Wernicke Encephalopathy Caused by Avoidance-Restrictive Food Intake Disorder in a Child: A Case-Based Review.

BACKGROUND: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. CASE PRESENTATION: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. CONCLUSIONS: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.

Status epilepticus in BRAF-related cardio-facio-cutaneous syndrome: Focus on neuroimaging clues to physiopathology.

OBJECTIVE: Cardio-facio-cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical-radiological patterns and discuss the underlying physiopathology. METHODS: We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic BRAF variants who experienced SE during a 5-year period. RESULTS: Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE/within 72 hours from SE termination in 5/7 events. Acute/early post-ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2/7, focal area of pcASL perfusion change in 2/7, focal cortical T2/FLAIR hyperintensity in 2/7. Follow-up images were available for 4/7 SE. No acute changes were detected in 2/7 (MRI performed 4 days after SE termination). SIGNIFICANCE: Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long-term adverse neurological outcome. PLAIN LANGUAGE SUMMARY: Cardio-facio-cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio-facio-cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio-facio-cutaneous syndrome patients from long-term brain damage.

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome.

BACKGROUND: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. METHODS: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. CONCLUSION: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

Successful stem cell collection for atypical teratoid rhabdoid tumor in an extremely low-body weight child: A case report.

The use of peripheral blood hematopoietic stem cells for bone marrow reconstitution after myeloablative therapy is well established in children with malignant disorders. However, the peripheral blood hematopoietic stem cells collection in very low-body weight (≤10 kg) children remains a significant challenge because of technical and clinical issues. A male newborn affected by atypical teratoid rhabdoid tumor, diagnosed prenatally, received two cycles of chemotherapy following surgical resection. After an interdisciplinary discussion, it was decided to intensify the treatment with high-dose chemotherapy followed by autologous stem cell transplantation. After 7 days of G-CSF administration the patient underwent hematopoietic progenitor cells-apheresis collection. The procedure was performed in the pediatric intensive care unit, using two central venous catheters and Spectra Optia device. The cell collection procedure was completed in 200 min, during which time 3.9 total blood volumes were processed. During apheresis we did not observe electrolyte alterations. No adverse events were recorded during or immediately following the cell collection procedure. Our report describes the feasibility of performing large volume leukapheresis without complications in an extremely low-body weight patient weighing 4.5 kg using the Spectra Optia apheresis device. No catheter-related problems occurred, and apheresis was completed without any adverse event. In conclusion, we believe that very low-body weight pediatric patients need a multidisciplinary approach to manage central venous access, hemodynamic monitoring, cell collection, prevention of metabolic complications to improve safety, feasibility, and efficiency of stem cell collection procedures.

Needleless inhaled anesthesia with sevoflurane: Advantages of a simplified approach for children with spinal muscular atrophy undergoing intrathecal administration of nusinersen.

BACKGROUND: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. AIMS: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period. METHODS: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events. RESULTS: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). CONCLUSION: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration.

KETASER01 protocol: What went right and what went wrong.

OBJECTIVE: To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. METHODS: KETASER01 is a multicenter, randomized, controlled, open-label, sequentially designed, non-profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. RESULTS: During the 5-year recruitment phase, a total of 76 RCSEs treated with third-line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). SIGNIFICANCE: The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials.

Multisystem Inflammatory Syndrome in Children and Acute Kidney Injury: Retrospective Study of Five Italian PICUs.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) manifests with heart dysfunction and respiratory failure some weeks after a severe acute respiratory syndrome coronavirus disease 2 infection. The aim of our study was to explore the prevalence, severity, timing, and duration of acute kidney injury (AKI) in MIS-C patients. Furthermore, we evaluated which clinical variables and outcomes are associated with AKI. DESIGN: Multicenter retrospective study. SETTING: Five tertiary hospital PICUs in Italy. Data were collected in the first 7 days of PICU admission and renal function was followed throughout the hospital stay. PATIENTS: Patients less than 18 years old admitted to the PICU for greater than 24 hours with MIS-C. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected the following data, including: demographic information, inflammatory biomarkers, lactate levels, Pa o2 /F io2 , ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function (serum creatinine, urinary output, fluid balance, and percentage fluid accumulation), Vasoactive-Inotropic Score (VIS), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Index of Mortality 3. AKI was diagnosed in eight of 38 patients (21%) and severe AKI was present in four of eight patients. In all cases, AKI was present at PICU admission and its median (interquartile range) duration was 3.5 days (1.5-5.7 d). We did not identify differences between AKI and no-AKI patients when not making correction for multiple comparisons, for example, in weight, ejection fraction, pSOFA, Pa o2 /F io2 , and lactates. We failed to identify any difference in these groups in urine output and fluid balance. Exploratory analyses of serial data between no-AKI and AKI patients showed significant differences on lymphocyte count, NT-proBNP value, ejection fraction, pSOFA, Pa o2 /F io2 , and VIS. CONCLUSIONS: In this multicenter Italian PICU experience, MIS-C is associated with AKI in one-in-five cases. In general, AKI is characterized by an associated reduction in glomerular filtration rate with a self-limiting time course.

