A New Frontier of Neonatal Epilepsy Research:

Empowering Bedside Workers to Recognize Subclinical Seizures in Neonates through EEG Monitoring and Quantitative EEG

By Vaidhehi Veena Sanmugananthan

Seizures are alterations in neurologic function characterized by excessive, hypersynchronous activity of networks of neurons in the brain.1,2 Epilepsy is characterized by recurrent seizures that are unprovoked.1,2 Seizures can be diagnosed and monitored using a tool called an electroencephalogram (EEG), which permits the non-invasive observation of electrophysiological dynamics of the brain by measuring brain electrical fields through an array of electrodes that are placed on the scalp.3 Acute neonatal seizures are the most common expression of neurological injury among newborns that are critically-ill or comatose in neonatal intensive care units (NICUs).1,4 Ultimately, these neonates are at risk of developing neuro-developmental disabilities which could severely affect their quality of life.

Dr. Cecil Hahn is a neurologist, clinical neurophysiologist and researcher at Toronto’s SickKids Hospital studying epilepsy, neurocritical care, and neonatal neurology. He has made it his goal to find ways to maximize the outcomes for newborns with acute seizures. To do this, he has tailored his research questions to complement his clinical work in neonatal neurocritical care. We sat down with Dr. Hahn to discuss some of the key questions and challenges that he tries to tackle in his work as a clinicianinvestigator in neonatal neurocritical care and epilepsy, a very niche and exciting field in pediatric neurology.

Why are seizures and seizure intervention in neonates the focal point of Dr. Hahn’s research?

According to Dr. Hahn, different types of seizures may occur in critically ill patients, some of which are harder to detect than others. By applying continuous EEG monitoring, his team has identified that about 25% of children who are in a coma in the ICU are experiencing electrographic seizures, and that “about 70-80% of those seizures are what we call subclinical seizures, or non-convulsive seizures.” It is difficult or impossible to notice these subclinical seizures by looking at the patient; the only way to identify them is by using EEG. One of the major challenges faced in neonatal neurocritical care research is identifying “whether those subclinical seizures are also causing harm [and] whether they also warrant treatment”.

What sorts of interventions can be made in the ICU to identify subclinical seizures in neonates?

In order to address the challenge of identifying and learning about subclinical seizures in neonates, Dr. Hahn and his team have been working on improving the standard of neonatal care at SickKids Hospital and finding new ways to recognize subclinical seizures in the ICU. Surprisingly, it is not a universal standard of care to do brain monitoring on all critically ill newborns. However, SickKids has played a leading role in the implementation of EEG-based brain monitoring5 alongside other types of physiological monitoring (e.g., heart, respiration) in NICU care.

Critical care EEG monitoring is not without its challenges. Formal EEG interpretation can only be done by clinical neurophysiologists who have specialized in this field. According to Dr. Hahn, there are not enough such experts available to actively monitor EEGs on every newborn in the NICU and accurately pinpoint whether seizures are occurring. This creates a large constraint on identifying the occurrence of subclinical seizures in critically ill newborns.

How can we empower ICU bedside caregivers to recognize seizures?

In light of these limitations, Dr. Hahn and his team have been developing a new type of EEG display that will hopefully empower bedside caregivers who are not typically trained to interpret EEGs to recognize subclinical seizures in newborns. Their aim is to create “a monitor that would display brain activity that’s simplified enough that it could be interpreted by someone who’s not an EEG expert in order to recognize subclinical seizures.”

Dr. Cecil Hahn

MD, MPH, FRCPC; Senior Associate Scientist, Program in Neurosciences and Mental Health, SickKids Research Institute; Staff Neurologist, Division of Neurology, SickKids Hospital; Associate Professor, Department of Pediatrics (Neurology), Associate Member, Institute of Medical Science, University of Toronto

Quantitative EEG6 is a method used to transform the raw EEG signal into a visually simplified signal, typically through color coding, time-compression, and reducing the number of EEG channels to take up less display space on a monitor. Dr. Hahn’s team has evaluated the sensitivity and specificity7 of quantitative EEG displays for seizure detection by EEG experts and non-experts (e.g. ICU nurses, ICU physicians). Based on this work, Dr. Hahn feels that anyone can learn how to recognize seizures using these tools. “You don’t need to know a lot about EEG, or seizures; there is a characteristic ‘fingerprint’ of what a seizure looks like, which anyone can learn to recognize with about an hour of training.”

How has quantitative EEG been useful in a clinical setting?

According to Dr. Hahn, quantitative EEG displays have been helpful in several cases when seizures have occurred in the middle of the night. ICU caregivers who are not typically trained in reading regular EEGs have been able to use quantitative EEG displays to recognize seizures occurring in their newborn patients, which has enabled them to treat their seizures quickly. As exciting as this implementation is, he emphasizes that this tool does not replace the expertise of clinical neurophysiologists like himself. “You still need confirmation of seizures by an expert, but quantitative EEG can shorten the time between seizure occurrence, recognition and treatment, and can empower bedside caregivers to make timely treatment decisions.”

What has been shared here is just the tip of the iceberg of Dr. Hahn’s research in neonatal neuromonitoring. His work-to-date demonstrates an extensive multi-dimensional research approach that aims to simultaneously develop a fundamental understanding of the impact of acute neonatal seizures, as well as develop creative solutions for their identification through technology and education that can be applied in a clinical setting. “Research operates at a very different timeframe from clinical care, in that can take years to see progress. But research discoveries, can have an impact well beyond the individual patient.”

We look forward to seeing what’s to come in Dr. Hahn’s journey in identifying and understanding subclinical seizures in neonates.

References

1. Pisani F, Facini C, Pavlidis E, Spagnoli C, Boylan G. Epilepsy after neonatal seizures: Literature review. European Journal of Paediatric Neurology. 2015 Jan 1;19(1):6–14.

2. Stafstrom CE, Carmant L. Seizures and Epilepsy: An Overview for Neuroscientists. Cold Spring Harb Perspect Med. 2015 Jun;5(6):a022426.

3. Cohen MX. Where Does EEG Come From and What Does It Mean? Trends in Neurosciences. 2017 Apr 1;40(4):208–18.

4. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 Dec 10;37(52):7596–609

5. McCoy B, Hahn CD. Continuous EEG monitoring in the Neonatal Intensive Care Unit. Journal of Clinical Neurophysiology. 2013;30(2):106–14.

6. Stewart CP, Otsubo H, Ochi A, Sharma R, Hutchison JS, Hahn CD. Seizure identification in the ICU using quantitative EEG displays. Neurology. 2010;75(17):1501–8.

7. Department of Health [Internet]. Disease Screening - Statistics Teaching Tools - New York State Department of Health. [cited 2022Oct26]. Available from: https://www.health.ny.gov/diseases/ chronic/discreen.htm#:~:text=Sensitivity%20refers%20to%20a%20 test%27s,have%20a%20disease%20as%20negative.