Abstract
Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.
Case presentation
A 64-year-old woman was admitted to our hospital with a 10-day history of fever and dyspnea treated at home with ceftriaxone.
Her medical history included hypertension, gastroesophageal reflux disease, hyperuricemia, dyslipidemia, obstructive sleep apnea and paroxysmal atrial fibrillation. Her medications were: irbesartan/hydrochlorothiazide, acetylsalicylic acid, pantoprazole, rosuvastatin, allopurinol and bisoprolol.
She was febrile (39 °C) with marked dyspnea. Neurological examination was unremarkable. Laboratory tests were significant for lymphocytopenia with increased transaminases and LDH. Oxygen saturation was low, thereby oxygen therapy was administered (Table 1). Chest X-ray showed reduction of the parenchymal transparency in basal region of right lung.
A continuous positive airway pressure had to be started. A nasopharyngeal swab resulted positive for SARS-CoV-2; antiviral therapy with darunavir/cobicistat, associated with hydroxychloroquine were started. After 24 h, she was taken to Intensive Care Unit: she was sedated and mechanical ventilation was started. Antiviral plus antibiotic therapies were continued for 10 days. After 23 days bronchial aspirate turned negative for SARS-CoV-2.
On day 25 she woke up when sedation was weaned; she was drowsy and complained of blurred vision. She showed an altered mental status, a decreased left nasolabial fold, the tone and the strength were slightly decreased in the legs, and all deep tendon reflexes were reduced symmetrically. Brain CT and CTA were consistent with hemorrhagic Posterior Reversible Encephalopathy Syndrome (PRES; Fig. 1a, b).
In the following days spontaneous breathing was restored. No epileptic seizures were reported during hospitalization.
On day 56 a brain MRI showed a reduction of the bilateral edema with bilateral occipital foci of subacute hemorrhage (Fig. 1c, d). A second nasopharyngeal swab was negative for SARS-CoV-2, and she was alert and fully oriented with a normalization of blurred vision.
Discussion
PRES is characterized by acute impairment in level of consciousness, headache, visual disturbances and seizures, with cortical/subcortical vasogenic edema, involving predominantly the parietal and occipital regions bilaterally [1]. PRES is commonly associated with blood pressure fluctuations, renal failure, autoimmune conditions, sepsis, preeclampsia or eclampsia and immunosuppressive-cytotoxic drugs. In our patient the sepsis (Table 1) was due to Staph. Epidermidis, that has never been associated with PRES, and did not induce a shock condition as is usually the case in septic PRES [2,3,4]. None of the drugs given to our patient has been associated with PRES [5].
Several studies suggested a key role of endothelial dysfunction (ED), combined with hemodynamic stress (hypertensive crisis) and immunological activation with release of cytokines (TNF-α, IFN-γ, IL-1) able to activate endothelial cells, thus increasing vascular permeability. ED is a principal determinant of microvascular perfusion: by shifting the vascular equilibrium towards a more pro-inflammatory, pro-coagulant and proliferative state, it leads to ischaemia and inflammation with edema [6].
This is the second report of hemorrhagic PRES in COVID-19, and these other two patients were very similar to ours.[7].
Mounting evidence suggests that the SARS-Cov2 directly infects endothelial cells causing diffuse inflammation [8,9,10]. The pivotal host cell receptor for the entry of SARS-CoV-2 into the cells is the Angiotensin-Converting Enzyme 2, which is also expressed by the brain endothelium [9, 11]. Varga et al. [10] showed the presence of viral elements within endothelial cells in different vascular beds, suggesting a role of an ED in the systemic toxicity caused by the virus.
In our patient we can rule out the causes of PRES listed above. A contribution from the respiratory distress was unlikely since PRES developed during mechanical ventilation. We hypothesize that SARS-CoV-2 may have caused a cerebrovascular ED which in turn was responsible for both the hemorrhagic lesions and the for the disruption of the blood brain barrier with vasogenic edema.
Availability of data and material
Our data are available upon request to the corresponding author.
Abbreviations
- COVID-19:
-
Corona virus disease 19
- CTA:
-
Computed tomography angiography
- ED:
-
Endothelial dysfunction
- SARS-Cov2:
-
Severe acute respiratory syndrome covid 2
References
Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334(8):494–500. https://doi.org/10.1056/NEJM199602223340803
Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J (2006) Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol 27(10):2179–2190
Racchiusa S, Mormina E, Ax A, Musumeci O, Longo M, Granata F (2019) Posterior reversible encephalopathy syndrome (PRES) and infection: a systematic review of the literature. Neurol Sci 40(5):915–922. https://doi.org/10.1007/s10072-018-3651-4
Toledano M, Fugate JE (2017) Posterior reversible encephalopathy in the intensive care unit. Handb Clin Neurol 141:467–483. https://doi.org/10.1016/B978-0-444-63599-0.00026-0
Pilato F, Distefano M, Calandrelli R (2020) Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome: clinical and radiological considerations. Front Neurol 11:34. https://doi.org/10.3389/fneur.2020.00034
Fugate JE, Rabinstein AA (2015) Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 14(9):914–925. https://doi.org/10.1016/S1474-4422(15)00111-8
Franceschi AM, Ahmed O, Giliberto L, Castillo M (2020) Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol. https://doi.org/10.3174/ajnr.A6595
Guo J, Huang Z, Lin L, Lv J (2020) Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J Am Heart Assoc 9(7):e016219. https://doi.org/10.1161/JAHA.120.016219
Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G (2020) Hypertension, thrombosis, kidney failure, and diabetes: is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. https://doi.org/10.3390/jcm9051417
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5
Natoli S, Oliveira V, Calabresi P, Maia LF, Pisani A (2020) Does SARS-Cov-2 invade the brain? Translational lessons from animal models. Eur J Neurol. https://doi.org/10.1111/ene.14277
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Not applicable. This case has been described retrospectively, without the patient undergoing procedures and tests other than those she already had to undergo to treat her clinical condition. This research was performed in accordance with GCP and the ethical standards laid down in the 1964 Declaration of Helsinki.
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Princiotta Cariddi, L., Tabaee Damavandi, P., Carimati, F. et al. Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. J Neurol 267, 3157–3160 (2020). https://doi.org/10.1007/s00415-020-10001-7
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DOI: https://doi.org/10.1007/s00415-020-10001-7