Fighting autoinflammation in FIRES: The role of interleukins and early immunomodulation.

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies.

Life-sustaining treatment decisions in pediatric intensive care: an Italian survey on ethical concerns.

OBJECTIVES: To investigate how life-sustaining treatment (LST) decisions are made and identify problematic ethical concerns confronted by physicians and nurses in pediatric intensive care within Italy. METHODS: An 88-question online survey was created, based on a previous qualitative study conducted by this team. The survey was designed to identify how LST decisions were managed; contrasting actual practices with what participants think practices should be. Replies from physicians and nurses were compared, to identify potential inter-professional ethical tensions. The study also identified participants' principal ethical concerns. Moreover, open-ended questions elicited qualitative perspectives on participants' views. The survey was pilot-tested and refined before initiation of the study. RESULTS: 31 physicians and 65 nurses participated in the study. Participants were recruited from pediatric intensive care units across five Italian cities; i.e., Florence, Milan, Padua, Rome, Verona. Statistically significant differences were identified for (a) virtually all questions contrasting actual practices with what participants think practices should be and (b) 14 questions contrasting physician replies with those of nurses. Physicians and nurses identified the absence of legislative standards for LST withdrawal as a highly problematic ethical concern. Physicians also identified bearing responsibility for LST decisions as a major concern. Qualitative descriptions further demonstrated that these Italian pediatric intensive care clinicians encounter significantly distressing ethical problems in their practice. CONCLUSIONS: The results of this study highlight a need for the development of (a) strategies for improving team processes regarding LST decisions, so they can be better aligned with how clinicians think decisions should be made, and (b) Italian LST decision-making standards that can help ensure optimal ethical practices.

Botulism during SARS-CoV-2 pandemic: The importance of differential diagnoses.

Botulism is a neuroparalytic syndrome caused by a neurotoxin produced by Clostridium botulinum. We describe a patient with neurological symptoms associated with intoxication by Clostridium botulinum and infection by SARSCoV2. This report underlines that it is mandatory, even in case of SARS-CoV-2 positivity, to investigate all the causes of a clinical pattern.

Comparison between sedation room and operating room in central venous catheter positioning in children.

BACKGROUND: Placement of central venous access devices is a clinical procedure associated with some risk of adverse events and with a relevant cost. Careful choice of the device, appropriate insertion technique, and proper management of the device are well-known strategies commonly adopted to achieve an optimal clinical result. However, the environment where the procedure takes place may have an impact on the overall outcome in terms of safety and cost-effectiveness. METHODS: We carried out a retrospective analysis on pediatric patients scheduled for a major neurosurgical operation, who required a central venous access device in the perioperative period. We divided the patients in two groups: in group A the central venous access device was inserted in the operating room, while in group B the central venous access device was inserted in the sedation room of our Pediatric Intensive Care Unit. We compared the two groups in terms of safety and cost-effectiveness. RESULTS: We analyzed 47 central venous access devices in 42 children. There were no insertion-related complications. Only one catheter-related bloodstream infection was recorded, in group A. However, the costs related to central venous access device insertion were quite different: €330-€540 in group A versus €105-€135 in group B. CONCLUSION: In the pediatric patient candidate to a major neurosurgical operation, preoperative insertion of the central venous access device in the sedation room rather than in the operating room is less expensive and equally safe.

