NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children.

BACKGROUND: Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of specific biomarkers, such as cytokines, neurotrophic factors, and neuron-specific enolase (NSE). NSE is associated with neuronal damage, while neurotrophic factors play a neuroprotective role due to their ability to modulate neuronal precursor biosynthesis, such as doublecortin (DCX). However, the relationships between the expression of these factors and the severity and outcome of TBI are not understood. METHODS: To determine whether the concentrations of neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]), DCX, and NSE in the CSF of children with TBI correlate with the severity of brain damage and neurologic outcome, we prospectively collected CSF samples from 32 children at 2 and 48 hours after admission for severe TBI and from 32 matched controls. Severity of TBI was evaluated by Glasgow Coma Scale and neurologic outcome by Glasgow Outcome Score. RESULTS: Early NGF, DCX, and NSE concentrations correlated significantly with the severity of head injury, whereas no correlation was found for BDNF and GDNF. Furthermore, NGF and DCX upregulation and lower NSE expression were associated with better neurologic outcomes. No significant association was found between BDNF and GDNF expression and outcome. CONCLUSIONS: Nerve growth factor (NGF), doublecortin (DCX), and neuron-specific enolase concentrations in the CSF are useful markers of brain damage following severe traumatic brain injury (TBI). NGF and DCX upregulation correlates also with better neurologic outcome and could be useful to obtain clinical and prognostic information in children with severe TBI.

Craniopagus: the Thessaloniki-Rome experience.

OBJECT: A case of two female Greek twins conjoined at the left frontal and orbital regions is described. These conjoined twins were transferred to the Pediatric Neurosurgical Unit of the Gemelli Hospital, Catholic University Medical School, at the age of 4 months for possible surgical division. METHOD: Multiple diagnostic investigations, which included in particular advanced imaging techniques, demonstrated an independent cerebral vascularization of the two babies and excluded significant intracranial malformations. Such an accurate evaluation of the anatomy of the craniopagus at the level of the cranial junction allowed the feasibility of the surgical correction to be established. CONCLUSIONS: The operation was carried out by a multidisciplinary team in a single stage. The operating team included two distinct teams of neurosurgeons and anesthesiologists as well as a plastic surgeons' team. Both babies survived the operation. The postoperative course was uneventful. Both twins were discharged in good clinical and neurological condition after a 3-week period of hospitalization.

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants.

OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.

Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants.

The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.

[The management of the child with head injury: our experience]. / Il management del bambino con trauma cranico: nostra esperienza.

OBJECTIVES: To analyze the group of children admitted to our Pediatric Intensive Care Unit (PICU) for neurotrauma and describe the management algorithms adopted by us for pediatric head injury. METHODS: All the children affected by head injury and admitted to PICU since november 1992 to november 2000 have been examined. Injury severity has been classified using the Glasgow Coma Score (GCS), while the long term neurological outcome with the Glasgow Outcome Score (GOS). We have described the clinical presentation, the kind and dynamics of injury and the clinical outcome one month after discharge. RESULTS: 210 children with head injury have been identified. Among them: 38 were affected by mild head injury, 50 by a moderate one and 122 by a severe one. The most frequent cause of injury has been represented by car accidents and motorbike or bicycle falls. The overall outcome has resulted good (GOS 4-5) in all children affected by mild or moderate head injury; on the other side, patients with severe injury have presented the following scores: GOS 1 (dead children) 14.7%, GOS 2 (persistent vegetative state) 1.6%, GOS 3 (severe disability) 22.2%, GOS 4 (mild disability) and GOS 5 (no disability) 61.5%. CONCLUSION: A correct management of children with head injury helps clinicians to improve outcome and to reduce mortality. Therapeutics algorithms suggested by us could be useful for the management of this kind of patients, not only when they are affected by a severe head injury but, also, when they suffer from a mild one, that is the most common event in the emergency room departments.

Early changes of pulmonary mechanics to predict the severity of bronchopulmonary dysplasia in ventilated preterm infants.

OBJECTIVES: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity. METHODS: Pulmonary mechanics were studied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed using a previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcome was classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4). RESULTS: Of the 52 infants, 39 survived to 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patent ductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10 days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probability of developing severe BPD. Respiratory system resistance did not show any predictive value. CONCLUSIONS: Our findings indicate that low lung compliance values determined on the 7th and 10th days of life are a reliable predictive tool of the severity of later BPD.

Intracranial hemorrhage at the onset of thrombotic thrombocytopenic purpura in an infant: therapeutic approach and intensive care management.

Thrombotic thrombocytopenic purpura (TTP) is quite rare in infancy and must be treated intensively as a life-threatening disease. Diffuse vascular thromboses may occur, and neurologic involvement is a cornerstone of the diagnosis of TTP. We describe a case of an infant who presented with a sudden cerebral hemorrhage and subsequently developed the typical clinical features of TTP. Emergency treatment in the Pediatric Intensive Care Unit (PICU) consisted of plasma therapy and exchange-transfusion (EXT) to arrest the intravascular process and the exsanguinating blood loss. Exchange-transfusion is a life-saving procedure that is rarely performed after the neonatal age.

Ruptured intracranial mycotic aneurysm presenting as cerebral haemorrhage in an infant: case report and review of the literature.

A 2-month-old male infant presented with intracranial haemorrhage caused by ruptured intracranial mycotic aneurysm. Computed tomography and cerebral selective angiography revealed a large haematoma in the left sylvian fissure and a mycotic aneurysm of a peripheral branch of the middle cerebral artery. Despite the successful surgical removal, the child did not recover from the initial brain injury and died 2 months later. There have been fewer than 10 reported cases of infantile mycotic aneurysms and its occurrence in the absence of infectious endocarditis is exceptionally rare.

Preemptive analgesia with tramadol and fentanyl in pediatric neurosurgery.

Preemptive analgesia is based on administration of an analgesic before a painful stimulus generates, so as to prevent the subsequent rebound mechanism. Tissue injury results in disruption of the processing mechanisms of noxious stimuli afferent to the CNS (central nervous system) by way of an increase of inputs in the spinal cord. These reactions may be reduced by the administration of opioids. Few studies on preemptive analgesia with opioids in children are available, and none of them is concerned with pediatric neurosurgery. Tramadol and fentanyl are synthetic opioids which are relatively new and act through the activation of pain-inhibitory mechanisms. We conducted a randomized, prospective trial on the preemptive effects in children of these two analgesic drugs, administered according to three different protocols: tramadol as a bolus (1 mg/kg); tramadol by continuous infusion (150 microg/kg per h); fentanyl by continuous infusion (2 microg/kg per h). In all, 42 children undergoing major neurosurgical operations were enrolled in the study, 14 in each treatment group. Each treatment was started at the induction of general anesthesia and continued throughout the entire duration of the operation. The postoperative pain evaluation was conducted in the Pediatric Intensive Care Unit at the end of the surgical operations and involved comparison of any changes in behavioral (AFS scale and CHEOPS score) and hemodynamic (heart rate, respiratory rate, systolic and diastolic arterial pressure, oxygen saturation, O(2) and CO(2) partial pressure) parameters. Only 2 children, both in group A, needed further drug administration postoperatively. No significant side effects were noticed in any of the three groups, except that in group A there was a higher incidence of nausea and vomiting. Tramadol efficacy seems to be better when it is administered in continuous infusion; this treatment modality also leads to fewer adverse effects. Fentanyl, in contrast, proved to be superior to tramadol in the treatment of postoperative pain. In conclusion, preemptive analgesia is a valid technique for the treatment of acute pain in children undergoing major neurosurgical operations.

Surfactant treatment in a pediatric burn patient with respiratory failure.

This report describes surfactant treatment in a burned infant with severe respiratory failure. In this patient the instillation of surfactant rapidly improved compliance, oxygen index (OI), and alveolar-capillary oxygen gradient (AaDO2), while the need for oxygen supplementation and peak positive pressure drastically decreased. The treatment was repeated after 12 hours. Although the baby had severe clinical course complications as a Gram-negative sepsis and a subglottic stenosis, she was weaned from oxygen therapy and mechanical ventilation in few weeks. Surfactant dysfunctions seem to play a central role in the respiratory insufficiency of burned patients, and its exogenous replacements could improve their outcome.

[Pulmonary function tests as a predictor of chronic lung disease in ventilated preterm infants]. / Le prove di funzionalità respiratoria nella predittività della patologia polmonare cronica del neonato pretermine in ventilazione meccanica.

BACKGROUND: The objective of this study was to determine if the value of respiratory system compliance and lung resistance could be a good predictor of chronic lung disease (CLD) in an early stage of this disease. METHODS: The study was carried out on 48 preterms infant (BW < 1500 g) who were ventilated for respiratory distress, calculating pulmonary mechanics at 3, 5, 7 and 10 days of life with a standardized protocol of measurements. RESULTS: Infants who did not develop CLD showed higher values of respiratory system dynamic compliance (Crsdyn) than the CLD group since the 5th day of life (p < 0.001). The values of lung resistance show a statistical significant difference between groups since the 7th day of life. CONCLUSIONS: These findings indicate that, with a well standardized method of measurements, the value of Crsdyn can well be a good predictor and a sensible prognostic factors for CLD.

Acute hydrocephalus as a consequence of mumps meningoencephalitis.

