis of the literature examining dystonia from the perspective of brain networks and it provides grounding for the perspective of dystonia as disorder of network function.
Collapse
Affiliation(s)
- Jason S. Gill
- Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX, United States
| | - Megan X. Nguyen
- Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX, United States
| | - Mariam Hull
- Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
| | - Meike E. van der Heijden
- Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX, United States
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United State
| | - Ken Nguyen
- Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX, United States
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United State
| | - Sruthi P. Thomas
- H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, United States
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Roy V. Sillitoe
- Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX, United States
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United State
- Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
- Development, Disease Models and Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX, United States
| |
Collapse
|
44
|
Miskiewicz M, Hidalgo Perea S, Magruder M, Abdelgawad A. Risk Factors of Infectious Complications in Pediatric Patients With Cerebral Palsy After Spinal Arthrodesis. Clin Spine Surg 2023; 36:E397-E401. [PMID: 37348066 DOI: 10.1097/bsd.0000000000001471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 05/17/2023] [Indexed: 06/24/2023]
Abstract
STUDY DESIGN This was a retrospective study. OBJECTIVE The main objective of this study was to investigate (1) whether pediatric patients with cerebral palsy (CP) have higher rates of postoperative infectious complications after spinal fusion and (2) risk factors for postoperative infections. SUMMARY OF BACKGROUND DATA Prior studies have shown that patients with CP undergo corrective spine surgery more often than the general population, yet typically have worse postoperative outcomes. Further investigation is needed to improve our understanding of the perioperative factors that place children with CP at greater risk of postoperative infectious complications. PATIENTS AND METHODS The 2019 "American College of Surgeons National Surgical Quality Improvement Program" Pediatric database was used for patient data. The univariable analysis compared the prevalence of preoperative comorbidities and perioperative factors between children with and without CP. Multivariable logistic regression modeling was used to ascertain independent risk factors for postoperative infectious complications. RESULTS A total of 4445 patients were included in the study; 606 (13.63%) patients had CP and 3839 (86.37%) did not. Patients with CP were more likely to have several notable preoperative comorbidities, and the rate of developing any infectious complication was more than 7 times greater in the CP cohort than in the control cohort (14.36% vs 1.88%; P <0.001). Multivariable analysis revealed CP [odds ratio (OR): 3.55, CI: 2.25-5.60; P <0.001], American Society of Anesthesiologists class 3 or higher (OR: 2.10, CI: 1.29-3.42; P = 0.003), and hematologic disorders (OR: 2.01, CI: 1.06-3.83; P = 0.033) to be independent risk factors for increased postoperative infectious complications. CONCLUSIONS CP is an independent risk factor for the development of 30-day postoperative infectious complications in pediatric patients. In addition, the American Society of Anesthesiologists class 3 or higher and hematologic disorders were risk factors for postoperative infections after spinal fusion surgery.
Collapse
Affiliation(s)
- Michael Miskiewicz
- Renaissance School of Medicine, Stony Brook University Hospital Stony Brook, NY
| | - Sofia Hidalgo Perea
- Renaissance School of Medicine, Stony Brook University Hospital Stony Brook, NY
| | - Matthew Magruder
- Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY
| | - Amr Abdelgawad
- Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY
| |
Collapse
|
45
|
Wang Y, Zhang P, Li C. Systematic review and network meta-analysis of robot-assisted gait training on lower limb function in patients with cerebral palsy. Neurol Sci 2023; 44:3863-3875. [PMID: 37495708 PMCID: PMC10570202 DOI: 10.1007/s10072-023-06964-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 07/14/2023] [Indexed: 07/28/2023]
Abstract
OBJECTIVE This study aimed to evaluate the effectiveness of robot-assisted gait training (RAGT) in treating lower extremity function in patients with cerebral palsy (CP) and compare the efficacy differences between different robotic systems. METHODS PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, CBM, and Wanfang databases were searched to collect randomized controlled trials of RAGT for lower extremity dysfunction in patients with CP from the time the databases were created until December 26, 2022. The D and E of Gross Motor Function Measure-88 (GMFM-88) assessed lower limb motor function. Berg Balance Scale (BBS) was used to assess balance function. Walking endurance and speed were assessed using the 6-minute walk test (6MWT) and walking speed. The modified Ashworth Scale (MAS) was used to assess the degree of muscle spasticity in the lower extremities. The Cochrane Risk Assessment Scale and the Physiotherapy Evidence Database (PEDro) scale were used for qualitative assessment in the studies included. RevMan 5.4 was used for data merging and statistical analysis. R 4.2.0 and ADDIS 1.16.8 were used to map the network relationships and to perform the network meta-analysis. RESULTS A total of 14 studies were included in the review. The meta-analysis showed that RAGT significantly improved GMFM-88 D and E, BBS, and 6MWT scores in CP patients compared with conventional rehabilitation. However, for walking speed and MAS, the intervention effect of RAGT was insignificant. The network meta-analysis showed that the best probability ranking for the effect of the 3 different robots on the GMFM-88 D score was LokoHelp (P = 0.66) > Lokomat (P = 0.28) > 3DCaLT (P = 0.06) and the best probability ranking for the GMFM-88 E score was LokoHelp (P = 0.63) > 3DCaLT (P = 0.21) > Lokomat (P = 0.16). CONCLUSION RAGT positively affects walking and balance function in patients with CP, while efficacy in improving gait speed and muscle spasticity is unknown. The best treatment among the different robots is LokoHelp. Future high-quality, long-term follow-up studies are needed to explore the clinical efficacy of RAGT in depth.
