Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor

Abstract

Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor. For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to 1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic, and paresthesia-inducing DBS settings in three patients with essential tremor, and 2) determine how much better of an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally-segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic, and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements, and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n=10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n=12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side effects.

Deep Brain Stimulation for Tremor: Is There a Common Structure?

“…We believe that either the VPL nucleus is not included in our VIM DBS patients or there may be a habituation of the VPL to electrical stimulation. Nevertheless, computational models of DBS have shown a good correlation with an improvement of symptoms and reduction of adverse effects [13,14,27,45]. Considering the possible variations of the localization of the DRTT, also described in this atlas, we believe that the DRTT in the PSA/caudal Zi could be the common structure stimulated at different places in both our cohorts as well as in the other mentioned studies, as illustrated in Figure 1.…”

“…While numerous studies have suggested that the stimulation site correlated with the best clinical results in PD patients is located in the superior and lateral part of the STN [27,28,29,30], PSA DBS in PD patients have also suggested a positive effect on rigidity and bradykinesia. These findings should, however, be taken cautiously since the experience with PSA DBS is limited.…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…The further development of new electrodes is also underway, with the goal of permitting more precise shaping and steering of the electrical field, through the use of multiple contacts along the electrode shaft [337,338], in order to better control unintended spread and optimal shaping of current flow. Obviously, the freedom of being able to use additional electrode contacts must be balanced against the resulting more complex programming requirements.…”

Use of efficacy probability maps for the post-operative programming of deep brain stimulation in essential tremor

“…There have been several traditional methods described for the programming of DBS for ET [6–8]. These methods involve evaluating each of the four contacts for the threshold for both side effects and efficacy, adjusting the various parameters in a consistent pattern.…”