With interest we read the article by Hixon et al. about a study of three patients with posterior reversible encephalopathy syndrome (PRES) in the context of severe SARS-CoV-2 infections [1]. Additionally, 32 other cases with SARS-CoV-2 associated PRES were discussed and it was concluded that early recognition of the condition is warranted as only half of the patients achieved full recovery by the time of publication. The study is appealing but raises concerns and comments.

The main limitation of the study is the diagnosis “PRES” [1]. PRES is diagnosed upon the clinical presentation and upon the MRI findings [2]. The most common clinical manifestations include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits [2]. On MRI lesions associated with PRES are usually located in the occipital areas and show up as hyperintensity on diffusion weighted imaging (DWI) and hyperintensity on apparent diffusion coefficient (ADC) maps (vasogenic edema). Vascular irregularities are frequently seen. PRES is additionally characterised by spontaneous resolution of these lesions within a few days [3]. However, less than 50% of the included patients recovered until the time of reporting, thus not fulfilling a major diagnostic criterion of PRES. Furthermore, DWI hyperintensity was detected in only a small portion of the cohort. Further arguing against the diagnosis “PRES”. Two of the three patients presented in detail had visual impairment even 12 months after diagnosing COVID-19 respectively PRES.   

A further limitation is that among patients diagnosed as PRES but without spontaneous resolution of the lesions, differentials were not appropriately excluded. Differentials of PRES include acute demyelinating encephalopathy (ADEM), immune-encephalitis, viral encephalitis, ischemic stroke, stroke-like lesions, cerebral vasculitis, drug-induced leukoencephalopathy, and pontine and extra-pontine myelinolysis. Missing in this respect are cerebro-spinal fluid (CSF) investigations, imaging with contrast medium, EEG, and angiography of cerebral arteries. Considering differentials is crucial as treatment and management varies considerably between these entities.

The number of patients with SARS-CoV-2 associated PRES exceeds 32. As per the end of June 2021 an additional amount of at least 12 further patients had been reported (table 1). Age of these patients ranged from 10y to 90y. Seven patients were male and 5 female (table 1) Latency between onset of COVID-19 and onset of PRES ranged between 1 and 70 days (table 1). The most frequent presentation of PRES was seizures, confusion and cognitive impairment.

PRES is hypothesised to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation [2]. Disturbed auto-regulation and endothelial dysfunction are triggered by renal failure, preeclampsia and eclampsia, autoimmune conditions, or immunosuppression [2]. We should be told which of these triggers were present in the 35 patients of the index study.

In the results section the observational period is wrong [1]. Most likely the authors mean “26^th February 2021”. 

Overall, the study has several limitations which challenge the results and their interpretation. These limitations should be addressed before drawing final conclusions.