New research at the University of Cincinnati Neuroscience Institute has shown that spreading depolarisations can be measured by the placement of electroencephalograph (EEG) electrodes on the scalp. Head of the research team, Jed Hartings (research associated professor, Department of Neurosurgery, University of Cincinnati Neuroscience Institute, USA) speaks to NeuroNews about the discovery and its potential to change current practice.
What were the findings of your research? How was it conducted?
We know how to identify spreading depolarisations from intracranial EEG recordings, that is, by placing electrodes directly on the brain. In this study, we wanted to know whether these waves could be observed with non-invasive EEG recordings from scalp electrodes. So what we did is combine the techniques – measure EEG both invasively and non-invasively – and then compare the non-invasive scalp data with confirmed spreading depolarisations identified invasively.
What we found, in a series of 18 patients, is that the majority of spreading depolarisations had clear manifestations in the scalp EEG recordings. Typically, the spreading depolarisations were observed as reduced amplitudes of the scalp-recorded brain waves. These depressions developed over about 10 minutes and lasted about 30 minutes before recovery. When spreading depolarisations occurred continuously, repeating every 20-30 minutes, they maintained a continuous suppression of the scalp EEG that could last hours to more than a day.
How will this discovery change current practice?
The clinical science of spreading depolarisation is in a relatively early stage of development, but progress in recent years has been solid, and it is accelerating. Evidence increasingly shows that spreading depolarisations, or certain patterns of them, are causally related to development of brain lesions and contribute to poor outcomes. This is a major breakthrough, since there has never been a method to look inside the black box of the injured brain and measure a mechanism of developing damage.
Still, significant advances are needed before this emerging field translates to clinical practice. We need to better understand the clinical significance of different patterns of spreading depolarisations, and we need to make information from monitoring more easily accessible at the bedside. Then there is the big question: what can we do to treat and prevent these events? What is the optimal treatment protocol once they are detected? These questions will take years to answer, and the answers will be refined over decades.
How will the placement of EEG electrodes on the scalp work to measure depolarisations?
EEG techniques for measuring depolarisations would likely be very similar to current practice. In fact, the EEG recordings in our study were performed using clinically standard techniques. This is one reason it was so surprising to find evidence of spreading depolarisations in our data. The evidence has been there all along. The data just have to be viewed and analysed the right way to recognise these events.
To optimise the technique, minor changes to current clinical practice might be necessary. We need to explore, for instance, whether a certain type of electrode picks up these signals better than other types, and modifications to EEG amplifier hardware could also enhance detection. Software for displaying the data would need to be modified to identify spreading depolarisations in real-time at the bedside. We need to be able to view trends in EEG activity over long time periods.
Why was this discovery not made sooner? How exactly was the discovery made?
It is incredible that spreading depolarisations were discovered in 1944 – 70 years ago – and only now are we learning how to see them in patients with methods that have been used clinically for decades. It is not because depolarisations are uncommon – they occur in about half of patients with severe brain trauma. Most likely, we did not see them sooner because we were not looking at the data with enough perspective. Customary practice is to analyse brain waves on the scale of seconds. But to see these events, the scale needs to be hours. As an analogy, you could describe a forest by walking through it and focusing on individual leaves, branches, and trees. But you would get a very different picture by describing the flow of terrain – hilltops, streams, and valleys – from, say, a satellite view. We are just now learning how to analyse this landscape view of brain activity.
What is the next step in the development of non-invasive EEG? Is there currently a device in use or, if not, are there any plans to develop one?
Moberg Research, in Ambler, Pennsylvania, USA, is a company that specialises in neurointensive care monitoring and has decades of experience in EEG recordings. They have taken an active interest in spreading depolarisations, and see this as a growth area in clinical neurophysiology. Currently they are developing a new EEG amplifier with advanced features designed to optimise detection of spreading depolarisations. It should be available next year, and we are quite excited about it.
Apart from the hardware, a lot of work still needs to be done in signal processing and data display to develop software that will make all of this information readily available to clinicians at the bedside. We are still at a point where EEG recordings are analysed by specialists off-line to identify these events. That is not very helpful for patients, but I am confident that bedside applications will be a reality in the future. It is a very solvable problem.