Collapse
Affiliation(s)
- Yueying Wang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Peipei Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Chao Li
- Department of Rehabilitation and Physiotherapy, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
| |
Collapse
|
46
|
Bentum LS, Ohene LA, Agyare VA, Laari L, Ampomah MO. Fathers' experiences of caring for children living with cerebral palsy: A qualitative study in a low resourced socioeconomic context, Ghana. J Pediatr Nurs 2023; 73:e100-e106. [PMID: 37543505 DOI: 10.1016/j.pedn.2023.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 08/07/2023]
Abstract
BACKGROUND In Ghana, little is known about fathers' experiences caring for children with cerebral palsy. PURPOSE The purpose of this study is to explore a. the caregiving demand and burden on fathers of children with cerebral palsy and b. describe the caregiving consequences and coping strategies of fathers of children with cerebral palsy. DESIGN AND METHODS The study utilized an exploratory, descriptive qualitative approach with a sample size of fifteen fathers purposively selected. The study used a semi-structured interview guide to conduct a one-on-one interview with participants. The analysis performed was thematic and content analysis. RESULTS The results revealed complexities of care demand and burden; thus, meeting the child's needs resulted in physical and mental exhaustion, frequent hospital visits, and substantial financial implications for fathers. CONCLUSIONS We conclude that the family, particularly fathers, need support to embrace the challenging care roles as parents to children with cerebral palsy. It is evident that caring for children is mainly reserved for mothers in the African context. However, the demanding nature of care for a child with a developmental disability requires the involvement of both parents to meet the child's care needs and reduce the caregiver's care burden. PRACTICE IMPLICATIONS Health professionals, particularly nurses must initiate and advocate for fathers' active participation in daily childcare. Tailored supportive care for families with children with disabilities in sub-Saharan Africa is required.
Collapse
Affiliation(s)
- Lucy Selorm Bentum
- Department of Public Health Nursing, University of Ghana, Legon, P.O Box LG 43, Accra, Ghana
| | - Lillian Akorfa Ohene
- Department of Public Health Nursing, University of Ghana, Legon, P.O Box LG 43, Accra, Ghana.
| | | | - Luke Laari
- Department of Public Health Nursing, University of Ghana, Legon, P.O Box LG 43, Accra, Ghana
| | - Menford Owusu Ampomah
- Department of Adult Health Nursing, University of Ghana, Legon(,) P.O Box LG 43, Accra, Ghana
| |
Collapse
|
47
|
Javvaji CK, Vagha JD, Meshram RJ, Taksande A. Assessment Scales in Cerebral Palsy: A Comprehensive Review of Tools and Applications. Cureus 2023; 15:e47939. [PMID: 38034189 PMCID: PMC10685081 DOI: 10.7759/cureus.47939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 10/28/2023] [Indexed: 12/02/2023] Open
Abstract
Cerebral palsy (CP) is a complex neurological condition characterized by motor dysfunction affecting millions worldwide. This comprehensive review delves into the critical role of assessment in managing CP. Beginning with exploring its definition and background, we elucidate the diverse objectives of CP assessment, ranging from diagnosis and goal setting to research and epidemiology. We examine standard assessment scales and tools, discuss the challenges inherent in CP assessment, and highlight emerging trends, including integrating technology, personalized medicine, and neuroimaging. The applications of CP assessment in clinical diagnosis, treatment planning, research, and education are underscored. Recommendations for the future encompass standardization, interdisciplinary collaboration, research priorities, and professional training. In conclusion, we emphasize the importance of assessment as a compass guiding the care of individuals with CP, issuing a call to action for improved assessment practices to shape a brighter future for those affected by this condition.
Collapse
Affiliation(s)
- Chaitanya Kumar Javvaji
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Jayant D Vagha
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Revat J Meshram
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Amar Taksande
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| |
Collapse
|
48
|
Ghorashi T, Darvish H, Bakhtiari S, Tafakhori A, Kruer MC, Mozdarani H. A biallelic loss-of-function variant in TMEM147 causes profound intellectual disability and spasticity. Neurogenetics 2023; 24:311-316. [PMID: 37668766 DOI: 10.1007/s10048-023-00734-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/27/2023] [Indexed: 09/06/2023]
Abstract
Intellectual disability (ID), occurring in syndromic or non-syndromic forms, is the most common neurodevelopmental disorder. Although many cases are caused by single gene defects, ID is highly genetically heterogeneous. Biallelic variants in the transmembrane protein TMEM147 have recently been linked to intellectual disability with dysmorphic facial features. TMEM147 is believed to localize to the endoplasmic reticulum membrane and nuclear envelope and also involved in biogenesis of multi-pass membrane proteins. Here, we report two patients born to a consanguineous family with a novel loss-of-function variant; (NM_001242597.2:c.193-197del) in TMEM147 causing intellectual disability and spasticity. Whole exome sequencing and validating Sanger sequencing were utilized to confirm the identified causal variant. Our findings were in line with the previously described patients with TMEM147 variants manifesting intellectual disability as a major clinical sign but also featured spasticity as a phenotypic expansion. This study provides additional evidence for the pathogenicity of TMEM147 mutations in intellectual disability and expands the phenotypic and variant spectrum linked to this gene.
