Low and High Frequency Hippocampal Stimulation for Drug-Resistant Mesial Temporal Lobe Epilepsy

Abstract

ObjectiveElectrical stimulation of the hippocampus offers the possibility to treat patients with mesial temporal lobe epilepsy (MTLE) who are not surgical candidates. We report long‐term follow‐up results in five patients receiving low or high frequency hippocampal stimulation for drug‐resistant MTLE.Materials and MethodsThe patients underwent stereotactic implantation of quadripolar stimulating electrodes in the hippocampus. Two of the patients received unilateral electrode implantation, while the other three received bilateral implantation. Stimulation of the hippocampal electrodes was turned ON immediately after the implantation of an implantable pulse generator, with initial stimulation parameters: 1 V, 90–150 μs, 5 or 145 Hz. The frequency of seizures was monitored and compared with preimplantation baseline data.ResultsTwo men and three women, aged 27–61 years were studied, with a mean follow‐up period of 38.4 months (range, 30–42 months). The baseline seizure frequency was 2.0–15.3/month. The five patients had an average 45% (range 22–72%) reduction in the frequency of seizures after hippocampal stimulation over the study period. Low frequency hippocampal stimulation decreased the frequency of seizures in two patients (by 54% and 72%, respectively). No implantation‐ or stimulation‐related side effects were reported.ConclusionsElectrical stimulation of the hippocampus is a minimally invasive and reversible method that can improve seizure outcomes in patients with drug‐resistant MTLE. The optimal frequency of stimulation varied from patient to patient and therefore required individual setting. These experimental results warrant further controlled studies with a large patient population to evaluate the long‐term effect of hippocampal stimulation with different stimulation parameters.

Deep brain stimulation for drug‐resistant epilepsy

“…27 Most significantly, descriptive analysis of stimulation parameters used during the long-term follow-up of the SANTE cohort found no favorable parameters in frequency, voltage, or pulse width. 47 There were no differences between cycling and continuous stimulation, 23 and no association between output voltage and seizure reduction. 42 Yet, lowfrequency (5 Hz) HC stimulation seemed optimal in other patients with hippocampal sclerosis.…”

“…Robust clinical trials demonstrate seizure frequency reductions of 40% following short-term ANT stimulation, 3 and 26%-40% following short-term HC stimulation, [34][35][36][37] in patients with primarily focal epilepsies. Pooled responder rates (seizure reduction ≥50%) were >70% for both ANT 9,18,19,[21][22][23][24][26][27][28][29][30][31][32][33] and HC-stimulated 13,14,[34][35][36][41][42][43][44][45][46][47] patients. Indeed, a recent meta-analysis found statistically significant reductions in seizure frequency secondary to ANT-DBS (high-quality evidence) and HC-DBS (moderate-quality evidence), but not for any other targets.…”

“…For instance, HC stimulation has been trialed empirically for temporal epilepsies, 13,14,[34][35][36][37][39][40][41][42][43][44][45][46][47] and CMT stimulation seems more effective for Lennox-Gastaut syndrome and in generalized seizures. For instance, HC stimulation has been trialed empirically for temporal epilepsies, 13,14,[34][35][36][37][39][40][41][42][43][44][45][46][47] and CMT stimulation seems more effective for Lennox-Gastaut syndrome and in generalized seizures.…”

“…35,36 Perhaps for HC stimulation, it is worthwhile considering 2 distinct subpopulations-one with normal MRIs and the other with hippocampal sclerosiswith the hypothesis that neuronal reduction and/or electrical resistance in sclerosed neural tissue may hinder stimulation. 47 Patients without structural abnormality on MRI also responded better to ANT-DBS, 29 although another study found no such association. 47 Patients without structural abnormality on MRI also responded better to ANT-DBS, 29 although another study found no such association.…”

Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation

“…In this study, we expand on the role of waveform by introducing a novel concept: although it is known that stimulation frequency of pulses is important (when the “frequency” of stimulation is reported, this typically indicates the timing of pulses and not the signal frequency content), it is also important to consider high-order power (frequency content in harmonics across the spectrum). Indeed, these results may change our interpretation of low vs. high pulse frequency stimulation, as low-frequency with harmonics may have similar harmonic components as high-frequency stimulation3940414243. Conversely, these results may impact very high (kHz) pulse frequency stimulation where sub-harmonics may be important, noting that pulse-shapes influence harmonics4445464748.…”