DISCHARGE-1: Depolarisations in ISChaemia after subarachnoid HAemoRrhaGE-1

• Applicant: Professor Dr. Jens P. Dreier
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2009 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 73500270

The term cytotoxic oedema describes the ‘Tsunami’-like process of neuronal swelling in the brain that is ignited when passive cation influx across the cellular membranes exceeds ATP-dependent sodium pump activity followed by water influx. Dependent on the capacity to recruit additional pump activity, the cytotoxic oedema is reversible or not. Thus, the cytotoxic oedema marks the transition from life to neuronal death in those neurological conditions that place the highest health burden on our society in terms of mortality, morbidity and economic costs: stroke and hypoxia. Diffusion-weighted imaging is clinically used for early detection of cytotoxic oedema but unsuitable for continuous bedside monitoring. Extensive experimental work has established that cortical spreading depolarisation (CSD) is the mechanism that causes and maintains the cytotoxic oedema. Technology has been developed recently to record CSDs in patients using subdural electrode strips. The here proposed prospective, multicentre, diagnostic study will make use of this for real-time diagnosis of delayed ischaemic stroke, a model disease for stroke since it develops under the eyes of the intensivist several days after the initial aneurysmal subarachnoid haemorrhage. It is aimed to characterise CSDs and determine a cut-off value that will allow future neuroprotective treatment stratification. This will translate the CSD concept into clinical practice, provide novel targets for treatment development and a novel type of proof of concept study on neuroprotectants that allows very early selective intervention.

• DFG Programme: Clinical Trials
• Participating Person: Professor Dr. Peter Vajkoczy