High-frequency oscillations during hypersynchronous-onset and low-voltage fast-onset temporal lobe seizures: Pathophysiological links and clinical implications

• Applicant: Dr. Jan Schönberger
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Pediatric and Adolescent Medicine
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 361763863

Temporal lobe epilepsy (TLE) is the most frequent partial epilepsy and often drug-resistant. If patients have generalized tonic-clonic seizures (GTCSs), their safety and quality of life is severely impaired. It is largely unclear why some seizures generalize secondarily, while others do not. Recent rodent model studies suggest that mesial temporal lobe seizures arise based on different cellular mechanisms, which are reflected by specific electroencephalography (EEG) seizure-onset and propagation patterns. New approaches to intracranial EEG analysis might be helpful in revealing these mechanisms in TLE patients, and possibly allow to estimate the likelihood of secondary generalization shortly after seizure onset. This hypothesis is based on two animal model findings: GTCSs were often observed after low-voltage fast (LVF) activity, whereas hypersynchronous-onset (HYP) seizures often remained focal. Besides, these two seizure-onset patterns were accompanied by different sub-bands of high-frequency oscillations (HFOs): LVF activity was associated with an increase in ripple activity (80-200 Hz), while HYP seizures co-occurred with fast ripples (250-500 Hz). In human beings these correlations have not yet been demonstrated, although both LVF and HYP pattern have been reported in TLE patients. HFOs are a promising biomarker of pathogenic networks in epilepsy patients, and converging lines of evidence indicate an involvement in ictogenesis as well. The first goal of this project is to demonstrate in TLE patients that fast ripples reflect a distinct pattern of neuronal activity that plays a key role in the initiation of HYP-onset seizures. Ripples, on the other hand, are to be characterized as a correlate of the cellular interactions that generate LVF-onset seizures. The second goal is to show that the risk of GTCSs is low if fast ripples occur in the seizure-onset zone and high if ripple-band activity is increased in onset and propagation areas. If this was true, HFO analysis might also be helpful for therapeutic decision making in TLE patients.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Jean Gotman, Ph.D.