Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature

Abstract Objectives To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. Study design A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. Results Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. Conclusions Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.

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Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01144-y ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Nicola Principi ◽

Susanna Esposito

Keyword(s):

Nervous System ◽

Pediatric Patients ◽

Signs And Symptoms ◽

Complete Recovery ◽

Underlying Disease ◽

Neurological Complications ◽

Neurological Manifestations ◽

Increased Risk ◽

The Central Nervous System ◽

Almost All

Abstract Background Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development. Main findings Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates. Conclusions Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.

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Can nurses improve self-management among pediatric patients? A systematic review and meta-analysis

European Journal of Public Health ◽

10.1093/eurpub/ckz185.604 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

A Mele ◽

A Nardi ◽

G P Prencipe ◽

G Migliara ◽

A Massimi ◽

...

Keyword(s):

Systematic Review ◽

Educational Intervention ◽

Pediatric Patients ◽

Meta Analysis ◽

Educational Interventions ◽

Risk Of Bias ◽

Ed Visits ◽

Meta Analyses ◽

Almost All

Abstract Background Few studies report educational interventions for pediatric patients with asthma or diabetes type 1 as a fundamental instrument to engage them and improve their health. The aim of this systematic review and meta-analysis was to synthesize evidence about behavioral changes in life style, disease management and clinical outcome in pediatric patients after a structured educational intervention delivered by nurses. Methods A systematic review of the literature was carried out in MEDLINE, Scopus and CINHAL including only RCTs. Methodological quality of the studies was assessed using Cochrane tool. Meta-analyses on HbA1c reduction for diabetes and hospitalization, emergency department (ED) visits and medication for asthma were carried-out. Results Of the 3559 papers initially retrieved, 5 regarding diabetes and 19 asthma met the inclusion criteria for the systematic review and 14 for the meta-analyses. Included studies were highly heterogeneous in terms of type of intervention and follow-up duration. Almost all the studies showed an improvement but only few were statistically significant. All studies regarding diabetes showed a low risk of bias (only one RCTs had a high risk of bias in one domain), while almost all RCTs on asthma showed a high risk of bias. The pooled mean differences in favor of the experimental groups were: HBA1c -0.02 (IC95%: -0.26 - 0.22), Hospitalization 0.58 (IC95%: 0.19 - 1.78), Medication -0.10 (IC95%: -0.43 - 0.23), ED Visits 0.82 (IC95%: 0.44 - 1.54). Conclusions There is a general agreement about the central role of educational intervention delivered by nurses to pediatric patients and the assessment of the behavioral changes after educational interventions is strongly recommended in pediatric population. However, more efforts are requested in designing studies on patients with asthma and to program more appropriate follow-up and periodic recall in order to engage pediatric patients in the management of their own chronic disease. Key messages educational intervention delivered by nurses to pediatric patients with asthma or diabetes type 1 as a fundamental instrument to engage them. more efforts are requested in designing studies on patients with asthma and to program more appropriate follow-up and periodic recall in order to engage pediatric patients.

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Involvement of Nervous System in Kawasaki Disease

Journal of Pediatric Neurology ◽

10.1055/s-0037-1606615 ◽

2017 ◽

Vol 17 (01) ◽

pp. 001-007

Author(s):

Andreas Giannopoulos ◽

Maria Gogou

Keyword(s):

Nervous System ◽

Kawasaki Disease ◽

Hormone Secretion ◽

Cranial Nerves ◽

Neurological Complications ◽

Neurological Manifestations ◽

Medical Database ◽

Inappropriate Antidiuretic Hormone Secretion ◽

Central Nervous System Dysfunction ◽

Increased Risk

AbstractThe aim of this study was to summarize the published reports about neurological manifestations of Kawasaki disease and underlying mechanisms. PubMed was used as the source for medical database. The prevalence of neurological complications is estimated to range from 1.1 to 3.7% and can include strokes, inflammation of central nervous system, dysfunction of cranial nerves, behavioral disorders as well as syndrome of inappropriate antidiuretic hormone secretion. Their incidence is usually associated with an increased risk for coronary artery aneurysms. In particular, the involvement of facial nerve seems to be a marker of disease severity. Although prognosis is generally remarkable, serious complications may arise in some cases. The early initiation of appropriate therapy prevents the appearance of neurological manifestations in children with Kawasaki disease.

