Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.

ObjectivesRepetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) with frequencies 5–20 Hz is an expanding non-invasive treatment for chronic neuropathic pain (NP). Outcome data, however, show considerable inhomogeneity with concern to the levels of effect due to the great diversity of treated conditions. The aim of this review was to survey the literature regarding the efficacy and safety of M1 rTMS, and the accuracy to predict a positive response to epidural motor cortex stimulation (MCS) which is supposed to give a more longstanding pain relief.MethodsA systematic literature search was conducted up to June 2019 in accordance with the PRISMA guidelines. We used the PICO Model to define two specific clinical questions: (1) Does rTMS of M1 relieve NP better than sham treatment? (2) Can the response to rTMS be used to predict the effect of epidural MCS? After article selection, data extraction, and study quality assessment, the certainty of evidence of treatment effect was defined using the GRADE system.ResultsData on 5–20 Hz (high-frequency) rTMS vs. sham was extracted from 24 blinded randomised controlled trials which were of varying quality, investigated highly heterogeneous pain conditions, and used excessively variable stimulation parameters. The difference in pain relief between active and sham stimulation was statistically significant in 9 of 11 studies using single-session rTMS, and in 9 of 13 studies using multiple sessions. Baseline data could be extracted from 6 single and 12 multiple session trials with a weighted mean pain reduction induced by active rTMS, compared to baseline, of −19% for single sessions, −32% for multiple sessions with follow-up <30 days, and −24% for multiple sessions with follow-up ≥30 days after the last stimulation session. For single sessions the weighted mean difference in pain reduction between active rTMS and sham was 15 percentage points, for multiple sessions the difference was 22 percentage points for follow-ups <30 days, and 15 percentage points for follow-ups ≥30 days. Four studies reported data that could be used to evaluate the accuracy of rTMS to predict response to MCS, showing a specificity of 60–100%, and a positive predictive value of 75–100%. No serious adverse events were reported.ConclusionsrTMS targeting M1 can result in significant reduction of chronic NP which, however, is transient and shows a great heterogeneity between studies; very low certainty of evidence for single sessions and low for multiple sessions. Multiple sessions of rTMS can maintain a more longstanding effect. rTMS seems to be a fairly good predictor of a positive response to epidural MCS and may be used to select patients for implantation of permanent epidural electrodes. More studies are needed to manifest the use of rTMS for this purpose. Pain relief outcomes in a longer perspective, and outcome variables other than pain reduction need to be addressed more consistently in future studies to consolidate the applicability of rTMS in routine clinical practice.

Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements.

Background/Aim: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. Methods: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11–14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. Results: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1–2 and 1–3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 ± 21% and 77 ± 22% for the clinically used and the predicted electrode contacts, respectively. Conclusions: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined.

Background and Importance: Twiddler's syndrome is a rare complication of DBS. This condition occurs when the IPG is consciously or inadvertently rotated in its pocket, resulting in torsion and possible dislodgement of implanted electrodes, with subsequent loss of function. Methods: Here we present a patient diagnosed with Twiddler's syndrome. The patient presented with straining cables at the neck five months after bilateral Gpi DBS and an x-ray demonstrated Twiddler's syndrome. Initial revision with preventive measures proved futile. After some time the condition recurred, now with dislocation of one of the intracerebral electrodes. In a second revision the IPG was placed under the pectoralis muscle, which has so far prevented further rotation. Results and Conclusion: While Twiddler's syndrome is fairly uncommon, it remains to be a risk associated with DBS, recognizing the potential risks and signs might allow for preventive measures avoiding dislocation of the intracerebral electrodes.