Aqueductal stenosis can result from mumps meningoencephalitis. We report a case of acute hydrocephalus from an aqueductal stenosis developed immediately after a clinically evident mumps infection. The patient, aged two years, was treated with an antiedema therapy, and a ventriculoperitoneal shunt was placed. His clinical conditions rapidly improved. Only mumps virus was found in his cerebrospinal fluid culture. This case probably represents the earliest hydrocephalus from mumps, among those reported in the literature.

A scoring system to predict the evolution of respiratory distress syndrome into chronic lung disease in preterm infants.

OBJECTIVE: The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. DESIGN: Clinical study. SETTING: Neonatal intensive care unit. PATIENTS: The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1,250 g. The results obtained with both scoring systems were then compared. RESULTS: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 +/- 2.3 weeks; BW: 1,058 +/- 143 g) were normal and 82 (GA: 27.5 +/- 3.9 weeks: BW: 838 +/- 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0% and a sensitivity of 92.7% on the 3rd day of life; on the 5th day of life the specificity was still 95.5%, while sensitivity remained 92.7%. The areas under the ROC curves plotted with both scoring systems tested were similar. CONCLUSIONS: The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life.

Intraventricular streptokinase infusion in acute post-haemorrhagic hydrocephalus.

Neonatal post-haemorrhagic hydrocephalus is a clinical condition with a high mortality and long-term morbidity. Its clinical management is difficult and not well standardized. We describe the case of a term baby suffering from acute intracranial hypertension caused by an intraventricular and thalamic haemorrhage. In this case, the external ventricular drain inserted to control intracranial pressure was ineffective because of repeated obstructions due to blood clots. Continuous intraventricular infusion of streptokinase of 20,000 U/day allowed quick lysis of the clots, drainage of the cerebrospinal fluid and relief from the coma. Although it did not prevent a permanent ventriculoperitoneal shunt, we obtained reabsorption of the intraventricular haemorrhage without rebleeding complications. We suggest the use of low-dose fibrinolytic infusion through an external drain for the treatment of acute intracranial hypertension following intraventricular haemorrhage in term infants.

Cryptorchidism associated with meningomyelocele.

OBJECTIVE: The authors studied 75 male infants with meningomyelocele (MMC) to analyse the association with cryptorchidism. METHODS: All infants were diagnosed at birth and surgically corrected after 24-48 h. Testes were classified undescended in accordance with Kaplan. The associated malformations, the exact levels of the lesion (surgical report) and the presence of hydrocephalus and the cremasteric reflex have each been assessed. RESULTS: In these patients a higher incidence of cryptorchidism (14.8%) was found than in the normal population. Lesion level (L2-L3) and absence of cremasteric reflex was higher in children with associated cryptorchidism. Infants with MMC and undescended testes showed no increased incidence of hydrocephalus and sexual hormone levels remained within the normal range. These results suggest that the cremaster muscle could be a major factor involved in testis descent through the inguinal canal. CONCLUSIONS: The authors propose that spinal cord lesion, as well as neurologic dysfunction, is of major importance in the pathophysiology of cryptorchidism in spina bifida.

[Diffuse axonal lesions in childhood]. / La lesione Assonale Diffusa in età pediatrica.

OBJECTIVE: About 48% of all primary traumatic intracranial lesions are represented by so-called Diffuse Axonal Injury (DAI): a pathologic condition characterized by multiple microscopic lesions and hemorrhage at the level of midline cerebral structures, in the subcortical grey matter, and/or within the brainstem. The natural history of DAI is depressing: 100% of the patients deteriorate rapidly to coma and approximately 50% die, while 50% remain in a vegetative state or with severe neurological deficits. In the present report, we describe the results of a study aimed to evaluating the cerebral hemodynamics and the neuroradiological findings observed in four children (6, 8, 10 and 12 years old) affected by DAI. METHODS: All the patients had been admitted to the Pediatric Intensive Care Unit with Glasgow Coma Score (GCS) of 5. On admission, all patients underwent mechanical ventilation, antiedemigen and barbiturates therapy. Serial CT scan and Transcranial Doppler Sonography (TCD) examinations were carried out in all children. TCD of the middle cerebral arteries was performed through the temporal window. The children underwent insertion of a ventricular catheter for intracranial pressure monitoring. Follow-up time has been, respectively, 4 years, 3 years, 7 and 1 months. RESULTS: The Glasgow Outcome Score (GOS) of three children is 2 (persistent vegetative state), while the GOS of the one child is 3 (severe neurological deficits). CONCLUSION: DAI results in unfortunate prognosis and large health care costs. The proper medical management of this condition should be based on TCD and SjO2 and CEO2 evaluations, in order to monitor efficaciously the cerebral blood flow.

Salicylate intoxication using a skin ointment.

