Interactions between deep brain stimulation and levodopa in Parkinson's disease

Objective: To quantify the effects of deep brain stimulation (DBS) of globu s pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuation s and dyskinesia in PD and to determine how the response to levodopa was mo dified by DBS. Background: Patients report that DBS reduces levodopa-induce d motor fluctuations and dyskinesia throughout the day, but this has not be en objectively measured. Further, the means by which DBS alters the respons e to levodopa to improve motor fluctuations is unknown. Methods: Twelve sub jects, six with bilateral GPi electrodes and six with bilateral STN electro des, were studied 12 to 33 months after surgery. To quantify motor fluctuat ions and dyskinesia, subjects were monitored hourly throughout 2 waking day s with their usual oral medications, 1 day with DBS on and 1 day with DBS o ff, with subjects and nurse raters blinded to DBS status. To examine the ef fects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and 1 day with DBS off, again un der double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and d yskinesia scores. Results: DBS raised the mean tapping speed and reduced th e coefficient of variation during the waking day. This was achieved by incr easing the lowest or trough tapping speed between doses of antiparkinson me dications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the pe ak response nor the duration of response to levodopa was affected by DBS. T he study was not powered to detect differences between GPi and STN stimulat ion and the only difference that approached significance was that GPi reduc ed peak dyskinesia and STN tended to increase peak dyskinesia. Conclusion: DBS objectively reduces motor fluctuations. This is achieved by reduction o f drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alte rnative strategy to prolonging the effects of each dose of levodopa as a me ans to reduce motor fluctuations.