Background aims: Umbilical cord blood (UCB) infusion is being investigated as a treatment for a r... more Background aims: Umbilical cord blood (UCB) infusion is being investigated as a treatment for a range of neurological conditions, primarily because of its potent immunomodulatory effects mediated via paracrine signaling. Although initial research mainly utilized autologous UCB, allogeneic samples from a sibling or unrelated donor have now become more common. With the use of allogeneic UCB, questions have arisen surrounding the necessity for human leukocyte antigen (HLA) matching, preparative regimens and immunosuppressant drugs. To investigate the safety of allogeneic UCB for the treatment of neurological conditions and the impact of HLA mismatching and immunosuppresion, the authors conducted a systematic review of the safety of allogeneic UCB infusion for neurological conditions. Methods: A systematic review of published and gray literature was conducted to investigate the safety of allogeneic UCB infusions for neurological conditions. Results: Authors identified 10 studies using allogeneic UCB to treat autism spectrum disorder, cerebral palsy, stroke, traumatic brain injury and various other conditions. A total of 361 participants (with at least 442 UCB infusions) received a range of HLA-matched/untyped allogeneic units and cell doses, with the majority not administered post-infusion immunosuppression. There were no reported serious adverse events definitely or probably related to the allogeneic UCB infusion, nor later potential complications such as graft-versushost disease or teratoma formation. Conclusions: Although variability between studies is high, the available data do not identify safety concerns with allogeneic UCB infusion for the treatment of neurological conditions, even with variable HLA matching or no immunosuppression.
BACKGROUND Cerebral palsy (CP) is the most common motor disability of childhood. Its early identi... more BACKGROUND Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function. METHODS A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination. RESULTS Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP. CONCLUSION Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community.
Background and ObjectivesCerebral palsy (CP), the most common motor disability of childhood, is v... more Background and ObjectivesCerebral palsy (CP), the most common motor disability of childhood, is variably diagnosed. We hypothesized that child neurologists and neurodevelopmentalists, often on the frontlines of CP diagnosis in North America, harbor uncertainties regarding the practical application of the most recent CP consensus definition from 2006.MethodsWe conducted a cross-sectional survey of child neurologists and neurodevelopmentalists at the 2022 Child Neurology Society Annual Meeting. Attendees were provided the 2006 CP consensus definition and asked whether they had any uncertainties about the practical application of the definition across four hypothetical clinical vignettes.ResultsOf 230 attendees, 164 responded to the closing survey questions (71%). 145/164 (88%) expressed at least one uncertainty regarding the clinical application of the 2006 definition. Overwhelmingly, these areas of uncertainty focused on: 1) Age, both with regards to the minimum age of diagnosis and ...
Supplemental Material, Placenta_Preterm_BR_22-11-19 for The Role of the Placenta in Perinatal Str... more Supplemental Material, Placenta_Preterm_BR_22-11-19 for The Role of the Placenta in Perinatal Stroke: A Systematic Review by Bithi Roy, Susan Arbuckle, Karen Walker, Catherine Morgan, Claire Galea, Nadia Badawi and Iona Novak in Journal of Child Neurology
AIM The aim of this review was to determine the effectiveness of hand splinting for improving han... more AIM The aim of this review was to determine the effectiveness of hand splinting for improving hand function in children with cerebral palsy (CP) and brain injury. METHOD A systematic review with meta-analyses was conducted. Only randomized and quasi-randomized controlled trials in which all participants were children aged 0 to 18 years with CP or brain injury and a hand splint (cast, brace, or orthosis) were included. RESULTS Six studies met the inclusion criteria. No study included participants with a brain injury; therefore, the results relate only to CP. Five studies investigated 'non-functional hand splints' and one investigated a 'functional hand splint'. Moderate-quality evidence indicated a small benefit of non-functional hand splints plus therapy on upper limb skills over therapy alone (standard mean difference [SMD]=0.81, 95% confidence interval [CI]=0.03–1.58), although benefits were diminished 2 to 3 months after splint wearing stopped (SMD=0.35, CI À0.06 ...
The general movements (GMs) assessment is recognised as one of the most important tools in the ea... 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.
Neonates who undergo major surgery are at risk of neurodevelopmental disability. The General Move... more Neonates who undergo major surgery are at risk of neurodevelopmental disability. The General Movements Assessment (GMA) is a valid and reliable method to predict neurodevelopment, however, there are minimal data on the applicability among infants post-surgery. To describe GMs trajectories following neonatal surgery. Prospective cohort study. 217 infants following major cardiac and non-cardiac neonatal surgery. Infants were assessed following surgery at term age (mean 40weeks, SD 2.3), and at 3months of age (mean 12weeks, SD 1.6) using the GMA and the Bayley Scales of Infant and Toddler Development III. GMA videos were independently scored by three advanced trained assessors, two blinded to infant details. The most common result in the writhing period was 'poor repertoire' (n=117, 54%), however, 99 (84%) of these infants had normal fidgety movements. For infants with normal writhing (n=75, 34%), only four had absent fidgety movements. Cramped synchronised movements were seen in 10 infants, and three of these were rated as absent fidgety. There was no significant difference between the surgical groups. In total, 24 infants (11%) had absent fidgety movements and lower scores on average in all subtests of the BSID-III than those with normal fidgety movements. This is the first report describing GMs trajectories in infants who have undergone neonatal surgery. Similar to other high risk infant populations, this group showed a high proportion of poor repertoire writhing movements, however, most infants demonstrated normal fidgety movements and development at 3months of age.
