Scalp electroencephalogram analysis to determine whether the occurrence of high frequency oscillations mirrors the propensity for and disease activity of epilepsy in children

• Applicant: Dr. Margarita Maltseva
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530582215

Innovative research on epilepsy has led to considerable improvement in our knowledge of its predisposing conditions and trusted biomarker, high-frequency oscillations (HFOs). Therefore, our understanding of epilepsy has grown substantially, and as a consequence, prevention of epilepsy is a possibility. HFOs were first identified using intracranial electrodes that directly recorded the oscillations in brain structures. Electroencephalograms (EEGs) measure electrical oscillations simultaneously generated by the neural network. However, these brainwaves are about five times faster than those routinely recorded in clinical EEGs. They are called ripples and occur at frequencies of 80–500 Hz. They can be seen in any routine EEG recording as long as the sampling rate is high enough. HFOs are most visible in children (likely due to better skull conductivity), during sleep, and when epileptic spikes (pathological discharges in EEGs) are recorded in patients. Although spikes are currently favored for diagnosing epileptic activity, they can be abundant even in the absence of seizures. The use of HFOs in scalp EEGs to directly measure epileptogenesis, seizure propensity, and disease activity in non-invasive clinical routines would be a ground-breaking approach. This would allow precision medicine to be applied to all individuals affected by seizures regardless of etiology. In our project, we will analyze scalp EEG data and correlated clinical aspects of children with different underlying etiologies—unprovoked first seizure, neonatal hypoxic ischemic encephalopathy, and perinatal stroke—independent of age. These groups are generally at higher risk of developing epilepsy. However, it is not yet possible to predict the patient’s individual risk and assess who would actually benefit from preventive therapy. For this purpose, we will first compare patients with clinical seizures and abnormal EEGs to those at risk but without active epilepsy at the time of the EEG. We hypothesize that HFO rates are higher in children with active seizures/epilepsy than in those at risk of but no active epilepsy. In the next step, we will analyze a subgroup of the above patients that developed epilepsy during the course of a two-year follow-up period. We aim to demonstrate that the occurrence of HFOs precedes the development of epilepsy and that high HFO rates indicate patients more likely to develop epilepsy. Thus, HFOs, as a biomarker of seizure propensity, can inform the testing of future antiepileptic treatments. In addition to the proposed risk groups, many other patients could benefit from the employment of HFOs as an epilepsy biomarker because the risk of the disorder is high in traumatic brain injury, adult stroke, cardiovascular disease, and dementia. Early education and improved prognostication can reduce families’ anxiety as well as insecurity and, therefore, improve quality of life.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professorin Dr. Julia Jacobs-LeVan