Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury

Abstract

Importance: Periodic discharges (PDs) that do not meet seizure criteria, also termed the ictal interictal continuum, are pervasive on electroencephalographic (EEG) recordings after acute brain injury. However, their association with brain homeostasis and the need for clinical intervention remain unknown.

Objective: To determine whether distinct PD patterns can be identified that, similar to electrographic seizures, cause brain tissue hypoxia, a measure of ongoing brain injury.

Design, setting, and participants: This prospective cohort study included 90 comatose patients with high-grade spontaneous subarachnoid hemorrhage who underwent continuous surface (scalp) EEG (sEEG) recording and multimodality monitoring, including invasive measurements of intracortical (depth) EEG (dEEG), partial pressure of oxygen in interstitial brain tissue (Pbto2), and regional cerebral blood flow (CBF). Patient data were collected from June 1, 2006, to September 1, 2014, at a single tertiary care center. The retrospective analysis was performed from September 1, 2014, to May 1, 2016, with a hypothesis that the effect on brain tissue oxygenation was primarily dependent on the discharge frequency.

Main outcomes and measures: Electroencephalographic recordings were visually classified based on PD frequency and spatial distribution of discharges. Correlations between mean multimodality monitoring data and change-point analyses were performed to characterize electrophysiological changes by applying bootstrapping.

Results: Of the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55 [15] years), 32 (36%) had PDs on sEEG and dEEG recordings and 21 (23%) on dEEG recordings only. Frequencies of PDs ranged from 0.5 to 2.5 Hz. Median Pbto2 was 23 mm Hg without PDs compared with 16 mm Hg at 2.0 Hz and 14 mm Hg at 2.5 Hz (differences were significant for 0 vs 2.5 Hz based on bootstrapping). Change-point analysis confirmed a temporal association of high-frequency PD onset (≥2.0 Hz) and Pbto2 reduction (median normalized Pbto2 decreased by 25% 5-10 minutes after onset). Increased regional CBF of 21.0 mL/100 g/min for 0 Hz, 25.9 mL/100 g/min for 1.0 Hz, 27.5 mL/100 g/min for 1.5 Hz, and 34.7 mL/100 g/min for 2.0 Hz and increased global cerebral perfusion pressure of 91 mm Hg for 0 Hz, 100.5 mm Hg for 0.5 Hz, 95.5 mm Hg for 1.0 Hz, 97.0 mm Hg for 2.0 Hz, 98.0 mm Hg for 2.5 Hz, 95.0 mm Hg for 2.5 Hz, and 67.8 mm Hg for 3.0 Hz were seen for higher PD frequencies.

Conclusions and relevance: These data give some support to consider redefining the continuum between seizures and PDs, suggesting that additional damage after acute brain injury may be reflected by frequency changes in electrocerebral recordings. Similar to seizures, cerebral blood flow increases in patients with PDs to compensate for the increased metabolic demand but higher-frequency PDs (>2 per second) may be inadequately compensated without an additional rise in CBF and associated with brain tissue hypoxia, or higher-frequency PDs may reflect inadequacies in brain compensatory mechanisms.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Dr. Claassen reported receiving honoraria from serving on the Advisory Board of Actelion for study development.

Figures

Figure 1. Four examples of periodic discharge frequencies on dEEG in four patients

The final coded PD frequency was determined according to the predominant frequency considering the entire minute PDs were contained in. The segments shown here exhibit PD-frequencies of approximately 0.5 Hz (A), 1 Hz (B), 1.5 Hz (C), 2.5 Hz (D). PDs shown in B, C, and D had no consistent correlate on sEEG. Abbreviations: dEEG, Depth/Intracortical EEG; sEEG, Surface/Scalp EEG; PD, Periodic Discharge; Hz, Hertz

Figure 2. Frequency of periodic discharges (PDs) on dEEG and multimodality monitoring parameters

A, Brain oxygen, B-C, Local and global cerebral blood flow, D, Intracranial Pressure. Frequency of 0 corresponds to absence of PDs. Values represent medians with interquartile ranges (25–75). Significant differences to respective values at 0 Hz revealed by bootstrapping (500 repetitions) are marked with an asterisk. Abbreviations: dEEG, Depth/Intracortical EEG; PbtO2, Interstitial Partial Brain Oxygen Tension; rCBF, Regional Cerebral Blood Flow; CPP, Cerebral Perfusion Pressure; ICP, Intracranial Pressure

Figure 3. Interstitial brain oxygen (PbtO2) at the onset of high frequency periodic discharges (≥2.0 Hz)

Episodes: n= 27 in n= 8 patients. PbtO2 normalized to maximum. Significant differences of respective time points in comparison with PbtO2 at 5–10 min before high frequency PD onset revealed by bootstrapping (500 repetitions) are marked with an asterisk.

Figure 4. Interstitial brain oxygen tension in relation to surface EEG periodic discharges

A, PbtO2 in relation to all PDs on sEEG categorized according to discharge frequency. B, PbtO2 in relation to low frequency PDs (0.5–1.5 Hz) categorized according to lateralized (right or left) and generalized PD distribution on sEEG. Lateralized PDs: n= 14 patients, generalized PDs: n=9 patients. C, PbtO2 in relation to high frequency PDs (2.0–2.5 Hz) categorized according to lateralized (right or left) and generalized PD distribution on sEEG. Laterlized PDs: n= 5 patients, Generalized PDs: n=5 patients. Abbreviations: PbtO2, Interstitial brain oxygen; sEEG, Scalp/surface EEG; PDs, Periodic Discharges