Safety and feasibility of nucleus accumbens stimulation in five patients with epilepsy

Abstract

In five adult patients with intractable partial epilepsy, safety and feasibility of chronic bilateral electrical stimulation of the nucleus accumbens (NAC) were assessed, also providing initial indications of therapeutic efficacy. Concurrent medication remained unchanged. In this phase 1 trial, clinical outcome parameters of interest were Quality of Life in Epilepsy questionnaire (QOLIE-31-P), Beck Depression Inventory, Mini International Neuropsychiatric Interview, neuropsychological testing, and Liverpool Seizure Severity Scale. Those data were obtained after 6 months of NAC stimulation and compared to the equivalent assessments made directly before implantation of electrodes. Additionally, monthly frequencies of simple partial seizures, complex partial seizures (CPS), and generalised tonic-clonic seizures (GTCS) were assessed during 3 months before electrode implantation and at the end of 6-month NAC stimulation. Proportion of responders, i.e. ≥50 % reduction in frequency of disabling seizures (sum of CPS and GTCS), was calculated. Main findings were unchanged psychiatric and neuropsychological assessment and a significant decrease in seizure severity (p = 0.043). QOLIE-31-P total score trended towards improvement (p = 0.068). Two out of five participants were responders. The median reduction in frequency of disabling seizures was 37.5 %. In summary, we provide initial evidence for safety and feasibility of chronic electrical stimulation of the NAC in patients with intractable partial epilepsy, as indicated by largely unchanged neurocognitive function and psychiatric comorbidity. Even though our data are underpowered to reliably assess efficacy, the significant decrease in seizure severity provides an initial indication of antiictal efficacy of NAC stimulation. This calls for larger and at best randomised trials to further elucidate efficacy of NAC stimulation in patients with pharmacologically intractable epilepsy.

Fig. 1

Distal electrode position in the NAC, depicted postoperatively with CT-fused presurgical T1–MRI in coronal and axial view (red circles). Both distal contacts of the quadripolar electrodes were placed in the NAC as intended, the third contact within the transition area to the medial border of the abutting internal capsule and the highest, i.e. the fourth contact at a point in the most medial part of the capsule or in the transition area to the caudate. Asterisks mark the medial and ventral border of the NAC region. The red square depicts an electrode lead to the left anterior nucleus of thalamus

Fig. 2

Time course of mean frequency of simple partial (SPS), complex partial (CPS) and generalised tonic–clonic seizures (GTCS). Following 3 months of seizure survey before electrode implantation (black arrow, surgery), stimulation of the nucleus accumbens (NAC) was started 22.4 days (±10.5) days post-surgery (red arrow, DBS on). Frequency of all seizure types was assessed 3 and 6 months after onset of NAC stimulation (black arrow, 6-month follow-up). After 6 months of NAC stimulation, frequency of CPS has increased, whereas that of GTCS has decreased. DBS: deep brain stimulation