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Aim: To describe the distribution of neuroimaging patterns in a term/late preterm population-based cohort with cerebral palsy (CP), ascertain associations between neuroimaging patterns and neonatal well-being, estimate the proportion with antenatal or perinatal timing of neuropathology, and apply this information to the understanding of common mechanisms of brain injury and causal pathways., Method: The cohort for this observational study comprised 1348 persons born between 1999 and 2017 in Victoria, Australia. Using algorithms designed for the study, neonatal well-being and timing of brain injury were tabulated for the whole cohort and across neuroimaging patterns and birth epochs., Results: Clinical and demographic profiles, neonatal well-being, and timing of brain injury differed across neuroimaging patterns. An estimated 57% of the cohort had a complicated neonatal period. Timing of brain injury was antenatal in 57% and perinatal in 41%. A decrease in the relative proportions of perinatal timing of brain injury was observed over a period when the rates of CP in live births at term decreased., Interpretation: This study begins to bridge the knowledge gap about causation in CP, moving towards better description of the main mechanisms of brain injury and their contribution within CP cohorts, and facilitating the ability to monitor changes over time and the success of preventive measures., What This Paper Adds: In a population-based, term/late preterm cohort with cerebral palsy, 57% had a complicated neonatal period. In the same cohort, 57% had presumed antenatal timing of brain injury. The relative proportion with perinatal injury decreased over time., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Aim: To better understand parents' beliefs about causation in cerebral palsy (CP) and the emotions related to those beliefs., Method: We surveyed 226 parents of children with CP aged 1 to 18 years, recruited from the Victorian Cerebral Palsy Register, to evaluate their beliefs about the causes of CP, including genetic causes, causes specific to their own child, and their attitudes and emotions in relation to these., Results: Although 92% of participants reported that understanding the causes of their child's CP was important, uncertainty about the cause was expressed by 13%. The most frequently endorsed causal factors, in general and in their own child respectively, were intrapartum hypoxia (81%, 36%) or brain damage (69%, 22%), brain damage during pregnancy (73%, 28%), and preterm birth (66%, 28%). Genetic causes were deemed relevant by 13% of participants and hospital or professional error by 16%. Parents shared related feelings of anger (59%), sadness (80%), guilt (61%), and confusion (53%); parental anger was more likely when their child's CP was attributed to intrapartum events., Interpretation: Substantial parental interest in understanding the causes of CP, together with uncertainty about the causes, parents' causal attributions, and significant emotional sequelae, highlight a strong need for provision of information and support for families of children recently diagnosed with CP., What This Paper Adds: Understanding the causes of their child's cerebral palsy (CP) was important to parents. Parents most often endorsed intrapartum factors as a cause of CP. Parents reported experiencing strong emotions about the causes of their child's CP., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Purpose: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy., Methods: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes., Results: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury., Conclusions: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To provide an updated description of the rates, trends, and predictors of mortality of individuals with cerebral palsy (CP), born in the Australian state of Victoria between 1970 and 2012., Method: Data were extracted for 4807 individuals (2091 females; 2716 males). The probability of survival to 30th June 2017 was calculated using the Kaplan-Meier method. Mortality rates were calculated per 1000 person-years using age strata and compared with population mortality rates to produce mortality ratios. Cox proportional hazards regression was used to calculate hazard ratios for selected demographic and clinical characteristics and to estimate the effect of birth epoch on 15-year survival., Results: There were 666 recorded deaths. Compared to the general population, mortality was higher for all persons with CP and highest for children aged 1 to 15 years (45-62 times). We observed 35% improvement in the probability of survival to 15 years for births in the 2000s relative to the 1970s (hazard ratio 0.65, 95% confidence interval [CI] 0.49, 0.86), but only 4% improvement for the subgroup with complex CP (hazard ratio 0.96, 95% CI 0.69, 1.33)., Interpretation: The observed improvements in survival for those born in the 2000s is likely related predominantly to a proportional reduction in complex CP within the cohort., What This Paper Adds: Length of survival improved for Australians with cerebral palsy (CP) born this millennium. Improved survival was mainly because of a proportional reduction in complex CP. A small improvement in length of survival was seen for children with complex CP., (© 2022 Mac Keith Press.)

Objective: To determine the frequency of paroxysmal nonepileptic events in children with cerebral palsy due to brain injury who have epilepsy and to describe the factors associated with paroxysmal nonepileptic events. Methods: Retrospective, population-based study of children from the Victorian CP Register born 1999-2006. Neuroimaging, medical records, electroencephalograms (EEG), and EEG requests were analyzed. Results: Of the included 256 children, 87 had epilepsy. EEGs (with video correlation) were available for 82 of 87. Eighteen (18/82, 22%) had epileptic events captured on EEG. Twenty-one (21/82, 26%) had paroxysmal nonepileptic events captured on EEG. The majority (13/18, 77%) of children with epileptic events also had paroxysmal nonepileptic events captured. Ten parents and carers continued to report events as epileptic despite there being no ictal EEG correlate for specific events on multiple EEGs. There were no clear associations to identify which children would have ongoing paroxysmal nonepileptic events reported. Conclusions: Paroxysmal nonepileptic events were captured on EEG in one-fourth of children from this cerebral palsy cohort with epilepsy and available EEG. Half the parents and carers reported previously identified paroxysmal nonepileptic events as epileptic on subsequent EEGs, highlighting the need for clearer counseling so that parents better understand seizure semiology in children with EEG-proven paroxysmal nonepileptic events.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To describe post-neonatally acquired (PNN) cerebral palsy (CP) in terms of temporal trends in prevalence, clinical and sociodemographic profiles, known causes and associations between causes, and sociodemographic variables., Method: Numerator data, a count of children with PNN-CP confirmed at 5 years of age (n = 523), was drawn from two Australian state CP registers (birth years 1973-2012). Poisson regression was used to investigate temporal trends in the prevalence of PNN-CP by 5-year intervals, calculated per 10 000 live births. Using data from all state and territory Australian CP registers (n = 469), distributions of clinical characteristics, PNN-CP causes, and sociodemographic factors were tabulated (birth years 1995-2012). χ 2 and logistic regression analyses were used to assess associations between sociodemographic profile, Australian reference data, and known causes., Results: A significant temporal decline in PNN-CP in Victoria (p = 0.047) and Western Australia (p = 0.033) was observed. The most common proximal causes of PNN-CP were cerebrovascular accidents (34%, n = 158), infection (25%, n = 117), and non-accidental injuries (12%, n = 58). Children born to teenage mothers, Aboriginal and/or Torres Strait Islander mothers, or children born in remote areas were over-represented in this cohort compared with reference data (all p ≤ 0.001). Infectious causes were strongly associated with teenage motherhood (odds ratio 3.0 [95% confidence interval 1.1-8.2], p = 0.028) and remote living (odds ratio 4.5 [95% confidence interval 2.0-10.2], p < 0.001)., Interpretation: Although prevalence of PNN-CP has declined, the over-representation of priority populations, and the relative severity of a condition that is largely preventable, suggest the need for more specific primary preventive measures and support., What This Paper Adds: Prevalence of post-neonatally acquired (PNN) cerebral palsy (CP) in Australia significantly declined between 1973 and 2012. Cerebrovascular accidents are the most common proximal cause of PNN-CP. Children born in remote areas are at greater risk of PNN-CP., (© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objective: To examine the influence of subtests that require fine motor responses on measures of intellectual ability, and compare three approaches to minimizing motor demands while assessing cognitive abilities in adolescents with cerebral palsy (CP) to the traditional method of the Wechsler Intelligence Scale for Children - Fifth edition (WISC-V). Method: Seventy adolescents with CP ( M  = 14 years 6 months, SD  = 10 months) who were able to provide either a verbal or point response were assessed using the WISC-V administered via Q-interactive. The pencil-to-paper version of Coding was also administered. Performance on Block Design and pencil-to-paper Coding was compared to Visual Puzzles and Coding on Q-interactive, respectively. Full Scale IQ (FSIQ) scores derived according to the Traditional method of the WISC-V were compared to alternative estimates of FSIQ derived according to the Q-interactive, Nonmotor, and Motor-free methods, which minimized motor demands. Results: An additional 7-12% of participants were able to respond to Visual puzzles and Coding on Q-interactive compared to Block Design and pencil-to-paper Coding, respectively, and performance was marginally but significantly better. For 54 adolescents (Gross Motor Function Classification System (GMFCS) Level I-III) who were able to obtain FSIQ scores, the Traditional method underestimated FSIQ by 3-6 points compared to the alternative methods and the difference was most pronounced for those with more severe CP as measured by the GMFCS. Conclusion: Adolescents with CP are at an inherent disadvantage when cognitive ability is assessed using the Traditional method of the WISC-V. Findings suggest clinicians should employ the Nonmotor or Motor-free methods when assessing IQ in adolescents with CP.

Aim: This 10-year follow-up study examined cognitive change in a cohort of children with cerebral palsy from preschool to adolescence at the group and individual levels., Methods: The Wechsler Preschool and Primary Scale of Intelligence was administered to 80 children with cerebral palsy (mean = 4 years 6 months, standard deviation = 7 months) at baseline (Time 1). At 10-year follow-up (Time 2), 28 adolescents (mean = 14 years 6 months, standard deviation = 9 months) returned for assessment with the Wechsler Intelligence Scale for Children. Motor-free intelligence quotient (IQ) scores were calculated and paired-samples t-tests and the Reliable Change Index (RCI) were used to investigate change in IQ over time., Results: At the group level, nonverbal IQ scores declined significantly. At the individual level, RCI indicated nine and 11 children showed a clinically significant decline in Full Scale IQ (FSIQ) and nonverbal IQ scores, respectively. Decline in FSIQ was related to a history of seizures whereas decline in nonverbal IQ was associated with higher initial IQ., Conclusion: Cognitive abilities in children with cerebral palsy evolve over time and selective deficits may not be observable until a later age, highlighting the importance of repeated cognitive assessment throughout childhood and adolescence., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels., Method: In this retrospective case-control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (n = 1290). We compared mean and abnormal levels of alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β-hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups., Results: Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; p < 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p < 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p < 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight., Interpretation: Abnormal second-trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases., (© 2021 John Wiley & Sons Ltd.)

Background: The most commonly used intelligence tests - the Wechsler Scales - do not provide standardised procedures for assessing children with motor impairment, and as a result, may underestimate the intelligence quotient (IQ) of young people with CP., Aims: To characterise a motor-free cognitive profile of adolescents with CP using the Wechsler Intelligence Scale for Children - Fifth edition (WISC-V) and explore the influence of clinical factors on cognitive abilities., Methods and Procedure: The WISC-V was used to assess cognitive abilities in 70 adolescents (M = 14 years 6 months, SD = 10 months). Sixty-six adolescents (Gross Motor Function Classification System (GMFCS) Level I, n = 26 ; II, n = 23; III, n = 15; IV, n = 1; V, n = 1) obtained either a Motor-free IQ or index score using the motor-free method., Outcomes and Results: MFIQ and index scores fell below the normative data and rates of borderline and impaired cognitive abilities were significantly higher in the CP group. Scores showed an uneven cognitive profile with a relative strength in verbal abilities. Severity of motor impairment and small for gestational age (SGA) were associated with lower IQ scores. A history of seizures was related to lower verbal abilities., Conclusions and Implications: Cognitive abilities of adolescents with CP are significantly below expectation compared to normative data. Severity of motor impairment, SGA, and seizures need to be recognised by health professionals as risk factors for cognitive impairment. A substantial proportion of adolescents showed borderline cognitive abilities, constituting a group with CP which are relatively neglected in the literature., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Progressive musculoskeletal pathology is ubiquitous among children with cerebral palsy (CP). Corrective surgery places them at risk of major blood loss and red blood cell (RBC) transfusion. Significant variability exists in uptake of perioperative patient blood management (PBM) strategies. This study aimed to examine factors contributing to RBC transfusion and assist in future development of care pathways., Methods: A retrospective review at a tertiary paediatric hospital was undertaken to identify patients with CP undergoing either primary spinal fusion or single event, multilevel surgery (SEMLS) between 2010 and 2015. Solely soft tissue procedures were excluded. Data collected included demographics, Gross Motor Function Classification System level, surgical details, perioperative PBM and transfusion rates. Univariable analysis was performed to assess contributing factors to RBC transfusion., Results: A total of 36 spinal fusion and 98 SEMLS patients were included. Preoperatively, 12% were anaemic, but only 19% had a ferritin checked. Overall, 49 patients (37%) received RBC transfusions. Intraoperative usage of tranexamic acid and cell salvage was 89% and 81%, respectively, for the spine cohort, and 22% and 3% for the SEMLS cohort. Successively higher Gross Motor Function Classification System levels, sodium valproate usage, longer surgical times, spinal fusion, pelvis instrumentation and more osteotomies were associated with RBC transfusion., Conclusion: More than one-third of CP patients who underwent major orthopaedic surgery received RBC transfusion. As expected, the more severely affected patients undergoing longer procedures were at highest risk. Significant improvements can be made in PBM to help optimize patients for surgery and minimize the need for transfusion., (© 2020 Royal Australasian College of Surgeons.)

Aim: To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy (CP) and to identify CP characteristics associated with abnormal biomarker levels., Method: In this retrospective case-control data linkage study, we matched mothers of 435 singletons with CP from a population register to their cFTS records and selected 10 singleton pregnancy controls per case. We compared mean and abnormal levels (expressed as multiples of the median [MoMs]) of pregnancy-associated plasma protein-A (PAPP-A), beta subunit of human chorionic gonadotrophin (β-hCG), and nuchal translucency between cases and controls and between CP subgroups., Results: Compared with control pregnancies, CP pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01 MoM, p=0.02) and β-hCG (0.93 vs 0.99 MoM, p=0.02). Biomarker levels in CP pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A (p<0.01), 1.4 times for β-hCG (p=0.12), and 2.6 times for low PAPP-A and β-hCG together (p=0.04). In cases with CP, an abnormally low PAPP-A level was associated with moderate preterm birth, low Apgar scores, and Gross Motor Function Classification System level V. Low β-hCG was associated with very low birthweight., Interpretation: Low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to CP., What This Paper Adds: Low first-trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. Causal pathways involving preterm birth, term neonatal encephalopathy, and genetic syndromes may be implicated., (© 2020 Mac Keith Press.)

