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Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 102711

Special Issue Editor


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Guest Editor
1. Associate Professor, Department of Clinical and Experimental Medicine, The University of Pisa, Pisa, Italy
2. Head of Infant Neurology and Stella Maris Infant Lab for Early-intervention (SMILE), IRCCS Fondazione Stella Maris, Pisa, Italy
Interests: advanced brain imaging; early brain damage; early diagnosis; neuroplastic mechanisms; early intervention paradigms; parent-infant intersubjectivity and environmental enrichment

Special Issue Information

Dear Colleagues,

Currently, early detection of CP (Cerebral Palsy) and related neurodevelopmental disorders is considered one of the major challenges in pediatric healthcare, holding the highest odds of producing ground-breaking changes in child healthcare in the near future. An important international effort review publication lead by Prof. Novak (JAMA, 2017) has provided the guideline on the topic and pointed out that the time of diagnosis and the beginning of intervention typically start months after the first clinical signs may be observed.

The still existing diagnostic lag presents a major burden in the amelioration of the long-term outcome. It has been demonstrated that the response to the intervention is more significant the earlier services are initiated, likely due to the greater level of brain plasticity during the first weeks of life. Parallel to the early detection efforts, the improved understanding of childhood development, neurodevelopmental disorders and neuralplasticity is leading to an increased value, availability, and utilization of early intervention services.

I invite you to participate in this Special Issue, which aims to collect the most recent evidence of assessments and interventions for young children at high risk of, or with a diagnosis of Cerebral Palsy. The manuscripts may include any format (data driven, systematic review, state-of-the-art review) that may contribute to the further understanding of the role of early detection and intervention of CP for later neurodevelopmental outcome. This includes, but is not limited to, manuscripts on neuroimaging, neurophysiology, or behavioral assessments techniques for the detection, prediction or classification of CP, its severity, comorbidities, and long term neurodevelopmental outcomes. Equally important will be the inclusion of reports or protocols about interventions that focus on the population within the first three years of life.

Dr. Andrea Guzzetta
Guest Editor

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Keywords

  • Cerebral palsy
  • Early brain damage
  • Neuroimaging, neurophysiology
  • Early diagnosis
  • Early intervention
  • Environmental enrichment
  • Parent-infant intersubjectivity
  • Neuroplastic mechanisms
  • Cortical reorganization

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Published Papers (15 papers)

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21 pages, 3706 KiB  
Article
Correlates of Normal and Abnormal General Movements in Infancy and Long-Term Neurodevelopment of Preterm Infants: Insights from Functional Connectivity Studies at Term Equivalence
by Colleen Peyton, Christa Einspieler, Toril Fjørtoft, Lars Adde, Michael D. Schreiber, Alexander Drobyshevsky and Jeremy D. Marks
J. Clin. Med. 2020, 9(3), 834; https://doi.org/10.3390/jcm9030834 - 19 Mar 2020
Cited by 20 | Viewed by 3675
Abstract
Preterm infants born before 32 weeks gestation have increased risks for neurodevelopmental impairment at two years of age. How brain function differs between preterm infants with normal or impaired development is unknown. However, abnormal spontaneous motor behavior at 12–15 weeks post-term age is [...] Read more.
Preterm infants born before 32 weeks gestation have increased risks for neurodevelopmental impairment at two years of age. How brain function differs between preterm infants with normal or impaired development is unknown. However, abnormal spontaneous motor behavior at 12–15 weeks post-term age is associated with neurodevelopmental impairment. We imaged brain blood oxygen level-dependent signals at term-equivalent age in 62 infants born at <32 weeks gestation and explored whether resting state functional connectivity (rsFC) differed with performances on the General Movement Assessment (GMA) at 12–15 weeks, and Bayley III scores at two years of corrected age. Infants with aberrant general movements exhibited decreased rsFC between the basal ganglia and regions in parietal and frontotemporal lobes. Infants with normal Bayley III cognitive scores exhibited increased rsFC between the basal ganglia and association cortices in parietal and occipital lobes compared with cognitively impaired children. Infants with normal motor scores exhibited increased rsFC between the basal ganglia and visual cortices, compared with children with motor impairment. Thus, the presence of abnormal general movements is associated with region-specific differences in rsFC at term. The association of abnormal long-term neurodevelopmental outcomes with decreased rsFC between basal ganglia and sub-score specific cortical regions may provide biomarkers of neurodevelopmental trajectory and outcome. Full article
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8 pages, 555 KiB  
Article
Association between Gait Deviation Index and Physical Function in Children with Bilateral Spastic Cerebral Palsy: A Cross-Sectional Study
by Tadashi Ito, Koji Noritake, Hiroshi Sugiura, Yasunari Kamiya, Hidehito Tomita, Yuji Ito, Hideshi Sugiura, Nobuhiko Ochi and Yuji Yoshihashi
J. Clin. Med. 2020, 9(1), 28; https://doi.org/10.3390/jcm9010028 - 20 Dec 2019
Cited by 20 | Viewed by 4677 | Correction
Abstract
This study examined the association between Gait Deviation Index (GDI) and the five-times-sit-to-stand test (FTSST) or gait speed results, which represent mobility and muscle strength of the lower extremities in ambulatory children with Gross Motor Function Classification System (GMFCS) level I and II [...] Read more.
