key: cord-1000789-6gicgsj8
authors: Mahammedi, Abdelkader; Saba, Luca; Vagal, Achala; Leali, Michela; Rossi, Andrea; Gaskill, Mary; Sengupta, Soma; Zhang, Bin; Carriero, Alessandro; Bachir, Suha; Crivelli, Paola; Paschè, Alessio; Premi, Enrico; Padovani, Alessandro; Gasparotti, Roberto
title: Imaging of Neurologic Disease in Hospitalized Patients with COVID-19: An Italian Multicenter Retrospective Observational Study
date: 2020-05-21
journal: Radiology
DOI: 10.1148/radiol.2020201933
sha: 525091845619915b072f0802323ff2a6259fcc5c
doc_id: 1000789
cord_uid: 6gicgsj8

Of 725 consecutive hospitalized patients with coronavirus disease 2019, 108 (15%) had acute neurologic symptoms necessitating neurologic imaging.

All images were obtained as per standard of care protocols. MRI scans of brain and spine were obtained with 1.5-T scanners with standardized protocols. Gadopen-tetate dimeglumine (0.1 mmol/kg gadobutrol [Gadovist; Bayer, Berlin, Germany]) was used for contrast materialenhanced studies.

The neurologic imaging characteristics that were evaluated are listed in Table 1 . All scans were initially analyzed by the institution's own neuroradiologists. Subsequently, all images were reviewed by three neuroradiologists in consensus (R.G., L.S., and A.C., with 30, 14, and 32 years of neuroradiology experience, respectively).

Continuous variables are presented as means 6 standard deviations and were compared between patients with altered mental status by using the Student t test; categoric variables are presented as frequencies with percentages. All statistical analyses were performed by using software (Stata, version 15; StataCorp, College Station, Tex). P , .05 was indicative of a statistically significant difference.

A total of 725 consecutive hospitalized patients with COVID-19 were reviewed. Of these 725 patients, 108 (15%) met the eligibility criteria (Fig 1) . Of the 108 patients, 107 (99%) were examined with unenhanced brain CT, 17 (16%) with head and neck CT angiography, and 20 (18%) with brain MRI. Of the 20 patients who underwent brain MRI, 10 (50%) underwent MRI with and without intravenous contrast material, 10 (50%) underwent head and neck MR angiography, and three underwent additional MRI of the whole spine for evaluation of lower extremity weakness. Table 2 summarizes the demographic characteristics, medical history, and neurologic characteristics. The most common neurologic symptoms were altered mental status in 64 of the 108 patients (59%) and ischemic stroke in 34

Imaging of Neurologic Disease in Hospitalized Patients with COVID-19: An Italian Multicenter Retrospective Observational Study E271 10 had acute ischemic infarcts and two had intracranial hemorrhage. Seventy-one of the 108 patients (66%) had no acute findings on brain CT scans; seven of the 20 patients who underwent MRI (35%) had acute abnormalities on brain MRI scans. There was a statistically significant association between the prevalence of altered mental status and patient age (mean age, 72 years 6 11 vs 64 years 6 18; P = .007).

The main neurologic imaging hallmark was acute ischemic infarcts, which were present in 34 of the 108 patients (31%) (30 [28%] on CT scans and four [20%] on MRI scans). Of these infarcts, 19 (18%) were large (15 in the middle cerebral artery territory, two in the posterior cerebral artery territory, two in the anterior cerebral artery territory), 11 (10%) were small, three (3%) were cardioembolic, and one (1%) had an hypoxic-ischemic encephalopathy pattern. Six of the 108 patients (6%) had intracranial hemorrhages, with subarachnoid hemorrhage being the most common (n = 3, 3%). Additional neurologic imaging findings are shown in Table 1 . (12) Note.-Numbers are numbers of patients (numerator/ denominator), with percentages in parentheses. FLAIR = fluid-attenuated inversion recovery, IV = intravenous, MS = multiple sclerosis, PRES = posterior reversible encephalopathy syndrome. * One patient with Miller-Fisher syndrome, a regional variant of Guillain-Barré syndrome, had both cranial nerve and cauda equina enhancement. A 62-year-old man presented with bilateral facial nerve palsy, ophthalmoplegia, areflexia, and polyradiculopathy. Results of real-time reverse-transcriptase polymerase chain reaction assay of the cerebrospinal fluid were negative for severe acute respiratory syndrome coronavirus 2. † A 60-year-old man without history of seizures presented with first time convulsion (Fig 2) . Real-time reverse transcriptase polymerase chain reaction assay of the cerebrospinal fluid was negative for severe acute respiratory syndrome coronavirus 2. ‡ One patient, a 53-year-old woman, presented with seizures and altered mental status.

(31%). Of the 108 patients, 31 (29%) had no known past medical history and 77 (71%) had at least one of the following chronic disorders: coronary artery disease (n = 25, 23%), cerebrovascular disease (n = 15, 14%), hypertension (n = 55, 51%), and diabetes (n = 30, 28%). Of the 31 patients without known past medical history (age range, 16-62 years) (29%), 

Our study demonstrated that the neurologic imaging features of hospitalized patients with COVID-19 were variable, without a specific pattern but dominated by acute ischemic infarcts and intracranial hemorrhages. We also showed that the neurologic MRI spectrum may include posterior reversible encephalopathy syndrome, hypoxicischemic encephalopathy, exacerbation of demyelinating disease, and nonspecific cortical pattern of T2 fluid-attenuated inversion-recovery hyperintense signal with associated restriction diffusion that may be caused by systemic toxemia, viremia, and/or hypoxic effects (9) . Currently, we have a poor mechanistic understanding of the neurologic symptoms in patients with COVID-19, whether these are arising from critical illness or from direct central nervous system invasion of severe acute respiratory syndrome coronavirus 2 (10). Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome that could be a trigger for ischemic strokes, probably related to the prothrombotic effect of the inflammatory response (3, 11) . Our results showed a lower prevalence of central nervous system symptoms than the Wuhan experience (8) (15% vs 25%, respectively); however, the prevalence of ischemic strokes was higher in our study (31% vs 11%). Furthermore, our findings also support the suggested potential for CO-VID-19-associated Guillain-Barré syndrome and variants (12) . None of our patients showed abnormal parenchymal or leptomeningeal enhancement. In conclusion, neurologists and neuroradiologists should be familiar with the broad spectrum of neurologic imaging patterns associated with COVID-19. 

Coronavirus disease 2019 (COVID-19) Situation Report -115

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A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Nervous system involvement after infection with COV-ID-19 and other coronaviruses

COVID-19: consider cytokine storm syndromes and immunosuppression

Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence?

We thank all patients and their families involved in the study.Author contributions: Guarantors of integrity of entire study, A.M., R.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors;