key: cord-0838046-ijxsoohh
authors: van den Enden, Antoon J.M.; van Gils, Lennart; Labout, Joost A.M.; van der Jagt, Mathieu; Moudrous, Walid
title: Fulminant Cerebral Edema as a Lethal Manifestation of COVID-19
date: 2020-07-03
journal: Radiol Case Rep
DOI: 10.1016/j.radcr.2020.06.053
sha: 0880c0d0d212f9aeb8288857e8d96d7f3fdbf41b
doc_id: 838046
cord_uid: ijxsoohh

The contribution of neurological symptomatology to morbidity and mortality after infection with Severe Acute Respiratory Syndrome-associated Coronavirus (SARS CoV II), is ill-defined. We hereby present a case of a 57-year old male patient, in excellent physical condition, who was admitted to the Intensive Care Unit (ICU), with respiratory distress duo to SARS CoV II-induced bilateral pneumonia. After two weeks at the ICU, with respiratory conditions improving, the patient developed lethal cerebral edema. This case advocates regular wake-up calls in Coronavirus disease 2019 (COVID-19) patients for neurological (radiological) evaluation, to provide rapid diagnosis and a therapeutic window for fulminant central nervous system complications.

We would like to re-submit our revised manuscript "Fulminant Cerebral Edema as a Lethal Manifestation of COVID-19" for consideration in your journal.

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In December 2019, human infection with a newly identified Severe Acute Respiratory Syndromeassociated Coronavirus (SARS CoV) was first reported from Wuhan, China [1] . In the spring of 2020, the world witnessed a major outbreak of the virus which causes Coronavirus disease 2019 (COVID-19).

With the continuing SARS CoV 2 epidemic, Intensive Care Units (ICU) around the world face a substantial increase in patients requiring ventilatory support. Morbidity and mortality due to COVID-19 is largely attributed to respiratory distress after onset of bilateral pneumonia. The contribution of the non-respiratory symptomatology of COVID-19 to prognosis is currently unclear. As shown by a recent case series, the presenting symptomatology of an infection with SARS CoV II can include gastrointestinal symptoms e.g. diarrhea or vomiting, as well as neurological manifestations including headache, anosmia and dizziness [2] [3] [4] . While recent editorials call for enhanced clinical concern for central nervous system pathology within the course of SARS CoV 2 infection, a direct correlation between an infection with this viral agent and neurological morbidity remains unclear [5] [6] [7] . We present a case of extensive cerebral edema in an ICU-patient with hypoxic respiratory distress, caused by COVID-19 bilateral pneumonia.

On March 18, 2020 a 57 year old male presented to our hospital. His medical history noted hypertension and his body mass index was 28 kg/m 2 . He was in an excellent physical condition and was regular swimmer. The patient developed fatigue and fever after a trip to Austria on March 9 th . Over the course of a few days his symptoms worsened with dyspnea, nausea, vomiting and diarrhea. He presented at the emergency department with acute respiratory distress, with tachypnea (40 breaths/min), arterial desaturation (88%) and an arterial blood gas analysis with a paO2 level of 47 mmHg. Oxygen therapy was administered using a non-rebreathing mask. Chest X-ray showed diffuse bilateral infiltrates (figure 1) and PCR on a nasopharyngeal swab tested positive for SARS CoV 2.

Inflammatory parameters on admission were high, with CRP of 303 mg/liter (reference range: 0-10 mg/liter) and white-cell count of 10.2 x 10 9 /liter (reference range: 4-10 x 10 9 /liter). On admission to the ICU, the patient was immediately intubated for respiratory failure due to Acute Respiratory Distress Syndrome (ARDS). He also developed acute kidney injury for which continuous renal 

The observed signs and symptoms of COVID-19, likely due to a direct inflammatory response in the respiratory tract, include cough, dyspnea and fever. SARS CoV infections target the angiotensin converting enzyme (ACE) 2 receptor and thereby gain entry to the human body to replicate [8] . During earlier coronavirus outbursts, including during the Middle East respiratory syndrome (MERS) coronavirus outbreak in 2012, reports have been published on coronavirus spreading to the central nervous system by directly infestation of the central nervous system (CNS) [9] [10] [11] [12] . Several hypotheses on CNS infiltration have been formulated, including viral transmission from the nasal cavity via the olfactory nerve [13] , but a recent report did not find direct viral CNS entry [14] . We hereby present a case of massive and rapidly fatal cerebral edema in a patient who was admitted to the ICU with severe ARDS due to COVID-19. In this case, the absence of histopathological evidence or cerebrospinal fluid analysis complicates determination of a certain diagnosis. The differential diagnosis in this case includes: (massive) cerebral venous sinus thrombosis (CVST), hemorrhagic/necrotizing (viral) encephalitis (and thereby developing reactive cerebral edema) and (massive) vasculitis [15] . SARS CoV 2 is the latest descendent in the strain of coronaviruses, with prior fellow species suggested to (directly) cause necrotizing encephalitis. CT scan showed multiple juxtacortical hemorrhages (figure 4), which may well fit the diagnosis of cranial sinus thrombosis. Remarkably, cortex involvement was limited, making arterial infarction less suspect as a cause for cerebral vasogenic edema. Of note, hypercoagulability in COVID-19 has recently been well described and was present in this patient despite treatment with therapeutic LMWH [16] . 

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