This study examined the association between Gait Deviation Index (GDI) and the five-times-sit-to-stand test (FTSST) or gait speed results, which represent mobility and muscle strength of the lower extremities in ambulatory children with Gross Motor Function Classification System (GMFCS) level I and II spastic cerebral palsy. In this cross-sectional, observational study, three-dimensional gait analysis data were obtained during gait trials to evaluate the GDI in 35 children (age 5–16 years) with spastic palsy. Motor function was evaluated using FTSST and gait speed. Gross motor function was evaluated using GMFCS. Children with GMFCS level II spastic cerebral palsy demonstrated lower GDI (p < 0.001) and poorer FTSST (p = 0.031) than those with GMFCS level I spastic cerebral palsy. Correlation analysis showed that FTSST results were significantly correlated with GDI (r = −0.624; p < 0.001). Motor function may be important for the maintenance of gait quality in patients with GMFCS level I and II spastic cerebral palsy and should not be ignored. In conclusion, reduction in gait impairment may affect the values of FTSST and GDI in patients with spastic cerebral palsy who can ambulate without an assistive device. Full article
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17 pages, 2181 KiB  
Article
Machine Learning of Infant Spontaneous Movements for the Early Prediction of Cerebral Palsy: A Multi-Site Cohort Study
by Espen A. F. Ihlen, Ragnhild Støen, Lynn Boswell, Raye-Ann de Regnier, Toril Fjørtoft, Deborah Gaebler-Spira, Cathrine Labori, Marianne C. Loennecken, Michael E. Msall, Unn I. Möinichen, Colleen Peyton, Michael D. Schreiber, Inger E. Silberg, Nils T. Songstad, Randi T. Vågen, Gunn K. Øberg and Lars Adde
J. Clin. Med. 2020, 9(1), 5; https://doi.org/10.3390/jcm9010005 - 18 Dec 2019
Cited by 64 | Viewed by 7719
Abstract
Background: Early identification of cerebral palsy (CP) during infancy will provide opportunities for early therapies and treatments. The aim of the present study was to present a novel machine-learning model, the Computer-based Infant Movement Assessment (CIMA) model, for clinically feasible early CP prediction [...] Read more.
Background: Early identification of cerebral palsy (CP) during infancy will provide opportunities for early therapies and treatments. The aim of the present study was to present a novel machine-learning model, the Computer-based Infant Movement Assessment (CIMA) model, for clinically feasible early CP prediction based on infant video recordings. Methods: The CIMA model was designed to assess the proportion (%) of CP risk-related movements using a time–frequency decomposition of the movement trajectories of the infant’s body parts. The CIMA model was developed and tested on video recordings from a cohort of 377 high-risk infants at 9–15 weeks corrected age to predict CP status and motor function (ambulatory vs. non-ambulatory) at mean 3.7 years age. The performance of the model was compared with results of the general movement assessment (GMA) and neonatal imaging. Results: The CIMA model had sensitivity (92.7%) and specificity (81.6%), which was comparable to observational GMA or neonatal cerebral imaging for the prediction of CP. Infants later found to have non-ambulatory CP had significantly more CP risk-related movements (median: 92.8%, p = 0.02) compared with those with ambulatory CP (median: 72.7%). Conclusion: The CIMA model may be a clinically feasible alternative to observational GMA. Full article
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11 pages, 706 KiB  
Article
The Pooled Diagnostic Accuracy of Neuroimaging, General Movements, and Neurological Examination for Diagnosing Cerebral Palsy Early in High-Risk Infants: A Case Control Study
by Catherine Morgan, Domenico M. Romeo, Olena Chorna, Iona Novak, Claire Galea, Sabrina Del Secco and Andrea Guzzetta
J. Clin. Med. 2019, 8(11), 1879; https://doi.org/10.3390/jcm8111879 - 5 Nov 2019
Cited by 85 | Viewed by 8621
Abstract
Introduction: Clinical guidelines recommend using neuroimaging, Prechtls’ General Movements Assessment (GMA), and Hammersmith Infant Neurological Examination (HINE) to diagnose cerebral palsy (CP) in infancy. Previous studies provided excellent sensitivity and specificity for each test in isolation, but no study has examined the pooled [...] Read more.
