Chronic subthalamic nucleus stimulation reduces medication requirements inParkinson's disease

Objective: To reduce antiparkinsonian medication in parkinsonian patients w ith bilateral high frequency subthalamic nucleus (STN) stimulation. Backgro und: Parkinsonian syndromes are characterized by hyperactivity of the STN. Preliminary data indicate that functional inactivation of the STN may reduc e the requirement for dopaminergic therapy in PD. Methods: Bilateral quadri polar leads were implanted stereotactically in the STN of seven patients wi th advanced PD (mean age, 57.4 years; mean disease duration, 15.4 years). H igh-frequency stimulation was applied for 24 hours a day. Following implant ation, antiparkinsonian medication was reduced to the minimum possible and stimulation was gradually increased. The patients were evaluated in the pra ctically defined "off" and "on" conditions using the Unified Parkinson's Di sease Rating Scale (UPDRS) and the Schwab & England scale. The average foll ow-up was 16.3 +/- 7.6 months. A battery of neuropsychological tests was ap plied before and 9 months after the implant. Results: Parkinsonian features improved in all patients-the greatest change seen in rigidity, then tremor , followed by bradykinesia. Compared with the presurgical condition, off-dr ug UPDRS motor scores improved by 41.9% on the last visit (p = 0.0002), UPD RS activities of daily living (ADL) scores improved by 52.2% (p = 0.0002), and the Schwab & England scale score improved by 213% (p = 0.0002). The lev odopa-equivalent daily dose was reduced by 65%. Night sleep improved in all patients due to increased mobility at night; and in five patients insomnia was resolved. All patients gained weight after surgery and their appetite increased. The mean weight gain at the last follow-up was 13% compared with before surgery. During the last visit, the stimulation amplitude was 2.9 /- 0.5 V and the total energy delivered per patient averaged 2.7 +/- 1.4 W x 10(-6) The results of patient self-assessment scales indicated a marked i mprovement in five patients and a moderate improvement in the other two. Th e neuropsychological data showed no changes. Side effects were mild and tol erable. In all cases, a tradeoff between the optimal voltage and the severi ty of side effects made it possible to control parkinsonian signs effective ly. The most marked side effects directly related to STN stimulation consis ted of ballistic or choreic dyskinesias of the neck and the limbs elicited by contralateral STN stimulation above a given threshold voltage, which var ied depending on the individual. Conclusions: Parkinsonian signs can be con trolled by bilateral high-frequency STN stimulation. The procedure is well tolerated. On-state dyskinesias were greatly reduced, probably due to the r eduction of total antiparkinsonian medication. Bilateral high-frequency STN stimulation compensated for drug reduction and elicited dyskinesias, which differ from those observed following dopaminergic medication. ADL improved significantly, suggesting that some motor tasks performed during everyday chores, and that are not taken into account in the UPDRS motor score, also improved.