Identifying non-invasive imaging markers of neuroinflammation in treatment pharmacoresistant epilepsy

Approximately 6 million people in Europe have active epilepsy, making it the most common serious neurological disorder. The mechanisms underlying the development of epilepsy are still poorly understood, but there is accumulating evidence that inflammation plays an important role. However, the understanding of neuroinflammation in human epilepsy is in its infancy, and imaging studies of neuroinflammation in epilepsy are largely restricted to experimental animal models, or human positron emission tomography studies, a scarce technology. There is a need to identify biomarkers of inflammation using more readily available technologies, such as magnetic resonance imaging (MRI) and serum biomarkers.

Mechanistic blood biomarkers could greatly enhance drug discovery by providing novel therapeutic targets, enriching trial populations and facilitating early surgical evaluation in drug-resistance. The primary goal of this study is to detect signatures of brain inflammation in people with epilepsy using MRI markers of neuroinflammation and simultaneous correlation with blood serum markers of peripheral inflammation. This will be investigated using free-water diffusion imaging and blood serum analysis.

Understanding brain connectivity in epilepsy is also important given that even focal seizures may be generated in context of distributed epileptogenic brain networks. Whether the properties of structural and functional networks have significant for seizure control after pharmacological treatment remains unknown. Therefore, a secondary goal of this study is to determine whether structural and functional MRI measures of brain connectivity can differentiate between patients with well controlled and poorly controlled focal seizures. This will be investigated using imaging measures of brain connectivity.

The target population for this work is 15 patients with well-controlled focal epilepsy, 15 patients with poorly controlled focal epilepsy, and 15 healthy controls. Patients will be recruited from the Walton Centre NHS Foundation Trust (WCFT), while healthy volunteers will be recruited via email sent out across the University of Liverpool and WCFT. MRI scanning and blood sampling will both take place at the Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, following assessment for suitability for MRI scanning as per standard clinical protocol. Advanced image analysis techniques will be used to investigate neuroinflammation and to model brain connectivity.

If it is identified that neuroinflammation is prevalent in only patients with uncontrolled seizures, this may suggest that MRI markers of neuroinflammation could be used as a non-invasive biomarker to predict treatment response in epilepsy. The ultimate goal of this programme of work is to be able to reliably prospectively stratify people with a new diagnosis of epilepsy as to their likely chance of future seizure control.