Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic
therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of
temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of
brain inflammation at disease onset was predictive of spontaneous recurrent
seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator
protein, a biomarker of
inflammation, was imaged by means of positron emission tomography (PET) 2 and 4weeks post-
status epilepticus using [
18F]-PBR111. Translocator
protein was highly upregulated 2weeks post-
status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P<0.001), whereas 4weeks post-
status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P<0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of
disease (acute, latent - first
seizures appearing around 2weeks post-
status epilepticus - and chronic phases), for a total of 12weeks, in order to determine SRS frequency for each subject (range 0.00-0.83SRS/day). We found that regional PET uptake at 2 and 4weeks post-
status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic
epilepsy (P<0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator
protein PET imaging at 2weeks post-
status epilepticus, we accurately predicted the frequency of SRS (R=0.92; R2=0.86; P<0.0001) at the onset of
epilepsy. This study not only demonstrates non-invasive imaging of translocator
protein as a prognostic
biomarker to ascertain SRS frequency, but also shows its capability to reflect the severity of depression-like and sensorimotor-related comorbidities. Our results are an encouraging step towards the development of anti-epileptogenic treatments by providing early quantitative assessment of SRS frequency and severity of comorbidities with high clinical relevance.