We read with interest the article by Tortajada-Soler et al. on two patients, a 66 years-old male (patient-1) and a 64 years-old male (patient-2), with severe SARS-CoV-2 infection, which was complicated by posterior reversible encephalopathy syndrome (PRES) in both of them.1 Both patients required mechanical ventilation because of COVID-19 pneumonia and received polypragmatic treatment but the outcome was favourable in both patients without neurological deficits (patient-2) respectively minimal neurological deficits (patient-1).1 The study is excellent but has limitations that raise concerns and should be discussed.
We disagree with the diagnosis PRES.1 PRES is characterised by the presence of headache, visual disturbances, seizures, confusion, and vasogenic edema in the occipital or parietal lobes. Neither patient-1 nor patient-2 presented with headache, visual impairment, or confusion after discontinuation of the sedoanalgesia. Only patient-1 developed seizures. Cerebral MRI was not indicative of PRES in both patients.
PRES is characterised on imaging by vasogenic edema, which shows up on multimodal MRI as hyperintensity on diffusion-weighted images (DWI) as well as on apparent diffusion coefficient (ADC) maps. However, results of DWI and ADC maps were not reported for both patients.1 As long as this pattern is not confirmed on multimodal MRI, the diagnosis PRES remains questionable.
A limitation of the study is that none of the two patients underwent a spinal tap with examination of the cerebrospinal fluid (CSF). CSF examinations are mandatory to rule out differential diagnoses such as immune or infectious encephalitis, acute, disseminated encephalomyelitis (ADEM), acute necrotising encephalopathy (ANE), acute, hemorrhagic, necrotizing encephalopathy (AHNE), and acute, hemorrhagic leucoencephalitis (AHLE). All these conditions have been reported in association with SARS-CoV-2 infections.2–4 To rule out these differential diagnoses it is crucial to examine the CSF including PCR for SARS-CoV-2, a virus panel, cytokines and chemokines, and to measure specific antibodies for autoimmune encephalitis (AIE). Particularly in patient-2 is cerebral imaging highly suggestive of AHNE. Cerebral lesions showed a multifocal distribution and had a hemorrhagic and necrotizing component.1
Patient-1 received midazolam, fentanyl, propofol, noradrenalin, dobutamin, lopinavir, ritonavir, hydroxyl-chloroquine, ceftriaxone, levofloxacin, dexamethasone, tocilizumab, baricitinib, interferon-β, diazepam, levetiracetam, and lacosamide in addition to mechanical ventilation and hemofiltration.1 Pateint-2 received a similar therapeutic regimen but without anti-seizure drugs (ASDs).1 However, there is no discussion on the influence of these compounds or their combination on the development of the neurological and neuroimaging abnormalities.
We also disagree with the electroencephalography (EEG) diagnosis of “encephalopathy‿.1 The EEG may show focal or diffuse slowing, or focal or generalised epileptiform discharges, but no “encephalopathy‿. We should know if epileptiform discharges were recorded or just slowing. What specific elements were recorded on the second EEG in patient-1 after he developed recurrent focal seizures with secondary generalisation?
Overall, the interesting study has limitations that put the results and their interpretation into perspective. Clarifying these limitations would strengthen the conclusions and could improve the study. Before diagnosing SARS-CoV-2-related PRES, alternative diagnoses must be ruled out.
Funding: no funding was received.
Data access statement: all data are available from the corresponding author.
Ethics statement: not applicable.
Author contribution: JF: design, literature search, discussion, first draft, critical comments, final approval.
Disclosures: the author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data access statement: not applicable.
Compliance with Ethics Guidelines: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
