Project Details
Projekt
DISCHARGE-2: Depolarizations in ISCHemia after subARachnoid hemorrhaGE-2
Applicant
Professor Dr. Jens P. Dreier
Subject Area
Clinical Neurology; Neurosurgery and Neuroradiology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 570363796
In our recent prospective, observational, multicenter, cohort, phase III diagnostic trial of 180 patients with subarachnoid hemorrhage (SAH), DISCHARGE-1, the strongest predictor of long-term outcome was brain damage detected by MRI 2 weeks after the hemorrhage. Most prominent causes of damage were intracerebral hemorrhage (ICH), and infarction due to either early (ECI), or delayed cerebral ischemia (DCI). DISCHARGE-1 revealed that 151/180 (84%) patients had ICH and/or ECI and 98/170 (58%) delayed infarcts. Ten/180 died early. Patients lost 46±73ml of brain tissue to ICH and ECI and 36±80ml to DCI. The latter could be saved if we knew effective treatments, as DCI is potentially modifiable because it allows treatment before or shortly after the insult. Delayed infarct volume was higher in comatose than in awake patients (48±92ml vs. 23±74ml, P<0.001). Coma limits neurological assessment. In high-risk patients, it is thus hardly possible to identify and treat those who suffer from this complication. However, neurosurgical intervention, such as a burr hole for extraventricular drainage or a craniotomy, is often indicated early after SAH, allowing patients to have probes implanted subdurally after both clipping and coiling of the aneurysm. This enables recording of the entire period of ischemic stroke development, early treatment stratification according to real-time changes in diagnostic measures, and then re-assessment of these measures after neuroprotective intervention. Spreading depolarizations (SDs) play an important role as biomarkers in this concept because they are the electrocorticography (ECoG) correlate of the initial, still reversible phase of neuronal cytotoxic edema and spread far from stressed zones, allowing even remote detection of newly developing injury. In DISCHARGE-1, for each recording day, we determined the total (cumulative) SD-induced depression duration (TDDD). While the a priori defined 60-minute-cutoff of TDDD indicated a reversible delayed deficit, a 180-minute-cutoff indicated new infarction. Therefore, we suggested that rescue treatment should be initiated when a 60-min cutoff is reached for the 24-hour period just elapsed to prevent progression of injury to infarction. However, automated ECoG analysis must first be developed before neuromonitoring-guided proof-of-concept interventional trials can be performed. To this end, we propose DISCHARGE-2 as an observational cohort study, in which machine learning (ML) will be effectively used to develop automated SD evaluation. ML models will be trained and tested on the retrospective dataset of DISCHARGE-1 and then validated using the new prospectively recruited DISCHARGE-2 cohort. For the usually comatose patients who are at high risk for DCI, effective therapeutic strategies cannot be developed until there is an effective diagnostic tool to target therapeutic interventions. Therefore, we would like to take the first logical step and develop precision medicine for DCI.
DFG Programme
Clinical Trials
