A 50-year-old man with Parkinson's disease has been on levodopa/carbidopa for 8 years. He now has disabling motor fluctuations with 'off' periods of 4–5 hours daily despite optimised oral dosing. Which intervention has the strongest evidence for reducing 'off' time in this scenario?

• A Amantadine extended release
• B Addition of entacapone
• C Deep brain stimulation of the subthalamic nucleus ✓
• D Dose fractionation of levodopa into more frequent smaller doses

Explanation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) provides the most sustained and significant reduction in 'off' time and dyskinesias in advanced Parkinson's disease with motor complications. The EARLYSTIM trial showed benefit even in relatively early motor fluctuations. Entacapone (COMT inhibitor) modestly extends levodopa effect and is useful but inferior to DBS for severe fluctuations. Amantadine ER (ALLAY-LID trial) primarily targets dyskinesias rather than motor fluctuations. Dose fractionation provides marginal benefit in severe cases.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.