Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes

Abstract

Objective: Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood.

Methods: We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury.

Results: Intracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p = 0.001), blood pressure (p < 0.001), and respiratory rate (p < 0.001). There were trends for rising cerebral perfusion pressure (p = 0.03) and intracranial pressure (p = 0.06) seen after seizure onset. Intracortical seizure-associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p = 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively).

Interpretation: We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside.

© 2013 American Neurological Association.

Figures

Figure 1

Three illustrative intracortical seizure cases (A through C) are displayed (ipsilateral scalp EEG each in the top 4 and minidepth EEG in the bottom 6 to 7 channels; all bipolar montage). Case A intracortical seizure with surface seizure: 54 year old woman with poor grade SAH (Hunt Hess 5, APACHE-2 27), that underwent clipping of an anterior communicating artery aneurysm. Case B intracortical seizure with ictal-interictal continuum surface recording: 47 year old man with poor grade SAH (Hunt Hess 5, APACHE-2 14), that underwent clipping of a right anterior cerebral artery aneurysm. Case C intracortical seizure with non-ictal patterns on surface recordings: 57 year old woman with poor grade SAH (Hunt Hess 4, APACHE-2 17), that underwent clipping of an anterior communicating artery aneurysm. Right lower panel shows baseline tissue status based on microdialysis and partial brain tissue oxygenation averaged for all patients over 60 minutes prior to intracortical seizure onset indicating an overall non-ischemic state (median glucose 1.7mmol/L [IQR 1.2–2.4], pyruvate 110umol/L [IQR 80–148], lactate 2.8mmol/L [IQR 1.9–3.6], LPR 25 [IQR 21–28], PbtO2 24.4mmHg [IQR 4.7–63.0]). Only two events were preceded by an LPR >40 and 9 had a cerebral glucose of 0.7 of below, no event was preceded by metabolic crisis (LPR > 40 and brain glucose < 0.7mmol/L).

Figure 2

Grouped data of physiologic changes associated with the onset of intracortical seizures. Spectrograms (upper three panels) displayed as relative changes on a group level, demonstrate increases in EEG power predominantly in the 2–5 Hz frequency range, first seen in the minidepth EEG recording (third panel from top) followed by contra- (top panel) and ipsilateral scalp (second panel from top) recordings. Spectrograms reveal clear changes in EEG power recorded both form the minidepth as well as the scalp, which precedes the seizure onset determined by visual inspection of raw EEG tracings (indicated as “0” on the x-axis and by the vertical red line). Physiology recordings: Timing of increases in cardiovascular (heart rate, mean arterial pressure) and respiratory (respiratory rate, minute ventilation [not shown]) parameters coincides with detection of first intracortical spectral power changes, while rising intracranial pressure is only detected later when seizures become recognizable on inspection of the raw EEG. Global brain metabolism increases sharply for a short time as suggested by the transient drop in jugular bulb oxygenation (approximately 2 minutes after seizure onset). This lasts for several minutes followed by gradual return to pre seizure baseline global metabolism (approximately 8 minutes after seizure onset). There is a small drop of partial brain tissue oxygenation starting 5 minutes after seizure onset. While cerebral perfusion pressure rises with increase in mean arterial pressure at the time the first spectrogram changes are recognizable on the minidepth recording, there is a very delayed increase in regional cerebral blood flow seen starting about 10 minutes after seizure onset. Physiology graphs are displayed as means (blue lines) with one standard error of the mean (shaded area).

Figure 3

46 year old man with SAH (HH grade 4, modified Fisher score 4) underwent clipping of an anterior communicating artery aneurysm who experienced several depth and surface seizures. Here displayed is a depth seizure (spectrogram at top of the Figure) on post bleed day 9 with a drop in PbtO2 from 15 to 1 mmHg following seizure onset and a drop in regional cerebral blood flow. There is a delayed rise of rCBF starting approximately 15 minutes after seizure onset accompanied by an improvement of PbtO2 to baseline values.

Figure 4

Surface EEG findings. Spectrograms for intracortical seizure events stratified into those without and those with surface EEG correlate (panels A and B, respectively). rCBF did not change for those with isolated intracortical seizures while those with IIC or seizures on the surface showed a delayed rise starting approximately 10 minutes after onset (panel C). For those with seizures on the surface (red graph; right lower panel) a brief rise in PbtO2 was followed by a pronounced persistent drop, while a brief period of hyperoxia was not followed by a PbtO2 dip for those without concomitant surface seizures. Physiology graphs are displayed as means (blue lines minidepth only seizures, green lines ictal-interictal continuum or seizures on surface EEG, red line seizures on the surface) with one standard error of the mean (shaded area). Baseline cerebral tissue status characterized by pre-seizure microdialysis (interstitial lactate; pyruvate; LPR, lactate pyruvate ratio; and glucose) and partial brain tissue oxygenation (PbtO2) averaged over 60 minutes preceding intracortical seizure onset stratified by surface EEG findings (white box – no seizures or ictal interictal surface EEG findings, light grey box – ictal interictal surface EEG findings, dark grey box – seizures on surface EEG; * P=0.002).

Figure 5

Three month functional outcome after SAH stratified by EEG background activity and presence of intracortical or surface seizures.

Figure 6

Model illustrating the relationship between acute brain injury complicated by seizures and secondary brain injury accounting for findings made in the current study. Physiologic observations supported by significant changes or trends are indicated by white boxes. Observations made in isolated cases or by visualization of grouped graphs but that were not found to be significant are kept in grey boxes.