There is currently no approved treatment that can prevent onset of spontaneous seizures associated with brain injury, and many cases of PTE are refractory to antiseizure medications. Post-traumatic epilepsy (PTE) is one of the most devastating long-term, network consequences of traumatic brain injury (TBI). 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.
In this review, we describe acute and chronic imaging methods that detect biomarkers for PTE and potential mechanisms of epileptogenesis. Several recent reviews have provided a comprehensive overview of this subject (Neurobiol Dis, 123, 2019, 3 Neurotherapeutics, 11, 2014, 231). 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. 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. 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. Severe TBI can result in long‐term disability. 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. These findings point to iron deposition as a key factor in the development of ICCs after developmental ZIKV infection. Behavioral tests conducted at 5–6 weeks of age revealed greater deficits in mice with the most extensive iron deposition and calcification of subcortical regions, such as thalamus. Microglial activation was widespread initially and later delineated the sites of ICC formation. A regional analysis of the brains of susceptible mice (C57BL/6J and 129S1/SvImJ strains) revealed the presence of iron initially in regions containing many ZIKV-immunoreactive cells, but then spreading to regions containing few infected cells, most notably the thalamus and the fasciculus retroflexus. Brain iron deposits were evident by Perls’ staining at 2 weeks post infection, becoming increasingly dense and coinciding with calcium buildup and the formation of ICCs. Here, we examined the time course of ICC development and the role of iron deposition in this process, in 3 genetically distinct inbred strains of mice. Using a mouse model of developmental ZIKV infection, we reported widespread calcifications in the brains of susceptible mice that correlated in multiple ways with the behavioral deficits observed. Intracranial calcifications (ICC) are the most common neuropathological finding in the brains of children exposed in utero to the Zika virus (ZIKV).
These efforts are likely to produce both new biomarkers and treatment targets for PTE. inflammation and changes in functional and structural brain-wide connectivity. Accumulating evidence from ongoing preclinical studies in TBI support insight into processes involved in epileptogenesis, e.g. Preclinical imaging data from the posttraumatic brain are rich in information, yet examination of their specific relevance to epilepsy is lacking. Experimental models and preclinical longitudinal, multimodal imaging studies allow follow-up of complex cascade of events initiated by traumatic brain injury, as well as monitoring of treatment effects. Some promising imaging biomarker candidates for posttraumatic epileptogenesis have been identified, but more are required to provide the specificity and sensitivity for accurate prediction. A long latent phase offers a potential window for prophylactic treatment strategies to prevent epilepsy onset, provided that the patients at risk can be identified. Posttraumatic epilepsy (PTE) is a major neurodegenerative disease accounting for 20% of symptomatic epilepsy cases.