Ronald M Salomon

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

BACKGROUNDnDeep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinsons disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD.nnnMETHODSnThirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months.nnnRESULTSnAs hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient.nnnCONCLUSIONSnThis study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.

Deep brain stimulation in early Parkinson's disease: Enrollment experience from a pilot trial

BACKGROUNDnDeep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinsons disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression.nnnMETHODSnWe are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events.nnnRESULTSn30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion.nnnCONCLUSIONnThis report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long-term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD.

The Effects of Physical Quality of Life, Time, and Gender on Change in Symptoms of Anxiety and Depression after Liver Transplantation

Previous research demonstrated that physical health-related quality of life (HRQOL) improves after liver transplantation, but improvements in mental HRQOL are less dramatic. The aim of this study was to test the effects of physical HRQOL, time post-transplant, and gender on pre- to post-transplant change in anxiety and depression. Longitudinal HRQOL data were prospectively collected at specific times before and after liver transplantation using the SF-36® Health Survey (SF-36), Center for Epidemiologic Studies Depression Scale (CES-D), and Beck Anxiety Inventory (BAI). Within-subject change scores were computed to represent the longest follow-up interval for each patient. Multiple regression was used to test the effects of baseline score, time post-transplant, gender, and SF-36 physical component summary scores (PCS) on change in BAI and CES-D scores. About 107 patients (74% male, ageu2009=u200954u2009±u20098xa0years) were included in the analysis. Time post-transplant ranged 1 to 39xa0months (meanu2009=u20099u2009±u20098). Improvement in symptoms of anxiety and depression was greatest in those patients with the most severe pre-transplant symptoms. Significant improvement in symptoms of depression occurred after liver transplant, but the magnitude of improvement was smaller with time suggesting possible relapse of symptoms. Better post-transplant physical HRQOL was associated with a greater reduction in symptoms of anxiety and depression after liver transplantation. This demonstrates clear improvements in post-transplant mental HRQOL and the significant relationships between physical and mental HRQOL.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

BACKGROUNDnDeep brain stimulation provides significant symptomatic benefit for people with advanced Parkinsons disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinsons disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra.nnnOBJECTIVEnWe report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinsons disease and discuss previous failed attempts at neuroprotection.nnnMETHODSnWe recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinsons disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts.nnnRESULTSnThirty subjects with Hoehn & Yahr Stage II idiopathic Parkinsons disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different.nnnCONCLUSIONSnThis study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinsons disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinsons disease.

Neuropsychological Effects of Deep Brain Stimulation in Subjects with Early Stage Parkinson's Disease in a Randomized Clinical Trial

BACKGROUNDnDeep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinsons disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial.nnnOBJECTIVEnThe purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD.nnnMETHODSnThirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups.nnnRESULTSnTwo serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded.nnnCONCLUSIONSnThe results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.