Journal of neonatal-perinatal medicine, Jan 27, 2022
BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm inf... more BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm infants. Stroke in preterm infants is different from stroke in term infants, given the differences in brain maturation and the mechanisms of injury exclusive to the immature brain. We conducted a systematic review to explore the epidemiology and pathogenesis of periventricular hemorrhagic infarction (PVHI), perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) in preterm infants. METHODS: Studies were identified based on predefined study criteria from MEDLINE, EMBASE, SCOPUS and WEB OF SCIENCE electronic databases from 2000 -2019. Results were combined using descriptive statistics. RESULTS: Fourteen studies encompassed 546 stroke cases in preterm infants between 23 -36 weeks gestational ages and birth weights between 450 -3500 grams. Eighty percent (436/546) of the stroke cases were PVHI, 17% (93/546) were PAIS and 3% (17/546) were CSVT. Parietal PVHI was more common than temporal and frontal lobe PVHI. For PAIS, left middle cerebral artery (MCA) was more common than right MCA or cerebellar stroke. For CSVT partial or complete thrombosis in the transverse sinus was universal. All cases included multiple possible risk factors, but the data were discordant precluding aggregation within a meta-analysis. CONCLUSION: This systematic review confirms paucity of data regarding the etiology and the precise causal pathway of stroke in preterm infants. Moreover, the preterm infants unlike the term infants do not typically present with seizures. Hence high index of clinical suspicion and routine cUS will assist in the timely diagnosis and understanding of stroke in this population.
Best Service Best Time Author Group (2020). Efficacy of a knowledge translation approach in chang... more Best Service Best Time Author Group (2020). Efficacy of a knowledge translation approach in changing allied health practitioner use of evidence-based practices with children with cerebral palsy a before and after longitudinal study. Disability and Rehabilitation, 1-14.
Background aims: Umbilical cord blood (UCB) infusion is being investigated as a treatment for a r... more Background aims: Umbilical cord blood (UCB) infusion is being investigated as a treatment for a range of neurological conditions, primarily because of its potent immunomodulatory effects mediated via paracrine signaling. Although initial research mainly utilized autologous UCB, allogeneic samples from a sibling or unrelated donor have now become more common. With the use of allogeneic UCB, questions have arisen surrounding the necessity for human leukocyte antigen (HLA) matching, preparative regimens and immunosuppressant drugs. To investigate the safety of allogeneic UCB for the treatment of neurological conditions and the impact of HLA mismatching and immunosuppresion, the authors conducted a systematic review of the safety of allogeneic UCB infusion for neurological conditions. Methods: A systematic review of published and gray literature was conducted to investigate the safety of allogeneic UCB infusions for neurological conditions. Results: Authors identified 10 studies using allogeneic UCB to treat autism spectrum disorder, cerebral palsy, stroke, traumatic brain injury and various other conditions. A total of 361 participants (with at least 442 UCB infusions) received a range of HLA-matched/untyped allogeneic units and cell doses, with the majority not administered post-infusion immunosuppression. There were no reported serious adverse events definitely or probably related to the allogeneic UCB infusion, nor later potential complications such as graft-versushost disease or teratoma formation. Conclusions: Although variability between studies is high, the available data do not identify safety concerns with allogeneic UCB infusion for the treatment of neurological conditions, even with variable HLA matching or no immunosuppression.
BACKGROUND Cerebral palsy (CP) is the most common motor disability of childhood. Its early identi... more BACKGROUND Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function. METHODS A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination. RESULTS Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP. CONCLUSION Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community.
Background and ObjectivesCerebral palsy (CP), the most common motor disability of childhood, is v... more Background and ObjectivesCerebral palsy (CP), the most common motor disability of childhood, is variably diagnosed. We hypothesized that child neurologists and neurodevelopmentalists, often on the frontlines of CP diagnosis in North America, harbor uncertainties regarding the practical application of the most recent CP consensus definition from 2006.MethodsWe conducted a cross-sectional survey of child neurologists and neurodevelopmentalists at the 2022 Child Neurology Society Annual Meeting. Attendees were provided the 2006 CP consensus definition and asked whether they had any uncertainties about the practical application of the definition across four hypothetical clinical vignettes.ResultsOf 230 attendees, 164 responded to the closing survey questions (71%). 145/164 (88%) expressed at least one uncertainty regarding the clinical application of the 2006 definition. Overwhelmingly, these areas of uncertainty focused on: 1) Age, both with regards to the minimum age of diagnosis and ...
