A Novel DBS Paradigm for Axial Features in Parkinson's Disease: A Randomized Crossover Study

Jessica A. Karl*, Bichun Ouyang, Steven Goetz, Leo Verhagen Metman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Background: High-frequency (130–185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low-frequency (60–80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a “dual-frequency” programming paradigm (interleave-interlink, IL-IL) to address both axial and appendicular symptoms. In IL-IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high-frequency stimulation, HFS) aims to control appendicular symptoms. Methods: We performed a randomized, double-blind crossover trial comparing patients’ previously optimized IL-IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity (CGI-S). Secondary outcome measures included blinded motor evaluations, timed tests, patient/caregiver questionnaires, and Personal KinetiGraphs (PKG). Results: Twenty-five patients were enrolled, and 20 completed. The patient/caregiver CGI-S for gait/balance (P = 0.01) and appendicular symptom control (P = 0.001), and the blinded rater MDS-UPDRS-III (−5.22, P = 0.02), CGI-S gait/balance (P = 0.01), and CGI-S speech (P = 0.02) were better while on IL-IL. Scores on Parkinson's Disease Quality of Life (P = 0.002) and Freezing-of-Gait Questionnaires (P = 0.04) were better on IL-IL. The Timed-Up-and-Go was 9.8% faster (P = 0.01), with 11.8% reduction in steps (P = 0.001) on IL-IL. There was no difference in PKG bradykinesia (P = 0.18) or tremor (P = 0.23) between paradigms. Conclusions: Our results prompt consideration of this novel programming paradigm (IL-IL) for PD patients with axial symptom impairment as a new treatment option for both axial and appendicular symptoms.

Original languageEnglish (US)
Pages (from-to)1369-1378
Number of pages10
JournalMovement Disorders
Issue number8
StatePublished - Aug 1 2020


  • deep brain stimulation
  • freezing of gait
  • interleaving stimulation
  • low-frequency stimulation
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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