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.

Aims: To describe the prevalence of, and factors associated with, anxiety in 6-18-year-old children with cerebral palsy (CP) and determine how often clinicians screen for and manage anxiety in this group., Methods: Using a population CP register as the sampling pool, 569 families were approached by email, and 172 (mean age of children 12 years 7 months [SD 3 years 5 months]; 96 males) participated. Parents and, where able, children completed the Screen for Child Anxiety Related Emotional Disorders (SCARED). Parents also completed the Strengths and Difficulties Questionnaire. Children's medical records were searched for previous anxiety diagnoses and treatments., Results: Clinically significant anxiety was identified in 38% of children on parent reports and 46% on child reports. Girls were twice as likely to have anxiety (p = 0.02). Parent- and child-reported scores were strongly correlated (r = 0.853). Fewer parents of children with intellectual and communication impairments completed the survey. Based on the SCARED parent reports, anxiety was not identified by a clinician in 16 children (43%) with clinically significant anxiety., Conclusion: Anxiety symptoms are prominent among children with CP, indicating a need for routine screening. Available screening tools are unsuitable for children with more severe limitations in cognition and communication; further research is needed to address this gap., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Aim: To describe the characteristics of emergency department (ED) presentations due to complications from gastrostomy or gastrojejunal feeding tubes among children with cerebral palsy (CP), the complexity of complications and the management approaches taken., Methods: The Victorian CP Register was linked to the ED databases of Victoria's two tertiary paediatric hospitals, and data on presentations due to feeding tube complications were identified based on discharge diagnosis codes. Additional data on presentations were extracted from medical records., Results: Over 5 years, there were 234 ED presentations due to feeding tube-related complaints among a CP cohort (n = 2183). ED notes were located for 183 of the 234 presentations. The majority of presentations (90%) involved children with severe gross motor impairment. A total of 46% of presentations (n = 84) was triaged as lower urgency, and 68% (n = 124) took place between 08:00 am and 06:00 pm. The most common presenting complaint was tube dislodgement (n = 105; 70%). No investigations were recorded in the majority of cases, and in almost 90% of cases, the feeding tube was successfully replaced in the ED, usually by an ED physician (n = 74) and less frequently by a surgeon (n = 9), gastroenterologist (n = 2) or nurse (n = 8); 9% (n = 17) resulted in a hospital admission., Conclusions: Most ED presentations due to feeding tube complaints in children with CP are in children with severe gross motor impairment but are able to be managed in the ED. As such, it is likely that care givers and other health professionals could manage some of the complications experienced in primary health-care settings closer to home., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Aim: To investigate trends in birth prevalence of cerebral palsy (CP) overall and by gestational age, and examine the distribution of motor type, spastic topography, and severity using Australian CP Register data from 1995 to 2009., Method: Prenatal and perinatal CP data were collated from state/territory CP registers. Birth prevalence estimates per 1000 live births and per 1000 neonatal survivors (NNS) were calculated in five epochs. Data from three state registers with population-level ascertainment were used to investigate birth prevalence trends by gestational age using Poisson regression. Distribution of motor type, spastic topography, and moderate to severe disability (IQ≤50 and/or Gross Motor Function Classification System levels III-V) were evaluated within birthweight categories., Results: Birth prevalence of CP varied across population-level states but within each state declined significantly over time (p<0.05). Birth prevalence per 1000 neonatal survivors declined amongst children born before 28 weeks (South Australia, Victoria p<0.001) and those born at or after 37 weeks (Victoria p<0.001, Western Australia p<0.002). Across Australia the percentage of children with bilateral spastic CP declined amongst those born less than 1000g. The percentage of children with moderate to severe disability decreased (48%-34%, p<0.001)., Interpretation: Birth prevalence of CP declined. Encouragingly, the percentage of children with CP whose disability was moderate to severe also decreased., What This Paper Adds: Birth prevalence of cerebral palsy (CP) differed but declined across Australian states (1995-2009). Australian CP birth prevalence declined significantly amongst children born before 28 weeks and those born at or after 37 weeks. The percentage of children with moderate to severe disability decreased., (© 2018 Mac Keith Press.)

The authors aimed to describe the distribution of predominant and secondary motor types and compare functional profiles, comorbidities, and brain imaging patterns between dyskinetic and spastic cerebral palsy. Children recruited from a cerebral palsy register were assessed at age 5, 10, or 15. Motor types, topography, functional classifications, and comorbidities were recorded. Univariable logistic regression was used to compare dyskinesia with spasticity, with and without adjustment for topography. Neuroimaging classifications were extracted from the register. Of 243 children with spasticity or dyskinesia, the predominant motor type was spastic in 183 and dyskinetic in 56. Dyskinesia was associated with comparatively poorer function, total body involvement, and gray matter injury. After adjustment for topography, dyskinesia was associated with similar or better function. The study suggests that practical tools routinely incorporated into clinical practice would facilitate accurate and reliable classification of predominant and secondary motor types, topography, and functional abilities.

Aim: A population-based observational study design was used to describe the epidemiology of intellectual disability in cerebral palsy (CP) in terms of clinical and neuroimaging associations, and to report the impact of intellectual disability on utilization of health services and length of survival., Method: Population CP registry data were used to retrospectively assess the frequency of intellectual disability and strength of associations between intellectual disability and mobility, epilepsy, vision, hearing, communication, and neuroimaging patterns (n=1141). Data linkage was undertaken to assess usage of hospital inpatient and emergency department services. Survival analysis was performed in a 30-year birth cohort (n=3248)., Results: Intellectual disability, present in 45% of the cohort, was associated with non-ambulation (47% vs 8%), later walking (mean 2y 7mo vs 1y 9mo), hypotonic (8% vs 1%) or dyskinetic (9% vs 5%) CP, a quadriplegic pattern of motor impairment (42% vs 5%), epilepsy (52% vs 12%), more emergency and multi-day hospital admissions, and reduced 35-year survival (96% vs 71%). Grey matter injuries (13% vs 6%), malformations (18% vs 6%), and miscellaneous neuroimaging patterns (12% vs 4%) were more common in people with intellectual disability., Interpretation: Intellectual disability adds substantially to the overall medical complexity in CP and may increase health and mortality disparities., What This Study Adds: Cerebral maldevelopments and grey matter injuries are associated with higher intellectual disability rates. Health care is more 'crisis-driven' and 'reactive' in children with co-occurring intellectual disability. Length of survival is reduced in individuals with CP and co-occurring intellectual disability., (© 2018 Mac Keith Press.)

Background: Cerebral palsy (CP) is a clinical description for a group of motor disorders that are heterogeneous with respect to causes, symptoms and severity. A diagnosis of CP cannot usually be made at birth and in some cases may be delayed until 2-3 years of age. This limits opportunities for early intervention that could otherwise improve long-term outcomes. CP has been recorded in monozygotic twins discordant for the disorder, indicating a potential role of non-genetic factors such as intrauterine infection, hypoxia-ischaemia, haemorrhage and thrombosis. The aim of this exploratory study was to utilise the discordant monozygotic twin model to understand and measure epigenetic changes associated with the development of CP., Methods: We performed a genome-wide analysis of DNA methylation using the Illumina Infinium Human Methylation 450 BeadChip array with DNA from newborn blood spots of 15 monozygotic twin pairs who later became discordant for CP. Quality control and data preprocessing were undertaken using the minfi R package. Differential methylation analysis was performed using the remove unwanted variation (RUVm) method, taking twin pairing into account in order to identify CP-specific differentially methylated probes (DMPs), and bumphunter was performed to identify differentially methylated regions (DMRs)., Results: We identified 33 top-ranked DMPs based on a nominal p value cut-off of p  < 1 × 10 -4 and two DMRs ( p  < 1 × 10 -3 ) associated with CP. The top-ranked probes related to 25 genes including HNRNPL , RASSF5 , CD3D and KALRN involved in immune signalling pathways, in addition to TBC1D24 , FBXO9 and VIPR2 previously linked to epileptic encephalopathy. Gene ontology and pathway analysis of top-ranked DMP-associated genes revealed enrichment of inflammatory signalling pathways, regulation of cytokine secretion and regulation of leukocyte-mediated immunity. We also identified two top-ranked DMRs including one on chromosome 6 within the promoter region of LTA gene encoding tumour necrosis factor-beta (TNF-β), an important regulator of inflammation and brain development. The second was within the transcription start site of the LIME1 gene, which plays a key role in inflammatory pathways such as MAPK signalling. CP-specific differential DNA methylation within one of our two top DMRs was validated using an independent platform, MassArray EpiTyper., Conclusions: Ours is the first epigenome-wide association study of CP in disease-discordant monozygotic twin pairs and suggests a potential role for immune dysfunction in this condition., Competing Interests: This study was approved by The Royal Children’s Hospital Human Research Ethics Committee (project ID: 33050) and involved written informed consent from each participating family.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Aim: The aims of this study were to estimate the proportion of emergency department presentations attributable to children with cerebral palsy (CP), investigate the frequency of emergency department presentations in a CP cohort, and compare emergency department presentations among children with CP with those of other children., Method: This was a retrospective cohort study. The Victorian Cerebral Palsy Register was linked to the Victorian Emergency Minimum Dataset. Data on emergency department presentations for the CP cohort occurring between 2007 and 2014 and population control data were obtained., Results: The CP cohort (n=1748) had 7015 emergency department presentations during the 7-year period, accounting for 0.4% of the 1.69 million age-specific presentations during that time. The number of annual presentations per 1000 children rose with increasing CP severity. Compared with presentations among the general population, higher proportions of presentations among the CP cohort were preceded by ambulance arrivals (27% vs 8%), triaged as urgent (66% vs 32%), and required hospital admission (38% vs 12%)., Interpretation: The marked differences in presentations between the CP cohort and the general population in the proportions that were urgent and required ambulance arrivals and hospital admissions was an important finding. Strategies to ensure appropriate use of services, including encouragement to seek earlier assistance from primary care providers, may prevent problems escalating to the need for urgent care., What This Paper Adds: Children with cerebral palsy (CP) account for 0.4% of childhood emergency department presentations. More emergency department presentations among children with CP require ambulance arrival. More CP emergency department presentations are urgent and require hospital admission. Traditional emergency department triage scales seem less accurate for this group., (© 2017 Mac Keith Press.)

Aim: The overall aim was to investigate the feasibility and utility of linking a cerebral palsy (CP) register to an administrative data set for health services research purposes. We sought to compare CP hospital admissions to general childhood population admissions, and identify factors associated with type and frequency of admissions in a CP cohort., Method: The CP register for Victoria, Australia was linked to the state's hospital admissions database. Data pertaining to the admissions of a CP cohort (n=1748) that took place between 2007 and 2014 were extracted. Population data were also obtained., Results: Overall, 80% of the CP cohort (n=1401) had at least admission between 2007 and 2014, accounting for 11 012 admissions or 1.5% of all admissions in their age group. Compared to general population admissions, CP admissions were more costly and more likely to be elective (66% vs 57%; p<0.001), medical (71% vs 57%; p<0.001), and to take place in metropolitan hospitals (92% vs 78%; p<0.001). Increased CP severity and complexity were associated with having more admissions and a higher proportion of admissions attributable to respiratory illness., Interpretation: By linking with administrative data sets, CP registers may be useful for health services research and inform health service delivery., (© 2016 Mac Keith Press.)

Aim: Limited information exists on the ability of children with cerebral palsy (CP) to ride a two-wheel bicycle, an activity that may improve health and participation. We aimed to describe bicycle-riding ability and variables associated with ability to ride in children with CP (Gross Motor Functional Classification System [GMFCS] levels I-II) compared with children with typical development., Method: This case-control study surveyed parents of 114 children with CP and 87 children with typical development aged 6 to 15 years (115 males, mean age 9y 11mo, standard deviation [SD] 2y 10mo). Kaplan-Meier methods were used to compare proportions able to ride at any given age between the two groups. Logistic regression was used to assess variables associated with ability to ride for children with CP and typical development separately., Results: The proportion of children with CP able to ride at each level of bicycle-riding ability was substantially lower at each age than peers with typical development (p<0.001). While most children with typical development were able to ride independently by 10 years of age, 51% of children with CP classified as GMFCS level I and 3% of those classified as GMFCS level II had obtained independent riding in the community by 15 years of age. Variables associated with ability to ride for children classified as GMFCS level I were age and parent-rated importance of their child being able to ride., Interpretation: Some independently ambulant children with CP can learn to ride a bicycle, in particular if they are classified as GMFCS level I. Variables associated with ability to ride deserve consideration in shaping future efforts for the majority of this population who are not yet able to ride., (© 2016 Mac Keith Press.)

Objective: The goal of this study was to describe the prevalence, syndromes, and evolution of seizure disorders in children with cerebral palsy (CP) due to white matter injury (WMI)., Methods: For this population-based cohort study, brain MRI scans and medical records were reviewed in children in the Victorian Cerebral Palsy Register born between 1999 and 2006 recorded as having WMI. Children were excluded if they had features of an undiagnosed syndrome, associated cortical malformation or injury, or no medical contact in the preceding year. Included were 166 children with CP and isolated WMI due to presumed vascular insufficiency or hemorrhage; 87 were born preterm. Seizure and CP details were obtained from medical records and interviews, and EEG recordings were reviewed., Results: Forty-one children (25%) had seizures beyond the neonatal period. Four children had West syndrome, which resolved with treatment. Thirteen children had febrile seizures that they outgrew. Thirty children had focal epilepsy with seizure manifestations and EEG discharges typical of early-onset childhood occipital epilepsy or childhood epilepsy with centrotemporal spikes; 23 have outgrown these seizures. Two children had idiopathic generalized epilepsy; it was ongoing in 1 child. Fourteen children had evolution from 1 epileptic syndrome to another. At last follow-up (median age, 12.7 years; minimum age, 9.7 years), 80% had not had a seizure for >2 years., Conclusions: The electroclinical features of seizure disorders associated with CP and WMI are those of the age-limited, epileptic syndromes of childhood, with favorable outcome in the majority. The findings have important implications for counseling and drug treatment., (Copyright © 2017 by the American Academy of Pediatrics.)

