Congenital Myasthenic Syndrome Due to Choline Acetyltransferase Mutations in Infants

Congenital myasthenic syndromes are inherited disorders caused by various defects in neuromuscular transmission. Although the typical presentation is fatigable weakness with prominent cranial involvement, neonates can lack these hallmark manifestations, and in those with choline acetyltransferase gene mutations, basal electrophysiological testing can yield negative findings. The authors report the case of a male infant presenting at birth with oculomotor and bulbofacial weakness, hypotonia, clubfoot, and severe respiratory insufficiency. Electromyography showed myogenic signs, and basal repetitive nerve stimulation yielded negative findings. Since age 6 months, the infant had progressively improved, acquiring autonomous respiration. Prolonged subtetanic repetitive nerve stimulation disclosed a marked decremental response compatible with suspected congenital myasthenic syndrome with episodic apnea. Genetic testing identified 2 novel choline acetyltransferase mutations (R470X, F580C). Keeping a high clinical suspicion of this rare condition and undertaking early comprehensive electrophysiological assessments including prolonged repetitive nerve stimulation (10 Hz for 5 minutes) can expedite the diagnosis

Early Noninvasive Neurally Adjusted Ventilatory Assist Versus Noninvasive Flow-Triggered Pressure Support Ventilation in Pediatric Acute Respiratory Failure: A Physiologic Randomized Controlled Trial 17

Objective: Neurally adjusted ventilatory assist has been shown to improve patient-ventilator interaction in children with acute respiratory failure. Objective of this study was to compare the effect of noninvasive neurally adjusted ventilatory assist versus noninvasive flow-triggered pressure support on patient-ventilator interaction in children with acute respiratory failure, when delivered as a first-line respiratory support. Design: Prospective randomized crossover physiologic study. Setting: Pediatric six-bed third-level PICU. Patients: Eighteen children with acute respiratory failure needing noninvasive ventilation were enrolled at PICU admission. Interventions: Enrolled children were allocated to receive two 60-minutes noninvasive flow-triggered pressure support and noninvasive neurally adjusted ventilatory assist trials in a crossover randomized sequence. Measurements and Main Results: Primary endpoint was the asynchrony index. Parameters describing patient-ventilator interaction and gas exchange were also considered as secondary endpoints. Noninvasive neurally adjusted ventilatory assist compared to noninvasive flow-triggered pressure support: 1) reduced asynchrony index (p = 0.001) and the number of asynchronies per minute for each type of asynchrony; 2) it increased the neuroventilatory efficiency index (p = 0.001), suggesting better neuroventilatory coupling; 3) reduced inspiratory and expiratory delay times (p = 0.001) as well as lower peak and mean airway pressure (p = 0.006 and p = 0.038, respectively); 4) lowered oxygenation index (p = 0.043). No adverse event was reported. Conclusions: In children with mild early acute respiratory failure, noninvasive neurally adjusted ventilatory assist was feasible and safe. Noninvasive neurally adjusted ventilatory assist compared to noninvasive flow-triggered pressure support improved patient-ventilator interaction

The EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) initiative: background and protocol for the international SARS-CoV-2 infections registry

The outbreak of SARS-CoV-2 is the worst healthcare emergency of this century, and its impact on pediatrics and neonatology is still largely unknown. The European Society for Pediatric and Neonatal Intensive Care (ESPNIC) launched the EPICENTRE (ESPNIC Covid pEdiatric Neonatal Registry) international, multicenter, and multidisciplinary initiative to study the epidemiology, clinical course, and outcomes of pediatric and neonatal SARS-CoV-2 infections. EPICENTRE background and aims are presented together with protocol details. EPICENTRE is open to centers all over the world, and this will allow to provide a pragmatic picture of the epidemic, with a particular attention to pediatric and neonatal critical care issues

Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child

Abstract Background Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5\ua0\ub0C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm 3 , 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24\ua0h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4\ua0weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient\u2019s four limbs. MRI acquired after 3\ua0weeks showed that the previously reported alterations were no longer present. Conclusion This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM

MOESM1 of Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome

Additional file 1. Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome

Infant Botulism: Checklist for Timely Clinical Diagnosis and New Possible Risk Factors Originated from a Case Report and Literature Review

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood:multicenter evaluation and expert consensus

<p>A new acute respiratory distress syndrome (ARDS) definition has been recently issued: the so-called Berlin definition (BD) has some characteristics that could make it suitable for pediatrics. The European Society for Pediatric Neonatal Intensive Care (ESPNIC) Respiratory Section started a project to evaluate BD validity in early childhood. A secondary aim was reaching a consensus on clinical tools (risk factors list and illustrative radiographs) to help the application of BD.</p><p>This was an international, multicenter, retrospective study enrolling 221 children [aged greater than 30 days and less than 18 months; median age 6 (range 2-13) months], admitted to seven European pediatric intensive care units (PICU) with acute lung injury (ALI) or ARDS diagnosed with the earlier definition.</p><p>Patients were categorized according to the two definitions, as follows: ALI, 36; ARDS, 185 (for the American-European Consensus Conference (AECC) definition); mild, 36; moderate, 97; severe ARDS, 88 (for BD). Mortality (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 25 % for severe ARDS, p = 0.04) and the composite outcome extracorporeal membrane oxygenation (ECMO)/mortality (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 28.4 % for severe ARDS, p <0.01) were different across the BD classes, whereas they were similar using the previous definition. Mortality [HR 2.7 (95 % CI 1.1-7.1)] and ECMO/mortality [HR 3 (95 % CI 1.1-7.9)] were increased only for the severe ARDS class and remained significant after adjustment for confounding factors. PICU stay was not different across severity classes, irrespective of the definition used. There was significant concordance between raters evaluating radiographs [ICC 0.6 (95 % CI 0.2-0.8)] and risk factors [ICC 0.92 (95 % CI 0.8-0.97)].</p><p>BD validity for children is similar to that already reported in adults and mainly due to the introduction of a "severe ARDS" category. We provided clinical tools to use BD for clinical practice, research, and health services planning in pediatric critical care.</p>