Can Levodopa Challenge Testing Predict the Effect of Deep Brain Stimulation? One-Year Outcomes in a Chinese Cohort

Abstract

Objective: Our study examined whether levodopa challenge test (LCT) results could predict quality of life (QoL) outcomes after surgery to implant subthalamic nucleus deep brain stimulation (STN-DBS) electrodes to treat advanced Parkinson’s disease (PD).Methods: Forty patients with STN-DBS underwent a follow-up 1 year after implantation surgery to analyze the correlation between preoperative levodopa impact test results and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS) III motor score, postoperative PD Questionnaire-39 (PDQ-39) score, and PDQ-39 improvement.Results: Improvements in QoL were associated with several preoperative characteristics including preoperative UPDRS-III tremor, UPDRS-III tremor (off-60) (p = 0.049), UPDRS-III tremor (off-120) (p = 0.012), Mini-Mental State Examination (p = 0.012), and PDQ-39 (p = 0.012) before surgery. Multiple linear regression model using preoperative MMSE [odds ratio (OR) = 0.342, 95% confidence interval (CI) = 0.051–2.297], preoperative UPDRS-III tremor (OR = 2.099, 95% CI = 0.585–7.535), UPDRS-III tremor (off-60) [OR = 1.316, 95% CI = 0.804–2.154, UPDRS-III tremor (off-120) OR = 0.913, 95% CI = 0.691–1.207], correctly classified 88.5% of patients.Conclusion: Levodopa challenge test results cannot predict the effect of DBS. However, the test can be incorporated into a regression prediction model to the quality of life of PD patients after DBS with other preoperative factors.

Parkinson's Disease Tremor Differentially Responds to Levodopa and Subthalamic Stimulation

“…On balance, this cohort appeared representative of the average population of PD patients presenting with tremor, with patient characteristics 23,24 and treatment outcomes being comparable to other studies 16,25,26 . Although levodopa responsiveness was strongly correlated with STN‐DBS response overall, the lack of levodopa responsiveness in predicting STN‐DBS outcomes for the specific motor sub‐items was interesting; this observation has previously been reported by a number of other studies 6,7,26–29 . The possibility that STN‐DBS has additional effects on brain networks, rather than just mimicking the effect of dopamine, could potentially explain this discrepancy, especially for tremor 30 .…”

“…16,25,26 Although levodopa responsiveness was strongly correlated with STN-DBS response overall, the lack of levodopa responsiveness in predicting STN-DBS outcomes for the specific motor sub-items was interesting; this observation has previously been reported by a number of other studies. 6,7,[26][27][28][29] The possibility that STN-DBS has additional effects on brain networks, rather than just mimicking the effect of dopamine, could potentially explain this discrepancy, especially for tremor. 30 According to the "dimmer-switch model" theory, 2 PD tremor is triggered by pathological activity in the striato-pallidal circuit (switch), which is then amplified by cerebello-thalamo-cortical circuit, therefore, producing the tremor and modulating its amplitude (dimmer).…”

“…Levodopa-responsiveness was defined as the difference between the on-MED and off-MED scores on the UPDRS III scale. 9 Levodopa response was also specifically calculated for overall tremor (items 20, 21), rest tremor (item 20), postural tremor (item 21), akinesia (items 19,23,24,25,26,31), rigidity (item 22), posture and gait (items 27,28,29,30), and speech (item 18) sub scores.…”

Tremor in Parkinson’s Disease: From Pathophysiology to Advanced Therapies

“…However, patients with dopamineresistant tremor might show a poor response in the LCT [59,[107][108][109]. Hence, the LCT may not be a reliable indicator for candidacy and repressiveness to DBS in the case of refractory PD tremor [110,111]. DBS electrodes replace and mimic the therapeutic effect produced by lesioning therapies but without inducing significant brain lesions, which provides the advantage of reversibility.…”