Improving communication toward ICU families to facilitate understanding and reduce stress. Protocol for a multicenter randomized and controlled Italian study.

OBJECTIVE: Families of ICU patients have a pressing need for information: they find themselves suddenly in a complex technical environment often because of a life-threatening illness of a loved one. Some evidence suggests that specific communication tools (like websites or brochures) could improve the experience of ICU families. DESIGN: Randomized, multicenter, stepped wedge trial for large-scale assessment of the effectiveness of a multitasking intervention to improve communication with families of critically ill patients. MAIN OUTCOME: correct understanding of the prognosis. SECONDARY OUTCOMES: correct understanding of medical treatments, prevalence of anxiety, depression and post-traumatic stress symptoms in the first ICU week. Prevalence of PTSD 6 months from ICU discharge. Empathy and burnout among ICU staff. Prevalence of refusals for tissues/organ donation, and medical claims. SUBJECTS: 2100 ICU relatives of critically ill patients. INTERVENTIONS: The intervention employs specific tools especially designed to raise the correctness of information and to improve the quality of communication: a website presenting the ICU world and justifying the relatives' emotions, with a webpage specifically dedicated to each participating ICU; a standard brochure; eight posters for the families' waiting room and a signboard for the ICU door. MEASUREMENTS AND MAIN RESULTS: The study plans to assess these materials in up to 300 Italian ICUs that will participate, according to a five waves program, each one with randomized starting order. This way the effect of the intervention will be evaluated simultaneously. CONCLUSION: This is an educational study, aiming to spread good medical practices, while also verifying their real effectiveness in a large number of ICUs. TRIAL REGISTRATION NUMBER: NCT03438175.

Impact of positive end expiratory pressure on cerebral hemodynamic in paediatric patients with post-traumatic brain swelling treated by surgical decompression.

INTRODUCTION: The objective of our present study is to evaluate the impact of different PEEP levels on cerebral hemodynamic, gas exchanges and respiratory system mechanics in paediatric patients with post-traumatic brain swelling treated with decompressive craniectomy (DC). MATERIALS AND METHODS: A prospective physiologic study was carried out on 14 paediatric patients presenting with severe traumatic brain swelling treated with DC. Transcranial Doppler ultrasonography was performed on the middle cerebral artery bilaterally after DC. After assessment at ZEEP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), central venous pressure (CVP) and gas exchanges were recorded at PEEP 4 and PEEP 8. RESULTS: From ZEEP to PEEP 8, the compliance of respiratory system indexed to the weight of the patient significantly increased (P = 0.02) without ICP modifications. No significant variation of the MAP, CPP, Vmed, the total resistance of respiratory system and ohmic resistance of the respiratory system indexed to the weight of the patients was observed. CVP significantly increased between ZEEP and PEEP 8 (P = 0.005), and between PEEP 4 and PEEP 8 (P = 0.05). CONCLUSIONS: PEEP values up to 8 cmH20 seem to be safe in paediatric patients with a severe post-traumatic brain swelling treated with DC.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01).

INTRODUCTION: Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. METHODS AND ANALYSIS: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. ETHICS AND DISSEMINATION: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02431663; Pre-results.

A cannabinoid-intoxicated child treated with dexmedetomidine: a case report.

INTRODUCTION: In the last 20 years, the rate of exposure to marijuana has increased dramatically, even in the pediatric population. Effects of intoxication are variable, more severe neurological symptoms can be observed following ingestion, thus hospital or intensive care unit admission is often required. Usually cannabinoids intoxicated patients are treated with administration of benzodiazepines or opioids, accepting the related risk of intubation and mechanical ventilation. Dexmedetomidine is a highly selective α2-adrenergic receptor agonist, with no effect on the respiratory drive and pattern and produces a good level of sedation, allowing to avoid the administration of other sedatives. To our knowledge, this is the first reported case of dexmedetomidine use to support a cannabis intoxicated patient. CASE PRESENTATION: A 19-month-old Caucasian boy was presented to our emergency department. At the time of his arrival, he was somnolent with paroxysms of agitation, breathing spontaneously and hemodynamically stable. The results of all investigations were negative, but the result of the immunochemical screening of his urine was positive for Δ(9)-tetrahydrocannabinol. The patient was admitted to the pediatric intensive care unit and treated with a continuous infusion of dexmedetomidine. CONCLUSIONS: Dexmedetomidine is a fairly safe and effective antidote for pediatric marijuana or natural cannabinoid exposures. Its properties and potential to allow for "cooperative" sedation make it a more attractive choice with fewer side effects than benzodiazepines or opioids.

