Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance.

BACKGROUND: The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. METHODS: Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. RESULTS: Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. CONCLUSIONS: Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.

Management of Cervical Kyphotic Deformity Associated With Loeys-Dietz Vasculopathy and Cardiac Transplantation: Case Report, Literature Review, and Strategies for Complex Skeletal Dysplasias.

Seventy-six percent of pediatric patients with Loeys-Dietz syndrome (LDS), a connective tissue disorder driven by a transforming growth factor-beta (TGF-B) pathway mutation, manifest cervical spine malformations. A prior series showed that 16% required surgical stabilization. Spine surgery in LDS is associated with an 88% complication rate due to poor bone quality and cerebrovascular ectasia. Of 77 patients with LDS, one patient who required spine surgery was identified in an institutional database from 2010 to 2020. A 15-year-old with LDS presented with symptomatic cervical myelopathy from a rapidly progressive and unstable cervical deformity. We performed a C5-6 corpectomy and an O-T2 posterior spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2). We achieved correction of her kyphosis and normalization of her neurologic status. She is neurologically well one year postoperatively with bony fusion. The management of a pediatric patient with LDS, orthotopic heart transplantation (OHT), and craniocervical deformity with instability is a novel challenge. Long-segment constructs are beneficial, rather than sparing the occiput or cervicothoracic junction. Off-label BMP may aid an LDS patient with TGF-B mutation and sternotomy. Surgeons should continue immunomodulatory and antiplatelet medications when required for OHT.

Chronic Ulcers and Malnutrition in an African Patient.

An 11-year-old girl with a congenitally malformed left hand, sickle cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared after trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months before transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous antibiotics and close management by a pediatric infectious disease specialist working for a nongovernmental organization (NGO) in her home country. Per NGO records, she had previously been  average weight-for-age. On presentation after international transfer, she was severely malnourished, with lesions covering âˆ¼35% of her body. In initial workup, leukocytosis of 21 × 103 cells per µL (79% neutrophils), hemoglobin of 6.1 g/dL, and mean corpuscular volume of 66 fL were found. Iron studies revealed an iron level of 18 µg/dL, ferritin level of 55 ng/mL, total iron binding capacity of 222 µg/dL, and transferrin saturation of 8%. Inflammatory markers were elevated, C-reactive protein was 20.1 mg/dL, and the erythrocyte sedimentation rate was 131 mm/h. A chest computed tomography scan revealed bilateral pulmonary nodules, the largest in her left upper lobe measuring 2.4 × 2.0 × 1.9 cm. Our panel of experts reviews the evaluation and treatment of this patient with extensive suppurative and ulcerative skin lesions and the factors considered in offering charity care to international patients.

Ferumoxytol-enhanced MRI for surveillance of pediatric cerebral arteriovenous malformations.

OBJECTIVE: Children with intracranial arteriovenous malformations (AVMs) undergo digital DSA for lesion surveillance following their initial diagnosis. However, DSA carries risks of radiation exposure, particularly for the growing pediatric brain and over lifetime. The authors evaluated whether MRI enhanced with a blood pool ferumoxytol (Fe) contrast agent (Fe-MRI) can be used for surveillance of residual or recurrent AVMs. METHODS: A retrospective cohort was assembled of children with an established AVM diagnosis who underwent surveillance by both DSA and 3-T Fe-MRI from 2014 to 2016. Two neuroradiologists blinded to the DSA results independently assessed Fe-enhanced T1-weighted spoiled gradient recalled acquisition in steady state (Fe-SPGR) scans and, if available, arterial spin labeling (ASL) perfusion scans for residual or recurrent AVMs. Diagnostic confidence was examined using a Likert scale. Sensitivity, specificity, and intermodality reliability were determined using DSA studies as the gold standard. Radiation exposure related to DSA was calculated as total dose area product (TDAP) and effective dose. RESULTS: Fifteen patients were included in this study (mean age 10 years, range 3-15 years). The mean time between the first surveillance DSA and Fe-MRI studies was 17 days (SD 47). Intermodality agreement was excellent between Fe-SPGR and DSA (κ = 1.00) but poor between ASL and DSA (κ = 0.53; 95% CI 0.18-0.89). The sensitivity and specificity for detecting residual AVMs using Fe-SPGR were 100% and 100%, and using ASL they were 72% and 100%, respectively. Radiologists reported overall high diagnostic confidence using Fe-SPGR. On average, patients received two surveillance DSA studies over the study period, which on average equated to a TDAP of 117.2 Gy×cm2 (95% CI 77.2-157.4 Gy×cm2) and an effective dose of 7.8 mSv (95% CI 4.4-8.8 mSv). CONCLUSIONS: Fe-MRI performed similarly to DSA for the surveillance of residual AVMs. Future multicenter studies could further investigate the efficacy of Fe-MRI as a noninvasive alternative to DSA for monitoring AVMs in children.