Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression

Abstract

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3-5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9-22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

Keywords: Spreading depolarization; electrocorticography; intracerebral hemorrhage; perihematomal edema; secondary brain damage.

Figures

Figure 1.

Serial axial brain computed tomography images on admission (a), after hematoma evacuation (b), after 10 days (c) and four weeks (d) of patients with (patient 2) an without (patient 1) perihematomal edema progression. Midline shift increased from 6 to 8 mm in patient 2. Panel E in patient 1 indicates a three dimensional reconstruction image showing the subdural electrode (black arrow) and intraperenchymal ICP probe (white arrow). ICP: intracranial pressure.

Figure 2.

Types of SDs: (a) ECoG indicates clusters of “ISDs” (n = 18 per 5 h) in a patient with significant PHE progression 24 h after hematoma evacuation; (b) Isolated spreading depolarization starting over channel D and spreading to channel A (c) ECoG during 5 h indicates clusters of stereotyped spreading depressions starting at channel D and spreading to channel A. ECoG: electrocorticography; ISD: isoelectric depolarization; SD: spreading depolarization; PHE: perihematomal edema.

Figure 3.

Incidence of SDs following primary intracerebral hemorrhage (a–c). All patients, with or without SDs, were included in the analysis. The total number of SDs by day was divided by the number of patients recorded in the corresponding time interval in order to obtain mean rates that can be compared across time. Black bars represent the number of all SDs (a). The subgroup of ISDs is shown to the right in white bars (b). Number of patients that underwent recording by day (c). ISD: isoelectric depolarization; SD: spreading depolarization.

Figure 4.

Percentage of one hour intervals in which episodes of ISD occurred across quartiles of MAP. The multivariable general linear model (GLM) with a logistic link function using GEE showed an independent association between MAP and occurrence of ISDs (P < 0.001). MAP: mean arterial pressure; GEE: general estimated equations; ISD: isoelectric depolarizations.

Figure 5.

Time course of SDs following primary intracerebral hemorrhage in patients with (a, black bars, N = 22) and without perihematomal edema progression (b, white bars, N = 4). All patients, including those without depolarizations, were included in the analysis. The total number of depolarizations by day was divided by the number of patients recorded in the corresponding time interval in order to obtain mean rates that can be compared across time. SD: spreading depolarization.