Effect of Locally Delivered Nimodipine Microparticles on Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.

Background: Recurrent spreading depolarizations (SDs) occur in patients after aneurysmal subarachnoid hemorrhage (aSAH), resulting in metabolic stress to brain. These events are closely associated with delayed cerebral ischemia. Preclinical data suggest that the beneficial effect of nimodipine demonstrated in clinical trials may be related to inhibition of SD rather than limitation of large artery vasospasm.

Methods: Subjects enrolled in a phase 3 trial of intraventricularly delivered, sustained-release nimodipine (EG-1962) versus standard of care oral nimodipine (NEWTON 2) who required surgical clipping had subdural strip electrodes implanted for monitoring of SD. SD was then scored blinded to NEWTON 2 allocation.

Results: Five subjects underwent electrocorticography monitoring of SD. Three of five patients had SD. There were fewer SDs, a lower rate of SD, and shorter depression durations in subjects treated with EG-1962 compared to standard of care. Outcomes were worse in the standard of care group, though there were baseline imbalances.

Conclusions: These results are consistent with a beneficial effect of locally delivered nimodipine (EG-1962) on SD after aSAH in more severely injured patients who are at risk of delayed cerebral ischemia related to SD. Larger studies are warranted to test this effect.