26.1 Introduction

Deep brain stimulation (DBS) has been used in an increasing frequency to treat refractory epilepsy. Three randomized clinical trials have been conducted which included patients with temporal lobe epilepsy: the SANTE study ¹ (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy), the Neuropace study ² (which included patients who received both neocortical and hippocampal close-loop stimulation), and a hippocampal DBS study. ³ The results from the SANTE and Neuropace studies were very similar, despite different paradigms and devices: around 15% of the patients became seizure-free. At this point, continuous, direct hippocampal stimulation apparently yielded better results: 50% of the patients became seizure-free after the procedure (▶Fig. 26.1).

26.2 Rationale

The hippocampus itself is often the main epileptogenic region in many patients with temporal lobe epilepsy, especially in patients with mesial temporal sclerosis. Hippocampal resection is able to make 70 to 80% of the patients seizure-free after surgery. ⁴ On the other hand, the hippocampus also represents a major relay for seizure spread and organization in patients with temporal neocortical seizures and in some patients with posterior quadrant foci. Inactivation or modulation of hippocampal activity might lead to seizure blockage or frequency reduction in these patients.

DBS has proven to be effective in a variety of neurological conditions, especially in movement disorders. ⁵ In Parkinson’s disease, for instance, it appears to block the activity of the subthalamic nucleus (STN) or globus pallidus internus, and is able to effectively reduce/block tremor and rigidity in these patients. It became clear that the effect of DBS is not a complete shutdown of the stimulated area (i.e., STN-DBS does not cause hemiballismus); on the other hand, it is clear that DBS can effectively modify the ongoing regional activity.

The hippocampus is part of the Papez circuit and is hard-wired to some of its structures such as the parahippocampus and fornix. Anterior nucleus DBS aimed to treat temporal lobe epilepsy by indirectly reaching the hippocampus and temporal lobe through the Papez circuit; both responsive and direct hippocampal stimulation aimed to do that by acting more directly in the target structure. Hippocampal stimulation (Hip-DBS) is very likely able to modulate the whole limbic system, though regional effects might be more profound. It is not clear yet if unilateral hippocampal stimulation could affect the Papez circuit bilaterally, as could be seen in rats; the hippocampal commissure is basically nonexistent in man, in contrast to rats, in which it is very conspicuous. Close-loop stimulation might prove effective when adequate biomarkers for seizure generation and spread might be defined.

26.3 Development Timeline

Hip-DBS was initially reported in the early 21st century almost simultaneously by the Mexican ⁶ , ⁷ and Belgian teams. ⁸ , ⁹ A small series was also reported from Switzerland, ¹⁰ and a randomized controlled trial was more recently reported from Brazil. ¹¹ These series used open-loop Hip-DBS. The Neuropace study explored closed-loop Hip-DBS.