BackgroundSeveral open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson’s disease (PD).Method25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson’s Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.ResultsThe DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains ‘stigma’ and ‘ADL’ improved only in the DBS group. The PDQ-39 summary index improved in both groups.ConclusionThis is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

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OBJECTIVEA growing number of studies are showing positive effects of deep brain stimulation (DBS) in the caudal zona incerta (cZi) in various tremor disorders, as well as motor symptoms of Parkinson’s disease (PD). The focus of the present study was to evaluate short- and long-term cognitive effects of bilateral cZi DBS in patients with PD.METHODSTwenty-five nondemented patients with advanced PD were recruited to participate in a randomized trial of cZi DBS versus best medical treatment (BMT). The patients in the BMT group were offered surgery after 6 months. Neuropsychological evaluations focusing on assessing verbal and visuospatial memory, attention, and executive function were conducted at baseline and at 6 and 24 months after surgery. Self-reported measures of depression, anxiety, and change in “frontal” behaviors were also completed at all assessment points.RESULTSBilateral cZi DBS in patients with PD generated few adverse cognitive effects. At the short-term follow-up after 6 months, no differences were found between patients randomized to BMT and patients randomized to DBS with regard to most of the cognitive domains assessed. A transient improvement in anxiety was, however, found in the surgical group. At the long-term follow-up 24 months after cZi DBS, no major changes in global cognitive functioning were found, although a decline in attention and self-reported executive function was noted.CONCLUSIONSWith the exception of a decline in attention and self-reported executive function, bilateral cZi DBS for PD in appropriately screened patients appears to be generally safe with regard to cognitive function, both in the short- and long-term perspective.

Background Long‐term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). Objectives The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery. Methods Thirty‐four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS). Results One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1–9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow‐up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11–14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off‐stimulation scores did not differ between year 1 and 10, this 20% deterioration of on‐DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year. Conclusions This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.