Assessing Impact of Levodopa Responsiveness on DBS Efficacy in Parkinson Disease

The efficacy of deep brain stimulation (DBS) to improve motor function in Parkinson disease (PD) may be related with patient responsiveness to levodopa and the type of DBS administered, according to study findings published in Frontiers in Human Neuroscience.

As a neurosurgical treatment for motor fluctuations and dyskinesia in patients with advanced PD, there are 2 main types of DBS studied in the disease: surgery within the subthalamic nucleus (STN) and globus pallidus interna (GPi). Noted as being similar and consistent, randomized clinical trials have reported subtle differences in the efficacy of both approaches.

Moreover, levodopa responsiveness has emerged as a significant, yet controversial factor in determining those who may benefit from DBS surgery. Described as the levodopa challenge test, studies have reported differing results on whether this preoperative assessment could serve as a predictor of DBS efficacy on motor function in PD.

“Most previous studies only enrolled patients undergoing STN-DBS, while the value of preoperative levodopa responsiveness as a predictor for GPi-DBS responsiveness has not been adequately studied,” expanded researchers.

Aiming to describe the value of levodopa responsiveness on predicting motor outcomes of patients with PD following the levodopa challenge test, researchers conducted a retrospective study of 38 patients with idiopathic PD who underwent STN-DBS (n = 18) or GPi-DBS (n = 20) surgery.

Researchers utilized the Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part III (MDS UPDRS-III) to examine motor function prior to surgery and at the last follow-up (median follow-up duration, 7 months), with levodopa responsiveness and type of DBS administration noted.

In their assessment, the short-term predictive value of the levodopa challenge test was identified in 4 key areas for the motor outcome of both DBS approaches in PD:

• a solid therapeutic effect of GPi-DBS in treating levodopa-responsive tremors
• a negative effect of age at the time of surgery on motor outcomes of STN-DBS
• a possible preference of STN- to GPi-DBS in levodopa-resistant tremor control
• a possible preference of GPi- to STN-DBS in elderly patients with PD who are responsive to levodopa
  

Specifically, via Pearson’s correlation analysis (R²), researchers found a positive correlation between preoperative levodopa challenge responsiveness and GPi-DBS responsiveness on the total score (R², 0.283; P = 0.016), but not on the non-tremor total score (R², 0.158; P = .083) of MDS UPDRS-III. This correlation remained significant after controlling for age at the time of surgery, which was not found for patients who underwent STN-DBS.

For those who underwent STN-DBS, a positive correlation between preoperative levodopa challenge responsiveness and STN-DBS responsiveness was found for the non-tremor total score (R², 0.290; P = .021), but not on the total score (R², 0.130; P = .141) of MDS UPDRS-III, inverse to that found for those given GPi-DBS.

Researchers note that the small sample size, short-term follow-up, non-randomized group allocation, and retrospective design serve as the main limitations of the study, which they say warrants a more extensive, randomized, prospective long-term study to confirm findings.

Reference

Lin Z, Zhang X, Wang L, et al. Revisiting the L-Dopa Response as a Predictor of Motor Outcomes After Deep Brain Stimulation in Parkinson’s Disease. Front Hum Neurosci. Published online February 4, 2021. doi:10.3389/fnhum.2021.604433