Introduction: Clinical guidelines recommend using neuroimaging, Prechtls’ General Movements Assessment (GMA), and Hammersmith Infant Neurological Examination (HINE) to diagnose cerebral palsy (CP) in infancy. Previous studies provided excellent sensitivity and specificity for each test in isolation, but no study has examined the pooled predictive power for early diagnosis. Methods: We performed a retrospective case-control study of 441 high-risk infants born between 2003 and 2014, from three Italian hospitals. Infants with either a normal outcome, mild disability, or CP at two years, were matched for birth year, gender, and gestational age. Three-month HINE, GMA, and neuroimaging were retrieved from medical records. Logistic regression was conducted with log-likelihood and used to determine the model fit and Area Under the Curve (AUC) for accuracy. Results: Sensitivity and specificity for detecting CP were 88% and 62% for three-month HINE, 95% and 97% for absent fidgety GMs, and 79% and 99% for neuroimaging. The combined predictive power of all three assessments gave sensitivity and specificity values of 97.86% and 99.22% (PPV 98.56%, NPV 98.84%). Conclusion: CP can be accurately detected in high-risk infants when these test findings triangulate. Clinical implementation of these tools is likely to reduce the average age when CP is diagnosed, and intervention is started. Full article
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11 pages, 223 KiB  
Article
The Predictive Accuracy of the General Movement Assessment for Cerebral Palsy: A Prospective, Observational Study of High-Risk Infants in a Clinical Follow-Up Setting
by Ragnhild Støen, Lynn Boswell, Raye-Ann de Regnier, Toril Fjørtoft, Deborah Gaebler-Spira, Espen Ihlen, Cathrine Labori, Marianne Loennecken, Michael Msall, Unn Inger Möinichen, Colleen Peyton, Annamarie Russow, Michael D. Schreiber, Inger Elisabeth Silberg, Nils Thomas Songstad, Randi Vågen, Gunn Kristin Øberg and Lars Adde
J. Clin. Med. 2019, 8(11), 1790; https://doi.org/10.3390/jcm8111790 - 25 Oct 2019
Cited by 31 | Viewed by 4546
Abstract
Background: Early prediction of cerebral palsy (CP) using the General Movement Assessment (GMA) during the fidgety movements (FM) period has been recommended as standard of care in high-risk infants. The aim of this study was to determine the accuracy of GMA, alone or [...] Read more.
