Emerging technologies and genetic mechanisms at the American Epilepsy Society Annual Meeting

Written by Alice Weatherston

This year the American Epilepsy Society’s (AES) Annual Meeting, which took place in Philadelphia on 4–8th December, highlighted the vast range of fascinating research taking place within the field of epilepsy. Bringing together more than 5000 professionals from across clinics, labs and industry, the abstracts presented discussed some of the key issues and advances in epilepsy research over the past year.
Two emerging themes from the meeting centered on increasing our understanding of the genetic basis of the condition for improved treatments as well as the development of advanced technologies for epilepsy management. We discuss these research themes and the related studies below.
Digital health and technologies
Novel technologies have provided a wealth of opportunity throughout neurological research; through innovative imaging techniques, genetic manipulation and even effective treatments for several chronic neurological diseases. In addition to this, focus is now also being placed on the role of technology in patient management and the new era of digital health – a topic that was explored broadly at AES 2015.

So far the role of technological devices in epilepsy monitoring specifically has been restricted due to concerns over device reliability. However, abstracts at AES highlighted the range of opportunities for the use of technology to enhance management of epilepsy in patients. The use of new technologies for seizure control and treatment was also widely discussed.

Technologies for monitoring

Notably, two new potentially effective personal monitoring devices were unveiled. Both devices have been designed to monitor clinical and subclinical seizure activity in the home environment and to provide an early warning system for seizure onset.

The devices included the EEG patch developed by The University of Utah and Epitel Inc. (both UT, USA), a two electrode, waterproof patch designed to collect seizure count data directly from the scalp, and the remarkably effective arm-worn Brain Sentinel® GTC Seizure Detection and Warning System. In a presentation of data from a Phase III, double-blind, prospective multicenter trial the Brain Sentinel® GTC Seizure Detection and Warning system indicated 100% seizure sensitivity for generalized tonic-clonic seizures (GTCS) through the recording of surface electromyography and audio data.

Finally, researchers from Johns Hopkins University (MD, USA) presented their work on machine learnt patient-specific algorithms in an effort to resolve reliability issues with current seizure detection technologies. The team ‘trained’ a seizure detection machine to continually learn new algorithms, allowing for the natural variation in seizure onset patterns and locations to be detected.

Technologies for treatment

Three further key studies highlighted emerging technologies for the control and treatment of epilepsy. Researchers at the University of Toronto (ON, Canada) presented a new closed-loop device for delivering a short electrical signal at the early or late stages of a seizure, reducing seizure frequency in some patients by up to 90%. Another study demonstrated the potential of electrodermal biofeedback, a technique that utilizes alterations in the skin’s electrical activity as an indication of seizures and a method for controlling them in drug-resistant epilepsy. Results indicated that one month of biofeedback training reduced seizure frequency by on average 40%.

Another team looked to enhance the power of the Responsive Neurostimulation System (RNS), currently the only FDA-approved intracerebral neuromodulation therapy for patients with drug-resistant focal epilepsy. The study investigated the safety and efficacy of a carbon nanotube-based strategy for expanding the area of influence of the RNS. Cytotoxicity testing and computational and experimental modeling confirmed the safety of the functionalized carbon nanotubes and demonstrated that the nanotubes could effectively expand the activation area of the RNS.
Unravelling the genetics
Genetic studies from AES 2015 spanned a range of topics; from identifying key developmental mutations leading to the onset of epilepsy, to personalizing medical approaches to the treatment of the condition. Personalized medicine in epilepsy is emerging as an area of research increasingly important for the ~30% of epilepsy patients that are resistant to antiepileptic drugs. Perhaps most notably, the utilization of pharmacogenomic testing and pharmacogenetic association studies have received primary attention within the field, and AES 2015 abstracts were no exception.

The Epi4K Consortium, who have previous experience in the identification of de novo mutations in childhood epileptic encephalopathies, confirmed the association with epileptic encephalopathy of seven genes previously identified (ALG13, CACNA1A, DNM1, GABRB3, GNAO1, IQSEC2) and presented the first report of SLC1A2 as an epilepsy gene.

A range of studies also explored the role of the influential SCN8A mutation in epilepsy. Specifically a missense mutation, N1768D, was found to alter sodium currents, resulting in the disruption of electrical signaling in the hippocampus, and a group of Danish insitutions presented results from an investigation broadening the forms of epilepsy linked to SCN8A mutations.

Another two key studies utilized whole-exome sequencing to diagnose and recommend personalized treatments for epilepsy patients and to evaluate the efficacy of pre-existing FDA-approved drugs for treatment, respectively.

At the British Columbia Children’s Hospital and the University of British Columbia (both BC, Canada), whole-exome sequencing revealed aberrations in 16 genes, resulting in definite/likely diagnoses in 16 patients and a possible diagnosis in 11 patients out of a total of 50. In half of the definite/likely diagnoses the whole-exome sequencing also influenced the treatment decision for the patients.

Finally, Emory University (GA, USA) researchers explored the potential of FDA-approved NMDA receptor antagonists in reducing faulty cell signaling between nerve cells, in an effort to decrease seizure frequency. Analysis of the two mutations of the NMDA receptor subunit indicated increased sensitivity to agonists in comparison to non-mutated receptors, potentially leading to a prolonged synapse response and overactivation of the receptors. NMDA receptor antagonists may therefore provide a novel therapeutic option.

Overall, it is clear to see that despite the obvious need for and advantages of new technologies within epilepsy research and treatment there is still essential work that is needed to fully understand condition development and it’s genetic basis. It will be fascinating to see the progress made in these areas throughout 2016.

To read more about the studies highlighted, visit the American Epilepsy Society Annual Meeting website.

Sources: American Epilepsy Society Annual Meeting press releases