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 PARTICIPANTSThis 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 (PbtO 2 ), 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. RESULTSOf 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 PbtO 2 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 (Ն2.0 Hz) and PbtO 2 reduction (median normalized PbtO 2 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...

Effect of epileptiform abnormality burden on neurologic outcome and antiepileptic drug management after subarachnoid hemorrhage

“…PET studies have shown that periodic patterns are associated with increased focal cerebral metabolism, similar to seizures (Struck et al ., 2016). A recent study investigating the association between periodic discharges on depth recordings and brain tissue oxygenation found that high frequency periodic discharges (≥ 2.0 Hz) were associated with brain tissue oxygenation (PbtO2) reduction, increased cerebral blood flow, and increased cerebral perfusion pressure (Witsch et al ., 2017). A similar study in patients with traumatic brain injury found that seizures and periodic discharges in depth recordings were associated with metabolic crisis as evidence by low brain glucose and elevated microdialysis lactate/pyruvate ratios (Vespa et al ., 2016).…”

“…We hypothesize that the higher probability of worse outcomes in patients with high EA burden in our cohort may be secondary to a similar process of increased metabolic demand in the injured brain. With increasing EA burden increased blood flow may not match metabolic demand and this may result in secondary brain injury (Witsch et al ., 2017). …”

New onset epilepsy among patients with periodic discharges on continuous electroencephalographic monitoring

“…Whereas LPDs are a product of increased excitatory neurotransmission, GPDs are proposed to emerge from selective synaptic failure in transient hypoxic settings. Although not evidence for their pathogenesis, a recent study of PPs found that low‐frequency (0.5‐1.5 Hz) GPDs have lower partial pressure of oxygen in interstitial brain tissue compared to similar‐frequency LPDs . This difference was lost for higher‐frequency periodic discharges (PDs) …”

“…Although not evidence for their pathogenesis, a recent study of PPs found that low‐frequency (0.5‐1.5 Hz) GPDs have lower partial pressure of oxygen in interstitial brain tissue compared to similar‐frequency LPDs . This difference was lost for higher‐frequency periodic discharges (PDs) …”

Unraveling the complexities of invasive multimodality neuromonitoring

“…Intracranial recordings detect seizures with much higher sensitivity than scalp EEG; in patients being monitored with both types of recordings, conventional scalp EEG misses up to 60% of seizures that are subsequently picked up with invasive methods. 11,71 Seizures identified with invasive recordings produce brain hypoxia 72 and metabolic dysregulation 66 (e.g., cerebral glycopenia and elevated lactate/pyruvate ratio), thus providing a rationale for using intracranial EEG monitoring to guide patient care.…”