Objective The international scope of critical neurological insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to pediatric intensive care units (PICUs) with acute neurological insults. Design Prospective study. Setting Multicenter (n=107 PICUs) and multinational (23 countries, 79% in North America and Europe). Patients Children aged 7d–17y admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, central nervous system infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. Interventions None. Measurements and main results We evaluated the prevalence and outcomes of children with pre-determined acute neurological insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category (PCPC) score ≥ 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurological insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and TBI subjects had the most unfavorable outcomes (49%). The most common neurological insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Conclusions Neurological insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurological diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

SummaryObjectiveTo summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.DesignSystematic review and meta-analysisEligibility criteriaStudies enrolling consecutive COVID-19 patients (probable or confirmed) presenting with neurological manifestations.Data sourcesPubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020.Data extraction and analysisTwo authors independently screened titles and abstracts retrieved by literature search. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.ResultsOf 2,455 citations, 350 studies were included in this review, providing data on 145,634 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence-2%). In COVID-19 patients aged >60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).ConclusionsUp to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.Systematic review registrationPROSPERO CRD42020181867.What is already known on this topicThe frequency of neurological manifestations including fatigue, myalgia, taste and smell impairments, headache and dizziness in COVID-19 patients has been reported in a few systematic reviews and meta-analyses. However, considerable heterogeneity has been observed in terms of methodological quality of the studies, severity of the disease, mean age and hospitalization status of the patients. The evidence regarding the frequency of neurological diagnoses including stroke, encephalitis, Guillain Barré syndrome (GBS) is also limited to case reports and case series and no data exists thus far on the pooled prevalence estimates for neurological diagnoses in COVID-19 patients.What this study addsTo the best of the authors’ knowledge, this is the largest systematic review and meta-analysis to date (including 350 studies with data on 145,634 cases) summarizing the evidence on the frequency of the full spectrum of neurological manifestations in COVID-19 patients in the overall, young and elderly populations. For the first time, our review reports the pooled prevalence of stroke in COVID-19 patients. Risk of bias, old age and disease severity were potential determinants of the frequency and nature of neurological manifestations as well as its association with mortality. Our review also highlights the need to develop reporting standards for studies describing the frequency of clinical features. Moreover, we note that this will be the first systematic review and meta-analysis on this subject to include studies reported in all languages.

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