Background: Early prediction of cerebral palsy (CP) using the General Movement Assessment (GMA) during the fidgety movements (FM) period has been recommended as standard of care in high-risk infants. The aim of this study was to determine the accuracy of GMA, alone or in combination with neonatal imaging, in predicting cerebral palsy (CP). Methods: Infants with increased risk of perinatal brain injury were prospectively enrolled from 2009–2014 in this multi-center, observational study. FM were classified by two certified GMA observers blinded to the clinical history. Abnormal GMA was defined as absent or sporadic FM. CP-status was determined by clinicians unaware of GMA results. Results: Of 450 infants enrolled, 405 had scorable video and follow-up data until at least 18–24 months. CP was confirmed in 42 (10.4%) children at mean age 3 years 1 month. Sensitivity, specificity, positive and negative predictive values, and accuracy of absent/sporadic FM for CP were 76.2, 82.4, 33.3, 96.8, and 81.7%, respectively. Only three (8.1%) of 37 infants with sporadic FM developed CP. The highest accuracy (95.3%) was achieved by a combination of absent FM and abnormal neonatal imaging. Conclusion: In infants with a broad range of neonatal risk factors, accuracy of early CP prediction was lower for GMA than previously reported but increased when combined with neonatal imaging. Sporadic FM did not predict CP in this study. Full article
27 pages, 2014 KiB  
Article
Cerebral Palsy: Early Markers of Clinical Phenotype and Functional Outcome
by Christa Einspieler, Arend F. Bos, Magdalena Krieber-Tomantschger, Elsa Alvarado, Vanessa M. Barbosa, Natascia Bertoncelli, Marlette Burger, Olena Chorna, Sabrina Del Secco, Raye-Ann DeRegnier, Britta Hüning, Jooyeon Ko, Laura Lucaccioni, Tomoki Maeda, Viviana Marchi, Erika Martín, Catherine Morgan, Akmer Mutlu, Alice Nogolová, Jasmin Pansy, Colleen Peyton, Florian B. Pokorny, Lucia R. Prinsloo, Eileen Ricci, Lokesh Saini, Anna Scheuchenegger, Cinthia R. D. Silva, Marina Soloveichick, Alicia J. Spittle, Moreno Toldo, Fabiana Utsch, Jeanetta van Zyl, Carlos Viñals, Jun Wang, Hong Yang, Bilge N. Yardımcı-Lokmanoğlu, Giovanni Cioni, Fabrizio Ferrari, Andrea Guzzetta and Peter B. Marschikadd Show full author list remove Hide full author list
J. Clin. Med. 2019, 8(10), 1616; https://doi.org/10.3390/jcm8101616 - 4 Oct 2019
Cited by 137 | Viewed by 15096
Abstract
The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3–5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form [...] Read more.
The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3–5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant’s later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III–V), including atypical arching and persistent cramped-synchronized movements. Asymmetrical segmental movements were strongly associated with unilateral CP. Circular arm movements were associated with dyskinetic CP. This study demonstrated that use of the MOS contributes to understanding later CP prognosis, including early markers for type and severity. Full article
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9 pages, 528 KiB  
Article
Use of the General Movements Assessment for the Early Detection of Cerebral Palsy in Infants with Congenital Anomalies Requiring Surgery
by Cathryn Crowle, Alison Loughran Fowlds, Iona Novak and Nadia Badawi
J. Clin. Med. 2019, 8(9), 1286; https://doi.org/10.3390/jcm8091286 - 22 Aug 2019
Cited by 7 | Viewed by 3804
Abstract
The general movements (GMs) assessment is recognised as one of the most important tools in the early detection of cerebral palsy (CP). However, there remains a paucity of data on its application to infants with congenital anomalies requiring surgery. This was a prospective [...] Read more.
The general movements (GMs) assessment is recognised as one of the most important tools in the early detection of cerebral palsy (CP). However, there remains a paucity of data on its application to infants with congenital anomalies requiring surgery. This was a prospective study of 202 infants (mean gestation 38 weeks, SD 2.2) who had undergone major surgery for congenital anomalies in the neonatal period. Infants were assessed at three months of age (mean 12 weeks, SD 1.6) and GMs videos were independently rated by three clinicians, two blinded to clinical details. Developmental follow-up was at three years of age. Of the twenty-five infants (9%) rated as having an absence of fidgety movements, 22 were seen at 3 years, and 17 had an abnormal outcome: 11 with CP, and 6 with a developmental disability. Infants with absent fidgety movements were 21.5 (95% CI 7.3–63.8) times more likely to have an abnormal outcome including CP. None of the infants with normal fidgety movements had a diagnosis of CP and 86% were assessed to be developing normally. The GMs assessment has predictive value for cerebral palsy and neurodevelopment for infants with congenital anomalies, and should be incorporated into routine follow-up to facilitate early referral. Full article
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8 pages, 529 KiB  
Article
Early Neurological Assessment in Infants with Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia
by Domenico M. Romeo, Sarah Bompard, Francesca Serrao, Giuseppina Leo, Gianpaolo Cicala, Chiara Velli, Francesca Gallini, Francesca Priolo, Giovanni Vento and Eugenio Mercuri
J. Clin. Med. 2019, 8(8), 1247; https://doi.org/10.3390/jcm8081247 - 18 Aug 2019
Cited by 11 | Viewed by 4644
Abstract
Early neurological assessment in infants with hypoxic ischemic encephalopathy (HIE) treated with hypothermia has not been systematically explored. The aims of the present study were to assess whether the Hammersmith Infant Neurological Examination (HINE) is a good tool to predict later neurodevelopmental outcomes [...] Read more.
