Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study.

OBJECTIVE: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH]. STUDY DESIGN: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months. RESULTS: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009). CONCLUSION: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis.

Etanercept improves lipid profile and oxidative stress measures in patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA). METHODS: Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected. RESULTS: Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period. CONCLUSION: This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA.

Population-based study of incidence and clinical characteristics of rheumatic fever in Abruzzo, central Italy, 2000-2009.

OBJECTIVE: To investigate the incidence and describe the characteristics of acute rheumatic fever (ARF) in the pediatric population in a community-based healthcare delivery system of the central Italy region of Abruzzo during 2000-2009. STUDY DESIGN: A retrospective study was conducted in Abruzzo to identify patients aged <18 years with a diagnosis of ARF between January 1, 2000, and December 31, 2009. Each patient's age, sex, date of diagnosis, age at disease presentation, and fulfilled Jones criteria were recorded. RESULTS: A total of 88 patients meeting the Jones criteria for the diagnosis of ARF were identified, with arthritis in 59.1% of the patients, carditis in 48.9%, erythema marginatum in 11.4%, 5.7% with chorea, and 4.6% with subcutaneous nodules. Residual chronic rheumatic heart disease was present in 44.3% of the children. Age at diagnosis ranged from 2.5 to 17 years (average, 8.7 ± 4.0 years). Twelve children (13.6%) were under age 5 years. The overall incidence rate of ARF was 4.1/100 000. The lowest incidence rate was documented in the year 2000 (2.26/100 000), and the highest in 2006 (5.58/100 000). CONCLUSION: Our data indicate that ARF has not disappeared in industrialized countries and still causes significant residual rheumatic heart disease. Pediatricians should routinely consider the diagnoses of streptococcal pharyngitis and ARF to reduce long-term morbidity and mortality.

Prolonged sporadic hemiplegic migraine associated with a novel de novo missense ATP1A2 gene mutation.

Hemiplegic migraine is a rare form of migraine characterized by periodic attacks of migraine with neurologic aura and transient hemiplegia. There are familial and sporadic cases, both on a genetic basis; we describe the case of a 6-year-old boy affected by sporadic hemiplegic migraine, showing a novel ATP1A2 gene missense mutation (p.Gly715Arg) in exon 16. Long-term treatment with flunarizine resulted in good clinical response and prevention of further attacks.

Biologics in children's autoimmune disorders: efficacy and safety.

Advances in understanding the pathogenesis of rheumatic diseases have led to the discovery of mechanisms of inflammation and autoimmunity and have made possible the invention of new target-specific drugs. Biologic drugs, designed to inhibit specific components of the immune system, such as cytokines, cytokine gene expression, and their complex interactions, have revolutionized the treatment options in pediatric rheumatology. Only three agents are currently available for treating juvenile idiopathic arthritis (JIA): etanercept, at the dose of 0.8 mg/kg once weekly, adalimumab at the dose of 24 mg/m(2) every 2 weeks, and abatacept at the dose of 10 mg/kg at weeks 0, 2, 4, and then every 4 weeks. They are well tolerated and relatively safe in children: Side effects are generally mild and include injection site reactions and infections. Infliximab, rilonacept, and canakinumab are also approved by the Food and Drug Administration for treatment of pediatric autoimmune disorders and are currently investigated in JIA. This review summarizes the current state of biologic drugs, their clinical application, and their efficacy and safety in the pediatric age.

Autoinflammatory syndromes: diagnosis and management.

During the last decades the description of autoinflammatory syndromes induced great interest among the scientific community. Mainly rheumatologists, immunologists and pediatricians are involved in the discovery of etiopathogenesis of these syndromes and in the recognition of affected patients. In this paper we will discuss the most important clues of monogenic and non-genetic inflammatory syndromes to help pediatricians in the diagnosis and treatment of these diseases.

Gradenigo's syndrome with lateral venous sinus thrombosis: successful conservative treatment.

Gradenigo's syndrome (GS) is a rare disease characterised by the triad otitis media, pain in the region innervated by the first and the second division of trigeminal nerve and abducens nerve palsy. Septic sinus thrombosis is one of the most frequent and relevant complication of GS; it is often due to persistent damage and late diagnosis. Computed tomography (CT) scan and magnetic resonance imaging (MRI) allow the correct diagnosis in most cases. Surgical therapy may be necessary for a better and more rapid resolution of the disease. We report the case of a 4-year-old child that was admitted for facial nerve palsy and abducens nerve palsy subsequent to a 2-week persistent pain in the right ear. MRI showed infective acute process of the right mastoid and partial ipsilateral sinus thrombophlebitis. The child was treated with high-dose intravenous antibiotics and with oral anticoagulants. A complete resolution of symptoms and radiological alterations were observed within 7 weeks. In conclusion, lateral sinus thrombosis and Gradenigo's syndrome are rare but potential fatal complications of otitis media and mastoiditis. High-dose intravenous antibiotics and a low dose of anticoagulant can achieve a complete recovery without surgery.