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21 pages, 3706 KiB

Open AccessArticle

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 17 | Viewed by 3111

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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8 pages, 555 KiB

Open AccessArticle

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 4224 | 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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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17 pages, 2181 KiB

Open AccessArticle

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 58 | Viewed by 6869

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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11 pages, 706 KiB

Open AccessFeature PaperArticle

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 - 05 Nov 2019

Cited by 73 | Viewed by 7634

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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11 pages, 223 KiB

Open AccessArticle

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 24 | Viewed by 3880

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

27 pages, 2014 KiB

Open AccessArticle

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. Marschik Show full author list Hide full author list

J. Clin. Med. 2019, 8(10), 1616; https://doi.org/10.3390/jcm8101616 - 04 Oct 2019

Cited by 113 | Viewed by 13479

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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9 pages, 528 KiB

Open AccessArticle

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 3441

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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8 pages, 529 KiB

Open AccessArticle

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 9 | Viewed by 4194

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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13 pages, 862 KiB

Open AccessArticle

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 4215

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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16 pages, 604 KiB

Open AccessArticle

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 - 08 Aug 2019

Cited by 18 | Viewed by 4242

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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18 pages, 397 KiB

Open AccessArticle

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 23 | Viewed by 4145

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 Scales^2ed (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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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13 pages, 266 KiB

Open AccessArticle

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 - 05 Apr 2019

Cited by 15 | Viewed by 4012

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

17 pages, 3710 KiB

Open AccessArticle

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 48 | Viewed by 5962

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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2 pages, 152 KiB

Open AccessCorrection

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 2695

Abstract

The authors wish to make the following corrections to this paper [...] Full article

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

13 pages, 992 KiB

Open AccessPerspective

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 - 03 Oct 2019

Cited by 73 | Viewed by 17813

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

(This article belongs to the Special Issue Early Diagnosis and Early Intervention for Children with Cerebral Palsy, First Three Years of Life)

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