Before Classifying Magnesium-sulphate as Effective in Supra-refractory Status Epilepticus Due to AIE, the Efficacy of Other Agents must be Excluded

Letter to the Editor, We were interested to read the article by Ray et al.[1] on a 28-year-old woman with supra-refractory status epilepticus (SRSE) despite general anesthesia, who benefited from magnesium sulfate infusions and in whom the SRSE was attributed to anti-GABA-B autoimmune encephalitis (AIE). The study is impressive, but some points should be discussed. The first point is that several antiepileptic drugs (AEDs) recommended for SRSE were not administered. These include propofol, pentobarbital, fenfluramine, ganaxolone, and purified cannabidiol. Propofol is known to have a similar effect to midazolam in refractory status epilepticus.[2] Fenfluramine was successfully administered to a patient with Lennox-Gastaut syndrome due to tuberous sclerosis complicated by SRSE.[3] Intravenous ganaxolone has been shown to be effective in a 34-year-old patient with SRSE due to SARS-CoV-2 infection.[4] Other non-drug options for the treatment of SRSE include electroconvulsive therapy, vagus nerve stimulation, and the ketogenic diet. The second point is that the cerebrospinal fluid (CSF) examinations were performed only once.[1] Since the SRSE persisted for at least 1 month and a questionable AIE was considered to be the cause of the SRSE, it would have been necessary to perform a CSF examination not only once but repeatedly. Repeated CSF examinations may offer a greater chance than a single puncture of establishing a definitive diagnosis with clearly positive anti-GABA-B antibodies and thus confirming a GABA-B-associated AIE. The third point is that the index patient was not tested for SARS-CoV-2.[1] Since the case obviously occurred during the pandemic, it would have been imperative to rule out SARS-CoV-2 infection as the trigger of AIE. Several cases of SARS-CoV-2-associated AIE were reported during the pandemic, with or without detection of AIE-associated antibodies. The fourth point is that cerebral magnetic resonance imaging (MRI) was performed without contrast.[1] To confirm the suspicion of AIE, it would have been useful to administer a contrast medium to see whether the lesions shown in Figures 1 and 2 stained or not. In summary, it can be said that the index study has limitations that relativize the results and their interpretation. Addressing these limitations could strengthen the conclusions and support the results of the study. Whether magnesium sulfate was really the agent that stopped the SRSE remains speculative, as the patient had been receiving other medications at the same time. Therefore, it is conceivable that not only magnesium but also the combination with other AEDs and immunosuppressants contributed to the favorable outcome of the index patient. We were pleased to read Ray et al.’s response to our comments on their article.[5] Their explanation of why they administered magnesium sulphate and did not apply any of the suggestions in our letter is thoughtful and understandable. They also confirm that the cerebral MRI and CSF examination were repeated twice after the initial examinations without any new information. However, they have not responded to point 3 regarding SARS-CoV-2 testing. Therefore, we would like to know whether SARS-CoV-2 infection has been ruled out as the cause of anti-GABA-B AIE. GABA-B AIE has previously been reported as a complication of SARS-CoV-2 infection.[2] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.