Optimising deep brain stimulation for treatment of epilepsy: a networks based approach

This PhD provides the opportunity to work with clinicians and scientists from GOS Institute of Child Health and a UK based biotechnology SME, Amber therapeutics, to develop deep brain stimulation (DBS) techniques for the treatment of childhood epilepsy.

Epilepsy is a common and chronic neurological condition affecting 1% of the population. One-third of children with epilepsy continue to have epileptic seizures despite multiple trials of anti-seizure medications. For selected candidates with focal-onset seizures, epilepsy surgery to resect the epileptogenic zone is a therapeutic option and is associated with high rates of seizure freedom.

However, for those patients with a non-identifiable seizure-onset zone or generalised-onset seizures, and drug resistance, there currently exist few efficacious treatment options. These children suffer multiple co-morbidities and reduced quality of life. There is a pressing need to develop effective therapy.

Increasingly epilepsy is considered a network disorder: these network disorders may underpin not only the seizure disorder but also associated co-morbidities such as cognitive, behavioural and social communication abnormalities. A small number of studies have shown that the network alterations gleaned from MRI and EEG are associated with clinical response to DBS therapy and may give information to its therapeutic mechanisms.

The thalamus has long been implicated as a critical propagation hub in the epileptogenic network of patients with drug-resistant seizures and is a focus for our current research. The centromedian nucleus of the thalamus is the stimulation target for our current studies and therefore an area of investigation for the detection of preoperative biomarkers of treatment success.

DBS is an emerging therapy that reduces seizure frequency and severity by preventing the propagation of epileptiform activity in the brain. There is provisional evidence that DBS is effective in treating patients with both focal and generalised onset. DBS provides a unique opportunity to modulate brain networks yet effects on brain networks and optimal stimulation paradigms are not yet well elucidated.