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(1) Background: Little is known about the impact of pathophysiological mechanisms that underlie the enhancement of excitotoxicity and the neuronal consequences of status epilepticus (SE), as well as the clinical consequences of secondary brain insults (SBI) in patients with SE on outcome; (2) Methods: Electronic searches were conducted in May 2020 using Medline via PubMed, Embase, and Google Scholar (#CRD42019139092). Experimental studies of animals or randomized, observational, controlled trials of patients with SE in indexed journals were included. There were no language or date restrictions for the published literature included in this review. Information was extracted on study design, sample size, SBI characteristics, and primary and secondary outcomes, including the timing of evaluation; (3) Results: Among the 2209 articles responding to our inclusion criteria, 56 were included in this systematic review. There are numerous experimental data reporting the deleterious effects associated with each of the SBI in animals exposed to SE. In humans, only the effect of target temperature management in hypothermia (32–34 °C) has been explored. (4) Conclusions: There is little experimental evidence that favors the control of secondary brain insult after SE. Further studies are required to assess the neuroprotective interest of secondary brain insult control after SE in humans.

Epileptic seizures in critically ill patients represent a major source of concern, because they are associated with significant mortality and morbidity rates. Despite recent advances that have enabled a better understanding of the global epidemiology of this entity, epileptic seizures in critically ill patients remain associated with a high degree of uncertainty and numerous questions remain unanswered. The present Special Issue aims to invite authors to contribute original research articles as well as review articles related to all aspects of epileptic seizures in critically ill patients, diagnosis, management, and outcomes.