Does a frequency threshold exist for periodic discharges recorded in the aftermath of acute brain injury above which brain tissue hypoxia occurs?
In a cohort study of 90 comatose patients with subarachnoid hemorrhage, increasing frequency of periodic discharges was associated with a stepwise increase of regional cerebral blood flow and a stepwise decrease of partial pressure of oxygen in interstitial brain tissue, with a drop to hypoxic values at a periodic discharge frequency of greater than 2.0 Hz.
The physiologic signature of high-frequency periodic discharges resembles that described for seizures, providing a rationale to interpret and potentially treat high-frequency periodic discharges as seizures.
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.
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.
Of the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55  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.
Witsch J, Frey H, Schmidt JM, Velazquez A, Falo CM, Reznik M, Roh D, Agarwal S, Park S, Connolly ES, Claassen J. Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury. JAMA Neurol. 2017;74(3):301-309. doi:10.1001/jamaneurol.2016.5325