Silvia Maria Modesta Pulitano

Prognostic factors and outcome of children with severe head injury: an 8-year experience

Abstract.Objectives: Our aim was to analyze prognostic factors and their association with outcome among children with severe head injury. Methods: We conducted a retrospective study among children with severe head injury admitted to our Pediatric Intensive Care Unit (PICU) from November 1992 to December 2000. The patients were immediately evaluated for the severity of head injury (Glasgow Coma Score, GCS), clinical presentation, cerebral axial tomography, early complications (hypoxia and hypotension), metabolic and hematological alterations and early post-traumatic seizures. Six months after injury we applied the Glasgow Outcome Score (GOS). Correlations with GOS were evaluated using univariate and multivariate logistic models. Results: In all, 122 children with severe head injury were identified. The patients presented the following scores: 18 (14.7.0%) children had a GOS of 1; 2 had a GOS of 2 (1.6%); 27 (22.2%) a GOS of 3 and 75 (61.5%) a GOS of 4 or 5. A low GOS was significantly and independently associated with low GCS, multiple trauma, the presence of hypoxia and hypotension, disseminated intravascular coagulation (DIC), hyperglycemia and early post-traumatic seizures. Hematological alterations (white blood cells) were also associated with a low GOS, though not significantly. Conclusion: In addition to GCS, types of trauma and brain lesion, hypoxia and hypotension, hemocoagulative disorders (DIC), hyperglycemia and early post-traumatic seizures are predictors of GOS. A knowledge of these prognostic factors and the correct management of children with severe head injury helps clinicians to improve outcome and to reduce morbidity and mortality.

Management of status dystonicus: Our experience and review of the literature

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase‐associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.

IL-1 β and IL-6 upregulation in children with H1N1 influenza virus infection

The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1β and IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1β and IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1β and IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1β and IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients.

Intraventricular nerve growth factor infusion: a possible treatment for neurological deficits following hypoxic-ischemic brain injury in infants

Abstract Objective and importance: Hypoxic–ischemic brain injuries in childhood are associated with poor neurological outcome. Unfortunately, no new therapeutic approaches have been proposed. Recently, animal studies show that nerve growth factor (NGF) can reduce neurological deficits following hypoxic–ischemic brain injuries. The objective of this study is to demonstrate the therapeutic effects of intraventricular NGF infusion in severe post-ischemic damage. Clinical presentation: Two infants, aged 9 and 8 months, with hypoxic–ischemic brain damage, secondary to prolonged cardiorespiratory arrest and stabilized after the conventional treatment, were treated with intraventricular NGF infusion. Before the therapy both infants were comatose with asymmetrical tetraparesis; their Glasgow Coma Scale (GCS) was 4 and 5, respectively. One month after the treatment, their GCS was 8 and 9, respectively. EEG examinations performed after the NGF infusion showed an increased alpha/theta ratio. MRI showed a reduction of malacic areas in the brain. A SPECT study, performed only in one infant, demonstrated that the NGF treatment resulted in an improvement of regional cerebral perfusion in right temporal and occipital cortices. Intervention: The drug utilized was 2.5S NGF purified and lyophilized from male mouse submaxillary glands. NGF infusion was started about 30 days after the hypoxic–ischemic brain injury. 0.1 mg NGF was administered via the external drainage catheter into the right cerebral ventricle once a day for 10 days consecutively. Conclusion: Our observations are interesting, but further studies are necessary to confirm the effects of NGF in hypoxic-ischemic brain injuries in infants.

Intramedullary epidermoid cyst presenting with abnormal urological manifestations.

Study design: Report of an epidermoid cyst with intramedullary localization.Objective: To describe an atypical presentation of intramedullary epidermoid cyst.Summary of background data: Intramedullary epidermoid cysts are rare entities with a marked variability in the clinical presentation, essentially of neurological pertinence.Methods: Case report of a spinal epidermoid cyst in a 13-year-old girl presenting with urological symptoms: she had a 12-month history of recurrent low urinary tract infections, urinary frequency and nocturnal enuresis. A urodynamic evaluation was performed and showed the presence of involuntary bladder contractions with detrusor instability and low bladder compliance. Magnetic resonance imaging of the spine demonstrated an intramedullary lesion of the dorsal spinal cord.Results: The mass was excised and 6 months after surgical excision, urological manifestations improved with decreased detrusor hyper-reflexia, increased bladder capacity and compliance and no later report of urinary tract infections.Conclusions: In our patient, unusual clinical manifestations of the tumor have delayed the diagnosis, but its complete removal has led to remission of symptoms. Detailed neurological examination and investigations are indicated in patients with clinical and urodynamic features, suggestive of neuropathic bladder.

