Leena Vainionpää

Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants.

Intrauterine inflammation may relate to neurologic disability among preterm children. We investigated the relationship between chorioamnionitis, cord serum cytokines, and neurologic outcome. Sixty-one consecutively born very preterm extremely low birth weight (ELBW) infants were prospectively enrolled. Histologic inflammation in placenta and umbilical cord and vascular pathology were evaluated. Cord sera were analyzed for five proinflammatory cytokines. Serial brain ultrasound and magnetic resonance imaging were performed for evaluation of intraventricular hemorrhage (IVH grade I–III) and white matter damage (WMD: cystic periventricular leukomalacia or IVH grade IV). Neurologic and neurocognitive outcomes were assessed at the corrected age of 2 y. The incidences of HCA, WMD, and abnormal neurologic outcome were 48%, 13% and 19%, respectively. HCA or high IL-6 in cord serum predicted spontaneous preterm labor with high accuracy. HCA increased the risk of IVH grade II-III. In HCA, without either clinical chorioamnionitis or histologic placental perfusion defect, the children had a low risk of WMD (0%) and a low risk of abnormal neurologic outcome (6%). In HCA, the concentration of IL-6 in cord serum was lower in children with abnormal neurologic outcome than in children with normal neurologic outcome. In HCA and placental perfusion defect (compound defect) the risk of abnormal neurologic outcome was high. Compound placental defect and WMD additively predicted abnormal neurologic outcome. We propose that HCA together with other insults (placental perfusion defect or maternal systemic infection) increases the risk of poor neurologic outcome in very preterm ELBW infants.

Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy.

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin‐like growth factor binding protein‐1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate‐treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy. Ann Neurol 1999;45:444–450

Psychological findings in preterm children related to neurologic status and magnetic resonance imaging.

Objective.u2003Preterm children experience learning disabilities more often than full-term children, but detailed information on their neuropsychological and neurologic determinants is lacking. We therefore examined these problems more closely and also studied if clinical neurologic examination and/or magnetic resonance imaging (MRI) can be used as tools to screen the preterm children at risk for these problems. Methods.u2003In a population-based study, the psychological performance of 42 preterm children with a birth weight <1750 g and of their matched controls was assessed at 8 years of age and the findings were then related to clinical neurologic examination and MRI. Learning disabilities of these children, reported by the teachers, were also studied. Results.u2003The cognitive ability of the preterm children, although in the normal range, was significantly lower than that of the control children. They performed particularly poorly in tasks requiring spatial and visuoperceptual abilities, which were associated with the finding of periventricular leukomalacia in MRI, especially with posterior ventricular enlargement. The preterm children with minor neurodevelopmental dysfunction (MND) had the most problems in neuropsychological tests, whereas the clinically healthy preterm children and those with cerebral palsy had fewer problems. The problems of MND children emerged in the domain of attention. They also experienced the most problems at school. Conclusions.u2003Visuospatial problems were associated with periventricular leukomalacia in MRI, but learning disabilities were most frequent among the preterm children with minor neurologic abnormalities. We recommend closer follow-up of preterm children with MND.

Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of Medication

Summary:u2003 Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment.

Cerebral palsy is characterized by protein mediators in cord serum

Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation‐matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B‐lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)–5, IL‐12, IL‐13, IL‐15, macrophage migration inhibitory factor, monocyte chemoattractant protein–3, monokine induced by interferon γ, and tumor necrosis factor–related apoptosis‐inducing ligand were higher in children with CP (p ≤ 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte‐macrophage colony‐stimulating factor, IL‐2, macrophage‐derived chemokine, and pulmonary and activation‐regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP.

Visual Field Constriction in 91 Finnish Children Treated with Vigabatrin

Summary: u2002Purpose: To study the prevalence and features of visual field constrictions (VFCs) associated with vigabatrin (VGB) in children.

Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children

We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.

Childhood Encephalopathies and Myopathies: A Prospective Study in a Defined Population to Assess the Frequency of Mitochondrial Disorders

Objectives. To assess the frequency of mitochondrial abnormalities in muscle histology, defects in respiratory chain enzyme activities, and mutations in mitochondrial DNA (mtDNA) in children with unexplained psychomotor retardation in the population of Northern Finland. Background. The frequency of mitochondrial diseases among patients with childhood encephalopathies and myopathies is not known. Frequencies are difficult to estimate because the clinical presentation of these disorders is variable. Methods. A total of 116 consecutive patients with undefined encephalopathies and myopathies were enrolled during a 7-year period in a hospital serving as the only neurologic unit for a pediatric population of 97u2009609 and as the only tertiary level neurologic unit for a pediatric population of 48u2009873. Biochemical and morphologic investigations were performed on muscle biopsy material, including oximetric and spectrophotometric analyses of oxidative phosphorylation, histochemistry, electron microscopy, and molecular analysis of mtDNA. Results. Ultrastructural changes in the mitochondria were the most common finding in the muscle biopsies (71%). Ragged-red fibers were found in 4 cases. An oxidative phosphorylation defect was found in 26 children (28%), complex I (n = 15) and complex IV (n = 13) defects being the most common. Fifteen percent of patients (n = 17/116) with unexplained encephalomyopathy or myopathy had a probable mitochondrial disease. Common pathogenic mutations were found in the mtDNA of only 1 patient (.9%). Conclusions. The common known mutations in mtDNA are rarely causes of childhood encephalomyopathies, which is in contrast to the considerable frequency of the common MELAS mutation observed among adults in the same geographical area. Biochemically and morphologically verified mitochondrial disorders were nevertheless common among the children, making the analysis of a muscle biopsy very important for clinical diagnostic purposes.

Clinical neurological findings of children with acute lymphoblastic leukaemia at diagnosis and during treatment

Serial neurological evaluation was performed on 40 consecutive children with acute lymphoblastic leukaemia (ALL) at the time of diagnosis and during treatment. Abnormal neurological signs were found in 23% of the patients, including some without neurological symptoms on admission. Six patients (15%) had abnormal funduscopy findings, papilloedema or preretinal haemorrhages, and 3 of them had increased intracranial pressure measured in connection with a diagnostic lumbar puncture but without blasts in their CSF. The reason for the increased intracranial pressure remained unclear. The development of neurological symptoms caused by peripheral neuropathy during induction therapy was related to the total dose and duration of vincristine therapy. The most severe walking difficulties, patients moving about on all fours for as long as 6 weeks–5 months, occurred in a group who were significantly younger than the other children (P<0.03). Fine and gross motor disturbances occurred in 18% and 30% of the whole patient group, respectively, after 2–3 years of therapy. Impaired short-term memory was observed in 21% of the patients after 2–3 years of therapy, indicating impaired CNS function. The results indicate that chemotherapy also seems to influence CNS abilities, since there was no significant difference between the patients treated with or without cranial irradiation. Neurological evaluation of children with ALL at diagnosis and during treatment is of value with respect to abnormal findings which persist and are not caused by leukaemia, in order to determine the types of difficulties involved and to consider intervention.

Nerve lesions after therapy for childhood acute lymphoblastic leukemia

The objective of the current study was to use somatosensory evoked potentials (SEP) to detect signs of nerve lesions in the peripheral nerve and in the central nervous system (CNS) after 3 years of treatment for childhood acute lymphoblastic leukemia (ALL).