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A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

Neurology International ◽

10.3390/neurolint13030041 ◽

2021 ◽

Vol 13 (3) ◽

pp. 410-427

Author(s):

Lauren O’Loughlin ◽

Nilo Alvarez Toledo ◽

Leon Budrie ◽

Randall Waechter ◽

Joanna Rayner

Keyword(s):

Systematic Review ◽

Immune Response ◽

Neurological Disorders ◽

Respiratory Symptoms ◽

Literature Search ◽

Pediatric Patients ◽

Neurological Manifestations ◽

Critical Factors ◽

Age Range ◽

Inflammatory Syndrome

SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain–Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.

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Meningoencephalitis associated with COVID-19: A systematic review

10.1101/2020.06.25.20140145 ◽

2020 ◽

Author(s):

Ritwick Mondal ◽

Upasana Ganguly ◽

Shramana Deb ◽

Gourav Shome ◽

Subhasish Pramanik ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Final Analysis ◽

Systemic Review ◽

Cochrane Library ◽

Neurological Involvement ◽

P Value ◽

Neurological Manifestations ◽

Medical Subject Headings ◽

Laboratory Findings

AbstractBackground and aimsWith the growing number of COVID-19 cases in recent times, the varied range of presentations is progressively becoming an addressing issue among clinicians. A significant set of patients with extra pulmonary symptoms has been reported worldwide. Neurological involvement in the form of altered mental status, loss of consciousness in considerable amounts has drawn attention of physicians all across the globe. Here we venture out to summarise the clinical profile, investigations and radiological findings among patients with SARS-CoV-2 associated meningoencephalitis in the form of a systematic review, which may aid clinicians in early diagnosis and prognostic evaluation of the disease.MethodologyThis review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th June, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2”, “COVID-19”, “meningoencephalitis” etc. All peer reviewed, case control, case report, pre print articles satisfying our inclusion criteria were involved in the study. The inclusion prerequisites comprised of confirmed SARS-CoV-2 cases with neurological manifestations, previous cases of SARS-CoV, MERS-CoV with neurological involvement provided all the studies were published in English language. Quantitative data was expressed in mean+/-SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p value of <0.05 considered to be statistically significant.ResultsA total of 43 cases were involved from 24 studies after screening from databases and preprint servers, out of which 29 of them had completed investigation profile and were included in the final analysis. Clincial and Laboratory findings as well as neuroimaging findings (CT, MRI and MRS) revealed consistent presentations towards association of COVID-19 with meningoencephalitis. Epileptogenic pictures were also evident on EEG (electroencephalogram) findings.ConclusionSARS-CoV-2 has been isolated from CSF as well as cerebrum of cases with meningoencephalitis depicting the natural tendency of the virus to invade the central nervous system. Speculations about retrograde olfactory transport or alternative haematogenous spread seem to be correlating with above findings. This review may raise the index of suspicion about COVID-19 among clinicians while attending patients with neurological manifestations.

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nCoV-2019 infection induced neurological outcome and manifestation, linking its historical ancestor SARS-CoV and MERS-CoV: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-92188-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ajay Prakash ◽

Harvinder Singh ◽

Phulen Sarma ◽

Anusuya Bhattacharyya ◽

Deba Prasad Dhibar ◽

...

Keyword(s):

Systematic Review ◽

Neurological Outcome ◽

Case Reports ◽

Meta Analysis ◽

Signs And Symptoms ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Cross Sectional ◽