Pharmacological Therapies for Pediatric and Neonatal ALI/ARDS: An Evidence-Based Review

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threating conditions still lacking a definite therapy and carrying a high mortality and morbidity, especially in children and infants. Albeit respiratory assistance and supportive therapies are crucial for ALI/ARDS, many drugs have been proposed to treat such syndromes through various mechanisms of action. On the whole the pharmacological therapy might play an important role in such a complex clinical situation but few evidence based data are available in pediatric and neonatal critical care. This review will focus on drugs directly available on the bedside, that is, medicines already administered in the practice or investigated in at least one clinical study. We will value the differences due to patients age and the various causes of the syndrome, that may affect the response to the pharmacological therapy. A special attention will be given to the drugs directly deliverable into the lungs, as this strategy allows a total availability to the lung tissue. The experimental background behind each drug will be discussed and then clinical data in neonates and infants will be presented, if available. Data coming from adult critical care and thought to be somehow pertinent for the pediatric setting will otherwise be reviewed. Quality and evidence for or against each therapy will be evaluated according to the Scottish Intercollegiate Guidelines Network statement and practical reminders for clinicians will accordingly be provided.

Interleukin and neurotrophin up-regulation correlates with severity of H1N1 infection in children: a case–control study

OBJECTIVE To evaluate the correlation between cytokine and neurotrophin expression and clinical findings, disease severity, and outcome of children with H1N1 influenza infection. METHODS A prospective observational clinical study was performed on 15 children with H1N1 infection, 15 controls with lower respiratory tract infections (LRTI), and 15 non-infected children. Plasma levels of interleukin (IL)-1β, IL-6, and neurotrophic factor (nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial derived neurotrophic factor (GDNF)) were measured using immunoenzymatic assays. RESULTS Significantly higher levels of IL-1β, IL-6, BDNF, and NGF were detected in patients with H1N1 infection compared to LRTI controls, while there was no significant variation in GDNF in the two groups. IL-1β, IL-6, BDNF, and NGF levels were significantly higher in H1N1 patients with more severe clinical manifestations compared to H1N1 patients with mild clinical manifestations. Of note, IL-6 was significantly correlated with the severity of respiratory compromise and fever, while NGF up-regulation was associated with the duration of cough. No correlation was found between interleukin and neurotrophic factor expression and outcome. CONCLUSIONS H1N1 infection induces an early and significant IL-1β, IL-6, BDNF, and NGF up-regulation. The over-expression of these molecular markers is likely to play a neuroimmunomodulatory role in H1N1 infection and may contribute to airway inflammation and bronchial hyper-reactivity in infected children.

Glycosaminoglycans: Urinary Excretion in Children with Myelomeningocele

Background: The main consequences of neurogenic bladder dysfunction are renal damage related to high intravesical pressure, vesicoureteral reflux (VUR) and urinary tract infections (UTIs). Neurologic impairment, UTIs and VUR are known to be linked with a potential for renal scarring. Of paramount importance as predisposing conditions for UTIs in neurogenic bladder are poor bladder drainage and detrusor-sphincter dyssynergy which cause further abnormalities on the internal bladder surface and, consequently, a bladder wall rich in glycosaminoglycans (GAGs). Materials and Methods: The aim of this study is to investigate the correlation between GAG excretion and bladder wall degeneration in 43 patients affected by spina bifida (SB) and 40 healthy age-matched control children. Results: The amounts of GAGs excreted vary greatly in SB patients aged from 0 to 5 years, and values are comparable to those observed in normal controls. They are significantly higher in children over 5 years of age. Conclusion: The increased excretion of GAGs in older SB patients is an important parameter in the evaluation of the physiopathological condition of the bladder wall and hence may be considered a possible marker for monitoring the beginning of bladder damage.

A severe case of infant botulism caused by Clostridium botulinum type A with concomitant intestinal viral infections

A 3-month-old male infant with a history of gastroesophageal reflux and constipation was diagnosed with cytomegalovirus infection and treated with gancyclovir for 40 days. At 5 months, he was admitted to the ‘‘Agostino Gemelli’’ Hospital in Rome because of severe constipation, difficulty in swallowing, loss of head control, and progressive lethargy. Neurological examination showed mild mydriasis with sluggishly reactive pupils and deep tendon areflexia. Mechanical ventilation was started because of respiratory failure. The initial diagnosis was severe infection and empirical therapy with sulbactam-ampicillin and acyclovir was started. Blood, urine, and cerebrospinal fluid were negative for bacteria. The electroencephalogram showed a diffuse non-specific pattern. PCR performed on the cerebrospinal fluid was positive for enterovirus RNA. Serological tests showed coxackie B4 infection. Ten days after hospitalisation, infant botulism was suspected. Faecal and serum specimens, tested at the National Reference Centre for Botulism, showed Clostridium botulinum type A spores but not toxin. Samples of home-made honey consumed during the few days before hospitalisation showed 0.2 spores/g of C. botulinum producing type B toxin. Electromyography with repetitive nerve stimulation showed a presynaptic neuromuscular block, typical of botulism. Additional faecal samples, collected every 3–4 days for 2 months, showed botulinal spores until day 40 of hospitalisation. After 43 days of mechanical ventilation, the infant was extubated. He was discharged after 67 days with complete recovery.

Rescue hypothermia for refractory hypercapnia.

Hypothermia may reduce the CO2 production by decreasing the metabolism of the cooled tissue. We describe the first clinical use of hypothermia to lower hypercarbia in a case of bronchiolitis related respiratory failure unresponsive to maximal respiratory support. In this case, hypothermia allowed sparing the use of extracorporeal life support. Conclusion Hypothermia might be useful for severe acute respiratory failure unresponsive to aggressive respiratory support.