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Stable long-term effects of deep brain stimulation in Parkinson’s disease

AAN 2021
Long-term results of the CSP468 VA/NINDS trial demonstrated that deep brain stimulation (DBS) therapy had a significant and stable effect on motor function of patients with Parkinson’s disease, regardless of whether the globus pallidus interna (GPi) or the subthalamic nucleus (STN) were targeted. This is remarkable in view of the progressive nature of Parkinson’s disease.

DBS of the GPi and STN are well-established therapies of Parkinson’s disease, but outcomes on the very long-term are lacking. At the AAN 2021 meeting, extended long-term outcomes – of up to 10 years in some cases – from the landmark CSP468 VA/NINDS multicentre, randomised-controlled trial (NCT01076452) were presented [1].

A subset of patients originally randomised to GPi or STN DBS and with visits completed at 2 years were followed for up to 10 years. Data included analyses at baseline (GPi n=152; STN n=147), 2 years (GPi n=85; STN n=70), 7 years (GPi n=68; STN n=49), and 10 years (GPi n=49; STN n=28). The primary outcome was change in score of the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (motor subscale) in the off medication/on stimulation state. At baseline, these scores were 43.2 in both groups.

Improvement in UPDRS motor scores was maintained across all times analysed, in both groups. In the STN group, the scores declined from 43.2 to 27.7 after 2 years (P<0.001), to 34.4 after 7 years (P<0.001), and to 28.3 after 10 years (P<0.001). In the GPi group, the scores were 25.8 after 2 years (P<0.001), 35.4 after 7 years (P<0.001), and 34.0 after 10 years (P=0.10). Improvements were generally similar over time, but with a trend favouring STN (P=0.09). Tremor subscales showed the greatest reduction, followed by rigidity. Bradykinesia subscores showed greater improvement at 7 and 10 years with STN DBS (P=0.03). The UPDRS I, II, and IV scores and quality of time based on motor diaries also demonstrated significant long-term improvements, regardless of target. The tremor subscales showed the greatest reduction over time, followed by rigidity subscores. Both targets had equal and significant medication reduction. Parkinson's Disease Questionnaire-39 (PDQ-39) total score no longer showed improvement at 7 or 10 years (either target).

The 4-year follow-up results of the INTREPID trial (NCT01839396) showed that use of a multiple-source, constant-current rechargeable DBS system is safe and effective for the long-term in patients with Parkinson’s disease [2]. INTREPID was a double-blinded, randomised, sham-controlled trial of a novel DBS device capable of Multiple Independent Current Control (MICC). Results of 120 patients showed continued improvement of the UPDRS part III in the off medication/on stimulation state (43.4 at baseline; 21.2 at 1 year; 22.6 at 2 years; 22.6 at 3 years; 25.6 at 4 years). Medication reductions were maintained, and PDQ-39 scores indicated ongoing improvements in most aspects of quality of life.

  1. Ostrem J, et al. 10 Year Clinical Outcomes of Subthalamic Nucleus versus Pallidal Deep Brain Stimulation for Parkinson’s Disease: VA/NINDS CSP #468F. S8.003, AAN 2021 Virtual Congress, 17-22 April.
  2. Vitek J, et al. Long-Term Evaluation of Deep Brain Stimulation for Treatment of Parkinson's Disease Using a Multiple-Source, Constant-Current Rechargeable System: 4-year Follow-Up of a Prospective, Double-Blind RCT. S8.004, AAN 2021 Virtual Congress, 17-22 April.

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