Authors :
Hugh Simpson, MBBS, PhD – Alfred Health; Katherine Nickels, MD – Mayo Clinic; Vaclav Kremen, PhD – Mayo Clinic; Vladimir Sladky, B . Eng. – Mayo Clinic; Benjamin Brinkmann, PhD – Mayo Clinic; Kai Miller, MD, PhD – Mayo Clinic; Jamie Van Gompel, MD – Mayo Clinic; Brian Lundstrom, MD, PhD – Mayo Clinic; Gregory Worrell, MD, PhD – Mayo Clinic; Nicholas Gregg, MD – Mayo Clinic
This is a Late-Breaking abstract.Rationale: Electrical brain stimulation for drug-resistant epilepsy is a rapidly evolving field. Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has high quality evidence for efficacy in focal epilepsy, while the role of DBS of other nuclei, such as the pulvinar nucleus, is unclear. In addition, the
utility of trial thalamic stimulation in selecting candidates for chronic stimulation during presurgical evaluation with intracranial EEG is uncertain.
Methods: A retrospective review was undertaken of all patients who had pulvinar sampling as part of routine presurgical evaluation and a trial of therapeutic stimulation during stereo-EEG (sEEG). Two patients met the inclusion criteria, both of whom had a posterior quadrant seizure onset zone. For comparison with ANT stimulation we screened a cohort of 5 individuals with mesial temporal lobe epilepsy who were implanted with a brain sensing and stimulation device (investigational Medtronic Summit RC+S™) that sampled bilateral ANT and hippocampus (HC). Of these, three received high frequency thalamic stimulation and were included in the study. _x000D_
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Thalamic stimulation was delivered with an amplitude of 3-5.8 mA, 90-200 us pulse width, at 145 Hz in a duty cycle pattern (on 1 minute, off 3-5 minutes). Patients were considered responders if a clear suppression of interictal epileptiform activity (IEA) was observed during periods of thalamic stimulation. This study was approved by the Mayo Clinic Institutional Review Board.
Results: For all five patients, both ictal and interictal epileptiform activity was seen in the thalamus (pulvinar or ANT) and cortical SOZ (parieto-occipital cortex or HC) channels. Three patients were considered responders to trial stimulation; one of the two pulvinar patients (Figure 1), and two of the three ANT patients. _x000D_
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A dependence on current amplitude was evident in the responses to trial stimulation. All three responders showed suppression of IEA with a current greater than 4 mA. Two of these three showed responses at 5 mA but not at 3 mA. The two non-responders (without suppression of IEA) were limited to a total current of 4 mA or less, due to an intolerance to higher amplitudes. _x000D_
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The electrophysiologic effects of stimulation were explored in more detail in the patient who responded to pulvinar stimulation. High frequency pulvinar stimulation showed a dramatic reduction in cortical interictal epileptiform activity during ‘stimulation on’ periods, with prompt return of discharges during the "stimulation off" phase (Figure 1). Quantitative review of the sEEG data corroborated the clinical observations
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Conclusions: High-frequency stimulation of the pulvinar nucleus can dramatically suppress IEA, similar to the effects of high-frequency ANT stimulation. Suppression of IEA in both pulvinar and ANT was dose-dependent, in that lower current amplitudes (≤4 mA) did not suppress the activity, while high amplitudes ( >4 mA) did. These findings support further study of the pulvinar as a target for DBS and suggest that current amplitude may be critical in all forms of thalamic DBS.
Funding: NIH UH3-NS095495. Medtronic donated the implanted device for some of the subjects in this study.