key: cord-0723793-g0kg4cz4
authors: Chauffier, Jeanne; Poey, Nora; Husain, Maya; Broucker, Thomas De; Khalil, Antoine; Lariven, Sylvie; Henry-Feugeas, Marie-Cécile
title: First Case of Mild Encephalopathy with Reversible Splenial Lesion in SARS-CoV-2 Infection
date: 2020-10-04
journal: Med Mal Infect
DOI: 10.1016/j.medmal.2020.09.018
sha: ee8e03304c9351daa035e60b7fa0363122c1ecd9
doc_id: 723793
cord_uid: g0kg4cz4

nan

J o u r n a l P r e -p r o o f (MERS), which to our knowledge had never previously been described as occurring over the course of this infection.

A 47-year-old man from French-speaking Africa with no medical history or daily treatment was driven to our emergency department on April 8, 2020 due to onset of confusion over the previous 48 hours. He also reported that a febrile dry cough and headache had occurred during the previous 15 days. On admission, he presented normal temperature (37.5° C), tachycardia (heart rate 107) and tachypnea (35 breaths per minute), slightly elevated blood pressure (150/84 mmHg) and oxygen saturation upon arrival of 94% in room air. Oxygen therapy was administered (2 liters per minute).

Neurological assessment revealed diffuse headache without meningism, several cognitive impairments, inattention without disorientation, psychomotor slowness, behavioral disorders, fabulations, false recognitions and anosognosia. In addition, the patient presented disinhibition, logorrhea, casual attitudes, and his Frontal Assessment Battery score was low Our patient showed several typical MERS-associated findings, including behavioral abnormalities, dysexecutive and memory disorder, benign course, EEG slowing and normal CSF (5). His MR brain lesion fulfilled the criteria for the most common and mildest form of cytotoxic lesion of the corpus callosum (6) . The location in the center of the splenium, its ovoid pattern and lack of any mass effect or contrast enhancement clearly identified the lesion as a primary cytotoxic callosal lesion and excluded a corpus callosum lesion due to other causes such as ischemia, tumor or acute disseminated encephalomyelitis.

Numerous etiologies, such as viral and bacterial infection, as well as epilepsy, hyponatremia, altitude sickness with hypoxemia, and iatrogenic origins have been reported for MERS (6) . The still unproven pathomechanism of cytotoxic lesion of the corpus callosum may involve cytokine network dysregulation and altered cerebrovascular autoregulation. In our patient, there was no evidence of cytokine release syndrome, and rapid reversibility of the clinical encephalopathy did not support this hypothesis. He had no alcoholic intoxication, no treatment and no epilepsy on electroencephalography. His oxygen blood pressure was 75 mmHg and while he had moderate hyponatremia, it was not enough to induce a drop in osmotic pressure.

The pathophysiology of this type of viral damage to the central nervous system remains unknown. Two hypotheses seem to prevail: neuron-to-neuron propagation, or vascular damage (7) (8).

We now know that angiotensin-converting enzyme 2 (ACE2) is a SARS-CoV-2 receptor. ACE2 protein is also abundantly expressed in the arterial and venous endothelial and smooth muscle cells (8) . Vascular damage, with rupture of the blood-brain barrier, inflammation and edema, may be involved. The isolated and central lesion of the splenium and the spontaneous resolution might support the assumption of microvascular pathway alterations.

Another key to understanding the neurotropism of the virus could be neuron-to-neuron propagation, from the nasal cavity to the olfactory bulb (7) (8). In our case, the patient had no anosmia or ageusia, and the cerebrospinal fluid (CSF) was free of inflammatory cells and of viral RNA as indicated by RT-PCR. MR images showed no nonspecific change suggestive of encephalitis and no hypersignal on FLAIR T2-weighted images similar to the hypersignal recently reported in a young Japanese man with SARS-CoV-2 in CSF (9) . The rapid resolution of his neurologic symptoms pointed to a vascular etiology, rather than encephalitis. MR angiography also indicated a vascular rather than an encephalitic explanation of our patient's brain perfusion heterogeneity.

In conclusion, this case of encephalopathy suggests that SARS-CoV-2 potentially caused the observed brain injury. Physicians should pay attention to neurological or psychiatric symptoms among patients with SARS-CoV-2 infection and should therefore perform brain MRI. While the pathophysiology is currently unknown, this case might support the hypothesis of microvascular damage caused by the virus in the central nervous system, as has been shown in other tissues.

Nervous system involvement after infection with COVID-19 and other coronaviruses

Guillain-Barré Syndrome associated with SARS-CoV-2 infection. IDCases [Internet

Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study

Central nervous system manifestations of COVID-19: A systematic review

Two newly proposed infectious encephalitis/encephalopathy syndromes

Cytotoxic Lesions of the Corpus Callosum That Show Restricted Diffusion: Mechanisms, Causes, and Manifestations

Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms

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