Background: Little is known about the quality of life (QOL) of young adults with cerebral palsy., Objective/hypothesis: This cross-sectional analysis compares the QOL of a cohort of young Australian adults with CP with a cohort of able-bodied peers to explore the relationship between QOL and impairments, functioning, and social participation., Methods: Young adults identified from the Victorian Cerebral Palsy Register were invited to complete a survey about QOL, gross motor function, independence in self-care, and social participation. QOL was assessed with the Quality of Life Instrument for Young Adults (YAQOL). A general population sample of young North American adults, who had completed the YAQOL was selected for comparison., Results: Surveys and consent forms were completed by 335 young adults or their proxies, an overall participation rate of 63% of those located. The mean age of the study participants was 24.7 [s.d = 2.8] years; 51% were male and 49% female. Two hundred and seven (62%) of the 335 participants self-reported their QOL. When compared with the general population sample, self-reporting participants had similar QOL scores for the social relationship and environmental context domains (p > 0.05), while QOL scores were lower for the physical health, psychological well-being, and role function domains (p < 0.001). There was no association between psychological well-being and variables related to body structure and gross motor function in young adults with CP., Conclusions: Contrary to the assumption that young adults with severe CP have low psychosocial well-being, it is apparent that these individuals can have good psychosocial well-being regardless of their disability., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: The aim of the study was to investigate the patterns of medical service use in children with cerebral palsy (CP), taking into account child and family characteristics., Methods: Nine hundred and one parents and carers of children registered with the Victorian CP Register were invited to complete a survey. Participants were asked about their child's appointments with general practitioners and public and private paediatric medical specialists over the preceding 12 months. Information on family characteristics and finances was also collected. Data on CP severity and complexity were extracted from the CP Register., Results: Three hundred and fifty parents and carers (39%) participated. Of these, 83% reported that their child had ≥1 appointment with a general practitioner over the preceding 12 months, while 84% had ≥1 appointment with a public or private paediatric medical specialist. Overall, 58% of children saw 2-5 different paediatric medical specialists, while 9% had appointments with ≥6 clinicians. Children with severe and complex CP were more likely to have had ≥1 appointment with a publically funded paediatric medical specialist and had seen a greater number of different clinicians over the study period. Family characteristics were not associated with service use., Conclusions: Children with CP are managed by a number of paediatric medical specialists, and they continue to see a range of specialists throughout adolescence. In Victoria, differences in service use are not based on family characteristics; instead the highest service users are those with severe and complex CP. For this group, care co-ordination and information sharing between treating clinicians are important, if gaps in care are to be avoided., (© 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Aim: The aim of this study was to describe the patterns of therapy service use for a sample of children and adolescents with cerebral palsy over a 1 year period and to identify factors associated with frequency of therapy and parental satisfaction with therapy frequency., Methods: Parents of 83 children completed a survey on their child's use of occupational therapy, physiotherapy and speech and language pathology services over the previous year. Participants were randomly selected from a sample stratified by age and Gross Motor Function Classification System (GMFCS) level., Results: During the year prior to survey completion, 83% of children had received occupational therapy, 88% had received physiotherapy and 60% had received speech and language pathology services. Frequency of therapy was higher for younger children (P < 0.01), those classified at GMFCS levels IV-V (P < 0.05) and those attending schools specifically for children with disabilities., Conclusions: Current structures for therapy service delivery for children with cerebral palsy are systems-based, and age-based funding systems and the organisation of services around the education system are preventing the delivery of needs-based therapy. Paediatricians that care for children and young people with cerebral palsy need to pay particular attention to those that may miss out on therapy due to age or school type, and support these families in accessing appropriate therapy., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Aim: To describe the distribution of impairments among persons with cerebral palsy (CP) in a large Australian cohort., Method: Records of persons on the Australian Cerebral Palsy Register (ACPR) (n=3466) born from 1996 to 2005 were reviewed to extract year of birth, sex, CP subtype, Gross Motor Function Classification System (GMFCS) level, and impairments in vision, hearing, speech, intellect, and epilepsy. The distributions of GMFCS levels and CP subtype were plotted, and the proportions of each level of impairment were tabulated and presented as stacked graphs within the GMFCS and CP subtype distributions., Results: The proportions of persons with CP with each associated impairment increased with increasing GMFCS level. Compared with other spastic CP subtypes, individuals with spastic quadriplegia had higher frequencies of all associated impairments. Other than epilepsy, which was most prevalent in persons with spastic quadriplegia (53%), all impairments were most frequent in non-spastic CP subtypes. Hearing impairment was recorded for 21% of persons with dyskinesia whereas the hypotonic subtype had the highest prevalence of visual impairment (57%), intellectual impairment (90%), and speech impairment (95%)., Interpretation: Distributions of associated impairments across all GMFCS levels and CP subtypes in a large cohort are presented in formats suitable for clinical use and discussion with families., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Aim: Males typically outnumber females in cerebral palsy (CP) cohorts. To better understand this 'male disadvantage' and provide insight into causal pathways to CP, this study used 1983 to 2009 Australian CP and population birth cohorts to identify associations and trends with respect to biological sex and CP., Method: Within birth gestation groups, sex ratios were calculated to evaluate any male excess in the CP cohort compared with livebirths, neonatal deaths, neonatal mortality and survival rates, neonatal survivors, and CP rates in survivors. Sex- and gestation-specific trends in neonatal mortality, CP rates, and CP sex ratios were assessed by plotting their annual frequencies and fitting quadratic curves., Results: Over-representation of males in preterm live births partly explained the male excess in the CP cohort after preterm birth, especially at 28 to 31 weeks. Higher CP rates in male neonatal survivors also contributed to the male excess in CP, particularly at <28 and 37+ weeks. Higher neonatal mortality rates in males at all gestations had little impact on the CP sex ratio. There was no clearly discernible change over time in the CP sex ratio., Interpretation: Gestation-specific associations between sex and CP provide insight into causal pathways to CP and suggest sex-specific differences in response to neuroprotective strategies., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Aim: Our aim was to build on previous research indicating that rates of cerebral palsy (CP) in the Australian state of Victoria are declining, and examine whether severity of impairments is also decreasing., Method: Data on individuals with CP were extracted from the Victorian Cerebral Palsy Register for birth years 1983 to 2009. The yearly rates of dichotomized categories for gross motor function, motor laterality, intellectual impairment, and epilepsy per 1000 neonatal survivors and proportions in the CP cohort were tabulated and plotted by birth gestation. Linear regression modelling was used to fit prediction curves; likelihood ratio tests were used to test for differences in trends between impairment severity groups., Results: Since the mid-1990s, CP rates declined in neonatal survivors of birth at all gestations. Our data suggest that the decreasing CP rates were associated with relatively greater decreases in the rates of Gross Motor Function Classification System levels III to V, bilateral CP, epilepsy, and intellectual impairment (all p<0.005). Some variation was seen between birth gestation groups., Interpretation: Declines in rates of CP of all levels of severity and complexity from the mid-1990s provides 'real-world' support for the effectiveness of concurrent neuroprotective strategies and continual innovation in perinatal practices., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Aims: In a population cohort of children with grey matter injury (GMI) and cerebral palsy (CP), we aimed to describe and classify magnetic resonance imaging characteristics specific to GMI, and to identify key structure-function associations that serve as a basis for rating GMI in clinically relevant ways., Method: Symmetry, extent of cerebral injury, and pathological pattern for 54 children (37 males, 17 females) with CP and a predominant GMI pattern on chronic-phase magnetic resonance imaging were related to gross motor function, motor type and topography, epilepsy, intellectual disability, blindness, and deafness., Results: Relative to mild GMI where there was no pallidal abnormality, severe GMI, comprising pallidal abnormality alone or in conjunction with other deep nuclear and generalized cortical-subcortical involvement, was strongly associated with Gross Motor Function Classification System levels IV to V (OR 35.7 [95% CI 3.5, 368.8]). Involvement of the basal ganglia was associated with non-spastic/mixed motor types, but predominantly where cortical-subcortical grey and white matter involvement was not extensive. The prevalence of epilepsy was highest where there was diffuse cortical-subcortical involvement and white matter loss., Interpretation: Better understanding of structure-function relationships in CP and GMI, and how to rate the severity of GMI, will be helpful in the clinical context and also as a basis for investigation of causal pathways in CP., (© 2015 Mac Keith Press.)