Early neurological assessment in infants with hypoxic ischemic encephalopathy (HIE) treated with hypothermia has not been systematically explored. The aims of the present study were to assess whether the Hammersmith Infant Neurological Examination (HINE) is a good tool to predict later neurodevelopmental outcomes at 2 year from birth in this population of infants. A total of 41 term born infants with HIE treated with hypothermia performed the HINE at 12 months and a neurodevelopmental assessment at 24 months. All the infants who had a global HINE score between 67 and 78 were able to walk independently at 2 years and reported a normal developmental quotient; language disorders were observed in a limited number of infants. HINE scores <67 were always associated with motor impairment. In conclusion, the HINE confirms its role as one of the early neurological examination tools for the diagnosis of high risk infants, even in infants with HIE treated with hypothermia. These results can be useful for clinicians involved in the follow up of these infants for early identification of motor disabilities and in planning appropriate intervention. Full article
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13 pages, 862 KiB  
Article
Motor Evoked Potentials as Potential Biomarkers of Early Atypical Corticospinal Tract Development in Infants with Perinatal Stroke
by Jesse L. Kowalski, Samuel T. Nemanich, Tanjila Nawshin, Mo Chen, Colleen Peyton, Elizabeth Zorn, Marie Hickey, Raghavendra Rao, Michael Georgieff, Kyle Rudser and Bernadette T. Gillick
J. Clin. Med. 2019, 8(8), 1208; https://doi.org/10.3390/jcm8081208 - 13 Aug 2019
Cited by 16 | Viewed by 4606
Abstract
Diagnosis of cerebral palsy (CP) after perinatal stroke is often delayed beyond infancy, a period of rapid neuromotor development with heightened potential for rehabilitation. This study sought to assess whether the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic [...] Read more.
Diagnosis of cerebral palsy (CP) after perinatal stroke is often delayed beyond infancy, a period of rapid neuromotor development with heightened potential for rehabilitation. This study sought to assess whether the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) could be an early biomarker of atypical development within the first year of life. In 10 infants with perinatal stroke, motor outcome was assessed with a standardized movement assessment. Single-pulse TMS was utilized to assess presence of MEPs. Younger infants (3–6 months CA, n = 5, 4/5 (80%)) were more likely to present with an MEP from the more-affected hemisphere (MAH) compared to older infants (7–12 months CA, n = 5, 0/5, (0%)) (p = 0.048). Atypical movement was demonstrated in the majority of infants with an absent MEP from the MAH (5/6, 83%) compared to those with a present MEP (1/4, 25%) (p = 0.191). We found that age influences the ability to elicit an MEP from the MAH, and motor outcome may be related to MAH MEP absence. Assessment of MEPs in conjunction with current practice of neuroimaging and motor assessments could promote early detection and intervention in infants at risk of CP. Full article
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16 pages, 604 KiB  
Article
Motor and Postural Patterns Concomitant with General Movements Are Associated with Cerebral Palsy at Term and Fidgety Age in Preterm Infants
by Fabrizio Ferrari, Carlotta Plessi, Laura Lucaccioni, Natascia Bertoncelli, Luca Bedetti, Luca Ori, Alberto Berardi, Elisa Della Casa, Lorenzo Iughetti and Roberto D’Amico
J. Clin. Med. 2019, 8(8), 1189; https://doi.org/10.3390/jcm8081189 - 8 Aug 2019
Cited by 18 | Viewed by 4666
Abstract
General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. [...] Read more.
