Neurologic Outcomes and Quality of Life in Children After Extracorporeal Membrane Oxygenation.

RATIONALE: Use of life support with extracorporeal membrane oxygenation (ECMO) is associated with brain injury. However, the consequences of these injuries on subsequent neurologic development and health-related quality of life (HRQoL) are poorly described in children. OBJECTIVES: The aim of this preliminary study was to describe short- and long-term neurologic outcomes in survivors of ECMO, as well as their HRQoL. DESIGN: Retrospective identified cohort with contemporary evaluations. SETTING: Necker Children's Hospital academic PICU. PATIENTS: Forty survivors who underwent ECMO (October 2014 to January 2020) were included in follow-up assessments in May 2021. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We first reviewed the outcomes of ECMO at the time of PICU discharge, which included a summary of neurology, radiology, and Pediatric Overall/Cerebral Performance Category (POPC/PCPC) scores. Then, in May 2021, we interviewed parents and patients to assess HRQoL (Pediatric Quality of Life Inventory [PedsQL]) and POPC/PCPC for children 3 years old or older, and Denver II test (DTII) for younger children. An evaluation of DTII in the youngest patients 1 year after ECMO decannulation was also added. Median age at ECMO was 1.4 years (interquartile range [IQR], 0.4-6 yr). Thirty-five children (88%) underwent a venoarterial ECMO. At PICU discharge, 15 of 40 patients (38%) had neurologic impairment. Assessment of HRQoL was carried out at median of 1.6 years (IQR, 0.7-3.3 yr) after PICU discharge. PedsQL scores were over 70 of 100 for all patients (healthy peers mean results: 80/100), and scores were like those published in patients suffering with chronic diseases. In May 2021, seven of 15 patients had a normal DTII, and 36 of 40 patients had a POPC/PCPC score less than or equal to 3. CONCLUSIONS: None of our patients presented severe disability at long term, and HRQoL evaluation was reassuring. Considering the risk of neurologic impairment after ECMO support, a systematic follow-up of these high-risk survivor patients would be advisable.

Low Dosing Norepinephrine Effects on Cerebral Oxygenation and Perfusion During Pediatric Shock.

Background: Cerebral hypoperfusion and impaired oxygen delivery during pediatric critical illness may result in acute neurologic injury with subsequent long-term effects on neurodevelopmental outcome. Yet, the impact of norepinephrine on cerebral hemodynamics is unknown in children with shock. We aimed to describe the norepinephrine effects on cerebral perfusion and oxygenation during pediatric shock. Patients and Methods: We conducted an observational multicentre prospective study in 3 French pediatric intensive care units. Children <18 years of age excluding traumatic brain injury were included in the study if they need norepinephrine for shock. Systemic and cerebral hemodynamics were compared between the time of initiation of norepinephrine (T0), and the steady-state (Tss). Cardiac output (CO) was measured using ultrasound. Cerebral perfusion was assessed on middle cerebral arteries (MCA) using transcranial doppler ultrasound. Cerebral tissue oxygen saturation (rScO2) was recorded using near infrared spectroscopy, and we calculated cerebral fractional tissue oxygen extraction (cFTOE = SpO2-rScO2/SpO2). Main Results: Fourteen children (median [IQR] age of 3.5[1; 13.5] years) were included. Norepinephrine at 0.2[0.1; 0.32] µg/kg/min significantly increased mean arterial blood pressure (61[56; 73] mmHg at Tss vs. 49[42;54] mmHg at T0, p=10-3) without change of CO. MCA velocities, pulsatility index, rScO2, and cFTOE did not significantly change between T0 and Tss. Some individuals observed variations in estimated CBF, which slightly improved in 7 patients, remained unchanged in 5, and was impaired in 2. No patient experienced significant variations of rScO2. Conclusions: Low-dosing norepinephrine, despite a homogeneous and significant increase in arterial blood pressure, had little effects on cerebral perfusion and oxygenation during pediatric shock. This reinforces the need for personalized tailored therapies in this population. Trial Registration: Clinicaltrials.gov, NCT03731104. Registered 6 November, 2018. https://clinicaltrials.gov/ct2/show/NCT03731104.

Postnatal Diagnostic Workup in Children With Arthrogryposis: A Series of 82 Patients.

OBJECTIVE: To describe a postnatal series of patients with arthrogryposis multiplex congenita by the causal mechanisms involved. METHODS: In this single-center study, the local data warehouse was used to identify patients with arthrogryposis multiplex congenita. Patients were classified into different etiologic groups. RESULTS: Of 82 patients included, the most frequent cause of arthrogryposis multiplex congenita was a neuromuscular disorder (39%), including skeletal muscle (n = 19), neuromuscular junction (n = 3), and peripheral nerve (n = 11) involvement. In other subgroups, 19 patients (23%) were classified by disorders in the central nervous system, 5 (6%) in connective tissue, 7 (8.5%) had mixed mechanisms, and 18 (22%) could not be classified. Contractures topography was not associated with a causal mechanism. Cerebral magnetic resonance imaging (MRI), electroneuromyography, and muscle biopsy were the most conclusive investigations. Metabolic investigations were normal in all the patients tested. Targeted or whole exome sequencing diagnostic rates were 51% and 71%, respectively. Thirty-three percent of patients died (early death occurred in patients with polyhydramnios, prematurity, and ventilatory dependency). DISCUSSION: The benefits of a precise diagnosis in the neonatal period include more tailored management of arthrogryposis multiplex congenita and better genetic information.