Collapse
Affiliation(s)
- Tahereh Ghorashi
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hossein Darvish
- Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Somayeh Bakhtiari
- Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA
- Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
| | - Abbas Tafakhori
- Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael C Kruer
- Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA.
- Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
| | - Hossein Mozdarani
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| |
Collapse
|
49
|
Martinie O, Karan P, Traverse E, Mercier C, Descoteaux M, Robert MT. The Challenge of Diffusion Magnetic Resonance Imaging in Cerebral Palsy: A Proposed Method to Identify White Matter Pathways. Brain Sci 2023; 13:1386. [PMID: 37891755 PMCID: PMC10605121 DOI: 10.3390/brainsci13101386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/19/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
Cerebral palsy (CP), a neuromotor disorder characterized by prenatal brain lesions, leads to white matter alterations and sensorimotor deficits. However, the CP-related diffusion neuroimaging literature lacks rigorous and consensual methodology for preprocessing and analyzing data due to methodological challenges caused by the lesion extent. Advanced methods are available to reconstruct diffusion signals and can update current advances in CP. Our study demonstrates the feasibility of analyzing diffusion CP data using a standardized and open-source pipeline. Eight children with CP (8-12 years old) underwent a single diffusion magnetic resonance imaging (MRI) session on a 3T scanner (Achieva 3.0T (TX), Philips Healthcare Medical Systems, Best, The Netherlands). Exclusion criteria were contraindication to MRI and claustrophobia. Anatomical and diffusion images were acquired. Data were corrected and analyzed using Tractoflow 2.3.0 version, an open-source and robust tool. The tracts were extracted with customized procedures based on existing atlases and freely accessed standardized libraries (ANTs, Scilpy). DTI, CSD, and NODDI metrics were computed for each tract. Despite lesion heterogeneity and size, we successfully reconstructed major pathways, except for a participant with a larger lesion. Our results highlight the feasibility of identifying and quantifying subtle white matter pathways. Ultimately, this will increase our understanding of the clinical symptoms to provide precision medicine and optimize rehabilitation.
Collapse
Affiliation(s)
- Ophélie Martinie
- Centre for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC G1M 2S8, Canada; (O.M.); (E.T.); (C.M.)
- Department of Rehabilitation, Université Laval, Québec, QC G1V 0A6, Canada
| | - Philippe Karan
- Department of Computer Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada; (P.K.); (M.D.)
| | - Elodie Traverse
- Centre for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC G1M 2S8, Canada; (O.M.); (E.T.); (C.M.)
- Department of Rehabilitation, Université Laval, Québec, QC G1V 0A6, Canada
| | - Catherine Mercier
- Centre for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC G1M 2S8, Canada; (O.M.); (E.T.); (C.M.)
- Department of Rehabilitation, Université Laval, Québec, QC G1V 0A6, Canada
| | - Maxime Descoteaux
- Department of Computer Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada; (P.K.); (M.D.)
| | - Maxime T. Robert
- Centre for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC G1M 2S8, Canada; (O.M.); (E.T.); (C.M.)
- Department of Rehabilitation, Université Laval, Québec, QC G1V 0A6, Canada
| |
Collapse
|
50
|
Huang S, Liu L, Huang Y, Fu C, Peng T, Yang X, Zhou H, Zhao Y, Xu Y, Zeng X, Zeng P, Tang H, He L, Xu K. Potential optimized route for mesenchymal stem cell transplantation in a rat model of cerebral palsy. Exp Cell Res 2023; 430:113734. [PMID: 37532123 DOI: 10.1016/j.yexcr.2023.113734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 07/04/2023] [Accepted: 07/26/2023] [Indexed: 08/04/2023]
Abstract
Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p<0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p<0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p<0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p<0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.
Collapse
Affiliation(s)
- Shiya Huang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China; School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Liru Liu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Yuan Huang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China; School of Medicine, South China University of Technology, Guangzhou, 510655, China
| | - Chaoqiong Fu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China; School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Tingting Peng
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Xubo Yang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Hongyu Zhou
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Yiting Zhao
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Yi Xu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Xiaoli Zeng
- Guangdong Xiangxue Stem Cell Regenerative Medicine Technology Co., Ltd, Guangzhou, 510120, China
| | - Peishan Zeng
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Hongmei Tang
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China
| | - Lu He
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China.
| | - Kaishou Xu
- Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510120, China.
| |
Collapse
|