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Aim: This paper introduces the Surveillance of Cerebral Palsy in Europe (SCPE) classification of events contributing to postneonatally acquired cerebral palsy, presents its interrater reliability, and describes the cases identified in the SCPE database. Method: The development of the classification, based on literature review and expert discussions, resulted in six main categories and 19 subcategories. The first chronological event designated as the primary event was mainly reported. Interrater reliability was assessed through online exercise providing 24 clinical vignettes representing single/complex pathways. Percent agreement and Gwet's AC1 index of reliability were estimated. Primary events were described using data of 221 children born between 2008 and 2012. Results: Thirty‐nine professionals (21 registries) participated in the reliability exercise. Substantial overall agreement was reached (0.75), with some contrast between complex (0.48, moderate agreement) and single events involved (0.89, almost perfect). The distribution of primary events showed that 32.1% were infections (category A), 23.1% head injuries (B), 15.4% related to surgery or medical interventions (C), 13.1% cerebrovascular accidents (D), 9.1% hypoxic brain damaging events of other origins (E), and 7.2% miscellaneous (F). Interpretation: This classification allows all the events involved to be recorded while consistently reporting the primary event, and may be used in different settings. What this paper adds: A standardized classification enables the description of the events contributing to postneonatal cerebral palsy (CP).The first chronological event in complex pathway leading to CP is coded.Category choice and coding of the primary event identify preventable situations.The detailed 2‐level classification is easy to use in various settings.Substantial overall interrater reliability shows that main categories can be consistently differentiated. [ABSTRACT FROM AUTHOR]

Aim: To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used in CP registers.Method: The classification system was based on pathogenic patterns occurring in different periods of brain development. The MRI classification system (MRICS) consists of five main groups: maldevelopments, predominant white matter injury, predominant grey matter injury, miscellaneous, and normal findings. A detailed manual for the descriptions of these patterns was developed, including test cases (www.scpenetwork.eu/en/my-scpe/rtm/neuroimaging/cp-neuroimaging/). A literature review was performed and MRICS was compared with other classification systems. An exercise was carried out to check applicability and interrater reliability. Professionals working with children with CP or in CP registers were invited to participate in the exercise and chose to classify either 18 MRIs or MRI reports of children with CP.Results: Classification systems in the literature were compatible with MRICS and harmonization possible. Interrater reliability was found to be good overall (k=0.69; 0.54-0.82) among the 41 participants and very good (k=0.81; 0.74-0.92) using the classification based on imaging reports.Interpretation: Surveillance of Cerebral Palsy in Europe (SCPE) proposes the MRICS as a reliable tool. Together with its manual it is simple to apply for CP registers. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to examine whether vigabatrin treatment had caused visual field defects ( VFDs) in children of school age who had received the drug in infancy. Method In total, 35 children (14 males, 21 females; median age 11y, SD 3.4y, range 8-23y) were examined by static Humphrey perimetry, Goldmann kinetic perimetry, or Octopus perimetry. The aetiologies of infantile spasms identified were tuberous sclerosis ( n=10), other symptomatic causes ( n=3), or cryptogenic ( n=22). Results Typical vigabatrin-attributed VFDs were found in 11 out of 32 (34%) children: in one out of 11 children (9%) who received vigabatrin for <1 year (group 1), in three out of 10 children (30%) who received vigabatrin for 12 to 24 months (group 2), and in seven out of 11 children (63%) who received vigabatrin treatment for longer than 2 years (group 3). VFDs were mild in five and severe in six children. Patients with tuberous sclerosis were at higher risk of VFDs (six out of 10 children). The mean cumulative doses of vigabatrin were 140.5, 758.8, and 2712g in group 1, 2, and 3, respectively. Interpretation VFDs were found in 34% of the cohort of children in this study. The rate of VFD increased from 9% to 63% as duration of treatment increased. The results of this study showed that the risk-benefit ratio should always be considered when using vigabatrin. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C>T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G>T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G>T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations. [ABSTRACT FROM AUTHOR]

Various syndromes of the Ras-mitogen-activated protein kinase (MAPK) pathway, including the Noonan, Cardio-Facio-Cutaneous, LEOPARD and Costello syndromes, share the common features of craniofacial dysmorphisms, heart defect and short stature. In a subgroup of patients, severe muscle hypotonia, central nervous system involvement and failure to thrive occur as well. In this study we report on five children diagnosed initially with classic metabolic and clinical symptoms of an oxidative phosphorylation disorder. Later in the course of the disease, the children presented with characteristic features of Ras-MAPK pathway-related syndromes, leading to the reevaluation of the initial diagnosis. In the five patients, in addition to the oxidative phosphorylation disorder, disease-causing mutations were detected in the Ras-MAPK pathway. Three of the patients also carried a second, mitochondrial genetic alteration, which was asymptomatically present in their healthy relatives. Did we miss the correct diagnosis in the first place or is mitochondrial dysfunction directly related to Ras-MAPK pathway defects? The Ras-MAPK pathway is known to have various targets, including proteins in the mitochondrial membrane influencing mitochondrial morphology and dynamics. Prospective screening of 18 patients with various Ras-MAPK pathway defects detected biochemical signs of disturbed oxidative phosphorylation in three additional children. We concluded that only a specific, metabolically vulnerable sub-population of patients with Ras-MAPK pathway mutations presents with mitochondrial dysfunction and a more severe, early-onset disease. We postulate that patients with Ras-MAPK mutations have an increased susceptibility, but a second metabolic hit is needed to cause the clinical manifestation of mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]