Research Summary

     

    Epilepsy [1, 2] is the second most common neurological disorder after strokes affecting over 1% of the world’s population [3]. In Spain, epilepsy approximately affects 400.000 individuals and there are about 20.000 new diagnostics per year [4]). In about 65% of patients with epilepsy, seizures are well-controlled with currently available anti-epileptic drugs [5, 6]. Another 5% could profit from resective therapy, i.e., from surgically removing a circumscribed region of the brain that generates seizures. In these cases, there is a 60–70% chance of gaining long-term remission [7]. Unfortunately, even with maximal available therapy, 30% of patients with epilepsy continue to have uncontrolled seizures, resulting in impaired quality of life and increased risk of injury, disability, and death. Thus, other therapeutic options for refractory epilepsy are needed.

     

    Within the framework of ICT for healthcare applications, this Project aims to make progress in the state-of-the-art of energy-efficient implantable devices for epilepsy care [8]. Such devices can be used for: (1) early identification of patients at risk for intractability, (2) accurately localizing abnormal neural activity prior to seizures in patients with uncontrolled epilepsy, and (3) developing novel therapeutics for these medically intractable epilepsies while minimizing or eliminating side effects.

     

    Different strategies for the treatment of epilepsy not responding to anticonvulsive medication, such as direct cooling [9], local drug delivery [10], magnetic field irradiation [11] and optical excitation [12], have been investigated but the most promising results have been obtained through electrical stimulation, in which this Project focuses.

     

    So far, the vagus nerve electrical stimulator (VNS) is the only FDA (U.S. Food and Drug Administration) approved medical device for the treatment of epilepsy (Cyberonics [13]). It is an open-loop (or non-responsive) device in that stimulation pulses are applied continuously and periodically on the brain tissue, no matter if a seizure is detected or not. Using this scheduled stimulation device, less than 3% of the treated patients obtain seizure freedom and only 30 to 40% show a reduction in seizure frequency of more than 50%. Another open-loop device which is currently seeking FDA approval (Medtronic [14]) relies on deep brain stimulation (DBS) of the anterior nucleus of the thalamus. A pilot study with humans showed a median reduction in total seizure frequency of about 50-60%, however, no patient became seizure-free and most of them experienced related adverse events which could be treated with changes to medications or stimulation settings. In both cases, the clinical tests revealed that a major problem with non-responsive devices is that intermittent or periodic stimulation tends to decrease in efficacy over time, due to the neurons acclimating to the stimulus [15]. A third device which is currently undergoing clinical studies, the RNS system by NeuroPace [16], follows a different approach. It uses a cranially implanted closed-loop architecture that triggers the stimulus to the immediate pre-ictal period, decreasing overall stimulus delivery over time and thus the likelihood of desensitization and neuronal damage. Thanks to this responsive strategy, the RNS system has demonstrated higher safety and tolerability but, unfortunately, the preliminary evidence for efficacy is still weak. In a feasibility study with 24 patients, the responder rate (≥50% reduction in seizures) was 43% for complex partial seizures and 35% for total disabling seizures. Thus, although all three devices, and many other non-commercial methods reported in the literature, are effective to some extent, they provide only modest improvement [17].

     

    Two major reasons are behind these moderate results. On the one hand, the basic mechanisms underlying the generation of seizures remain largely unknown except for certain distinct types of epilepsies, such as photosensitive epilepsy [18]. On the other hand, most of the devices reported so far were all developed several years ago, prior to new technological breakthroughs that are currently shaping the neuroscience field. For instance, current electrical stimulators, which are based on simple pacemaker technology and passive implanted electrodes, have experienced little changes since the advent of DBS in 1987. Therefore, it is likely that a better understanding of the seizure-generating (ictogenic) mechanisms (see [19] and references therein), fueled by the use of improved techniques and materials, may foster the design of more efficient epilepsy therapy devices.
Last update:
July 17, 2014