With interest we read the article by Baccarella et al. about two children with multisystem inflammatory syndrome (MIS) due to an infection with SARS-CoV-2, clinically manifesting with increased intra-cranial pressure (ICP) and as right sixth cranial nerve palsy and headache (patient-1), respectively as right sixth nerve palsy and papilledema (patient-2) [1]. Clinical manifestations resolved upon a spinal tap and application of the MIS-C protocol (steroids, intravenous immunoglobulins (IVIG), tocilizumab) (patient-1) and upon application of solely the MIS-C protocol (patient-2) [1]. We have the following comments and concerns.

We do not agree that patient-2 had an increased ICP [1]. The opening pressure on spinal tap was 14cm H₂O and there were no indirect signs of increased ICP on cerebral magnetic resonance imaging (MRI), suggesting that the ICP was normal. The speculation that the ICP was increased during the initial hospitalisation for COVID-19 is also unsupported. Thus, the title of the article is inappropriate. 

A further shortcoming is that there is no discussion about the discrepancy between normal ICP and papilledema in patient-2. An explanation should be provided for these discordant findings and it should be acknowledged that such a discrepancy is not unusual and has been previously reported [2]. Causes of papilledema in the absence of increased ICP, such as optic neuritis, anterior ischemic optic neuropathy (AION), compressive optic neuropathy, papillophlebitis, or neuroretinitis should be discussed. We should be informed about the neuro-ophthalmologic investigations of both patients. 
 

It is unclear why patient-2 received intravenous immunoglobulins (IVIG) and steroids during his first hospitalisation. We should be informed about the indication for these compounds. Additionally, all other drugs given to both patients during hospitalisation should be detailed. Since IVIG carry the risk of headache, thrombosis and aseptic meningitis as adverse reactions [3], it is conceivable that at least in patient-2 thrombosis of intracerebral veins could have been responsible for papilledema. 

Missing is how MIS was diagnosed in the two presented patients. Though it is mentioned that the diagnosis was established according to the Centers for Disease Control and Prevention diagnostic criteria [4], it remains unclear which criteria the two patients particularly met.

Though brain MRI was described as normal in both patients [1], we should be informed which modalities were applied, particularly if diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) were normal. 

Patient-1 was described with recovered heart function after lumbar puncture and application of the institutional MIS-C protocol, suggesting that the patient had reduced systolic function or heart failure on admission [1]. We should know the explanation for heart failure/systolic dysfunction, if the patient received specific treatment for it, and in case he did not receive specific treatment how to explain spontaneous recovery of heart function. Is it conceivable that the patient had experienced Takotsubo syndrome (TTS) triggered by headache, as has been previously reported as a trigger of TTS [5]. 

Both patients had double vision but it is not reported if the bulbs were in a concordant position and if double vision occurred in all bulb positions or only when looking into a certain direction. Supposing that diplopia occurred in all positions, all differentials of diplopia should be considered. 

The reported 6^th cranial nerve palsy in both patients may not only be due to increased ICP but could be also due to infectious neuropathy, retrograde invasion of the nerve by the virus, or cranial nerve involvement in Guillain Barre syndrome, increasingly recognised as a manifestation of COVID-19.

Overall, the study has several limitations, as outlined above, which should be met before drawing final conclusions.