Stimulation of the globus pallidus internus in the treatment of Parkinson's disease: Long-term results of a monocentric cohort

Abstract

Background: Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. Methods: Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). Results: The results show that GPi stimulation improves levodopa responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. Conclusions: The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the 'off'medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5 to 6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.

Therapeutic Strategies to Treat or Prevent Off Episodes in Adults with Parkinson’s Disease

“…Compared to best medical therapy, DBS improves "on" time without troublesome dyskinesia by approximately 4-5 hours, with up to two-thirds of patients achieving meaningful improvements in motor fluctuations by 6 months [227], [228]. These positive effects appear to last greater than 10 years in several long-term studies though the net effects on quality of life in comparison to pre-operative status seem to wane after 5 years presumably because of the inexorable progression of the disease [229], [230]. There has been recent interest in this treatment being considered earlier in the course of disease [231] and for DBS to be utilised as the first choice of device-assisted therapies when this is clinically appropriate.…”

“…Although STN DBS improves the severity of the motor symptoms of PD and has the potential to reduce dopaminergic medication requirements, it is also associated with an increased risk of cognitive and psychiatric complications [234], [235], [236]. Conversely, GPi stimulation is less likely to negatively impact mood and cognitive processing while resulting in greater reductions in dyskinesia [227], [228], [229]. GPi DBS however rarely allows for a major reduction in dopaminergic therapies [227], [228], [229].…”

“…Conversely, GPi stimulation is less likely to negatively impact mood and cognitive processing while resulting in greater reductions in dyskinesia [227], [228], [229]. GPi DBS however rarely allows for a major reduction in dopaminergic therapies [227], [228], [229]. Potential complications relate to the surgical procedure and hardware such as wound infections or erosions, lead migration/malposition, lead or extension fractures and component malfunctions [237], [238].…”

From medications to surgery: advances in the treatment of motor complications in Parkinson’s disease

“…Compared to best medical therapy, DBS improves “on” time without troublesome dyskinesias by a magnitude of 4.6–5 hours,115,116 with more than two-thirds of advanced PD patients achieving meaningful improvements in motor fluctuations with either STN or GPi DBS by 6 months 115. Although the magnitude of benefit declines over time, these positive effects on PD motor symptoms and fluctuations have been reported to last greater than 10 years in several long-term studies 117–119. This is far beyond the clinical responses achieved by oral pharmacologic and infusion therapies.…”

“…Unfortunately, the beneficial effects of DBS begin to wane beyond 5 years 117. Although initially, patients’ stimulation requirements have been shown to increase as the disease progresses,118 there are limited studies reporting on motor outcomes beyond 10 years.…”