To evaluate the association of spreading depolarizations (SD) after acute traumatic brain injury (TBI) with neurological outcomes and post-traumatic epilepsy (PTE).

Spreading depolarizations are slow waves of electrical activity that propagate across large areas of the brain, affecting synaptic activity and cerebral blood flow. The role of SDs in secondary brain injury and epileptogenesis after TBI is not known.

Retrospective cohort including adult patients with TBI who had electrocorticography (ECoG) monitoring after cranial surgery for hematoma evacuation and had a Glasgow Coma Scale (GCS) score of ≤12. Strip and depth electrodes (4-16 channels) were implanted. Poor neurological outcome was defined as a Modified Rankin Scale (mRS) score of ≥4 at discharge. The definition of PTE was the presence of unprovoked seizures occurring ≥7 days post-TBI (up to 4-year follow-up). 

We included 119 patients, and 16 patients (13.4%) had SDs recorded on ECoG. The mean age was 52 years old (SD=19.0), and 76% male (n=91). Median ECoG length was 123 hours (IQR 92); monitoring began 23.5 hours post-TBI (IQR 7.33), and first SD occurred at 28 hours (IQR 47.6). Seizures occurred in 25 patients (21%), with 9 (56%) also experiencing SDs (p=0.001). Only one (6%) SD patient developed PTE. Mortality was 62.5% for SD patients and 33.6% without SDs (p=0.019). All SD patients had an mRS of ≥4. Higher frequency of SDs was associated with worse mRS (p=0.034, OR=1.215). Ten SD patients (62.5%) experienced SD clusters (3/2h), with a mean of 2.2 (median=1.33) clusters/day within 72 hours post-TBI. There was a trend between increasing cluster frequency and worse outcome (p=0.07, OR=2.75).

Spreading depolarization burden is associated with death and poor neurological outcomes. While SDs commonly co-occurred with seizures, their association with PTE could not be determined. Future multicenter studies with larger cohorts may help elucidate whether SD contribute to PTE development.