Spreading Depolarizations Predict Future Brain Trauma

Jed A. Hartings, PhD

New research indicates a new way to predict future cognitive outcomes following a severe traumatic brain injury (TBI).

A team, led by Jed A. Hartings, PhD, Department of Neurosurgery, University of Cincinnati College of Medicine, examined whether the measurement of spreading depolarizations provide clinically meaningful information independent of other assessments.

The prospective, observational, multicenter cohort study included 138 patients who underwent surgery for traumatic brain injuries between 2009-2013 in 5 level 1 trauma centers.

To be eligible for the study, consecutive patients required neurological surgery for treatment of acute brain trauma.

Of the 138 patients deemed eligible, 104 were men and the median age was 45 years old. There was a median of 75.5 hours of electrocorticography.

For each patient, a 6-contact electrode strip was place on the surface of the brain during surgery for continuous electrocorticography during intensive care.

The investigators scored electrocorticography for depolarizations, following international consensus procedures and assessed six-month outcomes by the Glasgow Outcome Scale-Extended score.

The investigators found the occurrence of repetitive spreading depolarizations (clusters) in 51 patients (37%) was linked to poor neurologic recovery during intensive care and was a factor independently associated with 6-month functional outcomes.

A total of 2837 spreading depolarizations occurred in 83 patients (60.1%).

When compared with patients who did not have spreading depolarizations, this population had lower prehospital systolic blood pressure levels (mean [SD], 133 [31] mm Hg vs 146 [33] mm Hg; P = .03), more traumatic subarachnoid hemorrhage (depolarization incidences of 17 of 37 [46%], 18 of 32 [56%], 22 of 33 [67%], and 23 of 30 patients [77%] for Morris-Marshall Grades 0, 1, 2, and 3/4, respectively; P = .047), and worse radiographic pathology (in 38 of 73 patients [52%] and 42 of 60 patients [70%] for Rotterdam Scores 2-4 vs 5-6, respectively; P = .04).

For patients with depolarizations, 32 of 83 (39%) only had sporadic events that induced cortical spreading depression of spontaneous electrical activity. On the other hand, 51 of 83 patients (61%) exhibited temporal clusters of depolarizations (≥3 in a 2-hour span), while nearly half of those with clusters (23 of 51 [45%]) also had depolarizations in an electrically silent area of the cortex (isoelectric spreading depolarization).

Patients with clusters did not improve in motor neurologic examinations from pre-surgery to post-electectrocorticopgrapy, but other patients did improve.

Using a multivariate ordinal regression adjusting for baseline prognostic variable, the investigators found the occurrence of depolarization clusters had an odds ratio of 2.29 (95% CI, 1.13-4.65; P = 0.02) for worse outcomes.

“In this cohort study of patients with acute brain trauma, spreading depolarizations were predominant but heterogeneous and independently associated with poor neurologic recovery,” the authors wrote. “Monitoring the occurrence of spreading depolarizations may identify patients most likely to benefit from targeted management strategies.”

Advancements in treatment for traumatic brain injuries are often prevented by an inability to monitor pathological mechanisms in individual patients for targeted neuroprotective treatment.

The researchers believe the findings show spreading depolarizations are a common mechanism of secondary injury and should be considered for monitoring and treatment targeting in traumatic brain injuries.

The study, “Prognostic Value of Spreading Depolarizations in Patients With Severe Traumatic Brain Injury,” was published online in JAMA Neurology.