Paroxysmal Slow Wave Events as a diagnostic and predictive biomarker for post-traumatic epilepsy

Abstract

Traumatic brain injury (TBI) is a major global health concern, affecting more than 40 million people annually. While most cases are mild and present with light symptoms, repeated mild injuries can result in delayed brain pathologies, including cognitive decline, neuropsychiatric complications, and post-traumatic epilepsy (PTE). PTE refers to recurring, unprovoked seizures occurring at least one week after TBI. While the link between moderate to severe TBI and PTE is well established, the epileptogenesis after repetitive mild TBI (rmTBI) is seldom studied. Currently, there are no biomarkers to identify those at risk of developing PTE, and its diagnosis is challenging. Here, we used a rat model to study PTE following rmTBI and assessed human EEG data to identify potential biomarkers for PTE. We employed a closed head TBI model to induce rmTBI, and recorded brain activity using electrocorticography (ECoG) between 2- and 6-months post-injury. Behavioral assessments and post-mortem analysis were also conducted. In humans, we analyzed EEG recordings from the Temple University database to investigate the potential of EEG-derived features for diagnosing PTE. At 6 months post injury, 70% of rmTBI animals developed PTE, compared to 22% in the control group (P=0.01). While neurological assessments following injury did not predict PTE, paroxysmal slow wave events (PSWEs) were found to be a reliable biomarker for PTE prediction. In humans, the percentage time in PSWEs was significantly elevated in PTE patients with epileptiform activity. In conclusion, we suggest PSWEs as a non-invasive, cost-effective biomarker for PTE in rodents and human patients.