Supplemental Material, Placenta_Preterm_BR_22-11-19 for The Role of the Placenta in Perinatal Str... more Supplemental Material, Placenta_Preterm_BR_22-11-19 for The Role of the Placenta in Perinatal Stroke: A Systematic Review by Bithi Roy, Susan Arbuckle, Karen Walker, Catherine Morgan, Claire Galea, Nadia Badawi and Iona Novak in Journal of Child Neurology
AIM The aim of this review was to determine the effectiveness of hand splinting for improving han... more AIM The aim of this review was to determine the effectiveness of hand splinting for improving hand function in children with cerebral palsy (CP) and brain injury. METHOD A systematic review with meta-analyses was conducted. Only randomized and quasi-randomized controlled trials in which all participants were children aged 0 to 18 years with CP or brain injury and a hand splint (cast, brace, or orthosis) were included. RESULTS Six studies met the inclusion criteria. No study included participants with a brain injury; therefore, the results relate only to CP. Five studies investigated 'non-functional hand splints' and one investigated a 'functional hand splint'. Moderate-quality evidence indicated a small benefit of non-functional hand splints plus therapy on upper limb skills over therapy alone (standard mean difference [SMD]=0.81, 95% confidence interval [CI]=0.03–1.58), although benefits were diminished 2 to 3 months after splint wearing stopped (SMD=0.35, CI À0.06 ...
The general movements (GMs) assessment is recognised as one of the most important tools in the ea... 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.
Neonates who undergo major surgery are at risk of neurodevelopmental disability. The General Move... more Neonates who undergo major surgery are at risk of neurodevelopmental disability. The General Movements Assessment (GMA) is a valid and reliable method to predict neurodevelopment, however, there are minimal data on the applicability among infants post-surgery. To describe GMs trajectories following neonatal surgery. Prospective cohort study. 217 infants following major cardiac and non-cardiac neonatal surgery. Infants were assessed following surgery at term age (mean 40weeks, SD 2.3), and at 3months of age (mean 12weeks, SD 1.6) using the GMA and the Bayley Scales of Infant and Toddler Development III. GMA videos were independently scored by three advanced trained assessors, two blinded to infant details. The most common result in the writhing period was 'poor repertoire' (n=117, 54%), however, 99 (84%) of these infants had normal fidgety movements. For infants with normal writhing (n=75, 34%), only four had absent fidgety movements. Cramped synchronised movements were seen in 10 infants, and three of these were rated as absent fidgety. There was no significant difference between the surgical groups. In total, 24 infants (11%) had absent fidgety movements and lower scores on average in all subtests of the BSID-III than those with normal fidgety movements. This is the first report describing GMs trajectories in infants who have undergone neonatal surgery. Similar to other high risk infant populations, this group showed a high proportion of poor repertoire writhing movements, however, most infants demonstrated normal fidgety movements and development at 3months of age.
Journal of neonatal-perinatal medicine, Jan 27, 2022
BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm inf... more BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm infants. Stroke in preterm infants is different from stroke in term infants, given the differences in brain maturation and the mechanisms of injury exclusive to the immature brain. We conducted a systematic review to explore the epidemiology and pathogenesis of periventricular hemorrhagic infarction (PVHI), perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) in preterm infants. METHODS: Studies were identified based on predefined study criteria from MEDLINE, EMBASE, SCOPUS and WEB OF SCIENCE electronic databases from 2000 -2019. Results were combined using descriptive statistics. RESULTS: Fourteen studies encompassed 546 stroke cases in preterm infants between 23 -36 weeks gestational ages and birth weights between 450 -3500 grams. Eighty percent (436/546) of the stroke cases were PVHI, 17% (93/546) were PAIS and 3% (17/546) were CSVT. Parietal PVHI was more common than temporal and frontal lobe PVHI. For PAIS, left middle cerebral artery (MCA) was more common than right MCA or cerebellar stroke. For CSVT partial or complete thrombosis in the transverse sinus was universal. All cases included multiple possible risk factors, but the data were discordant precluding aggregation within a meta-analysis. CONCLUSION: This systematic review confirms paucity of data regarding the etiology and the precise causal pathway of stroke in preterm infants. Moreover, the preterm infants unlike the term infants do not typically present with seizures. Hence high index of clinical suspicion and routine cUS will assist in the timely diagnosis and understanding of stroke in this population.
Best Service Best Time Author Group (2020). Efficacy of a knowledge translation approach in chang... more Best Service Best Time Author Group (2020). Efficacy of a knowledge translation approach in changing allied health practitioner use of evidence-based practices with children with cerebral palsy a before and after longitudinal study. Disability and Rehabilitation, 1-14.
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