Neurosurgery at an earlier stage of Parkinson disease: A randomized, controlled trial

Centre d'Investigation Clinique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Neurology (Impact Factor: 8.29). 01/2007; 68(4):267-71. DOI: 10.1212/01.wnl.0000250253.03919.fb
Source: PubMed


Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function.
Twenty patients with PD of short duration (time elapsed since first symptom +/- SD: 6.8 +/- 1.0 years) with mild to moderate motor signs (Unified Parkinson's Disease Rating Scale III "off" medication: 29 +/- 12) who responded well to levodopa treatment were included in pairs, matched for age, duration and severity of disease, and impairment in socioprofessional functioning. Patients were prospectively randomized to undergo bilateral subthalamic nucleus stimulation (n = 10) or receive optimized medical treatment (n = 10). Parkinsonian motor scores, quality of life, cognition, and psychiatric morbidity were assessed at inclusion and at 6, 12, and 18 months after randomization.
Quality of life was improved by 24% in surgical and 0% in nonsurgical patients (p < 0.05). After 18 months, the severity of parkinsonian motor signs "off" medication, levodopa-induced motor complications, and daily levodopa dose were reduced by 69%, 83%, and 57% in operated patients and increased by 29%, 15%, and 12% in the group with medical treatment only (p < 0.001). Adverse events were mild or transient, and overall psychiatric morbidity and anxiety improved in the surgical group.
Subthalamic nucleus stimulation should be considered a therapeutic option early in the course of Parkinson disease.

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    • "A small randomized trial of bilateral STN DBS in 10 patients with early PD (mean duration of 7 years) compared to 10 matched medically treated controls [129] showed a significant benefit from DBS on quality of life, motor control and decrease in levodopa doses. More recently, Schuepbach et al. [130] conducted a randomized controlled trial comparing bilateral STN DBS to optimal medical management in 251 PD patients aged less than 60 years, with PD for more than 4 years but with motor fluctuations and dyskinesia for 3 years or less. "
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    ABSTRACT: For the last 50 years, levodopa has been the cornerstone of Parkinson's disease management. However, a majority of patients develop motor complications a few years after therapy onset. Deep brain stimulation has been approved by the FDA as an adjunctive treatment in Parkinson disease, especially aimed at controlling these complications. However, the exact mechanism of action of deep brain stimulation, the best nucleus to target as well as the best timing for surgery are still debatable. We here provide an in-depth and critical review of the current literature on this topic.
    No preview · Article · Nov 2013 · Translational Neurodegeneration
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    • "Depression was detected in 60% of operated young-onset PD which was equal to older-onset PD [7]. Moreover, four out of 10 patients younger than 55 years old, who underwent early STN-DBS, had transient depression [29]. "
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    ABSTRACT: Selection of patients with Parkinson's disease for neurostimulation of subthalamic nucleus (STN-DBS) is still poorly studied. To identify the impact of age and disease duration on the outcome of bilateral STN-DBS. 110 operated patients in a single center covering a large range of age and disease duration were retrospectively included and followed for up-to 5 years. Standardized UPDRS assessments were obtained at 0.5-1 and 3-5 years. Patients were stratified into three age groups (≤55, 56-64 and ≥65 years) and the middle age group was further stratified into 2 disease duration subgroups (<15years, ≥15 years). The age groups had comparable baseline data except for the predefined differences. Compared to baseline early and late intra-group "Med Off-Stim On" motor scores were significantly improved for all groups (p < 0.001). Mood/cognition were significantly improved in younger two groups (p = 0.008, 0.019) at 0.5-1 year. Inter-group comparisons showed significantly worse early and late axial scores for older patients (p < 0.05). All groups had comparable postoperative improvement except for the older group which had significantly less improvement of early UPDRS-II, late UPDRS-I, and early and late PIGD/axial scores. Different disease durations had no effect on the outcome except for worse Schwab and England Off-score in longer duration group (p = 0.02). Side effects of surgery and long-term management were similar. STN-DBS is an efficient treatment of advanced PD for all treated age-groups. Provided strict inclusion criteria are respected, older age and longer disease duration are associated with slightly worse effects mainly on L-dopa-resistant symptoms.
    Full-text · Article · Sep 2013 · Parkinsonism & Related Disorders
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    • "A prospective randomized trial of early DBS (PD duration mean = 2.1 years) in 30 patients has been commenced and at 3 months reports that surgical complication rate and lead placement were not significantly different in the early DBS group and were in keeping with reported data.75 In a randomized trial addressing the symptomatic effects of bilateral STN DBS in 10 patients with early PD (defined according to duration of disease and UPDRS III score) compared to 10 matched medically treated controls,76 a significant benefit from DBS on quality of life, motor signs, reduced motor complications, and L-dopa requirement was observed.68 The side effects of DBS were reported as temporary and mild. "
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    ABSTRACT: We review the current application of deep brain stimulation (DBS) in Parkinson disease (PD) and consider the evidence that earlier use of DBS confers long-term symptomatic benefit for patients compared to best medical therapy. Electronic searches were performed of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials to identify all article types relating to the timing of DBS in PD. Current evidence suggests that DBS is typically performed in late stage PD, a mean of 14 to 15 years after diagnosis. Current guidelines recommend that PD patients who are resistant to medical therapies, have significant medication side effects and lengthening off periods, but are otherwise cognitively intact and medically fit for surgery be considered for DBS. If these criteria are rigidly interpreted, it may be that, by the time medical treatment options have been exhausted, the disease has progressed to the point that the patient may no longer be fit for neurosurgical intervention. From the evidence available, we conclude that surgical management of PD alone or in combination with medical therapy results in greater improvement of motor symptoms and quality of life than medical treatment alone. There is evidence to support the use of DBS in less advanced PD and that it may be appropriate for earlier stages of the disease than for which it is currently used. The improving short and long-term safety profile of DBS makes early application a realistic possibility. Ann Neurol 2013;73:565–575
    Preview · Article · May 2013 · Annals of Neurology
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