
Journal of Neurology
1 3
Discussion
PRES is characterized by acute impairment in level of con-
sciousness, headache, visual disturbances and seizures, with
cortical/subcortical vasogenic edema, involving predomi-
nantly 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 (Table1) was due to Staph. Epider-
midis, that has never been associated with PRES, and did
not induce a shock condition as is usually the case in septic
PRES [2–4]. None of the drugs given to our patient has been
associated with PRES [5].
Several studies suggested a key role of endothelial dys-
function (ED), combined with hemodynamic stress (hyper-
tensive 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 prin-
cipal 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 inflamma-
tion [8–10]. 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 endothe-
lium [9, 11]. Varga etal. [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 ventila-
tion. 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 ofdata andmaterial
Our data are available upon request to the corresponding
author.
Funding This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflicts of interest The authors declare no potential conflicts of inter-
est with respect to the research, authorship, and/or publication of this
article.
Consent for publication A written informed consent was obtained from
the patient.
Ethics approval Not applicable. This case has been described retro-
spectively, 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.
References
1. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pes-
sin 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/NEJM1 99602 22334 0803
2. 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
3. Racchiusa S, Mormina E, Ax A, Musumeci O, Longo M, Granata
F (2019) Posterior reversible encephalopathy syndrome (PRES)
Fig.1 Radiological findings. a Brain axial CT on day 25 shows pos-
terior frontal and temporo-parieto-occipital symmetric bilateral
hypodensity of the subcortical white matter, and a tiny left occipi-
tal parenchymal hemorrhage. b Para-axial CTA scan confirms the
absence of vascular malformation and alterations of posterior circle
vessel caliber, suggestive of vasoconstriction mechanism. c Axial T2
Flair image on day 56 shows that vasogenic edema is reduced but still
detectable and d T2 Gradient-Echo reveals the onset of right temporal
hypodensity, correlated to hemorrhagic process