Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD.

BACKGROUND AND OBJECTIVES: We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). METHODS: In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with follow-up >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. RESULTS: Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03-0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03-0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01-0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33-33.26, p = 0.021). DISCUSSION: At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1).

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort.

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6-10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58-13.88%). At last follow-up (median 4 years after diagnosis, range 0.5-15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2).

Moyamoya syndrome and 6p chromosome rearrangements: Expanding evidences of a new association.

BACKGROUND: Moyamoya syndrome represents an etiologically heterogeneous cerebral evolutive angiopathy. It can be associated with both well-characterized and recently described genetic conditions with mendelian inheritance. CASE REPORT: We report the case of a moyamoya angiopathy in a prematurely born girl affected by congenital heart defect, mild facial dysmorphism, mild neurodevelopmental delay and borderline cognitive profile, associated to a de novo complex rearrangement involving the terminal segment of the short arm of chromosome 6. CONCLUSION: To the best of our knowledge, this is the second case described of pediatric moyamoya syndrome associated with a 6p complex rearrangement. Adding this case to the pertinent literature, we discuss the pathogenic role of rearrangements in 6p region in moyamoya syndrome and suggest to investigate in this region potential genes involved in angiogenesis or vascular homeostasis.

Pain therapy, pediatric palliative care and end-of-life care: training, experience, and reactions of pediatric residents in Italy.

UNLABELLED: Pediatric palliative care represents the ideal response to life-limiting and life-threatening diseases and requires a specific and multidisciplinary training. This study aims at evaluating in Italy the training programs offered in pain therapy and pediatric palliative care, the exposure, and the personal experience concerning end-of-life care management. The data have been obtained through a survey addressed to all the residents specializing in pediatrics in Italy. Three hundred forty-eight of 1,200 residents from 33 of the 41 schools of pediatrics existing in Italy responded to the questionnaire. One hundred seventy-four of them (50 %) declared they received training in end-of-life care at least once: 146 during their graduation course of medicine, 84 during the pediatric residency, and 54 in both occasions. Sixty percent of respondents were present at one death at least, with an increasing percentage in the last years of residency (91.5 % in the fifth year) but only 12 % were directly involved in the management (36.2 % in the fifth year); 5.7 % managed at least one communication of death; 12.6 % followed sedo-analgesia protocols. Only 11 % of residents felt ready to face end-of-life care management. CONCLUSION: The training in end-of-life care in Italy is not currently satisfactory. Further efforts are therefore required to create a comprehensive and multidisciplinary training.

The management of sickle cell pain in the emergency department: a priority for health systems.

OBJECTIVES: Pain is the most common reason for admission to the Emergency Department (ED) in patients with sickle cell disease (SCD). It can be associated with severe complications and impairs quality of life. Pain management in the ED should be well-defined and aggressive. The objective of this study was to evaluate pain management in the pediatric ED of a country recently facing SCD and to identify priority areas of intervention. METHODS: The charts of SCD children who had accessed the ED from January 2003 to December 2010 were retrospectively reviewed. Pain management was compared before and after 2008. During 2008, educational events on SCD-pain management involved the ED personnel. RESULTS: Twenty-three/28 patients (82%) accessed the ED for/with pain, of a total of 96/185 accesses for/with pain. Mean age was 5.9 years (range, 8 mo to 17.9 y). Fifty-four percent of the episodes resulted in hospital admissions, with a mean length of stay of 6.2 days. Pain was scored in 30% of the episodes; analgesics were administered in 50%. After the educational interventions, high score at triage was assigned more frequently (72% vs. 40%), waiting time for analgesics administration reduced (64 vs. 87 min), and use of Visual Analogue Scale increased (50% vs. 8%). DISCUSSION: Pain represents the main reason for admission to the ED in children with SCD even in countries recently facing SCD. Educational interventions obtained significant but still limited improvement in pain management. The diffusion of national guidelines with defined pain evaluation and treatment protocols represents a priority to further ameliorate care of SCD children.

Procedural pain in children: education and management. The approach of an Italian pediatric pain center.

Pain management should be warranted for all children in every situation. Italian legislation proposes a model for pain assistance based on specialized tertiary centers which provide direct clinical management for complex cases and assure continuous cooperation with hospitals and family pediatricians for managing painful conditions every day. The Procedural Pain Service of the University of Padua Department of Pediatrics applies such model for procedural pain management. We describe activities of Service since January 1, 2006 on two levels: education and training for territorial services and sedation-analgesia when required for invasive and painful procedures. Since 2006 to date, the Service team produced an internal protocol for procedural sedation, developed two master courses, and organized a training program for procedural pain management in the territorial context. Procedural sedation-analgesia service provided overall 10,832 sedations to perform 14,264 procedures for 3,815 patients, median age of 6 years old. The most frequently performed procedures were lumbar puncture and bone marrow aspiration, followed by gastroscopy and bronchoscopy. Most frequently administered drug combinations were local analgesia + intravenous midazolam alone or midazolam and propofol or midazolam and propofol and ketamine; most frequently used non-pharmacological methods were distraction using cartoons and bubbles. Minor adverse events were recorded in 281 cases (2.5%), the most common being desaturation (2.1%). In conclusion, our model functions on two integrated levels, and it can be considered generally applicable as a solution for pain management.

