Development and implementation of real-time excitability measurement in the injured human brain: a novel neurocritical care monitoring tool

Abstract

A key contributor to outcome following brain injury is the development of secondary injury. This evolves in the days following the primary insult and is driven by stressors such as spreading depolarisations (SD). Critical care management thus aims to recognise and respond to deleterious events with a view to preserving function. Currently however, we lack an ability to reliably monitor neuronal function at the bedside. Whilst we can record the DC-electrocorticography (ECoG), in-between pathophysiological transients the signal is difficult to interpret and the standard EEG may be suppressed, meaning that there may be long stretches of time where assessment of the functional integrity of the neurons is challenging. Furthermore, the hallmark ECoG features of SD present with a high degree of heterogeneity meaning that the effect of these events on the function of the neurons can be difficult to quantify. Since a cell’s ‘excitability’ is intrinsically linked to its normal operation, an alternative approach is to measure excitability. This thesis therefore describes the design and implementation of a new method to monitor excitability in the injured human brain using the Direct Cortical Response (DCR). The DCR is a mosaic of potentials evoked by precisely controlled electrical stimulation of the cortex. Fifteen patients were recruited. Excitability was undertaken during 105 SDs across 18 channels in 5 patients. My principal findings were 1) Excitability monitoring is feasible and safe; 2) Baseline DCR amplitude was stable enabling assessment of important SD characteristics such as duration; 3) DCR amplitude fell up to 10mins in advance of the DC-shift; 4) Changes in independent DCR components followed different time-courses during SD suggesting involvement of diverse mechanisms at various stages. I conclude that excitability monitoring is a safe, reliable and informative means of monitoring neuronal function that may improve understanding of SDs, and bedside identification of deterioration.