Stimulation of the subthalamic nucleus in Parkinson’s disease: a 5 year follow-up
Schupbach WM, Chastan N, Welter ML, et al.;
Commented by , 17 Jan 2006
Background
Surgical treatment of Parkinson’s disease has been revitalized in the last 15 years, subthalamic nucleus has been a popular target and deep-brain stimulation a popular method. Dramatic improvements have been reported in short-term, the question has been open how long the beneficial effects would last and if there would be any long-term safety issues.
Objective
The objective of this study was to provide 5 year follow up data on PD patients treated with bilateral stimulation of the subthalamic nucleus (STN).
Methods
Thirty seven consecutive PD patients treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Motor symptoms of PD were evaluated with and without levodopa treatment, as well as with and without bilateral STN stimulation.
The Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS) were used to assess neuropsychological functions and the mood.
Results
There were no severe peri- or immediate postoperative side effects. Six patients died and one was lost to follow-up. Five years after surgery UPDRS Part II (Activities of Daily Living Score) was improved during stimulation of the STN by 40% ("off" drug) and 60% ("on" drug).
UPDRS Part III (Motor Score) was improved by 54% ("off" drug) and 73% ("on" drug). The severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS score remained unchanged, but the cognitive performance declined significantly.
Persistent adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias and apathy.
The authors concluded that despite moderate motor and cognitive decline over time, which they interpreted to be probably due to disease progression, the marked improvement in motor function observed after surgery was sustained for 5 years.
Professor Emre's comments
Neurosurgical treatment of PD has a long history. Ablation procedures used for decades became almost forgotten following the introduction and dramatic success of levodopa treatment. After the long-term complications of levodopa emerged there was a renewed interest in surgical treatment.
The revival was kicked-off by reports of successful pallidal ablation surgery to treat severe dyskinesia. The number of targets were then enlarged by better understanding of basal ganglia motor circuitry to include subthalamic nucleus, and better characterization of nuclei in pallidum and thalamus; deep brain stimulation (DBS) was added to the ablation surgery and became popular because of obvious safety advantages in bilateral procedures.
The short term benefits of STN DBS have been well described (ref. 1), there was scarcity of data on the long-term outcome. This paper provides results on prospectively followed-up patients over five years.
The data confirm that although there is some decline over time, the benefits with regard to motor function are maintained over five years, ADL scores on stimulation-off drug were still better after five years, the score on stimulation-on drug, however were close to baseline values.
The decline over years in motor and cognitive function was thought to be due to disease progression, which is conceivable. Also recently, it was reported that there is no effect of DBS on the disease progression (ref. 2).
A number of persistent behavioural problems were noticed, which may be due to overstimulation of non-target areas or lack of adequate dopaminergic stimulation in limbic areas due to reduced amount of medication.
It was interesting that some of these adverse events resembled "dopamine dysregulation syndrome" including compulsive dopaminergic drug use and disinhibiton (ref. 3), which may be due to inadequate stimulation of pathways involved in reward systems.
This article confirms the long-term benefits of STN DBS, although the benefits somewhat decline over time. Thus, this method remains as a powerfull tool in the treatment of PD patients with motor complications, one should, however, be aware of possible persistent behavioural problems.
References
1. Limousin P, Krack P, Pollak P, et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. New England Journal of Medicine 1998; 339 (16); 1105-1111 (Free full text article)
2. Hilker R, Portman AT, Voges J, et al. Disease progression continues in patients with advanced Parkinson’s disease and effective subthalamic nucleus stimulation. Journal of Neurology, Neurosurgery and Psychiatry 2005; 76 (9); 1217-1221
3. Lawrence AD, Evans AH and Less AJ. Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry? Lancet Neurology 2003; 2 (10); 595-604