Aims: The aim of this study was to describe the pattern of tertiary paediatric emergency department (ED) use in children and young people with cerebral palsy (CP)., Methods: A retrospective analysis of ED data routinely collected at the two tertiary paediatric hospitals in Victoria, Australia, cross-matched with the Victorian Cerebral Palsy Register. Data pertaining to the ED presentations of 2183 registered individuals born 1993-2008 were obtained., Results: Between 2008 and 2012, 37% (n = 814) of the CP cohort had 3631 tertiary paediatric ED presentations. Overall, 40% (n = 332) of presenters were residing in inner metropolitan Melbourne; 44% (n = 356) in outer Melbourne; and 13% (n = 108) in regional Victoria. Presenters were more likely than non-presenters to be younger, non-ambulant and have epilepsy. In total, 71% of presentations were triaged as Australasian Triage Scale 1-3 (urgent), and 44% resulted in a hospital admission. Disorders of the respiratory, neurological and gastrointestinal systems, and medical device problems were responsible for 72% of presentations., Conclusion: Many of the tertiary paediatric ED presentations in this group were appropriate based on the high admission rate and the large proportion triaged as urgent. However, there is evidence that some families are bypassing local services and travelling long distances to attend the tertiary paediatric ED, even for less urgent complaints that do not require hospital admission. Alternative pathways of care delivery, and strategies to promote the management of common problems experienced by children and young people with CP in non-paediatric EDs or primary care settings, may go some way towards reducing unnecessary tertiary paediatric ED use in this group., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure-function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Standard intelligence tests such as the WPPSI-III have limitations when testing children with motor impairment. This study aimed to determine the proportion of children with cerebral palsy with sufficient verbal and motor skills to complete the WPPSI-III, to determine their comparative ability to complete tasks with and without a significant motor component, and to investigate short forms of the WPPSI-III as alternatives. Participants were 78 of 235 eligible 4-5 year old children with cerebral palsy resident in the Australian state of Victoria. Verbal IQ (VIQ), Performance IQ (PIQ), and Full-scale IQ (FSIQ) were determined using the WPPSI-III. Initial screening for pointing and verbal abilities determined which tests were attempted. The impact of speed was investigated by comparing scores on the Block Design subtest with and without an imposed time limit. FSIQ scores were calculated from two short forms of the WPPSI-III and compared to the full form. On screening, 16 children had inadequate pointing (14) and verbal abilities (2). FSIQ was obtained in 62 (82%) children. Strong associations were seen between completion of the entire test battery and topographical pattern, level of manual ability and level of gross motor function. Scores on subtests requiring manual ability were depressed relative to other scores. Children performed better using short forms of the WPPSI-III and, for a minority, when time limits were disregarded. In summary, children with cerebral palsy often lack the fine and gross motor skills necessary to complete the WPPSI-III, scoring relatively poorly on tasks requiring a fine motor response. Using short-form estimations of FSIQ comprised of subtests without a significant fine motor component has the potential to increase a child's FSIQ by approximately 5 points. These findings have important clinical implications when assessing a child with both motor and cognitive limitations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to review the distribution of neuroimaging findings from a contemporary population cohort of individuals with cerebral palsy (CP) and to facilitate standardization of imaging classification., Method: Publications from 1995 to 2012 reporting imaging findings in population cohorts were selected through a literature search, and review of the titles, abstracts, and content of studies. Relevant data were extracted, including unpublished data from Victoria, Australia. The proportions for each imaging pattern were tabulated, and heterogeneity was assessed for all individuals with CP, and for subgroups based on gestational age, CP subtype, and Gross Motor Function Classification System level., Results: Studies from three geographic regions met the inclusion criteria for individuals with CP, and two additional studies reported on specific CP subtypes. Brain abnormalities were observed in 86% of scans, but were observed least often in children with ataxia (24-57%). White matter injury was the most common imaging pattern (19-45%), although the proportions showed high heterogeneity. Additional patterns were grey matter injury (21%), focal vascular insults (10%), malformations (11%), and miscellaneous findings (4-22%)., Interpretation: This review suggests areas where further dialogue will facilitate progress towards standardization of neuroimaging classification. Standardization will enable future collaborations aimed at exploring the relationships among magnetic resonance imaging patterns, risk factors, and clinical outcomes, and, ultimately, lead to better understanding of causal pathways and opportunities for prevention., (© 2013 Mac Keith Press.)

Aim: The aim of this study was to describe the distribution of magnetic resonance imaging (MRI) patterns in a large population sample of children with cerebral palsy (CP) and to examine associations between MRI patterns, and antenatal and perinatal variables., Method: Data were retrieved from the Victorian CP Register for 884 children (527 males, 357 females) born between 1999 and 2006. Postneonatal MRI was classified for 594 children. For 563 children (329 males, 234 females) for whom classification was to a single MRI pattern, the frequency of each variable was compared between patterns and with the population frequency., Results: White matter injury was the most common MRI pattern (45%), followed by grey matter injury (14%), normal imaging (13%), malformations (10%), focal vascular insults (9%), and miscellaneous patterns (7%). Parity, birth gestation, level of neonatal care, Apgar score, and time to established respiration varied between MRI patterns (p<0.01). Nulliparity was most strongly associated with focal vascular insults, whereas multiparity was associated only with malformations. Grey matter injury was not associated with birth in a tertiary unit, but was strongly associated with severe perinatal compromise. The frequency of neonatal seizures and of nursery admissions was lowest among children with malformations., Interpretation: As known risk factors for CP are differentially associated with specific MRI patterns, future exploration of causal pathways might be facilitated when performed in pathogenically defined groups., (© 2013 Mac Keith Press.)

Unlabelled: Congenital cytomegalovirus (cCMV) is a contributing cause of neurodevelopmental disabilities including cerebral palsy (CP). In this case series we reviewed the neuroimaging findings of children with CP and cCMV infection in the context of the children's clinical profile., Participants: Children with CP and laboratory confirmed cCMV (n=12) reported to the Australian CP Register, born in South Australia and Victoria, 1993-2006, with magnetic resonance imaging (MRI) and/or computerized tomography (CT) report available. Clinical details and neuroimaging findings were tabulated and compared to published literature. Children in this series were mostly born at term (n=8), with symptoms or signs of cCMV (n=10) and had spastic quadriplegia (n=9), epilepsy (n=8), intellectual deficit (n=12), communication (n=10) and hearing impairments (n=9). All but one had abnormal neuroimaging findings reported on MRI or CT (n=11): most commonly brain malformations including disorders of neuronal migration (n=10), such as lissencephaly, pachygyria and polymicrogyria, and cerebellar hypoplasia (n=5). Other findings included ventricular dilatation (n=8), calcifications (n=7) and white matter abnormalities (n=6). This study suggests that brain malformations, calcifications, ventricular dilatation and cerebellar hypoplasia are common neuroimaging patterns in children with CP and cCMV infection. The presence of these findings should prompt investigations for congenital cytomegalovirus.

