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.

The objective of this review is to report evidence about the efficacy and potential of currently licensed drugs and new molecules beyond pre-clinical development for improving the chemotherapy of tuberculosis (TB). Rifapentine, a rifamycin with low minimum inhibitory concentration, long half-life and potent sterilizing activity in mice did not confirm its potential in a recent short-term clinical trial and is being extensively re-evaluated. Moxifloxacin, a fluoroquinolone, improved the activity of the standard drug regimen when substituted for ethambutol (EMB). It is being studied to shorten the duration of treatment for fully drug-susceptible TB (Remox study). Clofazimine, a fat-soluble dye with experimental activity against TB, but used only for leprosy in the last 50 years, requires further study because it has been included in a successful short 9-month combined drug regimen for the treatment of multidrug-resistant TB. The diarylquinoline TMC207 is the most promising among the new TB drugs because of its experimental and clinical rate of culture conversion. Also exciting, 200 mg daily doses in humans of the nitroimidazo-oxazine PA-824 and the nitro-dihydro-imidazooxazole OPC-67683 were safe and induced a bactericidal effect of respectively 0.098 ± 0.072 log(10) and 0.040 ± 0.056 log(10) per day. The new oxazolidinones PNU-100480 and AZD-5847 might be at least as active as linezolid and much less toxic. SQ109 is an EMB analogue that does not have cross-resistance with EMB and might have synergistic activity in combined regimens. Benzothiazinones and dinitrobenzamides show exciting in vitro anti-microbial activity and deserve careful attention.

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OBJECTIVEChildren 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.METHODSA 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.RESULTSFifteen 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).CONCLUSIONSFe-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.

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Background A rise in global temperatures is known to reduce calorie and nutrient availability through diminished yields and shifts in crop nutrient content. Insuffi cient calorie and nutrient intake can adversely aff ect nervous-system development in children. To quantify the eff ect of rising temperatures on paediatric neurological development in east Africa, we analysed total intake of calories, iron, and zinc in Kenya, Rwanda, Tanzania, and Uganda. We then used a model to predict the eff ect of rising temperatures on incidences of factors important for neurological development in children younger than 5 years. MethodsWe used data from meta-analyses from the fi elds of climate change, agriculture, economics, nutrition, and neurology referenced in the UN Intergovernmental Panel on Climate Change fi fth Assessment Report and obtained via a Web of Science search in January, 2015. We constructed a model of these meta-analyses to evaluate the eff ect of temperature on yields of all crops; yields on consumption demand elasticity; consumption on caloric intake; and caloric intake on the incidence of undernutrition, stunting, iron defi ciency anaemia in children under 5 years, and population zinc defi ciency. We calculated incidences of nutritional defi ciencies with and without the diluting eff ect of rising atmospheric CO 2 concentration on crop iron and zinc content.Findings Across Kenya, Rwanda, Tanzania, and Uganda, for every 1°C degree of warming we predict that mean calorie consumption would be reduced by 2•20% (95% CI 0•93-3•51); the percentage of undernourished children would increase by 2•40% (1•1-4•1); the incidence of moderate stunting would increase by 12•33% (11•47-13•52) and severe stunting would increase by 6•32% (5•87-6•93). The proportion of children under 5 years with iron defi ciency anaemia is predicted to increase by 1•62% (1•12-2•11) without CO 2 dilution eff ects and 3•00% ( 1•16-4•84) with CO 2 eff ects. The incidence of zinc defi ciency is predicted to increase by 1•20% (0•84-1•56) and 1•88% (0•64-3•13) with and without CO 2 eff ects. At the Paris Agreement target to limit mean global temperature rise to 2°C, we predict total additional cases above baseline (World Bank, 2010) of undernutrition, moderate and severe stunting to be 537 000 (258 000-949 000), 189 000 (91 000-334 000), and 97 000 (46 000-172 000). Compared with World Bank (2010) and Food and Agriculture Organization (2005) baselines, additional cases of iron and zinc defi ciency in children aged under 5 years are predicted to range from 49 000 to 380 000 and 28 000 to 126 000, with Rwanda and Tanzania predicted to have the fewest and most cases in both scenarios.Interpretation Although the combining of meta-analyses will propagate uncertainty, our meta-model is an attempt to quantify the eff ect of rising global temperatures on paediatric neurological development. Our fi ndings could be used in developing countries to support child nutrition programmes, and to justify investment in agricultural productivity and interventions to mit...