The Bayley Scales of Infant and Toddler Development, Third Edition reported lower pooled prevalences of motor and cognitive delays than the Second Edition. The pooled prevalence of cerebral palsy in infants born extremely preterm was reduced compared with previous meta-analyses.

Background and Purpose— Cerebral sinovenous thrombosis is a rare disease with severe neurological sequelae. The aim of this retrospective multicenter study was to investigate the clinical course, possible risk factors, and outcome of a cohort of neonatal patients with sinovenous thrombosis and, second, to estimate the incidence in The Netherlands. Methods— From January 1999 to March 2009, a review of all neonatal patients with sinovenous thrombosis from 6 tertiary neonatal intensive care units was performed. Population characteristics, clinical presentation, (prothrombotic) risk factors, neuroimaging, interventions, and neurodevelopment were evaluated. An estimated incidence was calculated based on the Netherlands Perinatal Registry. Results— Fifty-two neonates were included (39 boys) with a median gestational age of 39 weeks (range, 30 to 42 weeks; 5 preterm). An assisted or complicated delivery occurred in 32 of 52. Presenting symptoms developed at a median postnatal age of 1.5 days (range, 0 to 28 days) and consisted mainly of seizures (29 of 52). All sinovenous thrombosis cases were confirmed with MRI/MR venography. Multisinus thrombosis was most common followed by superior sagittal sinus thrombosis. FII G20210A mutation was present in 2 of 18 tested neonates (11%). Anticoagulation therapy (in 22 of 52) did not result in hemorrhagic complications. At follow-up (median age, 19 months; range, 3 to 72 months), moderate to severe neurological sequelae were present in 38%. The mortality was 10 of 52 (19%). A variable, although high yearly incidence of 1.4 to 12 per 100 000 term newborns was found. Conclusions— Neonatal sinovenous thrombosis is a multifactorial disease. The estimated incidence in The Netherlands seems higher than reported elsewhere.

Cerebral palsy due to perinatal injury to cerebral white matter is usually not caused by genetic mutations, but by ischemia and/or inflammation. Here, we describe an autosomal-recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship. The phenotype was recorded and evolution followed for over 20 years. Brain lesions were studied by diffusion tensor MR tractography. Homozygosity mapping with SNPs was performed for identification of the chromosomal locus for the disease. In the 14 Mb candidate region on chromosome 7q22, RNA expression profiling was used for selecting among the 203 genes in the area. In postmortem brain tissue available from one patient, histology and immunohistochemistry were performed. Disease course and imaging were mostly reminiscent of hypoxic-ischemic tetraplegic cerebral palsy, with neuroaxonal degeneration and white matter loss. In all five patients, a donor splice site pathogenic mutation in intron 14 of the AP4M1 gene (c.1137+1G-->T), was identified. AP4M1, encoding for the mu subunit of the adaptor protein complex-4, is involved in intracellular trafficking of glutamate receptors. Aberrant GluRdelta2 glutamate receptor localization and dendritic spine morphology were observed in the postmortem brain specimen. This disease entity, which we refer to as congenital spastic tetraplegia (CST), is therefore a genetic model for congenital cerebral palsy with evidence for neuroaxonal damage and glutamate receptor abnormality, mimicking perinatally acquired hypoxic-ischemic white matter injury.

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