Background: Functional abilities and social outcomes of young adults with cerebral palsy (CP) are relatively under-researched. Improvements in paediatric care have extended the expectation of achieving adulthood to 90%., Method: Young adults aged 20-30 years with CP (n = 335) were compared to a population-based control group (n = 2,152) of the same age. Motor function, self-care abilities, educational level, and social outcomes were determined by questionnaire., Results: Half the study group walked independently, but only 35.5% were independent in self-care. In comparison to their peers without disability, the study group's highest educational level was lower (p < .0001), as were rates of employment (36.3% compared with 80%), they were more likely to be living with parents (80% compared with 21%), to be single, and to have limited financial resources., Conclusion: Young adults with CP are functionally and socially disadvantaged in contrast with their peers without disability. Self-care dependence, intellectual disability, and communication impairments contribute to these outcomes but are not solely responsible.

This study aimed to determine differences in functional profiles and movement disorder patterns in children aged 4-12 years with cerebral palsy (CP) and periventricular white matter injury (PWMI) born >34 weeks gestation compared with those born earlier. Eligible children born between 1999 and 2006 were recruited through the Victorian CP register. Functional profiles were determined using the Gross Motor Function Classification System (GMFCS), Manual Abilities Classification System (MACS), Communication Function Classification System (CFCS), Functional Mobility Scale (FMS) and Bimanual Fine Motor Function (BFMF). Movement disorder and topography were classified using the Surveillance of Cerebral Palsy in Europe (SCPE) classification. 49 children born >34 weeks (65% males, mean age 8 y 9 mo [standard deviation (SD) 2 y 2 mo]) and 60 children born ≤ 34 weeks (62% males, mean age 8 y 2 mo [SD 2 y 2 mo]) were recruited. There was evidence of differences between the groups for the GMFCS (p=0.003), FMS 5, 50 and 500 (p=0.003, 0.002 and 0.012), MACS (p=0.04) and CFCS (p=0.035), with a greater number of children born ≤ 34 weeks more severely impaired compared with children born later. Children with CP and PWMI born >34 weeks gestation had milder limitations in gross motor function, mobility, manual ability and communication compared with those born earlier., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

To assess the measurement properties of a new QOL instrument, the Cerebral Palsy Quality of Life Questionnaire-Teen (CP QOL-Teen), in adolescents with cerebral palsy (CP) aged 13-18 years, examining domain structure, reliability, validity and adolescent-caregiver concordance. Based on age, 695 eligible families were invited to participate by mail. Questionnaires were returned by 112 primary caregivers (71.8% of questionnaires sent). 87 adolescents aged 12-18 years also completed the questionnaires. CP QOL-Teen, generic QOL instruments (KIDSCREEN, Pediatric Quality of Life Inventory), functioning (Gross Motor Function Classification System) and a condition-specific instrument (PedsQL-CP) were used. Principal components analysis produced seven scales: wellbeing and participation; communication and physical health; school wellbeing; social wellbeing; access to services; family health; feelings about functioning. Cronbach's alphas for the derived scales ranged from 0.81 to 0.96 (primary caregiver report) and 0.78 to 0.95 (adolescent report). Test-retest reliability (4 weeks) ranged from 0.57 to 0.88 for adolescent self-report and 0.29 to 0.83 for primary caregiver report. Moderate correlations were observed with other generic and condition specific measures of QOL, indicating adequate construct validity. Moderate correlations were observed between adolescent self-report and primary caregiver proxy report. This study demonstrates acceptable psychometric properties of both the adolescent self-report and the primary caregiver proxy report versions of the CP QOL-Teen., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: To establish a prevalence estimate for drooling and explore factors associated with drooling in a population sample of children with cerebral palsy (CP) aged 7 to 14 years living in Victoria, Australia., Method: A self-report questionnaire was used to collect data on drooling from parents of children born between 1996 and 2001, and registered with the Victorian Cerebral Palsy Register., Results: A total of 385 children (231 males, 154 females; mean age 10y 9mo [SD 1y 7mo], range 8-14y) were studied. The clinical type and distribution of CP were spastic (341), ataxic (16), dyskinetic (17), hypotonic (10), and unknown (1). Distribution in Gross Motor Function Classification System (GMFCS) levels was I (103), II (98), III (52), IV (63), V (61), and unknown (8). After adjustment for topographical pattern of motor impairment and GMFCS level, 40% were reported to have experienced drooling between 4 years of age and the time of completing the questionnaire. A significantly higher prevalence of drooling was found in children with poor gross motor function and in those with more severe presentations of CP, including poor head control, difficulty with eating, and inability to sustain lip closure (p<0.001 for each). Drooling was shown to be significantly associated with both intellectual disability and epilepsy in this group of children (p<0.001 for both)., Interpretation: With a prevalence of 40%, drooling is an important comorbidity in CP. It was considered severe in 15% of children. Poor oromotor function was associated with drooling and could be the target of interventions for this under-researched problem., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

Aim: This study used data collected prospectively since 1986 from a population-based cerebral palsy registry to explore the rates, predictors, trends, and causes of mortality for individuals born in Victoria, Australia, between 1970 and 2004., Method: Data were extracted for 3507 individuals (1972 males; 1535 females). The probability of survival before 31 May 2010 was determined using the Kaplan-Meier method; age-specific mortality rates were calculated per 1000 person-years and related to population rates. Using Cox proportional hazards regression, relative risks of mortality were estimated for different categories of chosen demographic and clinical variables. Causes were tabulated according to the direct cause of death., Results:   There were 418 deaths. Crude mortality was 20% at the age of 40 years. Relative to the population, mortality was highest in children aged under 15 years and decreased to twice the population rate at the age of 35 years. The strongest independent predictor of mortality was no independent ambulation (adjusted hazard ratio 6.2 [95% confidence interval 3.3-11.8]); additional predictors were severe intellectual impairment (3.0 [1.7-5.2]), epilepsy (1.4 [1.1-1.9]), deafness (2.6 [1.4-4.7]), and term birth (1.8 [1.3-2.4]). No improvement in survival was seen over time (unadjusted hazard ratio 1.00 [95% CI 0.99-1.01]). Respiratory causes were the most common direct causes of death., Interpretation: Rates, predictors, and causes of death for individuals with cerebral palsy in Victoria were similar to those found in other population cohorts. Lack of improvement in survival since 1970 was an unexpected finding that warrants further investigation., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

Aim: The aims of this study were to estimate the frequency of hearing loss in children with cerebral palsy (CP), to examine factors associated with hearing loss, and to describe aspects of hearing in a population sample of children with CP and hearing loss., Method: A systematic review of the international literature was undertaken, and data on the frequency of hearing loss or severe hearing loss were extracted from 14 data sets based on previously devised criteria. Six hundred and eight-five children with CP (406 males, 279 females) born in Victoria, Australia, between 1999 and 2004 were identified from the Victorian Cerebral Palsy Register. Children were included if they had an established post neonatal cause for their CP before the age of 2 years. Additional information was collected on 48 children with documented hearing loss based on a four-tone pure tone average in the better ear., Results: There was considerable variation in the definitions and proportions of hearing loss (range 4-13%) and severe hearing loss (range 2-12%) reported by CP registries in developed countries. In Victoria, 7% of individuals with CP had bilateral hearing loss of a moderate to profound degree, whereas the subgroup with a severe-profound degree of loss constituted 3% to 4% of the CP population., Interpretation: These population-based data are likely to more accurately reflect the true frequency of defined hearing loss in children with CP than previous reviews., (© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.)