Phenylephrine eye drops in pediatric patients undergoing ophthalmic surgery: incidence, presentation, and management of complications during general anesthesia.

BACKGROUND: Phenylephrine eye drops are widely used as mydriatic agent to reach the posterior segment of the eye. In literature, many reports suggest a systemic absorption of this agent as a source of severe adverse drug reactions. Hence, we reviewed our experience with topical phenylephrine in ophthalmic surgery. METHODS: In May 2006, following US guidelines publication, a standard operating procedure was issued in our operating rooms to standardize the use of phenylephrine eye drops in our practice. Two years later, after the occurrence of a cluster of serious adverse drug reactions in infants undergoing surgery, a review of phenylephrine safety and systemic complications incidence was performed. RESULTS: We observed 451 pediatric patients, and 187 met the inclusions criteria: Among them, 4 experienced hemodynamic complications due to phenylephrine eye drops. The incidence of major complications was 2.1%. CONCLUSIONS: Two different patterns of side effects occurred. The first one was a cardiovascular derangement with severe hypertension and heart rate alterations; the other one involved exclusively pulmonary circuit causing early edema. These clinical manifestations, their duration, and treatment responses are all explainable by alfa1-adrenergic action of phenylephrine. This hypothetic pathogenesis has been confirmed also by the usefulness of direct vasodilators (anesthetic agents) and by the negative outcome occurred in the past with the use of beta-blockers.

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)-1ß, 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-1ß, 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-1ß, 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-1ß, 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.

IL-1 ß 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-1 ß 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-1 ß 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-1 ß 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 IL1 ß 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.

Effects of positive end expiratory pressure (PEEP) on intracranial and cerebral perfusion pressure in pediatric neurosurgical patients.

BACKGROUND: Positive end expiratory pressure (PEEP) improves oxygenation by optimizing alveolar recruitment and reducing intrapulmonary shunt. Unfortunately, PEEP can interfere with intracranial pressure (ICP) by increasing intrathoracic pressure. We hypothesized that the use of different PEEP levels could have an effect on intracranial and cerebral perfusion pressure (CPP), gas exchange, respiratory system mechanics, and hemodynamics in pediatric patients undergoing major neurosurgical procedures. METHOD: Twenty-one consecutive pediatric patients undergoing surgical procedure for intracranial tumors were enrolled in this study, conducted between April 2008 and August 2009. Invasive radial pressure, central venous pressure (CVP), arterial oxygen saturation, ICP, and CPP were monitored. The middle cerebral artery mean velocity (V(med)) was determined by transcranial Doppler. At 0 cm H2O (ZEEP), the following parameters were recorded: systolic, mean, and diastolic arterial pressure, CVP, ICP, CPP, V(med), and arterial blood gases. After assessment at 0 PEEP (ZEEP), PEEP 4 and PEEP 8 were applied: all parameters were recorded at each level. RESULTS: The application of PEEP (from ZEEP to PEEP 8) significantly increased compliance of the respiratory system indexed to the weight of the patients (CrsI) (P=0.0001) without ICP modifications. No significant variations were observed in values of arterial pressure (MAP), CPP, V(med), total resistance of the respiratory system indexed to the weight of the patients (RRS(maxI)), and ohmic resistance of the respiratory system indexed to the weight of the patients (RRS(minI)). CVP significantly increased between ZEEP and PEEP 8 (P=0.02), and between PEEP 4 and PEEP 8 (P<0.05). Partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), partial arterial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2), and pH were not significantly modified. CONCLUSION: We describe cerebral hemodynamic responses to PEEP application in pediatrics. PEEP values up to 8 cm H2O seem to be safe in pediatric patients with intracranial neoplasm, and, in our opinion, PEEP should be applied immediately after surgery to restore lung recruitment.

Rescue hypothermia for refractory hypercapnia.

Hypothermia may reduce the CO(2) 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.