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.

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

“…205 Advances in neuroimaging software that allow serial volumetric imaging should allow a more quantitative and detailed analysis of the initial TBI injury and volume changes over time with and without progenitor cell treatment. 201 This approach is already being used in the evaluation of post-traumatic epilepsy 206,207 and Alzheimer's disease. 208 Resting Finally, newer MRI approaches which allow imaging of inflammation could provide insights into the course and distribution of inflammation throughout the initial and secondary injuries with and without progenitor cell treatment in both TBI and SNHL.…”

“…Advances in neuroimaging software that allow serial volumetric imaging should allow a more quantitative and detailed analysis of the initial TBI injury and volume changes over time with and without progenitor cell treatment 201 . This approach is already being used in the evaluation of post‐traumatic epilepsy 206,207 and Alzheimer's disease 208 . Resting state blood oxygen level dependent (BOLD) sequences and functional MRI (fMRI) have been used to analyze connectivity between various brain regions.…”

Posttraumatic epilepsy after traumatic brain injury and prophylactic administration of antiepileptic drugs

“… 6 Increasing computed tomography findings identify PTE outcomes 3–5 years following TBI: specially, 75% of patients with hemorrhagic contusions and related extracerebral hematoma had late PTE; only 16.7% of patients presenting intracerebral hemorrhage alone without extracerebral hematoma developed late seizures. 11 A recent pilot study further reported that lesions in the temporal lobe rather than overall injury severity were associated with the highest risk of PTE. 11 Brain blood barrier abnormalities predicting delayed, long-lasting seizures near the injured tissue are detectable on dynamic contrast-enhanced magnetic resonance imaging, gadolinium-enhanced T1, and T2-weighted fluid attenuated inversion recovery.…”

“… 11 A recent pilot study further reported that lesions in the temporal lobe rather than overall injury severity were associated with the highest risk of PTE. 11 Brain blood barrier abnormalities predicting delayed, long-lasting seizures near the injured tissue are detectable on dynamic contrast-enhanced magnetic resonance imaging, gadolinium-enhanced T1, and T2-weighted fluid attenuated inversion recovery. 11 …”

“… 11 Brain blood barrier abnormalities predicting delayed, long-lasting seizures near the injured tissue are detectable on dynamic contrast-enhanced magnetic resonance imaging, gadolinium-enhanced T1, and T2-weighted fluid attenuated inversion recovery. 11 …”