Do patients with late-stage Parkinson's disease still respond to levodopa?

Background: Late-stage Parkinson' disease (PD) is dominated by loss of autonomy due to motor and non-motor symptoms which can be marginally corrected by medications adjustments. However, controversy exists on the mechanisms underlying the apparent decrease of benefit from levodopa. Objective: To study the response to levodopa in late-stage PD (LSPD). Methods: 20 LSPD patients (Schwab and England ADL Scale 3 in MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (DBS) underwent an acute levodopa challenge test. MDS-UPDRS-III and the modified Abnormal Involuntary Movement Scale were evaluated in off and after administration of a supra-maximal levodopa dose. Results: LSPD patients had a median age of 78.8 (IQR: 73.5-82) and median disease duration of 14 years (IQR: 10-19.75). DBS patients had a median age of 66 (IQR: 61-72) and median disease duration of 18 years (IQR: 15-22). LSPD and DBS patients' MDS-UPDRS-III score improved 11.3% and 37% after levodopa, respectively. Rest tremor showed the largest improvement, while axial signs did not improve in LSPD. However, the magnitude of levodopa response significantly correlated with dyskinesias severity in LSPD patients. One third of LSPD and 9% of DBS patients reported moderate drowsiness. Conclusions: LSPD patients show a slight response to a supra-maximal levodopa dose, which is greater if dyskinesia are present, but it is frequently associated with adverse effects. A decrease in levodopa response is a potential marker of disease progression in LSPD.