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

Association of Cerebral Oxymetry with Short-Term Outcome in Critically ill Children Undergoing Extracorporeal Membrane Oxygenation.

BACKGROUND: Acute brain injury (ABI) is a frequent complication of pediatric extracorporeal membrane oxygenation (ECMO) that could be detected by continuous neuromonitoring. Cerebral near-infrared spectroscopy (NIRS) allows monitoring of cerebral oxygenation. OBJECTIVE: To assess whether an impaired cerebral oxygenation was associated with short-term outcome during pediatric ECMO. METHODS: We conducted a single-center retrospective study in a pediatric intensive care unit. Children under 18 years old were included if receiving veno-venous or veno-arterial ECMO with concurrent NIRS monitoring. Cerebral saturation impairment was defined as rScO2 under 50% or 20% from the baseline for desaturation, and above 80%. Cerebral imaging (magnetic resonance imaging or CT scan) was performed in case of neurological concern. A radiologist blinded for patient history identified ABI as any hemorragic or ischemic lesion, then classified as major or minor. Primary endpoint was the outcome at hospital discharge. Poor outcome was defined as death or survival with a pediatric cerebral performance category scale (PCPC) score ≥ 3 and/or a major ABI. Good outcome was defined as survival with a PCPC score ≤ 2 and/or a minor or no ABI. Secondary endpoint was mortality before PICU discharge. RESULTS: Sixty-three patients met inclusion criteria; 48 (76%) had veno-arterial ECMO. Mortality rate was 51%. Forty-eight of sixty-three patients (76%) evolved with a poor outcome, including 20 major ABI. Mean rScO2 in the right/left hemisphere was 73 ± 9%/75 ± 9%. Cerebral desaturation and decline of rScO2 below 20% from the baseline, regardless of side, were each associated with poor outcome (multivariable-adjusted odds ratio (OR), 4 [95%CI 1.2; 15.1], p = 0.03, and 3.9 [95%CI 1.1; 14.9], p = 0.04, respectively), as well as a mean right rScO2 < 70% during the ECMO course (adjusted OR, 5.6 [95%CI 1.3; 34], p = 0.04). Left rSCO2 ≥ 80% was inversely correlated with hospital mortality (adjusted OR of 0.14 [95%CI 0.02; 0.8], p = 0.04). CONCLUSIONS: Cerebral desaturation attested by NIRS was associated with a poor short-term outcome in children of all ages undergoing ECMO, and rScO2 > 80% seemed to be protective. NIRS monitoring might be included within multimodal neuromonitoring to assess the risk of the brain injury related to pediatric ECMO.

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.

Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.

BACKGROUND: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

Acute axonal neuropathy subtype of Guillain Barré syndrome in a French pediatric series: Adequate follow-up may require repetitive electrophysiological studies.

Different subtypes of Guillain Barré Syndromes (GBSs) are defined by their electrophysiological characteristics, acute inflammatory demyelinating neuropathy (AIDP), and acute motor/motor-sensory axonal forms (AMAN/AMSAN) with either reversible nerve conduction failure (RCF) or axonal degeneration. Our aim was to describe initial clinical and electrophysiological characteristics of axonal forms of GBS in a pediatric population and their short- and long-term evolution. Electroneuromyogram (ENMG) results were collected at diagnosis and at two months of evolution and interpreted using the recently proposed pattern of RCF vs axonal degeneration. Clinical evaluation was standardized using the GBS disability scale ("GBSds") at diagnosis, and then at 3, 6, and 12 months of evolution. Outcome was compared to those of patients with AIDP diagnosed within the same period. Eleven patients were included, among whom eight patients presenting with AMAN and three with AMSAN. Two subgroups were identified according to severity. Three patients had a severe form (GBSds ≥2 at 12 months), two of them presenting an axonal degeneration on ENMG studies. Seven patients had a less severe form (GBSds ≤1 at 12 months), five of them with RCF on ENMG studies. Axonal forms had a more severe evolution than demyelinating forms (n = 17) at 3 months (median GBSds 3 and 2, respectively), 6 months (2 and 0), and 12 months (1 and 0), (p < 0,05). Axonal forms of GBS in children have a more severe global outcome than demyelinating forms. Axonal degeneration in two successive early ENMGs may be a prognostic factor of poor outcome.