Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial

Background: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. Methods: Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. Results: At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Omega) and TEED (33.7/69.0/84.4/93.0 V2*mu s*Hz/Omega) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 mu s), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. Conclusion: In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Background Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. Methods We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1: 1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Findings Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363.3 mg/day [SE 41.8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245.8 mg/day [40.4]) in those assigned medical therapy alone (p<0.0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0.65 points [SE 0.15]) and did not change with medical therapy alone (-0.02 points [0.15]); the between-group difference in change from baseline was significant (p=0.0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1.26 points [SE 0.35]) and had increased with medical therapy alone (1.12 points [0.35]); the between-group difference was significant (p<0.0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. Interpretation In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications