Background: There are few studies on neonatal cerebral sinovenous thrombosis (SVT). Objectives: To describe the presentations, treatments, and outcomes of neonatal SVT and to assess infarction as a predictor of outcome. Design: Retrospective chart study. Setting: A tertiary pediatric hospital in Indianapolis, Ind. Patients: Forty-two children with neonatal SVT identified using International Classification of Diseases, Ninth Revision code searches from 1986 through June 2005 and review of neurology clinic records. Interventions: None. Main Outcome Measures: Cognitive impairment, motor impairment, and epilepsy at last clinic visit. Results: Gestational or delivery complications or risk factors and comorbid conditions such as dehydration, sepsis, and cardiac defects were common (gestational/ delivery factors in 82% [31 of 38 with available maternal data]; comorbid conditions in 62% [26 of the 42]). Twenty-four (57%) presented with seizures. Twentyfive (60%) had infarcts, which were hemorrhagic in 22. Only 27 (64%) of 42 received prothrombotic evaluations; none had persistent deficiencies of protein C, protein S, or antithrombin III. Three (7%) received heparin sodium. All other children received only supportive care. One child died. Outcome data were available for 29 (71%) of the 41 survivors; of these, 23 (79%) had impairment(s). Two were known to be in early intervention, and no further information was available. Of the remaining 27, 16 (59%) had cognitive impairment, 18 (67%) had cerebral palsy, and 11 (41%) had epilepsy. Infarction was associated with the presence of later impairment (P=.03). Conclusions: The presentation of neonatal SVT is often nonspecific, the diagnosis can be difficult to make, treatment beyond supportive care is rarely used, and outcomes can be severe. Further work is needed to develop standardized guidelines for the evaluation and treatment of neonatal SVT.

BackgroundDe novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia.ObjectivesTo delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations.MethodsDiagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes.ResultsWe report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes.ConclusionWe delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.

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Childhood epilepsy is frequent after perinatal stroke. Evidence of infarction on prenatal ultrasonography and a family history of epilepsy predict earlier onset of active seizures.

Cerebral venous thrombosis is an important cause of stroke in children. Understanding the natural history of the disease is essential for rational application of new interventions. We retrospectively identified 31 children with cerebral venous thrombosis confirmed by head computed tomography (4 patients) or by magnetic resonance imaging (27 patients). Risk factors, clinical and radiographic features, and neurologic outcomes were analyzed. There were 21 males and 10 females aged 1 day to 13 years (median 14 days). Nineteen (61%) were neonates. The most common risk factors included mastoiditis, persistent pulmonary hypertension, cardiac malformation, and dehydration. The chief clinical features were seizures, fever, respiratory distress, and lethargy. Fifteen patients had infarctions (8 hemorrhagic, 7 ischemic). Protein C and antithrombin III deficiency were the most common coagulopathies among 14 tested patients. On discharge, 11 patients were normal, 17 had residual deficits, and 2 patients died. Twenty-seven patients were followed from 1 month to 12 years (mean 22 months). At follow-up, 11 patients were normal, and 13 patients had development delay. One had residual hemiparesis and cortical visual impairment. Two had other deficits. Neonatal cerebral venous thrombosis is probably more common than previously thought, and outcomes are worse in this group. All children with cerebral venous thrombosis should be tested for coagulation disorders.

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Lacosamide is a US Food and Drug Administration (FDA)-approved antiepileptic drug for patients 17 years or older with partial epilepsy. There are sparse data on children. The objective of our study was to evaluate its efficacy/safety in children with refractory epilepsy. Forty children (mean age 14.3 years) were treated with lacosamide at our institution (adjunctive therapy in 36, monotherapy in 4). Fifteen patients had symptomatic focal epilepsy, 2 had cryptogenic focal epilepsy, 20 had symptomatic generalized epilepsy, and 3 had cryptogenic generalized epilepsy. Two had juvenile myoclonic epilepsy and 5 had Lennox-Gastaut syndrome. Forty-two percent had at least >50% reduction in seizure frequency, and 6 became seizure free. Average dose was 7 mg/kg/d and average follow-up was 9.2 months. Responders had a 76.5% mean decrease in seizures. Fifteen children experienced an adverse reaction and 7 discontinued lacosamide (4: Ineffective, I: insurance denial, 1: tremor, 1: behavior). Lacosamide is effective and well-tolerated in children with refractory epilepsy.