Early Management ◽

Neurological Signs

AbstractThe first systematic review and meta-analysis to help clinician to identify early signs and symptoms of neurological manifestation in COVID-19 positive patients which will further help in early management of patients. Present systematic review and meta-analysis aimed to discuss the prevalence of neurological involvement of the 2019-nCoV patients and assess the symptomatic trend of events as compared to the 2002 “SARS” and 2012 “MERS” pandemics. The articles were systematically screened through several search engine and databases. The articles published or in preprint were included in the study till 15th May 2020. The systematic review done as per the published literatures which included 31 cross sectional, observational studies and case reports which revealed neurological signs and symptoms in SARS-COV-2 disease. For meta-analysis, we included 09 observational and cross-sectional studies which included COVID-19 positive patients and assessed the predominance of various neurological signs and symptoms in COVID-19 patients with relation to SARS-2002 and MERS-2012. Data was analyzed by using the “MedCalc” Statistical Software version 19.2.6 and reported as pooled prevalence. Standard I2 test was used to analyze the heterogeneity. We have collected and screened about a total 2615articles, finally we have included 31articles for the systematic review and 09 for meta-analysis as per the inclusion/exclusion criteria. The analysis was made as per the prevalence rate of neurological symptoms in COVID-19 positive patients. The cumulative neurological outcome of SARS-2002 and MERS-2012 was assessed to get the trends which was further tried to correlate the events with the current pandemic. During the analysis severity and outcome of neurological manifestations range from simple headache to vague non-focal complaints to severe neurologic impairment associated with seizure or meningitis. Central and peripheral nervous system (CNS/PNS) manifestations were seen during the SARS-2002, MERS-2012 and COVID-19. However, none of the publication had primary or secondary objectives of searching neurological manifestations in the COVID-19 patients and the pathogenic mechanism which will subsequently strengthen the importance to start more prospective clinical trials. The prevalence of neurological signs and symptoms were taken as primary objective. Thereafter, the prevalence of each CNS/PNS symptoms was categorized and their prevalence studied. The selection of Bagheri et al., 2020 may be discussed because they have done the cross-sectional study with the neurological finding and correlated the data with prevalence of the COVID-19 positive patients. The proportion of patients presenting with neurological outcome and clinical/PCR positivity were done. We had searched and followed all the possible online/web source, still the data collection process may remain a limitation of work due to addition of several publications on COVID-19 every day. Due to lack of data of SARS-CoV and MERS-CoV, we have included the case reports, MERS and COVID-19 in CNS/PNS manifestations.

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Neurological Involvement in COVID-19

10.5772/intechopen.99309 ◽

2021 ◽

Author(s):

Valentina Opancina ◽

Kristijan Krstic ◽

Predrag Sazdanovic ◽

Nebojsa Zdravkovic ◽

Ruzica Radojevic Marjanovic ◽

...

Keyword(s):

Indirect Effects ◽

Case Reports ◽

Experimental Studies ◽

Neurological Complications ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Neural Tissues ◽

Neurological Conditions ◽

The Brain ◽

Common Target

The respiratory system is the most common target of COVID-19, however, various experimental studies and case reports have shown its affinity for neural tissues. In this chapter, we described pathogenesis and propagation of SARS-CoV-2 virus in the nervous system, potential routes of the SARS-CoV-2 invasion in the brain, as well as indirect effects of COVID-19 on multiorgan disorders. We have also presented all of the reported neurological manifestations in COVID-19 with an explanation of possible underlying pathways. Among patients who tested positive on SARS-CoV-2, various neurological irregularities have been described, affecting both the central and peripheral nervous systems. In general, neurological complications in COVID-19 patients occur within 1 and 14 days, in most cases on average on the 5th day of the incubation period. We have demonstrated all of the reported neurological findings, whereas the most commonly reported were headache, dizziness, myalgia, hypogeusia, hyposmia, and impaired consciousness. More serious neurological conditions in COVID-19 included meningitis, encephalitis, and ischemic or hemorrhagic stroke.

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A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

10.21203/rs.3.rs-96718/v1 ◽

2020 ◽

Author(s):

Medha Tandon ◽

Tejas R Mehta ◽

Maha Daimee ◽

Viral Patel ◽

Apoorv Prasad ◽

...

Keyword(s):

