Epilepsy is the most common chronic neurological disease. A correct diagnosis and prognosis remains a clinical challenge and needs the application of multiple criteria including patient history, brain MRI and electroencephalography recordings. The most reliable method is long-term video-EEG which is very costly, low through-put and, in Ireland, has very limited availability.Consequently, the majority of epilepsy patients are treated on the basis of the clinical features alone, leading to possible misdiagnosis.
Thus, there is an urgent need to develop biomarkers that support an accurate diagnosis and prognosis. These biomarkers have to be easily accessible, easily measurable and preferably linked to disease pathology.
Adenosine is an endogenous substance released in the brain after seizures and adenosine augmenting treatments have been proposed as novel therapy options in epilepsy. Adenosine is present in the lower micro molar range in the blood; however, no data on seizure-induced increases of adenosine in the blood have been reported to date. This may be because measurements to quantify blood adenosine levels depended on laboratory techniques such as HPLC which are poorly-suited to biomarker work.
Recently developed adenosine biosensors enable us now to detect changes in blood adenosine levels rapidly and reliably. These biosensors are suitable for point of care testing as they are easy to handle, require minimal equipment and a minimum blood volume. Pilot data by the applicant now determined a dramatic increase in blood levels of adenosine after seizures in different animal models and patients.
The project will undertake clinical and pre-clinical studies to establish the relationship between blood adenosine levels and seizure type and severity, timing of sampling and pathologic outcome. Together, these studies will establish blood adenosine measurement as a novel, sensitive and specific marker of seizure activity which can be used for seizure diagnosis and for prognosis of disease progression in patients.