This study used data from a population-based cerebral palsy (CP) registry and systematic review to assess the amount of heterogeneity between registries in topographical patterns when dichotomised into unilateral (USCP) and bilateral spastic CP (BSCP), and whether the terms diplegia and quadriplegia provide useful additional epidemiological information. From the Victorian CP Register, 2956 individuals (1658 males, 1298 females), born 1970-2003, with spastic CP were identified. The proportions with each topographical pattern were analysed overall and by gestational age. Binary logistic regression analysis was used to assess temporal trends. For the review, data were systematically collected on topographical patterns from 27 registries. Estimates of heterogeneity were obtained, overall and by region, reporting period and definition of quadriplegia. Among individuals born <32 weeks, 48% had diplegia, whereas the proportion for children born ≥ 32 weeks was 24% (p < 0.001). Evidence was weak for a temporal trend in the relative proportions of USCP and BSCP (p = 0.038), but much clearer for an increase in the proportion of spastic diplegia relative to quadriplegia (p < 0.001). The review revealed wide variations across studies in the proportion of diplegia (range 34-90%) and BSCP (range 51-86%). These findings argue against a topographical classification based solely on laterality., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to describe the distribution of motor severity levels and temporal trends in an Australian population cohort and to review the distribution of Gross Motor Function Classification System (GMFCS) levels across cerebral palsy (CP) registries worldwide., Methods: Data were extracted from the Victorian Cerebral Palsy Register for 3312 individuals (1852 males, 1460 females; mean age 21y 2mo [SD 9 y 6 mo]) with non-postneonatally acquired CP, born between 1970 and 2003. The proportions of each motor severity level were calculated and logistic regression analyses were used to assess trends over time. A systematic review of the literature was undertaken and GMFCS data were extracted based on previously devised criteria. The proportions were plotted and the degree of heterogeneity was assessed for each level., Results: Population data from Victoria suggested a proportional increase in mild motor impairment (GMFCS levels I/II) from 54% of all cases of CP in the 1970s to 61% in the 2000s. For nine CP registries worldwide, the mean proportions of each GMFCS level, from level I to V, were 34.2%, 25.6%, 11.5%, 13.7%, and 15.6% respectively. There was substantial heterogeneity between registries for all levels except level III., Interpretation: Despite the usefulness and reported reliability of the GMFCS, substantial variability was found in the distribution of GMFCS levels between population registries, particularly between levels I and II, suggesting greater classification uncertainty between these levels. Further research would be useful to determine whether routine collection of extra clinical information may facilitate more reliable classification., (© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.)

Aim: The aim of this study was to assess overall and gestational age-specific trends in the rate of cerebral palsy (CP) in Victoria, Australia, and to compare these findings with other population data., Method: Individuals born in Victoria from 1970 to 2004 with non-postneonatally acquired CP were identified from a population register; 3491 were included in the study (1963 males, 1528 females). After a literature review, comparison data were extracted from publications using previously devised inclusion criteria. Rates were calculated per 1000 live births for all CP and by gestational age group: these were tabulated and plotted by year of birth., Results: Data from nine registries, including the Victorian register, showed an increase in the rates of CP over the 1970s and 1980s, consistently seen in extremely preterm (<28 wks) survivors but also in those born at term (≥37 wks). Since the early 1990s, CP rates either stabilized or decreased, particularly for children born extremely preterm., Interpretation: Increases in the rates of CP during the 1970s and 1980s are in part because of the increasing survival of extremely preterm infants that occurred without a concomitant improvement in neurological outcomes. Evidence from population samples now suggests that this trend has been reversed since the mid- to late 1990s., (© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.)

Aim: For the 9% to 16% of children with cerebral palsy (CP) who have normal brain imaging, further testing for metabolic and/or genetic conditions has been recommended. This study aimed to identify a cohort of children with CP with normal magnetic resonance imaging (MRI), clinically review and describe the cases, and assess the value of testing for inherited metabolic disorders in these children., Method: Children with congenital CP born from 1999 to 2005 were selected from a population register. Normal MRI reports were identified and the scans reassessed. Children whose scans were performed before 18 months were excluded, as were children with spastic CP (Gross Motor Function Classification System [GMFCS] level I). The remainder were reviewed clinically and offered investigations., Results: Of 730 children identified, 515 had available imaging and 54 were confirmed as normal. Cases with non-spastic CP and those with milder clinical severity were more likely to have normal imaging. Twenty-three children (17 males, six females; mean age 6 y 11 mo, SD 1 y 10 mo, range 3 y 0 mo to 10 y 0 mo) were reviewed clinically and offered investigations. Twelve children had spasticity (11 with diplegia, one quadriplegia), three had dyskinesia, five ataxia, and three hypotonia. Two children functioned in GMFCS level I, 11 in level II, seven in level III and three in level IV. Four children with spasticity had unusual features. No alternative diagnoses were made., Interpretation: Although important to consider in individual cases, comprehensive metabolic testing failed to clarify the aetiology of CP further in this large cohort of children with normal MRIs, even those with atypical features., (© The Authors. Journal compilation © Mac Keith Press 2011.)

Aim: The aim of this study was to describe the distribution of types of motor disorder (motor type) in a population-based registry of children with cerebral palsy (CP), to examine any trends in motor type distribution over time, and to make comparisons with other populations., Method: Individuals born in Victoria, Australia, between 1970 and 2003 with congenital CP were identified from the Victorian Cerebral Palsy Register, 3297 of whom were included in the study (1840 males, 1457 females). Those who had a hypotonic motor type, those whose brain abnormality was believed to have developed after 28 days of life, and those with missing data were excluded from the study. The proportions of each motor type were calculated and plotted by year of birth. Logistic regression analyses were used to assess the mean change in odds per year of birth. A systematic review of the international literature was undertaken and comparison data were extracted based on previously devised criteria. The degree of heterogeneity was assessed and comparisons were made according to geographical region and reporting period., Results: In Victoria, the predominant motor types for individuals with CP born between 1970 and 2003 were spasticity (91%), ataxia (5%), and dyskinesia (4%). There was no clear trend for any motor type over time. The mean proportions from two other large data sets were similar but there was considerable heterogeneity between 29 individual CP registries, mainly because of differences in the classification of mixed motor types., Interpretation: A more objective method for determining the predominant motor type is required to make the classification of motor type in CP more consistent and reliable., (© The Authors. Journal compilation © Mac Keith Press 2010.)