Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease

N Engl J Med. 2003 Nov 13;349(20):1925-34. doi: 10.1056/NEJMoa035275.


Background: Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown.

Methods: We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up.

Results: As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide.

Conclusions: Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Adult
  • Aged
  • Antiparkinson Agents / therapeutic use
  • Combined Modality Therapy
  • Dyskinesia, Drug-Induced / etiology
  • Electric Stimulation Therapy* / adverse effects
  • Electrodes, Implanted
  • Female
  • Follow-Up Studies
  • Functional Laterality
  • Humans
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / classification
  • Parkinson Disease / drug therapy
  • Parkinson Disease / psychology
  • Parkinson Disease / therapy*
  • Severity of Illness Index
  • Subthalamic Nucleus* / physiology
  • Subthalamic Nucleus* / surgery


  • Antiparkinson Agents
  • Levodopa