General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. Video recordings performed after birth in 79 preterm infants were reviewed retrospectively. Thirty-seven infants developed cerebral palsy at 2 years corrected age and the remaining 42 showed typical development. GMs were assessed from preterm to fidgety age and GM trajectories were defined. The 11 motor and postural patterns were evaluated at each age and longitudinally, alone and in combination with GM trajectories. A logistic regression model was used to assess the association between GMs, concomitant motor and postural patterns, and cerebral palsy. We confirmed that high-risk GM trajectories were associated with cerebral palsy (odds ratio = 44.40, 95% confidence interval = 11.74–167.85). An association between concomitant motor and postural patterns and cerebral palsy was found for some of the patterns at term age and for all of them at fidgety age. Therefore, at term age, concomitant motor and postural patterns can support GMs for the early diagnosis of cerebral palsy. Full article
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18 pages, 397 KiB  
Article
Efficacy of the Small Step Program in a Randomized Controlled Trial for Infants under 12 Months Old at Risk of Cerebral Palsy (CP) and Other Neurological Disorders
by Linda Holmström, Ann-Christin Eliasson, Rita Almeida, Catarina Furmark, Ann-Louise Weiland, Kristina Tedroff and Kristina Löwing
J. Clin. Med. 2019, 8(7), 1016; https://doi.org/10.3390/jcm8071016 - 11 Jul 2019
Cited by 30 | Viewed by 4741
Abstract
The objective was to evaluate the effects of the Small Step Program on general development in children at risk of cerebral palsy (CP) or other neurodevelopmental disorders. A randomized controlled trial compared Small Step with Standard Care in infants recruited at 4–9 months [...] Read more.
The objective was to evaluate the effects of the Small Step Program on general development in children at risk of cerebral palsy (CP) or other neurodevelopmental disorders. A randomized controlled trial compared Small Step with Standard Care in infants recruited at 4–9 months of corrected age (CA). The 35-week intervention targeted mobility, hand use, and communication during distinct periods. The Peabody Developmental Motor Scales2ed (PDMS-2) was the primary outcome measure. For statistical analysis, a general linear model used PDMS-2 as the main outcome variable, together with a set of independent variables. Thirty-nine infants were randomized to Small Step (n = 19, age 6.3 months CA (1.62 SD)) or Standard Care (n = 20, age 6.7 months CA (1.96 SD)). Administering PDMS-2 at end of treatment identified no group effect, but an interaction between group and PDMS-2 at baseline was found (p < 0.02). Development was associated with baseline assessments in the Standard Care group, while infants in the Small Step group developed independent of the baseline level, implying that Small Step helped the most affected children to catch up by the end of treatment. This result was sustained at 2 years of age for PDMS-2 and the PEDI mobility scale. Full article
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13 pages, 266 KiB  
Article
Factors Associated with Parents’ Adherence to Different Types of Exercises in Home Programs for Children with Disabilities
by Carmen Lillo-Navarro, Joaquina Montilla-Herrador, Pilar Escolar-Reina, Silvana L. Oliveira-Sousa, Jose A. García-Vidal and Francesc Medina-Mirapeix
J. Clin. Med. 2019, 8(4), 456; https://doi.org/10.3390/jcm8040456 - 5 Apr 2019
Cited by 19 | Viewed by 4585
Abstract
There is a lack of knowledge with regard to the adherence to different types of exercises prescribed for children with disabilities. The aim was to examine parents’ adherence to prescriptions of different types of home exercises; to identify associated factors related to the [...] Read more.
There is a lack of knowledge with regard to the adherence to different types of exercises prescribed for children with disabilities. The aim was to examine parents’ adherence to prescriptions of different types of home exercises; to identify associated factors related to the parents, the children and the environment, and to assess the relative influence of the behaviour of health professionals. Parents (393) were recruited from 18 early intervention centres. A cross-sectional survey using a self-reported questionnaire was used to examine whether three types of exercises (“flexibility exercises”, “neuromotor development training” and “body mechanics and postural stabilisation”) were prescribed in their home programs; if the child had received exercises according to a prescription; and items related to the parents, child, environment, and health professionals. The adherence rates were different among the types of exercises. Parents with low perception of barriers and high self-efficacy had a higher adherence to neuromotor development training and postural stabilization, whereas parents with a high level of knowledge increased their odds of adherence to flexibility exercises. Health professionals’ behaviour had a distinct influence on the adherence to different exercises. This study suggests the need to specifically consider the types of exercises prescribed in the management of adherence to home programs. Full article
17 pages, 3710 KiB  
Article
Annexin A1 as Neuroprotective Determinant for Blood-Brain Barrier Integrity in Neonatal Hypoxic-Ischemic Encephalopathy
by Ruth Gussenhoven, Luise Klein, Daan R. M. G. Ophelders, Denise H. J. Habets, Bernd Giebel, Boris W. Kramer, Leon J. Schurgers, Chris P. M. Reutelingsperger and Tim G. A. M. Wolfs
J. Clin. Med. 2019, 8(2), 137; https://doi.org/10.3390/jcm8020137 - 24 Jan 2019
Cited by 51 | Viewed by 6501
Abstract
Blood-brain barrier (BBB) disruption is associated with hypoxia-ischemia (HI) induced brain injury and life-long neurological pathologies. Treatment options are limited. Recently, we found that mesenchymal stem/stromal cell derived extracellular vesicles (MSC-EVs) protected the brain in ovine fetuses exposed to HI. We hypothesized that [...] Read more.
