Combined early treatment in hemiplegic attacks related to CACNA1A encephalopathy with brain oedema: Blocking the cascade?

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs. Case description We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma. Discussion Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.

Listeria Meningitis in an Immunocompetent Child.

Listeria monocytogenes is a facultative anerobic, gram-positive bacillus that is isolated from the soil, vegetables, and wild or domestic animals. Listeria infection is usually found in the older adults, immunocompromised patients, pregnant women, and newborns, whereas it is rare in healthy infants and children. Listeria monocytogenes may cause meningitis, meningoencephalitis, brain abscess, pyogenic arthritis, osteomyelitis, and liver abscess in children. The course of meningoencephalitis by Listeria is often severe and even fatal. Complications such as acute hydrocephalus, brain abscess, and spine abscess can develop, and the mortality associated with listeriosis is significantly high. We present a case of a previously healthy 7-year-old boy who developed Listeria monocytogenes meningitis.

What Is the Best Initial Empirical Treatment of Suspected Sepsis in a Newborn Readmitted Soon after Discharge Home in an Era of Increased Resistance to Antibiotics? A Report of Two Cases.

Background Colonization/infection by antibiotic-resistant bacteria is becoming a major threat to health care systems. Case report Two septic neonates were readmitted in our hospital few days after hospital discharge. In both of them, microbiological workup revealed an infection caused by multiresistant pathogens. Noteworthy, one baby had received intensive care management for 4 weeks, whereas the other had been vaginally delivered and sent home on his second day of life. Conclusion These cases suggest that in countries and/or hospital with high prevalence of colonization/infection by resistant pathogens in nurseries, neonatal intensive care units, and obstetric wards, the choice of initial therapy of suspected sepsis in a neonate readmitted from home soon after discharge should take into account the possibility of an infection due to a multiresistant pathogen.

Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.

UNLABELLED: Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). CONCLUSIONS: In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial.

BACKGROUND: Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking. OBJECTIVES: To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT. METHODS/DESIGN: Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled. DISCUSSION: The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01257672.

Listeria meningitis complicated by hydrocephalus in an immunocompetent child: case report and review of the literature.

BACKGROUND: Listeria monocytogenes is a Gram-positive bacteria transmitted to human by animal stools, contaminated water and food. In children, Listeria monocytogenes typically affects newborns and immunocompromised patients often leading to invasive syndromes including sepsis, brain abscesses, meningitis, meningoencephalitis and rhombencephalitis. In healthy and immunocompetent children, Listeria meningitis is rare, but can progress rapidly and may be associated with severe complications (hydrocephalus, ventriculitis, cranial nerves palsy and cerebrospinal abscesses) and high mortality rate. CASE PRESENTATION: We describe a very uncommon case of meningoencephalitis due to Listeria monocytogenes in a 11-month-old immunocompetent girl. Cerebrospinal fluid (CSF) culture was positive on the second day. Antibiotic therapy was promptly started but the disease was complicated by neurological deterioration and decompensated hydrocephalus. The child required a very demanding pediatric and neurosurgical management and was discharged after 40 days without major sequelae. CONCLUSION: Listeria is difficult to isolate and it is not susceptible to first-line treatment for bacterial meningitis with extended-spectrum cephalosporins. Early recognition is therefore crucial for a positive outcome. Pediatricians have to perform close clinical monitoring of these children and be aware of possible complications. A review of all cases of Listeria meningitis complicated by hydrocephalus in healthy children has been performed, to provide an overview on clinical features, treatment options and outcome.

Bortezomib-Responsive Refractory Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

BACKGROUND: Anti-N-methyl-d-aspartate receptor encephalitis is a central nervous system inflammatory autoimmune disease affecting adults and children. The use of first- and second-line immunotherapies is supported. Recent reports suggest the efficacy of bortezomib in severe anti-N-methyl-d-aspartate encephalitis in adult patients not responsive to second-line treatment; there are no data about pediatric patients. PATIENT DESCRIPTION: We describe an eight-year-old child with anti-N-methyl-d-aspartate encephalitis not responsive to first- and second-line treatments who experienced marked clinical improvement after bortezomib administration. DISCUSSION: Bortezomib is a selective and reversible inhibitor of the 26S proteasome, which is used to treat oncologic and rare autoimmune disorders in pediatric patients. As observed in adult patients, bortezomib administration induced anti-N-methyl-d-aspartate antibody titer decline and clinical improvement with an acceptable risk profile. CONCLUSION: This is the first report of the use of bortezomib in children with anti-N-methyl-d-aspartate encephalitis; it could be a useful therapeutic option in children with refractory anti-N-methyl-d-aspartate encephalitis.

Monitoring adherence to guidelines of antibiotic use in pediatric pneumonia: the MAREA study.

