Abstracts

Rationale: Inflammation has been implicated in the underlying pathophysiology of drug resistant epilepsy. Elements of innate immunity such as IL-6 have been reported as elevated in epilepsy patient plasma. We hypothesized that sICAM5, a telencephalon-specific immunomodulator, as well as other chemokines and cytokines, would differentiate between epilepsy patient plasma and non-epileptic seizure patient plasma (controls). Methods: After obtaining IRB approval, patients in the UPenn EMU who consented had a single plasma sample drawn. The citrated sample was spun in a refrigerated centrifuge for 10 minutes and the supernatant was then stored at -80 degrees C until analyzed. The samples were analyzed using a MesoScale Sector 6000 electrochemiluminescent multiplexed ELISA platform. Analytes included not only sICAM5, but also GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-6, IL-8, TNF- α. We compared the epilepsy patient samples to the control samples using a T-test. Results: Two epilepsy patient samples and three psychogenic seizure patient samples were collected. The epilepsy patients averaged 33 years of age. One of the epilepsy patients had a history of oligodendroglioma with a seizure frequency in the Epilepsy Monitoring Unit (EMU) of 0-3 seizures per day, who was treated with lamotrigine, levetiracetam, and pregabalin. The other patient has tuberous sclerosis and averaged 28 seizures per day in the EMU, treated with levetiracetam, felbamate, lamotrigine and phenobarbital. The non-epileptic controls averaged 36 years old; treated with levetiracetam, lamotrigine, or no medication; and averaged less than 1 non-epileptic event per day. Three T-cell related analytes were strongly positive, while differences among the rest of the analytes were not significant. In epilepsy patients, sICAM5, an anti-inflammatory modulator, was present, but below the lower limit of detection (LLOD) relative to the standard curve. We estimated the concentration of sICAM5 in these epilepsy patients to be 0.1ng/ml. By contrast, the controls had an average value of 11.87 ng/ml, the difference being very significant (p = 0.0017). IL-2 levels in epilepsy patients were elevated: 4.24 pg/ml, versus 0.47 pg/ml in controls (P=0.0012). INF-gamma levels in epilepsy patients werealso elevated: 22.19 pg/ml, versus 2.09 pg/ml in controls (p=0.0040). Conclusions: The lesional drug resistant epilepsy patients show a pattern of plasma inflammatory markers consistent with a pro-inflammatory condition, supporting the inflammation hypothesis of drug resistant epilepsy. The pattern shows that the anti-inflammatory-T cell modulator sICAM5 is low, while the proinflammatory T-cell modulator IL-2 is high. In addition IFN-gamma, a typical product of T-cell activation is high. This pattern is consistent with persistent involvement of T-cells in the epileptic inflammatory process. At least in lesional drug resistant epilepsy, sICAM5 and other T-cell immunomodulators may be biomarkers of disease.