Prevalence, Clinical Features, Neuroimaging, and Genetic Findings in Children With Ataxic Cerebral Palsy in Europe.

BACKGROUND AND OBJECTIVES: To report on prevalence, associated impairments, severity, and neuroimaging findings in children with ataxic cerebral palsy (CP). METHODS: In children coded as having ataxic CP in the Central database of Joint Research Center-Surveillance of Cerebral Palsy in Europe (JRC-SCPE) and born during 1980-2010, birth characteristics, severity profiles including associated impairments, neuroimaging patterns, and the presence of syndromes were analyzed. Definitions were according to validated SCPE guidelines. Prevalence over time was estimated using Poisson regression. RESULTS: In total, 679 children with ataxic CP were identified in 20 European CP registers. The proportion with ataxic CP was 3.8% and varied from 0% to 12.9%. Prevalence over time showed no significant trend. Approximately 70% of children with ataxic CP were able to walk, and 40% had severe intellectual impairment and a high impairment index. Children with ataxic CP were mostly born at term (79%) and with normal birth weight (77%). Neuroimaging patterns revealed normal findings in 29%, brain maldevelopments in 28.5%, miscellaneous findings in 23.5%, and brain injuries in 19%, according to the SCPE classification. Genetic syndromes were described in 9%. DISCUSSION: This register-based multicenter study on children with ataxic CP provides a large sample size for the analysis of prevalence, severity, and origin of this rare CP subtype. Even with strict inclusion and classification criteria, there is variation between registers on how to deal with this subtype, and diagnosis of ataxic CP remains a challenge. Ataxic cerebral palsy differs from other CP subtypes: children with ataxic CP have a disability profile that is more pronounced in terms of cognitive than gross motor dysfunction. They are mostly term born and the origin rarely suggests acquired injuries. In addition to neuroimaging, a comprehensive genetic workup is particularly recommended for children with this CP type.

Corrigendum: Prognostic value of various diagnostic methods for long-term outcome of newborns after hypoxic-ischemic encephalopathy treated with hypothermia.

[This corrects the article DOI: 10.3389/fped.2022.856615.].

Prognostic Value of Various Diagnostic Methods for Long-Term Outcome of Newborns After Hypoxic-Ischemic Encephalopathy Treated With Hypothermia.

Introduction: Prediction of outcome in newborns with hypoxic-ischemic encephalopathy (HIE) has been modulated by hypothermia treatment (HT). We assessed the predictive value of diagnostic methods commonly used in neonates with HIE for short-term neurodevelopmental outcome and long-term neurological outcome. Materials and Methods: This longitudinal cohort study followed up 50 term newborns who underwent HT after HIE between July 2006 and August 2015, until preschool age. We estimated sensitivity and specificity for short-term neurodevelopmental outcome at 18 months and long-term neurological outcome at five years based on Amiel-Tison Neurological Assessment (ATNA), electroencephalography (EEG), and magnetic resonance imaging (MRI) performed in the neonatal period. Results: The accuracy of all neonatal methods tested was higher for long-term neurological outcome compared to the predictive accuracy for short-term neurodevelopmental outcome at 18-24 months. Sensitivity and specificity in predicting unfavorable long-term neurological outcome were: MRI (sensitivity 1.0 [95%CI 0.96-1.0]; specificity 0.91 [95%CI 0.86-1.0]), EEG (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 1.0 [95% CI 0.89-1.0]), and ATNA (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 0.91 [95%CI 0.76-0.98]). Conclusion: MRI is a powerful predictor of long-term neurological outcome when performed in the first week after HIE in HT treated infants, as are EEG and ATNA performed in the second or third week postnatally.

Children with Arteriovenous Malformations of the Central Nervous System: A Retrospective Study of 12 Pediatric Cases from a Single Tertiary Center in Slovenia.