BACKGROUND: Children are the most vulnerable population exposed to the use of antibiotics often incorrectly prescribed for the treatment of infections really due to viruses rather than to bacteria. We designed the MAREA study which consisted of two different studies: i) a surveillance study to monitor the safety/efficacy of the antibiotics for the treatment of pneumonia (CAP), pharyngotonsillitis and acute otitis media in children younger than 14 yrs old, living in Liguria, North-West Italy and ii) a pre-/post-interventional study to evaluate the appropriateness of antibiotic prescription for the treatment these infections. In this paper, we show only results of the appropriateness study about the antibiotic prescription for the treatment of pneumonia. METHODS: Patients included in this study met the following inclusion criteria: i) admission to the Emergency/Inpatient Dpt/outpatient clinic of primary care pediatricians for pneumonia requiring antibiotics, ii) informed written consent. The practice of prescribing antibiotics was evaluated before-and-after a 1 day-educational intervention on International/National recommendations. RESULTS: Global adherence to guidelines was fulfilled in 45%: main reason for discordance was duration (shorter than recommended). Macrolide monotherapy and cephalosporins were highly prescribed; ampicillin/amoxicillin use was limited. 61% of patients received >1 antibiotic; parenteral route was used in 33%. After intervention, i) in all CAP, cephalosporin prescription decreased (-23%) and the inappropriate macrolide prescriptions was halved and, ii) in not hospitalized CAP (notH-CAP), macrolides were prescribed less frequently (-25%) and global adherence to guidelines improved (+39%); and iii) in H-CAP antibiotic choice appropriateness increase. CONCLUSION: Prescribing practices were sufficiently appropriate but widespread preference for multidrug empirical regimens or macrolide in monotherapy deserve closer investigation.

Henoch-Schönlein purpura and drug and vaccine use in childhood: a case-control study.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood; nevertheless, its etiology and pathogenesis remain unknown despite the fact that a variety of factors, mainly infectious agents, drugs and vaccines have been suggested as triggers for the disease. The aim of this study was to estimate the association of HSP with drug and vaccine administration in a pediatric population. METHODS: An active surveillance on drug and vaccine safety in children is ongoing in 11 clinical centers in Italy. All children hospitalized through the local Paediatric Emergency Department for selected acute clinical conditions of interest were enrolled in the study. Data on drug and vaccine use in children before the onset of symptoms leading to hospitalization were collected by parents interview. A case-control design was applied for risk estimates: exposure in children with HSP, included as cases, was compared with similar exposure in children with gastroduodenal lesions, enrolled as controls. HSP cases were validated according to EULAR/PRINTO/PRES criteria. Validation was conducted retrieving data from individual patient clinical record. RESULTS: During the study period (November 1999-April 2013), 288 cases and 617 controls were included. No increased risk of HSP was estimated for any drug. Among vaccines, measles-mumps-rubella (MMR) vaccine showed an increased risk of HSP (OR 3.4; 95 % CI 1.2-10.0). CONCLUSIONS: This study provides further evidence on the possible role of MMR vaccine in HSP occurrence.

Oral Ondansetron versus Domperidone for Acute Gastroenteritis in Pediatric Emergency Departments: Multicenter Double Blind Randomized Controlled Trial.

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.

Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

A case of neonatal human parechovirus encephalitis with a favourable outcome.

Human parechoviruses (HPeVs) are a new family of neurotropic viruses that cause central nervous system (CNS) infections similar to enterovirus (EVs) meningoencephalitis in the neonatal period, resulting in white matter lesions that can be visualized with cranial ultrasonography and magnetic resonance imaging, and correlated to a large spectrum of neurological outcomes. HPeV should be suspected in neonates with signs and symptoms of sepsis-like illness or CNS disease. We report a case of neonatal HPeV encephalitis, diagnosed on the basis of clinical and radiological findings and HPeV RT-PCR, with a good neurological outcome.

Vaccine effectiveness against severe laboratory-confirmed influenza in children: results of two consecutive seasons in Italy.

OBJECTIVE: To evaluate the effectiveness of seasonal influenza vaccine in preventing Emergency Department (ED) visits and hospitalisations for influenza like illness (ILI) in children. METHODS: We conducted a test negative case-control study during the 2011-2012 and 2012-2013 influenza seasons. Eleven paediatric hospital/wards in seven Italian regions participated in the study. Consecutive children visiting the ED with an ILI, as diagnosed by the doctor according to the European Centre for Disease Control case definition, were eligible for the study. Data were collected from trained pharmacists/physicians by interviewing parents during the ED visit (or hospital admission) of their children. An influenza microbiological test (RT-PCR) was carried out in all children. RESULTS: Seven-hundred and four children, from 6 months to 16 years of age, were enrolled: 262 children tested positive for one of the influenza viruses (cases) and 442 tested negative (controls). Cases were older than controls (median age 46 vs. 29 months), though with a similar prevalence of chronic conditions. Only 25 children (4%) were vaccinated in the study period. The overall age-adjusted vaccine effectiveness (VE) was 38% (95% confidence interval -52% to 75%). A higher VE was estimated for hospitalised children (53%; 95% confidence interval -45% to 85%). DISCUSSION: This study supports the effectiveness of the seasonal influenza vaccine in preventing visits to the EDs and hospitalisations for ILI in children, although the estimates were not statistically significant and with wide confidence intervals. Future systematic reviews of available data will provide more robust evidence for recommending influenza vaccination in children.