Claudia Fantacci

Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Comparison of propofol versus propofol-ketamine combination in pediatric oncologic procedures performed by non-anesthesiologists.

Limited data are available on the best option (short acting sedatives, opioids, or ketamine) in oncologic procedural sedation performed by non‐anesthesiologists. The aim of the present prospective study is to compare the safety and efficacy of propofol–ketamine versus propofol alone, managed by trained pediatricians, in children with cancer undergoing painful procedures.

Neuroprotective role of nerve growth factor in hypoxic-ischemic injury. From brain to skin

Hypoxic-ischemic injuries (HII) of the brain, optic pathways, and skin are frequently associated with poor neurological and clinical outcome. Unfortunately, no new therapeutic approaches have been proposed for these conditions. Recently, experimental and clinical studies showed that nerve growth factor (NGF) can improve neurological deficits, visual loss and skin damage after HII. Based on these studies, we report the effects of NGF administration in different lesions of the brain, optic pathways and skin. 2.5S NGF purified and lyophilized from male mouse submaxillary glands was utilized for the treatment. NGF administration was started in absence of recovery after conventional and standardized treatment. One mg NGF was administered via the external catheter into the brain, by drop administration in the eye, and by subcutaneous administration in the skin. We treated 4 patients: 2 children with hypoxic-ischemic brain damage, an adult patient with an optic glioma-induced visual loss and a child with a severe crush syndrome of the lower left limb. After NGF treatment, we observed an amelioration of both neurological and electrophysiological function of the brain, a subjective and objective improvement of visual function, and a gradual improvement of ischemic skin lesion. No side effects were related to NGF treatment in all patients studied. Our observation shows that NGF administration may be an effective and safe adjunct therapy in patients with severe HII. The beneficial and prolonged effect on nerve function suggests a neuroprotective mechanism exerted by NGF on the residual viable neurological pathways of these patients.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report

ABSTRACT Background: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. Methods: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). Results: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. Conclusions: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

“Spontaneous” ping-pong fracture in newborns: case report and review of the literature

“Ping-pong” fractures (PPF) are depressed skull fractures typical of newborns. PPF usually result from head injury and, rarely, may cause severe long-term neurological sequelae. The management of PPF is still controversial. The goal of this paper is to present a case of “spontaneous” ping-pong fracture and to review the pertinent literature of the last 20 years. We report on a newborn who presented with a “spontaneous” parietal depressed skull fracture at birth. Preoperative computed tomography (CT) scan confirmed the PPF and excluded brain injuries. Neurosurgical intervention was performed on day 3 with immediate lifting of the fracture; the postoperative course was uneventful.During the last 20 years, 22 cases of “spontaneous ping-pong” fractures in newborn have been reported, with different clinical pictures and management but, generally, with a good outcome.“Ping-pong” fractures can occur in uneventful pregnancies and after uncomplicated vaginal or cesarean deliveries. CT scan, with low-dose protocol for infants, is the gold standard examination to evaluate the fracture and any associated brain lesions. Treatment is selected according to fracture characteristics.

Spontaneous Pneumomediastinum, Pneumopericardium and Pneumorrhachis as potential complications of 2009 pandemic influenza A (H1N1) virus infection in healthy children

We report on two cases of spontaneous pneumomediastinum and pneumopericardium, in one case associated with pneumorrhachis, occurring in two children suffering from the novel influenza H1N1 virus infection. At the admission both children presented with fever, violent dry cough, dyspnea and tachypnea. Radiological studies showed sizeable pneumomediastinum and pneumopericardium in both patients. One of the patients also a pneumorrachis. Children were initially treated by intravenous broad-spectrum antibiotics, antipyretics and a cough sedative. Oral Oseltamivir (60 mg twice daily for 5 days) was administered after the diagnosis of influenza A (H1N1) virus infection. Patients’ clinical condition quickly improved and children were discharged with a partial resolution of their radiological findings. Although these conditions are usually self-limiting and without respiratory or systemic consequences, their prompt recognition in children with H1N1 influenza virus infection is essential to establish fast and adequate therapy mainly related to the control of cough and the commencement of antiviral treatment.

Intravenous immunoglobulins in Melkersson-Rosenthal syndrome: A clinical and neuroimaging study

Melkersson-Rosenthal syndrome (MRS) is a rare, noncaseating granulomatous disease consisting of persistent or recurrent orofacial edema, relapsing peripheral facial paralysis and fissured tongue (1). Oligosymptomatic and monosymptomatic forms are more common than the complete triad (2). MRS is more frequent in young adults between the second and the third decades of life (3), while data about childhood are actually poor. This article is protected by copyright. All rights reserved.

Loss of tolerance for fishes previously tolerated in children with fish food protein induced enterocolitis syndrome

We describe two case reports presenting some novel information on fish FPIES. Fish FPIES to one fish does not always start at the same time to other fish. Additionally, development of tolerance to the index fish do not necessarily imply tolerance to other reactive fish. This reflects on the best management of children with FPIES fish.

Diagnostic criteria for acute food protein-induced enterocolitis syndrome. Is the work in progress?

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated gastrointestinal food allergic disorder. Some diagnostic criteria have been published for acute FPIES. Of course, they are not all the same, so the clinician must choose which ones to adopt for his/her clinical practice. We present here a brief review of these criteria and, through two clinical cases, show how the choice of one or the other can change the diagnostic destiny of a child with suspect FPIES.

Is food protein induced enterocolitis syndrome only a non IgE-mediated food allergy?

Food protein induced enterocolitis syndrome (FPIES) is classified as non-IgE-mediated or cell-mediated food allergy, although there is an atypical phenotype so defined for the presence of specific IgEs. All diagnostic criteria for FPIES include the absence of skin or respiratory symptoms of IgE-mediated type. We present four cases that suggest that specific IgEs may have a pathogenic role, resulting in the existence of different FPIES phenotypes. This could be important from a diagnostic and therapeutic point of view.