{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:03:04Z","timestamp":1790841784682,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> The incidence and the clinical presentation of neurological manifestations of coronavirus disease-2019 (COVID-19) remain unclear. No data regarding the use of neuromonitoring tools in this group of patients are available.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This is a retrospective study of prospectively collected data. The primary aim was to assess the incidence and the type of neurological complications in critically ill COVID-19 patients and their effect on survival as well as on hospital and intensive care unit (ICU) length of stay. The secondary aim was to describe cerebral hemodynamic changes detected by noninvasive neuromonitoring modalities such as transcranial Doppler, optic nerve sheath diameter (ONSD), and automated pupillometry.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Ninety-four patients with COVID-19 admitted to an ICU from February 28 to June 30, 2020, were included in this study. Fifty-three patients underwent noninvasive neuromonitoring. Neurological complications were detected in 50% of patients, with delirium as the most common manifestation. Patients with neurological complications, compared to those without, had longer hospital (36.8 \u00b1 25.1 vs. 19.4 \u00b1 16.9 days, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and ICU (31.5 \u00b1 22.6 vs. 11.5\u00b110.1 days, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) stay. The duration of mechanical ventilation was independently associated with the risk of developing neurological complications (odds ratio 1.100, 95% CI 1.046\u20131.175, <jats:italic>p<\/jats:italic> = 0.001). Patients with increased intracranial pressure measured by ONSD (19% of the overall population) had longer ICU stay.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Neurological complications are common in critically ill patients with COVID-19 receiving invasive mechanical ventilation and are associated with prolonged ICU length of stay. Multimodal noninvasive neuromonitoring systems are useful tools for the early detection of variations in cerebrovascular parameters in COVID-19.<\/jats:p>","DOI":"10.3389\/fneur.2020.602114","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T07:00:11Z","timestamp":1606460411000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Neurological Complications and Noninvasive Multimodal Neuromonitoring in Critically Ill Mechanically Ventilated COVID-19 Patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Denise","family":"Battaglini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Santori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikka","family":"Chandraptham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Iannuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Bastianello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Tarantino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Ball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Roberto","family":"Giacobbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Bassetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Uccelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Rieken Macedo","family":"Rocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Patroniti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iole","family":"Brunetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pelosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Robba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"NEJM."},{"key":"B2","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1002\/jmv.25681","article-title":"Emerging coronaviruses: genome structure, replication, and pathogenesis","volume":"92","author":"Chen","year":"2020","journal-title":"J Med Virol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","article-title":"Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR","volume":"25","author":"Corman","year":"2020","journal-title":"Eurosurveillance."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic manifestations of hospitalized patients with Coronavirus Disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1136\/jnnp-2020-323522","article-title":"Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke","volume":"91","author":"Al Saiegh","year":"2020","journal-title":"J Neurol Neurosurg Psichiatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1080\/17476348.2020.1778470","article-title":"Multiple organ dysfunction in SARS-CoV-2: MODS-CoV-2","volume":"14","author":"Robba","year":"2020","journal-title":"Exp Rev Respir Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1001\/jamaneurol.2020.2065","article-title":"Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review","volume":"77","author":"Zubair","year":"2020","journal-title":"JAMA Neurol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14273","article-title":"Acute-onset smell and taste disorders in the context of Covid-19: a pilot multicenter PCR-based case-control study","author":"Beltr\u00e1n-Corbellini","year":"2020","journal-title":"Eur J Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J Pathol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e625","DOI":"10.1097\/SCS.0000000000006601","article-title":"Coincidence of COVID-19 infection and smell: taste perception disorders","volume":"21","author":"Cetinkaya","year":"2020","journal-title":"J Craniofac Surg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/s13054-020-03121-z","article-title":"Neurological manifestations of COVID-19: a systematic review","volume":"24","author":"Nepal","year":"2020","journal-title":"Crit Care."},{"key":"B13","doi-asserted-by":"publisher","first-page":"105921","DOI":"10.1016\/j.clineuro.2020.105921","article-title":"Neurological manifestations of COVID-19 and other coronavirus infections: a systematic review","volume":"194","author":"Montalvan","year":"2020","journal-title":"Clin Neurol Neurosurg."},{"key":"B14","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA."},{"key":"B16","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"m606","DOI":"10.1136\/bmj.m606","article-title":"Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series","volume":"368","author":"Xu","year":"2020","journal-title":"BMJ."