Imaging biomarkers of posttraumatic epileptogenesis

Abstract

Traumatic brain injury (TBI) affects 2.5 million people annually within the United States alone, with over 300 000 severe injuries resulting in emergency room visits and hospital admissions. Severe TBI can result in long-term disability. Posttraumatic epilepsy (PTE) is one of the most debilitating consequences of TBI, with an estimated incidence that ranges from 2% to 50% based on severity of injury. Conducting studies of PTE poses many challenges, because many subjects with TBI never develop epilepsy, and it can be more than 10 years after TBI before seizures begin. One of the unmet needs in the study of PTE is an accurate biomarker of epileptogenesis, or a panel of biomarkers, which could provide early insights into which TBI patients are most susceptible to PTE, providing an opportunity for prophylactic anticonvulsant therapy and enabling more efficient large-scale PTE studies. Several recent reviews have provided a comprehensive overview of this subject (Neurobiol Dis, 123, 2019, 3; Neurotherapeutics, 11, 2014, 231). In this review, we describe acute and chronic imaging methods that detect biomarkers for PTE and potential mechanisms of epileptogenesis. We also describe shortcomings in current acquisition methods, analysis, and interpretation that limit ongoing investigations that may be mitigated with advancements in imaging techniques and analysis.

Keywords: MRI; biomarkers; imaging; posttraumatic epilepsy; traumatic brain injury.

Figure 1:

Patients who suffer from traumatic brain injury (TBI) may experience four distinct phases. Seizures that occur within 24 hours are immediate seizures, those that occur between 24 hours and 7 days after injury are early posttraumatic seizures (early PTS), and those that occur after 7 days are late posttraumatic seizures (late PTS). The latent period between the injury and the first late PTS can last 10 or more years after the TBI.