Letter to the Editor

With interest we read the article by Kania et al. about a 19-year female diagnosed with SARS-CoV-2 vaccination-triggered acute, disseminated, encephalomyelitis (ADEM) upon clinical presentation (headache, fever, neck/back pain, nausea, vomiting, and urinary retention), cerebral and spinal magnetic resonance imaging (MRI) findings (multiple, poorly demarcated, hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images located in both hemispheres, pons, medulla oblongata, and cerebellum, which partially enhanced), and cerebro-spinal fluid (CSF) investigations (pleocytosis of 294/3, elevated protein).1 Two weeks prior to presentation she had undergone a first vaccination with an mRNA-based SARS-CoiV-2 vaccine (Moderna).1 She partially recovered under methyl-prednisolone.1 The study is appealing but raises concerns and comments.

We do not agree that ADEM may be only due to viral infections or vaccinations.1 ADEM has been also reported following radio-chemotherapy,2 bacterial infections with E. coli,3 synthetic cannabinoids,4 viper venoms,5 herbal extracts,6 hyponatriemia, or genetic disease, such as X-lined Charcot Marie Tooth disease due to GJB1 mutations.7

Differential diagnoses were not appropriately excluded. We should know if immune encephalitis was excluded by determination of specific antibodies associated with immune encephalitis, such as NMDA, AMPAR, LGI1, NLBP12, etc.8 We should know if multifocal PRES due to porphyria had been excluded.9 Was the patient ever tested for SARS-CoV-2? The vaccination can be ineffective.

We should know for how long the patient had received ceftriaxone and acyclovir. Is it conceivable that the patient did not actually profit from steroids but rather from the antibiotic or the antiviral medication? How can the authors be sure that ADEM was due to the vaccination and not due to a viral agent, remaining undetected in the CSF? Oligoclonal bands were negative in the index patient suggesting that the condition was not immunogenic but rather infectious.

We should be informed if the CSF was tested for RNA of SARS-CoV-2. The CSF had been previously shown to be positive for virus RNA in single patients.10 However, most previous studies on SARS-CoV-2 infection associated ADEM have shown that the CSF was negative for virus RNA.11 We should be informed if the intra-thecal IgG production was elevated or not.

We should be informed about the imaging findings using imaging modalities other than T2/FLAIR.

Overall, the elegant study has several limitations, which challenge the results and their interpretation. Infectious agents need to be more thoroughly excluded. Differentials of ADEM need to be more widely considered. More details about imaging findings should be provided.

Informed Consent

Informed consent was obtained.

The study was approved by the institutional review board.

Conflict of Interest

The authors declare no conflict of interest.

Author Contributions

JF was involved in design, literature search, discussion, first draft, and critical comments.