},{"key":"B18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.bbi.2020.04.077","article-title":"COVID-19 presenting as stroke","volume":"87","author":"Avula","year":"2020","journal-title":"Brain Behav Immun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/s12975-020-00818-9","article-title":"COVID-19-related stroke","volume":"11","author":"Hess","year":"2020","journal-title":"Transl Stroke Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.nrleng.2020.05.008","article-title":"Ischaemic stroke and SARS-CoV-2 infection: a causal or incidental association?","volume":"35","author":"Barrios-L\u00f3pez","year":"2020","journal-title":"Neurolog"},{"key":"B21","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMc2019373","article-title":"Neuropathological features of Covid-19","volume":"383","author":"Solomon","year":"2020","journal-title":"N Engl J Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/s00134-019-05610-4","article-title":"Brain ultrasonography: methodology, basic and advanced principles and clinical applications. A narrative review","volume":"45","author":"Robba","year":"2019","journal-title":"Intensive Care Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.3171\/2018.11.JNS182077","article-title":"Optic nerve sheath diameter ultrasonography at admission as a predictor of intracranial hypertension in traumatic brain injured patients: a prospective observational study","volume":"132","author":"Robba","year":"2020","journal-title":"J Neurosurg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1097\/CCM.0b013e31819def97","article-title":"The sequential organ failure assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation","volume":"37","author":"Jones","year":"2009","journal-title":"Crit Care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e13319","DOI":"10.1111\/eci.13319","article-title":"Bloodstream infections in critically ill patients with COVID-19","volume":"50","author":"Giacobbe","year":"2020","journal-title":"Eur J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13054-017-1632-2","article-title":"The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study","volume":"21","author":"Rasulo","year":"2017","journal-title":"Crit Care."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1007\/s00134-018-5305-7","article-title":"Optic nerve sheath diameter measured sonographically as non-invasive estimator of intracranial pressure: a systematic review and meta-analysis","volume":"44","author":"Robba","year":"2018","journal-title":"Intensive Care Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1002356","DOI":"10.1371\/journal.pmed.1002356","article-title":"Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: a prospective observational study","volume":"14","author":"Robba","year":"2017","journal-title":"PLoS Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/ane.12527","article-title":"Non-invasive assessment of intracranial pressure","volume":"134","author":"Robba","year":"2016","journal-title":"Acta Neurol Scand."},{"key":"B30","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/ANA.0000000000000604","article-title":"Comparison of 2 automated pupillometry devices in critically Ill patients","volume":"32","author":"Robba","year":"2019","journal-title":"J Neurosurg Anesth"},{"key":"B31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.jcrc.2014.01.012","article-title":"Automated pupillometer for monitoring the critically ill patient: a critical appraisal","volume":"29","author":"Zafar","year":"2014","journal-title":"J Crit Care."},{"key":"B32","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1002\/ana.24943","article-title":"Early prediction of coma recovery after cardiac arrest with blinded pupillometry","volume":"81","author":"Solari","year":"2017","journal-title":"Ann Neurol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"82","DOI":"10.4103\/2152-7806.82248","article-title":"Pupillary reactivity as an early indicator of increased intracranial pressure: the introduction of the neurological pupil index","volume":"2","author":"Chen","year":"2011","journal-title":"Surg Neurol Intern."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1101\/2020.05.31.20118679","article-title":"Delirium incidence, duration and severity in critically Ill patients with COVID-19","author":"Khan","year":"2020","journal-title":"medRxiv [Preprint]"},{"key":"B35","doi-asserted-by":"publisher","first-page":"845","DOI":"10.3389\/fneur.2020.00845","article-title":"Neurological manifestations of severe SARS-CoV-2 infection: potential mechanisms and implications of individualized mechanical ventilation settings","volume":"11","author":"Battaglini","year":"2020","journal-title":"Front Neurol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e910","DOI":"10.1101\/2020.04.28.20082735","article-title":"Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy","volume":"95","author":"Benussi","year":"2020","journal-title":"Neurology."},{"key":"B37","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S2215-0366(20)30203-0","article-title":"Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic","volume":"7","author":"Rogers","year":"2020","journal-title":"Lancet Psychiatry."},{"key":"B38","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4266\/acc.2019.00451","article-title":"Prevention and management of delirium in critically ill adult patients in the intensive care unit: a review based on the 2018 PADIS guidelines","volume":"34","author":"Park","year":"2019","journal-title":"Acute Crit Care."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/bmj.h2538","article-title":"Outcome of delirium in critically ill patients: systematic review and meta-analysis","volume":"350","author":"Salluh","year":"2015","journal-title":"BMJ."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1001\/jama.291.14.1753","article-title":"Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit","volume":"291","author":"Ely","year":"2004","journal-title":"JAMA."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-16173-z","article-title":"Ultrasonographic measurement of the optic nerve sheath diameter and its association with eyeball transverse diameter in 585 healthy volunteers","volume":"7","author":"Kim","year":"2017","journal-title":"Sci Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.resuscitation.2015.08.023","article-title":"Association between blood pressure and outcomes in patients after cardiac arrest: a systematic review","volume":"97","author":"Bhate","year":"2015","journal-title":"Resuscitation."},{"key":"B43","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s12028-014-0046-0","article-title":"Participants in the International Multidisciplinary Consensus Conference on multimodality monitoring. monitoring of cerebral autoregulation","volume":"21","author":"Czosnyka","year":"2014","journal-title":"Neurocrit Care."},{"key":"B44","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1097\/ANA.0000000000000295","article-title":"Effects of prone position and positive end-expiratory pressure on noninvasive estimators of ICP","volume":"29","author":"Robba","year":"2017","journal-title":"J Neurosurg Anesthesiol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.602114\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T07:00:13Z","timestamp":1606460413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.602114\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,27]]},"references-count":44,"alternative-id":["10.3389\/fneur.2020.602114"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2020.602114","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,27]]},"article-number":"602114"}}