Agnese Suppiej

Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis

Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.

Neurodevelopmental outcome in preterm histological chorioamnionitis

The role of histological chorioamnionitis in neonatal neurological outcome is not yet fully understood. The present study aimed to assess the neurodevelopmental outcome of preterm babies born after pregnancy complicated by histological chorioamnionitis. Clinical data were prospectively collected for consecutive premature neonates born before 32 weeks of gestation, admitted to Neonatal Intensive Care Unit of Padua University from January 1998 to December 2001. Placental histology was performed. Outcome at 18 months of corrected age was evaluated by a standardized postal parental questionnaire. Among 104 placentas examined, 41 (39.4%) were diagnosed with histological chorioamnionitis. Reply to the postal questionnaire was available from 76.1% of the families. The relative risk of disability in vision, hearing, speech and motor development was higher in the histological chorioamnionitis than in the non-histological chorioamnionitis group, with statistical significance in speech delay (relative risk 2.37; 95% confidence interval: 1.33-4.22) and hearing loss (relative risk 2.76; 95% confidence interval:1.64-4,64). To our knowledge this is the first report suggesting preterm histological chorioamnionitis as a possible risk factor for hearing loss and speech delay.

Histological Inflammatory Responses in the Placenta and Early Neonatal Brain Injury

We investigated the relationship between the severity of histological inflammatory responses in the placenta, chorionic plate, and umbilical cord in conjunction with the intraventricular hemorrhage (IVH) risk in premature infants. Clinical data were prospectively collected for 287 consecutive premature neonates born before 32 completed weeks of gestation and admitted to the level III neonatal intensive care unit of the Department of Pediatrics at Padua University from January 1999 to December 2004. Placental histology for histological chorioamnionitis (HCA) was graded and scored according to Redline and others. The diagnosis of IVH (grades I–IV) was graded according to Volpes classification. Among the placentas of the 287 preterm examined infants, 68 (23.6%) were diagnosed with acute HCA. Overall incidence of IVH was 11.8%. Of 68 preterm neonates with HCA, 11 developed IVH (16.1%). Maternal HCA at the higher grades and stages increased the risk of IVH: 7 (64%) of the 11 preterm infants with maternal HCA grade 3 developed IVH (RR; 95% CI 2.05; 1.1–3.6) and 8 (73%) of the 11 preterm neonates with stage 3 developed IVH (RR; 95% CI 1.59; 1.0–2.5). Conversely, fetal inflammation was not associated with an increased risk of IVH. In conclusion, the IVH risk in preterm infants at less than 32 gestation weeks is significantly associated with severe grade and stage maternal HCA inflammatory scores.

Early-life sex-dependent vulnerability to oxidative stress: the natural twining model

Objectives: Twins represent a unique natural model for studying fetal adaptation to a suboptimal supply of nutrients in utero, the most likely cause of reduced fetal growth, which has been associated with cardiovascular risk. The proposed developmental origin of cardiovascular diseases may offer new venues for investigating the molecular basis of the well-known gender disparity in cardiovascular disease pathogenesis and progression. Early sex differences in oxidative stress, a mechanism of injury associated with both reduced fetal growth and cardiovascular diseases, have been so far poorly investigated. Thus, we aimed at evaluating oxidative stress in newborn twins by measuring oxidative stress biomarkers in cord blood. Methods: Blood samples were collected from umbilical cord of 80 premature twins. The oxidative stress biomarker15-F2t-isoprostane and the total antioxidant capacity (tAOC) were measured in cord plasma. Results: Males had higher levels of plasma 15-F2t-isoprostane than females. 15-F2t-isoprostane values remained greater in males than in females when considering like-sex or unlike sex pairs. No difference was found in tAOC levels. Conclusions: Our data suggest that sex-based differences in oxidant injury vulnerability occurring early in life could represent a biological mechanism contributing to gender disparity later in life.

Acute Disseminated Encephalomyelitis in Children: Focus on Relapsing Patients

This study investigated the possible prognostic factors for relapse, and the diagnostic criteria for multiple sclerosis and related disorders, in pediatric acute disseminated encephalomyelitis. The study population comprised 24 Italian children with a mean age at onset of 6.9 years, and a mean follow-up time of 52.8 months (range, 12-180). Clinical, neurophysiologic, spinal-fluid, neuroradiologic, and outcome features were investigated. All patients but 2, who were reclassified as exhibiting clinically isolated syndromes, fulfilled the new classification criteria for acute disseminated encephalomyelitis recently proposed by the International Pediatric Multiple Sclerosis Study Group. Three patients relapsed after 3 months, 2 years, and 8 years, respectively. By the second attack, the diagnosis of multiple sclerosis, as well as of multiphasic disseminated encephalomyelitis, could be rendered using the revised criteria of McDonald et al. Long-term follow-up seemed to confirm a chronic disease course in 2 children. We could not identify features at onset to predict outcomes of patients. However, early in follow-up, the appearance of oligoclonal immunoglobulin G bands in spinal fluid and the persistence of visual-evoked potential abnormalities were associated with poor outcomes.