Blood-brain barrier (BBB) disruption is associated with hypoxia-ischemia (HI) induced brain injury and life-long neurological pathologies. Treatment options are limited. Recently, we found that mesenchymal stem/stromal cell derived extracellular vesicles (MSC-EVs) protected the brain in ovine fetuses exposed to HI. We hypothesized that Annexin A1 (ANXA1), present in MSC-EVs, contributed to their therapeutic potential by targeting the ANXA1/Formyl peptide receptor (FPR), thereby preventing loss of the BBB integrity. Cerebral ANXA1 expression and leakage of albumin into the fetal ovine brain parenchyma after HI were analyzed by immunohistochemistry. For mechanistic insights, barrier integrity of primary fetal endothelial cells was assessed after oxygen-glucose deprivation (OGD) followed by treatment with MSC-EVs or human recombinant ANXA1 in the presence or absence of FPR inhibitors. Our study revealed that BBB integrity was compromised after HI which was improved by MSC-EVs containing ANXA1. Treatment with these MSC-EVs or ANXA1 improved BBB integrity after OGD, an effect abolished by FPR inhibitors. Furthermore, endogenous ANXA1 was depleted within 24 h after induction of HI in cerebovasculature and ependyma and upregulated 72 h after HI in microglia. Targeting ANXA1/FPR with ANXA1 in the immature brain has great potential in preventing BBB loss and concomitant brain injury following HI. Full article
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2 pages, 152 KiB  
Correction
Correction: Association between Gait Deviation Index and Physical Function in Children with Bilateral Spastic Cerebral Palsy: A Cross-Sectional Study. J. Clin. Med. 2020, 9, 28
by Tadashi Ito, Koji Noritake, Hiroshi Sugiura, Yasunari Kamiya, Hidehito Tomita, Yuji Ito, Hideshi Sugiura, Nobuhiko Ochi and Yuji Yoshihashi
J. Clin. Med. 2020, 9(2), 569; https://doi.org/10.3390/jcm9020569 - 19 Feb 2020
Cited by 2 | Viewed by 2924
Abstract
The authors wish to make the following corrections to this paper [...] Full article
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Perspective
Early Diagnosis and Classification of Cerebral Palsy: An Historical Perspective and Barriers to an Early Diagnosis
by Anna te Velde, Catherine Morgan, Iona Novak, Esther Tantsis and Nadia Badawi
J. Clin. Med. 2019, 8(10), 1599; https://doi.org/10.3390/jcm8101599 - 3 Oct 2019
Cited by 88 | Viewed by 19988
Abstract
Since the 1800s, there have been calls in the literature for the early diagnosis of cerebral palsy (CP). However, diagnosis still often occurs late, from 12 to 24 months in high income countries and as late as 5 years in low resource settings. [...] Read more.
Since the 1800s, there have been calls in the literature for the early diagnosis of cerebral palsy (CP). However, diagnosis still often occurs late, from 12 to 24 months in high income countries and as late as 5 years in low resource settings. This is after the optimal timeframe for applying interventions which could harness neuroplastic potential in the developing brain. Multiple barriers exist which affect clinicians’ confidence in diagnosing CP early. These range from the lack of definitive biomarkers to a lack of curative treatments for CP. Further barriers to diagnosis are proposed including; (a) difficulty finding a congruent fit with the definition of CP in an infant, where expected activity limitations might not yet be apparent; and (b) differences in the presentation of motor type and topography classifications between infants and children. These barriers may affect a clinicians’ confidence using “pattern recognition” in the differential diagnosis process. One of the central tenets of this paper is that diagnosis and classification are different, involving different instruments, and are more accurately conducted separately in infants, whereas they are fundamentally interconnected in older children and inform therapeutic decisions. Furthermore, we need to be careful not to delay early diagnosis because of the low reliability of early classification, but instead uncouple these two processes. Ongoing implementation of best practice for early detection requires creative solutions which might include universal screening for CP. Implementation and accompanying knowledge translation studies are underway to decrease the average age of diagnosis in CP. Full article
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