No abstract

BackgroundRecently, inflammatory cascades have been suggested as a target for epilepsy therapy. Positron emission tomography (PET) imaging offers the unique possibility to evaluate brain inflammation longitudinally in a non-invasive translational manner. This study investigated brain inflammation during early epileptogenesis in the post-kainic acid-induced status epilepticus (KASE) model with post-mortem histology and in vivo with [18F]-PBR111 PET.MethodsStatus epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while controls (N = 9) received saline. Translocator protein (TSPO) expression and microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [18F]-PBR111 volume of distribution (Vt) in volume of interests (VOIs) was quantified by means of kinetic modelling and a VOI/metabolite-corrected plasma activity ratio.ResultsAnimals with substantial SE showed huge overexpression of TSPO in vitro in relevant brain regions such as the hippocampus and amygdala (P < 0.001), while animals with mild symptoms displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO expression was associated with OX-42 signal but without obvious cell loss. Similar in vivo [18F]-PBR111 increases in Vt and the simplified ratio were found in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01).ConclusionBoth post-mortem and in vivo methods substantiate that the brain regions important in seizure generation display significant brain inflammation during epileptogenesis in the KASE model. This work enables future longitudinal investigation of the role of brain inflammation during epileptogenesis and evaluation of anti-inflammatory treatments.

Experiments in rats and PDE10A knock-out mice indicate that (18)F-JNJ41510417 binds specifically and reversibly to PDE10A in the striatum, suggesting that this new fluorinated quinoline derivative is a promising candidate for in vivo imaging of PDE10A using PET.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.