`Advanced neuromonitoring´ in status epilepticus

Status Epilepticus (SE) is the most extreme manifestation of an epileptic seizure. With an incidence of more than 40/100.000 per year, a significant morbidity and a mortality of up to 20% it is one of the most common neurological emergencies. SE is characterized by ongoing epileptic activity for more than 30 minutes. Although this definition is currently under debate, a seizure which has lasted for more than 5 minutes is unlikely to cease spontaneously and should therefore be treated as SE. The majority of patients with SE are controlled with intravenous benzodiazepines, around 20% are refractory to treatment with first and second line drugs and rapid institution of general anesthesia is necessary. Current research hypotheses regard SE as a complete breakdown of seizure inhibitory mechanisms, due to GABAergic failure. Until now most of the biomedical research aimed at understanding this disease has been carried out in animal models. Molecular mechanisms in humans leading to this breakdown of seizure inhibition are far from understood. This research proposal is intended to study the pathophysiological mechanisms of human refractory SE . Currently, there is an urgent need to explore the pathomechanisms leading to SE in vivo in humans to better understand SE at a molecular level and ultimately develop better treatment of the disease. The main goal of this project is to establish in vivo invasive monitoring techniques in patients with refractory SE. We aim to develop a novel neuromonitoring paradigm to study the time course of refractory SE, integrating data of neuronal metabolites, neurophysiology and neurological status at different stages of refractory SE. The specific aims of this study are: 1. To establish the feasibility of multimodal invasive monitoring in refractory SE in humans 2. To determine the impact of changes in antiepileptic drug-levels on brain metabolic changes and outcome 3. To determine whether duration and extent of brain physiological derangement is correlated with mortality and long-term functional outcome. We believe that this work will have a broad impact in biomedical research of SE, encouraging other researchers to apply this model or design similar ones for studying the pathophysiology of status epilepticus in humans, and making significantly less necessary the sustained use of animals that currently exists in this field.