The management of procedural pain at the Italian Centers of Pediatric Hematology-Oncology: state-of-the-art and future directions.

PURPOSE: The quality of life of children with cancer can be affected by the experience of cancer-related pain, treatment-related pain, procedural pain, generalized pain, and long-term chronic pain, and the consequences may be permanent. Treatment-related pain and procedural pain are often reportedly the most painful experiences relating to their illness. Procedural pain treatment is therefore now considered essential. This multicenter survey investigated how procedural pain is managed at Italian Pediatric Hematology-Oncology Centers. METHODS: From April to October 2010, questionnaires were collected from the directors and/or referent of the Italian Centers of Pediatric Hematology-Oncology about the management of lumbar punctures, bone marrow aspirates, and biopsies. RESULTS: We received responses from 67% of the centers (which performed a total of 13,271 procedures per year). Fifty percent of the procedures were performed in the operating room. The sedation-analgesia was provided "almost always" for 84% of procedures. Non-pharmacological treatments were used in 55% of the centers. The specialist who practiced analgesia was the anesthetist in 83.3% of the cases. CONCLUSIONS: A nationwide multicentre survey has been conducted for the first time to verify the management of procedural pain in Pediatric Hematology-Oncology patients. The results indicate that many aspects in the management of procedural pain appear consistent with the international guidelines. Some problems still remain, including the inability to ensure adequate sedation-analgesia in all the patients--often due to the lack of adequate staff, the frequent use of the operating room, and an underdeveloped use of non-pharmacological therapies.

Congenital central hypoventilation syndrome and hypoglycaemia.

UNLABELLED: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder typically presenting in infants with an impaired automatic control of breathing, particularly during sleep, and often associated with variable patterns of autonomic nervous system dysregulations. We studied three children who had CCHS associated with episodes of severe hypoglycaemia and hyperinsulinaemia; we discuss the possible relationship with impaired dopamine-beta-hydroxylase function. CONCLUSION: Hypoglycaemia and hyperinsulinaemia might be suspected in children with CCHS presenting with seizures and hyperhydrosis; though, further studies are needed to confirm this association.

The opinion of clinical staff regarding painfulness of procedures in pediatric hematology-oncology: an Italian survey.

BACKGROUND: Beliefs of caregivers about patient's pain have been shown to influence assessment and treatment of children's pain, now considered an essential part of cancer treatment. Painful procedures in hematology-oncology are frequently referred by children as the most painful experiences during illness. Aim of this study was to evaluate professionals' beliefs about painfulness of invasive procedures repeatedly performed in Pediatric Hemato-Oncology Units. METHODS: Physicians, nurses, psychologists and directors working in Hemato-Oncology Units of the Italian Association of Pediatric Hematology-Oncology (AIEOP) were involved in a wide-nation survey. The survey was based on an anonymous questionnaire investigating beliefs of operators about painfulness of invasive procedures (lumbar puncture, bone marrow aspirate and bone marrow biopsy) and level of pain management. RESULTS: Twenty-four directors, 120 physicians, 248 nurses and 22 psychologists responded to the questionnaire. The score assigned to the procedural pain on a 0-10 scale was higher than 5 in 77% of the operators for lumbar puncture, 97.5% for bone marrow aspiration, and 99.5% for bone marrow biopsy. The scores assigned by nurses differed statistically from those of the physicians and directors for the pain caused by lumbar puncture and bone marrow aspiration. Measures adopted for procedural pain control were generally considered good. CONCLUSIONS: Invasive diagnostic-therapeutic procedures performed in Italian Pediatric Hemato-Oncology Units are considered painful by all the caregivers involved. Pain management is generally considered good. Aprioristically opinions about pain depend on invasiveness of the procedure and on the professional role.

Procedural pain management in Italy: learning from a nationwide survery involving centers of the Italian Association of Pediatric Hematology-Oncology.

Procedural pain is an important aspect of care in pediatrics, and particularly in pediatric oncology where children often consider this to be the most painful experience during their illness. Best recommended practice to control procedural pain includes both sedative-analgesic administration and non-pharmacological treatments, practiced in an adequate and pleasant setting by skilled staff. A nationwide survey has been conducted among the Italian Centers of Pediatric Hematology-Oncology to register operators' awareness on procedural pain, state of the art procedural pain management, operators' opinions about pain control in their center, and possible barriers impeding sedation-analgesia administration. Based on indications in the literature, we discuss the results of the survey to highlight critical issues and suggest future directions for improvement. Future objectives will be to overcome differences depending on size, improve operators' beliefs about the complexity of pain experience, and promote a global approach to procedural pain.