Systematic Review ◽

Neurological Complications ◽

Common Finding ◽

Pathophysiological Mechanism ◽

Neurological Manifestations ◽

Protein Levels ◽

Csf Analysis ◽

Cell Counts ◽

Neurological Illness ◽

Elevated Protein

Abstract Background: Here we performed a systematic review of literature of CSF findings associated with neurological complications in coronavirus disease-2019 (COVID-19) to establish a pattern and understand the significance of CSF analysis which can possibly be useful in deciding prognosis and exploring therapeutic options in the future. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 in cerebrospinal fluid”, “SARS-CoV-2 and CNS Complication”.Results: We performed CSF analysis results in total of 113 patients from 67 papers. There were 7 patients out of 113 patients (6.2 %) were fatal and 35 patients (31 %) were considered severe and rest non-severe. Elevated cell counts (>5 cells/µL) were found in 43% (3/7) of the fatal cases, 25.7% (9/35) of the severe cases and 29.4% (15/51) of non-severe cases. The average CSF protein of 110.0 mg/dl found in fatal, and in 85.4mg/dl in non-fatal cases. Whereas, average CSF protein levels were 78 mg/dl in severe and 103 mg/dl in non-severe cases. In addition, 76.5% (13/17) of the patients with CNS complications and 74.1% (40/54) of the patients with a PNS manifestation showed elevated protein levels.Conclusion: The most common finding of CSF analysis in the setting of neurological manifestations in Covid-19 is noted to be elevated CSF protein with occasionally elevated, predominantly lymphocytic cell count. Interestingly, CSF protein is noted to be majorly elevated in all spectrums of severity of neurological illness including CNS and PNS complications. This may be indicative of only one common pathophysiological mechanism of neurological illness. In future, A combination of SARS-CoV-2 CSF RT-PCR, CSF IgM testing, and CNS targeting antibodies should be further studied to understand pathophysiology of neurological complications in Covid-19.

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Neurological Manifestations and Complications of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-39952/v1 ◽

2020 ◽

Author(s):

Ahmed Yassin ◽

Mohammed Nawaiseh ◽

Ala' Shaban ◽

Khalid Alsherbini ◽

Khalid El-Salem ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Early Recognition ◽

Case Reports ◽

Meta Analysis ◽

Age Groups ◽

Cerebrovascular Diseases ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Summary Estimate

Abstract Background: The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.Methods: A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.Results: 44 articles were included with a pooled sample size of 13480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2%, 95% CI, 17.2% to 28.1%), taste impairment (19.6%, 95% CI, 3.8% to 60.1%), smell impairment (18.3%, 95% CI, 15.4% to 76.2%), headache (12.1%, 95% CI, 9.1% to 15.8%), dizziness (11.3%, 95% CI, 8.5% to 15.0%), and encephalopathy (9.4%, 95% CI, 2.8% to 26.6%). Nearly 2.5% (95% CI, 1% to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.Conclusions: Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

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Neurological Manifestations in Leprosy: A Study in Tribal Community of Hill Tracts

Journal of Enam Medical College ◽

10.3329/jemc.v6i1.26373 ◽

2016 ◽

Vol 6 (1) ◽

pp. 10-14

Author(s):

Ahmed Tanjimul Islam ◽

Shamrin Sultana ◽

Matiur Rahman ◽

Md Azizul Hoque

Keyword(s):

Health Care ◽

Early Stage ◽

Correct Diagnosis ◽

Cranial Nerves ◽

Care Facility ◽

Health Care Facility ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Tribal Community ◽

Cross Sectional

Background: Leprosy is a chronic granulomatous infectious disease having major burden on humans over thousands of years. If untreated, it results in permanent damage to various systems and organs. So we designed this study to evaluate the neurological complications in early stage in adult leprosy patients.Objective: The aim of this study was to find out the pattern of neurological manifestations among adult leprosy patients.Materials and Methods: This cross-sectional hospital-based study on 85 adult tribal leprosy patients was conducted in a district level health care facility from January to December 2014 using simple, direct, standardized questionnaire including history and neurological examinations.Results: The commonest age group affected was 1830 years (62.4%). Male group was predominant (68.2%). Majority cases (66%) had multibacillary leprosy. At first visit 72.7% cases with neurological findings could not be diagnosed correctly by primary health care personnel. More than six months were required for correct diagnosis in 61.2% cases. Numbness was the commonest (74.5%) neurological symptom. In upper limb, motor findings were predominant with wasting in 50.9% cases. In lower limb, sensory findings were predominant with stock pattern sensory impairment being the commonest (56.4%). Ulnar nerve was the commonest peripheral nerve to enlarge with tenderness. Facial nerve was the commonest cranial nerve involved. All cases with multiple cranial nerves involvement were of multibacillary type. Due to physical disability 92.7% cases lost their jobs.Conclusion: In this study neurological involvement was found associated with severe disability.J Enam Med Col 2016; 6(1): 10-14

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