With interest, we read the article by Reyes-Ruiz et al. on a 14-year-old male with a 2-week history of fever, nausea, and photophobia, who additionally presented with headache, odynophagia, and vomiting on admission (1). Clinical examination revealed disorientation, neck stiffness, oral ulcerations, exaggerated tendon reflexes, and a positive Babinski sign on the right side (1). Cerebral magnetic resonance imaging showed cerebral edema, inflammation, hyperintensity, atrophy, and diffuse leptomeningeal enhancement (1). Cerebrospinal fluid (CSF) examination showed pleocytosis of 30/3 and a positive droplet digital polymerase chain reaction for SARS-CoV-2 (1). Acyclovir was given and the patient recovered completely within 3 weeks (1). The study is excellent but has limitations that are cause for concern and should be discussed.
The main limitation of the study is that no explanation for oral ulcerations and odynophagia was provided (1). The triad of SARS-CoV-2, oral ulcerations, and odynophagia has not been previously reported. Differential diagnoses that should therefore be adequately ruled out include Chagas disease; Behcet disease; monkeypox; disseminated Mycobacterium tuberculosis; HIV; lymphoma; syphilis; actinomyces; Leishmaniosis; use of doxycycline, mycophenolate, azithromycin or cyproterone; Crohn’s disease; candida; and emphysematous osteomyelitis.
The Chiari-I malformation is a common abnormality and irrelevant for the development of SARS-CoV-2-related encephalitis. It is believed to be a random association and has nothing to do with causality. Any other non-causal comorbidity could equally be cited. More important than acknowledging this random association is to discuss how the virus entered the CNS, whether it is possible to prevent cerebral invasion by the virus, and what the optimal treatment is of SARS-CoV-2-related encephalitis with evidence of the pathogen in the CSF.
The index patient had nausea, photophobia, and fever for 2 weeks (1). We are not informed of why the patient did not attend the hospital earlier and when frontal headache, odynophagia, and vomiting developed.
The clinical examination on admission described the patient as having “altered consciousness”. It should be reported whether the patient was in a state of somnolence, sopor, or coma. If sopor or coma, how was it possible to assess that there was disorientation?
No explanation is provided as to why the patient had cerebral atrophy. There is also no mention of whether there was already cognitive impairment prior to encephalitis.
It should be explained why the patient received piracetam as an anti-seizure drug. Piracetam has never been approved as an anti-epileptic drug and carries an increased risk for cerebral bleeding.
The patient received supplementary oxygen, suggesting that there was hypoxygenation (1). The cause of hypoxygenation is relevant, particularly if it was due to cerebral or lung disease. In this regard, were X-ray of the lungs or computed tomography of the thorax normal or indicative of pulmonary infection?
We disagree with the caption of panel D of Figure 1 (1). No leptomeningeal enhancement can be seen in this Figure.
There is a discrepancy between the individual history describing “frontal headache” and the second sentence of the discussion stating that the patient did not have headache (1). This discrepancy should be resolved. We disagree in this regard that “lymphopenia” and “increased neutrophils” are symptoms (1). These are laboratory findings and not something that a patient can report.
There is no mention of the levels of cytokines, chemokines, glial factors, or 14-3-3 in the CSF. These biomarkers have been shown to be elevated in the serum or CSF of patients infected with SARS-CoV-2 (2, 3).
Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and might improve the status of the study.
Footnotes
Conflicts of Interest
The Author declares that there are no commercial or financial relationships that could be construed as a potential conflict of interest.
- Received March 26, 2023.
- Revision received April 6, 2023.
- Accepted April 13, 2023.
- Copyright © 2023 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