Acute percutaneous salicylate intoxication is a rare event in children but can happen with a skin disease where salicylic acid, used as a keratolytic ointment, can be absorbed transcutaneously. Until now, few cases of transcutaneous salicylate intoxication have been reported in the literature. Our case report is about a 5-year-old girl with lamellar ichthyosis and an acute salicylate transcutaneous intoxication after the application of a skin ointment. The child had a fever, hyperpnoea with respiratory alkalosis, comatose state and oculogyric crisis. We would like to emphasize the danger of applying salicylic acid in children with extensive skin diseases and, therefore, it is advisable to measure the plasma salicylic levels so as to prevent eventual salicylate toxicity.

[Analgesic efficacy of ketorolac and fentanyl in pediatric intensive care]. / Efficacia analgesica del Ketorolac e del Fentanyl in Terapia Intensiva Pediatrica.

OBJECTIVE: To evaluate the efficacy of the two different drugs (Ketorolac and Fentanyl), used singularly or in association, in the management of postoperative pain in Picu. STUDY DESIGN: A randomized and prospective study. METHODS: 52 children were randomly assigned to receive intravenous Ketorolac and/or Fentanyl, according to four different analgesic treatments: A) Ketorolac 1.2 mg/kg every six hrs; B) Ketorolac 1.2 mg/kg (bolus) + 0.21 mg/ kg/hr; C) Fentanyl 1 gamma/kg/hr; D) Fentanyl 1 gamma/kg/hr + Ketorolac 0.21 mg/kg/hr. Each protocol was given to 13 children. The efficacy of treatments were evaluated by child's behaviour (Affective Facial Scale and CHEOPS score) and hemodynamical parameters (systolic and diastolic blood pressure, breathing rate, heart rate, oxygen saturation and oxygen arterial pressure) and analysed by statistical analysis. RESULTS: The children treated with protocol B (Ketorolac in continuous in infusion) showed better pain relief in respect to those treated with protocol A (Ketorolac in bolus), while the most efficient analgesia was obtained with the association of the two analgesic drugs (protocol D). Two cases of bradycardia, one case of hyperazotemia and one case of transaminase increase were noted. CONCLUSION: Ketorolac presents a good efficient analgesia, particularly evident when administered in continuous intravenous infusion. However, the association of this NSAID with an opioid drug can be favourably proposed in postoperative pain therapy of moderate to severe grade, since the confirmed analgesic efficacy is not aggravated by important side effects.

Intrasubject variability of repeated pulmonary function measurements in preterm ventilated infants.

This study set out to describe the variability and assess the reproducibility of repeated pulmonary function measurements in ventilated preterm infants. We measured tidal volume (VT), lung compliance (CL), and resistance (RL) in 16 infants (mean +/- SD: birthweight 1222 +/- 343 g) during spontaneous breathing and during mechanical ventilation, suppressing breathing efforts by mild hyperventilation. CL and RL were calculated from the equation of motion using linear regression analysis (LR), and by the Mead and Wittenberger method (MW). Flow and transpulmonary pressure were recorded for at least two consecutive periods, after which the esophageal tube was removed and replaced 1 hour later for a second set of recordings. The mean percent change (% delta) between the initial and the repeated measurements with their respective 95% confidence intervals were calculated. Reproducibility was assessed by the intraclass correlation coefficient (ICC) (total agreement = 1, good reproducibility > or = 0.75). The mean % delta between initial and repeat measurements during spontaneous breathing ranged from 11% to 14% for CL and VT, and from 22% to 32% for RL. The variation for RL was even higher when the analysis was done separately for the inspiratory and expiratory phase. CL and VT had good reproducibility (ICC > 0.9), while RL was significantly less reproducible (ICC < 0.75). Measurements obtained from mechanical breaths had less variability than from spontaneous breaths, ranging from 8% to 15% for CL and VT, and from 13% to 21% for RL. Reproducibility assessed by the ICC was good for most measurements during mechanical breaths. The variability and reproducibility of measurements were similar for both methods of analysis during mechanical ventilation, but during spontaneous breathing variability was larger with the MW method than with LR analysis. We concluded that VT and CL were reproducible during spontaneous and mechanical breathing. However, RL measurements were reproducible only during mechanical ventilation. The high variability of RL in spontaneously breathing preterm infants may reduce the clinical usefulness of this measurement for individual patients.

[Intracranial hemorrhage in Schoenlein-Henoch syndrome]. / Emorragia endocranica nella sindrome di Schoenlein-Henoch.

Henoch-Schoenlein syndrome (HSS) is one of the most common vasculitis in childhood. It is characterized by non-thrombocytopenic purpura, arthritis, abdominal pain, and sometimes intestinal haemorrhage and renal involvement. It may be complicated by haemorrhages in uncommon sites, such as lungs, testicles, bladder, and central nervous system. Neurological involvement in HSS is often underestimated, usually occurring with headache, irritability, and behavioural alterations, whereas endocranial haemorrhage is quite rare. We report a case of endocranial haemorrhage in a child with HSS.