BACKGROUND Arteriovenous malformation (AVM) of the central nervous system (CNS) is a developmental condition that consists of a focal mass of interconnected veins and arteries. This retrospective study was conducted at the only tertiary center in Slovenia and included 12 pediatric cases of AVM of the CNS, diagnosed between 2000 and 2020. MATERIAL AND METHODS The patients were collected based on the ICD coding system. All available medical documentation was reviewed. RESULTS Our cohort included 6 boys and 6 girls. The mean age of patients was 9.1 years, range 1 month to 16.3 years. The estimated incidence of pediatric AVM of the CNS in Slovenia is 0.22/100 000 children per year. Ten patients had brain AVM and 2 patients had spinal AVM. At first presentation, 7 patients presented with intracerebral hemorrhage, 2 with focal neurological deficits, 1 with epilepsy, 1 with chronic headache, and 1 patient was asymptomatic. Two patients had their first hemorrhage after an already-established diagnosis of AVM. Endovascular embolization was performed in 50%, surgical resection in 33%, and conservative treatment in 17% of patients. Five patients had no residual neurological sequelae, 6 had some neurological deficits, and 1 patient died. Complete obliteration of AVM was achieved in 3 patients treated with surgery. They all had a favorable outcome, with no or mild deficit. CONCLUSIONS The study findings support that early diagnosis and management are required to prevent neurological deterioration and vessel rupture from AVM. Endovascular embolization was the most commonly used procedure. Complete obliteration was associated with good neurological outcome.

The impact of birthweight on the development of cerebral palsy: A population-based matched case-control study.

BACKGROUND: Cerebral palsy (CP) is a common cause of physical impairment in children, especially in newborns who are small for gestational age (SGA). AIMS: The aim of our study was to investigate the association between birth weight and the risk of developing CP, controlling for gestational age and plurality. STUDY DESIGN: This retrospective, observational, case-control study was based on Slovenian Registry of Cerebral Palsy (SRCP) and Slovenian National Perinatal Information System (NPIS) data for the period 2002 to 2010. SUBJECTS: For each pregnancy that resulted in the birth of the newborn(s) who later developed CP (n = 254), three pregnancies with newborns who did not develop CP (n = 762) were selected and matched for gestational age and plurality. OUTCOME MEASURES: Diagnosis of CP was made at age 5 years or older by a developmental pediatrician trained in child neurology or a child neurologist using standard measures. RESULTS: Risk of CP increased progressively as birth weight percentiles fell below the 50th centile, with children in the lowest percentiles at greatest risk. Birth weight percentiles traditionally classified as SGA were an independent risk factor for developing CP, with an odds ratio of 2.43 (95% confidence interval 1.57, 3.73). CONCLUSIONS: The results of this study suggest that the risk for developing CP is inversely related to birth weight, even at birth weights that do not meet the standard definitions of SGA. SYNOPSIS - STUDY QUESTION: Does birth weight represent a potential risk factor for the development of cerebral palsy (CP) when controlling for gestational age and plurality? WHAT'S ALREADY KNOWN: Newborns who are small for gestational age (SGA) are at higher risk of developing CP according to published studies. However, different definitions of SGA (birth weight below the 10th, 5th, or 3rd percentile for gestational age) have been used by researchers and clinicians, making it difficult to compare studies. WHAT THIS STUDY ADDS: This study suggests that the risk of developing CP is inversely related to birth weight, even at birth weights that do not meet standard definitions of SGA.

Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia.

AIM: Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse disorders of neuromuscular transmission. Data on prevalence among children are scarce. Whole exome sequencing facilitated discovery of novel CMS mutations and enabled targeted treatment. Our aim was to identify the prevalence, genetic subtypes and clinical characteristics of CMS in pediatric population of Slovenia. METHODS: In this observational, national, cross-sectional study, medical records were retrospectively reviewed. Children with genetically confirmed CMS, referred over a 19 - year period (2000-2018) to the University Medical Centre, Ljubljana, Slovenia, were included in the study. Genetic and phenotypic characteristics were collected and prevalence of CMS in children was calculated. RESULTS: Eight children with a confirmed genetic mutation in 5 different genes (CHRNE, CHRND, RAPSN, CHAT, MUSK) causative of the CMS were identified. Calculated prevalence of genetically confirmed CMS was 22.2 cases per 1.000.000 children at the end of 2018. INTERPRETATION: The prevalence of genetically confirmed CMS in Slovenian children at the end of 2018 exceeds previously reported prevalence by more than two-fold, which suggests that prevalence in the literature is likely to be underestimated. Two extremely rarely detected mutations in MUSK and CHRND gene were detected and patient's clinical descriptions add important information on genotype-phenotype correlation.