With interest we read the article by Kenangil et al. about a 46 year old female who experienced a first tonic-clonic seizure (TCS) ever one month after a second dose vaccination with an inactivated virus-based vaccine (Sinovac) [1]. Clinical exam was normal but cerebral MRI revealed scattered T2-hyperintense lesions in the left thalamus, corona radiate bilaterally, left midbrain, and right parietal cortex, which did not enhance but were slightly hyperintens on diffusion weighted imaging (DWI) [1]. The patient was diagnosed with acute, disseminated encephalomyelitis (ADEM) like disease and was treated with steroids but without an obvious effect on the MRI lesions [1]. It was concluded that the case is unique and that clinicians should be aware of such a side effect of SARS-CoV-2 vaccinations [1]. The study is appealing but has several limitations which raise the following comments and concerns. A limitation of the case report is that venous sinus thrombosis (VST) has not been excluded as a differential of ADEM [1]. VST has been repeatedly reported as a complication of SARS-CoV-2 vaccinations in >300 patients so far [Finsterer, submitted]. No results of coagulation parameters, particularly D-dimer, and of magnetic resonance venography (MRV) were presented. Arguments in favour of a VST are that SARS-CoV-2 vaccinations can be complicated by VST, that the patient had developed a seizure, which is a frequent manifestation of a VST [2], one month after the second vaccination, that she was a smoker, that steroids were ineffective, and that hyperthyroidism can precipitate VST [3,4].

A further differential that has not been appropriately excluded is cerebral vasculitis. Though the patient did not complain about headache,cerebral vasculitis should have been considered but there is no mentioning of anti-neutrophil cytoplasmatic antibodies (ANCA) and no results of magnetic resonance angiography (MRA), of black blood sequences, or of conventional digital subtraction angiography (DSA). Missing in this respect are the susceptibility weighted imaging (SWI) sequences. Arguments for cerebral vasculitis are the slightly increased anti-neutrophil antibodies (ANA) and the mulita-locular DWI hyperintens / apparent diffusion coefficient (ADC) hypointens lesions. Arguments against vasculitis, however, are that the patient did not have headache, that cerebro-spinal fluid (CSF) investigations were completely normal, that the cerebral lesions did not enhance, and that steroids were ineffective. 

A third differential that has not been appropriately excluded is hyperthyroid respectively thyreotoxic encephalopathy. Thyreotoxicosis may manifest with atrial fibrillation or ischemic stroke due to Moya Moya disease. Arguments against hyperthyroidism however are that the patient did not present with confusion and that cerebral lesions did not resolve upon steroids or spontaneously. 

A fourth differential not excluded thoroughly is cardio-embolism. Since SARS-CoV-2 vaccinations can be complicated by myocarditis [5] it is conceivable that the multi-locular T2-hyperintens, DWI-hyperintens, and ADC hypointens lesions in fact represent subacute ischemic lesions originating from cardio-embolism. 

Missing is an extensive previous individual and family history particularly with regard to epilepsy. We should be told if the TCS was triggered or untriggered, if serum sodium levels were normal or decreased, if she had insomnia, fever or was under stress shortly before the TCS, and if the family history was negative or positive for epilepsy. Missing are the results of the electro-encephalography (EEG) recordings. Missing is the information if anti-seizure drugs (ASDs) were applied or not. 

Overall, we do not agree with the diagnosis ADEM-like disorder since several differential diagnoses, particularly VST, vasculitis, hyperthyreote encephalopathy, and ischemic, embolic stroke due to cardio-embolism were not appropriately excluded. As long as these differentials were not unequivocally excluded, SARS-CoV-2 vaccination associated ADEM should not be diagnosed in the presented patient.