Longitudinal Electroencephalographic (EEG) Findings in Pediatric Anti-N-Methyl-d-Aspartate (Anti-NMDA) Receptor Encephalitis The Padua Experience

To contribute to characterize electroencephalographic (EEG) activity in pediatric anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis, we reviewed electroclinical data of 5 children with anti-NMDA receptor encephalitis diagnosed in our department. We identified 4 longitudinal electroencephalographic phases: in the early phase, background activity was normal, with intermixed nonreactive slow waves; in the florid phase, background activity deteriorated with appearance of sequences of peculiar rhythmic theta and/or delta activity unrelated to clinical changes, unresponsive to stimuli and antiepileptic medications; in the recovery phase, these sequences decreased and reactive posterior rhythm re-emerged; electroencephalogram normalized 2 to 5 months after onset. In conclusion, in the presence of evocative clinical history, recognizing a characteristic longitudinal electroencephalographic activity could provide ancillary aspects addressing the diagnosis and the overall management of children with anti-N-methyl-d-aspartate receptor encephalitis; in particular, knowing that peculiar and recurrent paroxysmal nonepileptic rhythmic theta-delta patterns can occur in these patients could help distinguish paroxysmal epileptic and nonepileptic electroencephalographic activity.

Functional hemispheric asymmetries in humans: electrophysiological evidence from preterm infants.

In recent years, magnetic resonance imaging has allowed researchers to individuate the earlier morphological development of the right hemisphere compared with the left hemisphere during late‐gestational development. Anatomical asymmetry, however, does not necessarily mean functional asymmetry, and whether the anatomical differences between hemispheres at this early age are paralleled by functional specialisations remains unknown. In this study, the presence of lateralised electrical brain activity related to both pitch detection and discrimination was investigated in 34 prematurely‐born infants [24–34 gestational weeks (GWs)] all tested at the same post‐conceptional age of 35 weeks. By means of a frequency–change oddball experimental paradigm, with ‘standard’ tones at 1000 Hz (P = 90%) and ‘deviant’ tones at 2000 Hz (P = 10%), we were able to record higher right event‐related potential activity in the interval windows between 350 and 650 ms after stimulus onset. An explorative hierarchical cluster analysis confirmed the different distribution of the hemispheric asymmetry score in newborns < 30 weeks old. Here, we show electrophysiological evidence of the early functional right lateralisation for pitch processing (detection and discrimination) arising by 30 GWs, but not before, in preterm newborns despite the longer environmental sensorial experience of newborns < 30 GWs. Generally, these findings suggest that the earlier right structural maturation in foetal epochs seems to be paralleled by a right functional development.

Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome (ROHHADS) is a rare, but potentially lethal, pediatric disorder. To date, nearly 80 patients have been reported in the literature; however, the etiopathogenesis is still unclear and debated. Both genetic and paraneoplastic or immune-mediated causes have been supposed to be involved in this syndrome. Nonetheless, at this time, a diagnostic biomarker is not available and diagnosis is based exclusively on clinical criteria. Aiming to establish the immune-mediated pathogenesis, we report 2 children with a clinical picture consistent with ROHHADS and whose cerebrospinal fluid analysis disclosed an intrathecal synthesis of oligoclonal bands. Even if many aspects remain to be explained, this finding suggests that ROHHADS could share similar pathogenetic mechanisms with other immune-mediated central nervous system disorders, and even more important, it might pave the way to a therapeutic chance for these patients by means of immunotherapy.

Nonorganic (psychogenic) visual loss in children: a retrospective series.

Background: Few studies provide follow-up information or systematic investigation of prognostic parameters of nonorganic (psychogenic) visual loss in children. Methods: A retrospective case series analysis was performed on 58 patients younger than 16 years old who had nonorganic visual loss and underwent at least a 3-month follow-up clinic visit and/or telephone interview between 1992 and 2007 at a single institution in Italy. All patients underwent a full neurologic, ophthalmologic, and orthoptic evaluation. Visual electrophysiologic tests were performed in many patients as part of the evaluation. Neuroimaging was performed and psychiatric referral was made only as needed. We collected data on the age at onset, time to diagnosis of nonorganic visual loss, type and duration of visual symptoms, and concomitant psychologic or psychosocial difficulties. Results: Visual deficits consisted mostly of reduced visual acuity (76%) and visual field defects (48%). The diagnosis of nonorganic visual loss could be reached with confidence by means of observing inconsistent performance on a wide array of visual function tests, and, in doubtful cases, by means of electrophysiologic investigations. The mean time from onset to diagnosis was 3.1 months. The mean duration of visual symptoms from reported onset to disappearance was 7.4 months. Complete resolution of all visual symptoms occurred in 93% of patients and did so within 12 months of diagnosis in 85% of patients. There was no correlation between the duration of visual symptoms and age at onset, sex, time to diagnosis, type of ocular symptoms, or presence of psychosocial or psychologic difficulties. Conclusions: Our study extends the follow-up information and confirms the findings of previous investigators in showing that nonorganic visual loss in children generally resolves spontaneously within 1 year and that no major psychiatric disorders are present or will appear after diagnosis. However, psychosocial stressors are often present and may predispose to this manifestation. There are no obvious predictors of rate of recovery.

Ocular manifestations in the mucopolysaccharidoses – a review

Ocular manifestations are very common in all types of mucopolysaccharidoses (MPS) and often lead to visual impairment. They arise as a result of the accumulation of glycosaminoglycans deposits in ocular tissues or secondary to increased intracranial pressure. Typical ocular features in MPS include corneal clouding, retinopathy, glaucoma, optic disc swelling, optic atrophy, and ocular motility and refractive error problems. This paper reviews the ocular features in patients with MPS, discusses the diagnosis of these ocular features and the diagnostic problems that may arise in patients (children) with MPS, and highlights the central role ophthalmologists may play in the diagnosis and follow‐up of these patients.