Letter to the Editor
We read with interest the article by Forest et al. on a 10yo female with a history of acute disseminated encephalomyelitis (ADEM) at age 2y from which she recovered without sequelae who suffered SARS-CoV-2 related acute necrotizing encephalopathy (ANE) also known as acute necrotizing encephlaomyelitis (ANEM) at age 10 [1]. The patient required temporary intubation and artificial ventilation [1]. Methyl-prednisolone was ineffective but plasma exchange (PE) and intravenous immunoglobulins (IVIGs) were beneficial [1]. No long-term follow-up data were provided [1]. The study is appealing but carries limitations that raise concerns and should be discussed.
A limitation of the study is that differentials of ANE were not appropriately ruled out. RANBP2 variants can be also associated with acute, hemorrhagic, necrotizing leucoencephalopathy (AHNE) [2]. Therefore, we should know if there were any indications for bleeding. Particularly, we should know whether there was a hypointensity on susceptibility-weighted imaging (SWI) or hyperdensity on cerebral computed tomography (CCT). As long as not all differentials are appropriately ruled out, ANE should not be diagnosed.
Another limitation of the study is that antibodies associated with autoimmune encephalitis (AIE) were not determined. These antibodies are elevated in about half of the patients with AIE and have been also reported in patients with SARS-CoV-2 associated encephalitis [3].
We should know what specific features were found on magnetic resonance spectroscopy (MRS) that led to the result “necrosis”? The choline/NAA ratio and the choline/creatinine ratio should be provided [4]. Was lactate elevated on MRS?
Expansion of the cerebral lesion occurred under therapy with steroids [1]. Therefore, it cannot be ruled out that deterioration of MRI abnormalities was due to steroids. The patient had received IVIGs with a beneficial effect already for the ADEM at age 2 [1]. Why were IVIGs not immediately given at age 10 again?
There is no mention of the cerebrospinal fluid (CSF) levels of cytokines, chemokines, glial factors, and, 14-3-3. These parameters are commonly elevated in patients with SARS-CoV-2 associated CNS/PNS disease [5].
How did the authors rule out that the cerebral abnormalities visible on imaging were not residual defects from the ADEM at age 2? We should know if the patient had undergone cerebral imaging after recovery from ADEM and before onset of ANE.
The MRI showed cytotoxic edema of the chiasma and the optic tracts. Therefore, one would expect visual impairment. However, vision was not impaired in the index patient [1]. This discrepancy should be clarified.
No explanation for the reduced tendon reflexes on the lower limbs was provided [1]. One would expect exaggerated reflexes in a patient with a pyramidal lesion. Were there any indications for neuropathy or myopathy?
Regarding the treatment of ANE, we should know if recovery was achieved with PE, IVIGs, or both. Were PE and IVIGs applied simultaneously or sequentially?
A limitation of the study is that the long-term outcome was not described. Which functional status did the patient achieve after three or six months? What was the modified Rankin Scale at follow-up?
Overall, the interesting study has limitations that call the results and their interpretation into question. Clarifying these weaknesses would strengthen the conclusions and could improve the study.
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.
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.
Declaration of competing interest
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.
References
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