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.

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.

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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Hyperekplexia (MIM: 149400) is a neurological disorder characterized by an excessive startle response which can be caused by mutations in the alpha1-subunit (GLRA1) of the heteropentameric human inhibitory glycine receptor (hGlyR). These receptors facilitate fast-response, inhibitory glycinergic neurotransmission in the brainstem and spinal cord leading to a rapid modification and reduction of the excitatory startle response. Mutations in the beta-subunit of GlyR (glrb) occur in a murine model of hyperekplexia (spastic), but have not been detected in human hyperekplexia. Following mutation analysis of the human beta-subunit of hGlyR (GLRB) in a cohort of 22 hyperekplexia patients, we provide evidence to confirm that GLRB mutations can cause human hyperekplexia. A missense (G920A resulting in G229D) and a splice site mutation (IVS5+5G-->A) occurred together in a compound heterozygote with a transient hyperekplexia phenotype. Exon trap analysis revealed that IVS5+5G-->A results in the exclusion of exon 5 from GLRB transcripts. Electrophysiological studies showed reduced sensitivity to agonist mediated activation of the alpha1beta (G229D) GlyR suggesting that GlyR beta-subunits are not restricted to conferring modulatory influences and maintaining structural integrity, but may also play a functional role in hGlyR ligand binding.

Eight-year-old children treated with neonatal ECMO fall in the normal range of intelligence with problems with concentration and behavior. Long-term follow-up for children treated with neonatal ECMO should focus on early detection of (subtle) learning deficits.

ABSTRACT. Objective. We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest means of diagnosis and prevention.Methods. Charts and MR and ultrasound images of 5 preterm infants and 3 term infants with suspected bilirubin-associated brain damage were reviewed. Included were preterm infants with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150, the diagnosis was confirmed during the neonatal period. The others were picked up as outpatients and scanned at 12 or 22 months' corrected age. Three instances of term kernicterus were included for comparison of serial MRI in the neonatal period and early infancy: they were caused by glucose-6-phosphate dehydrogenase deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase deficiency.Results. Five preterm infants of 25 to 29 weeks' gestational age presented with total serum bilirubin (TSB) levels below exchange transfusion thresholds commonly advised. Mixed acidosis was present in 3 infants around the TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of displacing drugs. All failed to pass bedside hearing screen tests and had severe hearing loss on auditory brain response testing. Symmetrical homogeneous hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus pallidus was hyperintense on T1-weighted MR images in this child. The other infants presented with severe developmental delay as a result of dyskinetic quadriplegia and hearing loss. Globus pallidus was normal on T1-but hyperintense on T2-weighted MR images at 12 or 22 months' corrected age. Subthalamic involvement was documented in coronal fluid attenuated inversion recovery MRI in 2 infants. The term infants with classical clinical presentation in the neonatal period had MR behavior similar to the preterms, but pallidal injury was not recognized with targeted sonographic examination. Their

The authors report six neonates with enteroviral meningoencephalitis. Five infants presented with prolonged seizures, and one presented with systemic enteroviral disease. Cranial ultrasonography showed increased echogenicity in the periventricular white matter, and MRI confirmed mild to severe white matter damage in all infants, which looked similar to periventricular leukomalacia. Two infants developed cerebral palsy: one was neurologically suspect at age 18 months, and three were developmentally normal.