Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson’s disease

Abstract

Article abstract-The authors studied the effect of bilateral subthalamic nucleus stimulation on levodopa-induced dyskinesias in 24 consecutive parkinsonian patients with disabling dyskinesias. The improvement in the three subtypes of levodopa-induced dyskinesias was significant from the third postoperative month and was mainly due to the decrease in the daily dose of levodopa allowed by the stimulation-induced improvement in the motor score. NEUROLOGY 2000;55:1921-1923 A few years after beginning levodopa treatment, many patients with idiopathic PD develop motor fluctuations and levodopa-induced dyskinesias (LID), which may be more disabling than parkinsonism, especially in patients with young-onset PD. Chronic stimulation of the subthalamic nucleus (STN) is effective in treating parkinsonian motor symptoms and can be suggested to patients with severe motor fluctuations.1 Operating on the STN might theoretically be harmful to LID. Hemiballism can be induced by spontaneous lesions of the STN and by experimental high frequency stimulation of the STN in patients with PD as well. 2 We investigated the effect of STN stimulation on different types of LID in parkinsonian patients.Patients and methods. Twenty-four consecutive patients-12 men and 12 women-with severe PD and motor complications were bilaterally operated. The characteristics of these patients are summarized in table 1. The neurosurgical procedure has been described. 1Clinical evaluation was based on the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol and was performed after a 12-hour withdrawal of antiparkinsonian drugs.3 Patients were assessed twice before surgery and 3 and 12 months after the operation in "off "-drug and "on"-drug conditions, using Unified PD Rating Scale (UPDRS) motor scores and the dyskinesia duration and disability items of the UPDRS part IV. Levodopa-induced dyskinesias were evaluated during a levodopa challenge using the same suprathreshold dose as preoperatively.4 "Off "-period dystonia, onset-of-dose, and peak-dose dyskinesias were assessed separately using three scales encompassing the face, neck, and the four limbs, each scored from zero to four proportionally to severity. 5 The conditions of evaluation were not randomized and onset-of-dose dyskinesia was evaluated in "off "-stimulation condition at least 30 minutes after the neurostimulator was switched off. The patients were blinded but not the examiner. Results are presented as mean Ϯ SD values. The data were analyzed by analysis of variance for repeated measures, and by the paired t-test and the Wilcoxon signed-rank test when required. Results.Results are presented in table 2 and the figure. STN stimulation significantly reduced the UPDRS motor score. In the "off "-drug condition, the UPDRS motor scores decreased from 54.4 Ϯ 13.1 before surgery to 45.8 Ϯ 19.7 and 49.3 Ϯ 17.9 in the "off "-stimulation condition and to 18.3 Ϯ 12.3 and 18.2 Ϯ 8.8 in the "on"-stimulation condition at 3-and 12-month follow-ups, respectively. In the "on"-drug condition t...

STN DBS of Advanced Parkinson's Disease Experienced in a Specialized Monitoring Unit with a Prospective Protocol

“…Another noteworthy finding of this study is that the DBS was turned on at lowest level around 1.0 volt from the next day after surgery, which is different from the literature reports 6,11,12,14,16,19,20,28,31,34) . After turning on the minimal stimulation the next day after surgery, the medication was then optimized by attempting to gradually increase the medication to the demand for the best status of motor functions in harmony with the DBS programming.…”

“…Anti-parkinsonian medications were totally withdrawn at six months in nine (24.1%) of 42 patients. The mean LEDD in our study was one of the lowest results of the previous reports 6,11,12,14,16,19,20,28,31,34) . One of the many multi-factorial reasons for the use of about half of the LEDD used in other reports may be a strict dose readjustment following the early reduction of anti-Parkinsonian medications accompanied by the prolonged monitoring in MUMD.…”

Immediate and sustained relief of levodopa-induced dyskinesias after dorsal relocation of a deep brain stimulation lead

“…3,7,[11][12][13][14]19,21 Each of the cardinal features of PD (tremor, rigidity, bradykinesia) is improved by DBS, as are levodopa-induced dyskinesias, which are a complication of chronic dopaminergic therapy. Because the clinical effects of subthalamic DBS are so similar to the effects observed after ablation of the STN in primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian symptoms 1,5 and because hyperactivity of the STN is a physiological hallmark of the parkinsonian brain, 26 Benabid, et al,2,3 hypothesized that DBS achieves its effects by reversibly inhibiting STN activity.…”

Striatal dopamine–NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors

“…DA denervation causes overactivity and metabolic changes in the STN and its target areas (for a recent review, see Hirsch et al 2000) which can be prevented by STN lesion (Bergman et al 1990;Delfs et al 1995) and by glutamate antagonists (Vila et al 1999). Remarkably, surgical lesion as well as functional impairment (with deep brain stimulation) of STN improves parkinsonism and reduces levodopa-induced dyskinesias in humans (Fraix et al 2000;Obeso et al 2000).…”