Bilateral subthalamic nucleus stimulation and quality of life in advanced Parkinson's disease.

We examined the impact of the subthalamic nuclei (STN) deep brain stimulation (DBS) on the health-related quality of life (QoL) of patients with advanced Parkinson's disease (PD). Seventeen consecutive patients with refractory motor fluctuations and dyskinesia were included in the study (mean age, 60.9 +/- 7.7 years [range, 43-74 years]; disease duration, 16.4 +/- 8.5 years [range, 7-38 years]; mean off-medication Hoehn and Yahr stage, 4.23 +/- 0.66 [range, 2.5-5]). Each patient's assessment was carried out using common rating scales, following the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Dyskinesia and emotional state were evaluated through the Abnormal Involuntary Movement Scale (AIMS) and the Hospital Anxiety and Depression Scale (HAD). QoL was assessed by means of the Parkinson's Disease Questionnaire Spanish version (PDQ-39). Significant benefit was obtained in the motor manifestations and complications of disease, as well as in the functional state and mood (P < 0.001). Some QoL dimensions (mobility and activities of daily living) and the PDQ-39 Summary Index (PDQ-39SI) showed a significant improvement (P < 0.001). Benefit was modest (P < 0.05) for three other domains (emotional well-being, stigma, bodily discomfort) and nil for the rest. There was no correlation between the change obtained in the QoL (PDQ-39SI) and in the other variables. As measured by the PDQ-39, STN-DBS significantly improves important aspects of QoL in patients with advanced PD.     

Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.     

Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.

The efficacy of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) is well-established but little is known about the lifetime of implanted pulse generators (IPG). To investigate the lifetime of the bilaterally implanted Itrel II(R) (Medtronic, Minneapolis) pulse generator, the first 49 consecutive patients with PD having been operated on at our center for bilateral STN chronic stimulation were reviewed with noting of the stimulation parameters in use prior to IPG replacement. The mean electrical voltage was 3.2 +/- 0.3 V, mean pulse width was 65 +/- 10 mus, and mean frequency was 145 +/- 16 Hz. Replacement of an IPG was anticipated in 25% due to unilateral low-battery signaling, or end of life. In either case, replacement of the contralateral IPG was undertaken simultaneously. The mean IPG lifetime was 83 +/- 14 [40-113] months. The IPG lifetime correlated with the total electrical energy delivered (P = 0.002, r = -0.496). Unilateral IPG end-of-life generally led to subacute worsening of contralateral parkinsonism. In 25% of patients, there was also a worsening of axial symptoms leading to potential medical emergencies such as falls (10%), aspiration pneumonia (10%), or psychosis (5%). A close monitoring of patients and an anticipation of IPG replacement in the case of a low-battery signal are recommended.     

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS. © 2010 Movement Disorder Society     

Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

Most Parkinson's patients complain about sleep problems. The subjective effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on nocturnal disabilities and sleep quality was elucidated by the recently established Parkinson's disease sleep scale (PDSS). The DBS-treated group obtained significant improvement of motor function assessed by the Unified Parkinson's Disease Rating Scale. The mean total PDSS improved significantly after surgery whereas no change was found for the control group. Significant improvements of individual questions were obtained for overall sleep quality and motor symptoms whereas nocturia and daytime sleepiness did not change despite significant reduction of parkinsonian medication.     

Subthalamic nucleus deep brain stimulation for parkinson's disease after successful pallidotomy: clinical and electrophysiological observations.

Unilateral pallidotomy is an effective treatment for contralateral parkinsonism and dyskinesia, yet symptoms progress in many patients. Little is known about whether such patients obtain a useful response to subsequent bilateral subthalamic nucleus deep brain stimulation (STN DBS). Changes in Unified Parkinson's Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores, medication requirements, and dyskinesias were measured. Clinical outcomes were compared to patients with de novo STN DBS. Neuronal recordings were performed. STN DBS resulted in a significant reduction in UPDRS Motor scores (42.1%; 95% confidence interval [CI], 26.9-57.4; P = 0.03), comparable with de novo STN DBS surgery (41%; 95% CI, 26-46%; P < 0.001). There was also less change in dyskinesia duration and disability scores (P = 0.017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy.     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Mortality in patients with Parkinson's disease treated by stimulation of the subthalamic nucleus.

Subthalamic nucleus (STN) stimulation improves motor disability and quality of life in patients with advanced Parkinson's disease (PD). Short-term mortality is low, but little is known about long-term mortality. We assessed mortality and causes of death in 171 consecutive PD patients treated by STN stimulation. Surgery was performed after a median lagtime of 13 years from PD onset at a median age of 57 years. The median follow-up after surgery was 41 months. Sixteen patients died 8 to 83 months after neurosurgery. Poorer cognitive function was the only predictive factor for mortality (standardized mortality ratio = 2.9; 95% confidence interval [CI], 1.6-4.7; P < 0.0001). Based on a historical comparison of 118 operated patients with 39 nonoperated patients from a different population, survival among operated patients was not better (hazard ratio = 1.2; 95% CI, 0.7-2.1).     

MEP latency shift after implantation of deep brain stimulation systems in the subthalamic nucleus in patients with advanced Parkinson's disease.

Deep brain stimulation (DBS) into the subthalamic nucleus (STN) is a highly effective treatment for advanced Parkinson's disease (PD). The consequences of STN stimulation on intracortical and corticospinal excitability have been addressed in a few studies using transcranial magnetic stimulation (TMS). Although excitability measurements were compared between the STN stimulation OFF and ON condition, in these experiments, there are no longitudinal studies examining the impact of electrode implantation per se on motor excitability. Here, we explored the effects of STN electrode implantation on resting motor thresholds (RMT), motor evoked potential (MEP) recruitment curves, and MEP onset latencies on 2 consecutive days before and shortly after STN surgery with the stimulator switched off, thus avoiding the effects of chronic DBS on the motor system, in 8 PD patients not taking any dopaminergic medication. After surgery, RMT and MEP recruitment curves were unchanged. In contrast, MEP onset latencies were significantly shorter when examined in relaxed muscles but were unchanged under preactivation. We hypothesize that postoperatively TMS pulses induced small currents in scalp leads underneath the TMS coil connecting the external stimulator with STN electrodes leading to inadvertent stimulation of fast-conducting descending neural elements in the vicinity of the STN, thereby producing submotor threshold descending volleys. These "conditioning" volleys probably preactivated spinal motor neurons leading to earlier suprathreshold activation by the multiple corticospinal volleys produced by TMS of the motor cortex. These TMS effects need to be considered when interpreting results of excitability measurements in PD patients after implantation of STN electrodes.     

Estimating the costs of surgical innovations: the case for subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease.

We estimated the current cost of deep brain stimulation surgery targeted on the subthalamic nucleus. The method used was a cost analysis using typical resource use patterns and unit costs from a leading surgical centre, detailed equipment costs from the manufacturer, and sensitivity analysis. Resource use was based on patients with advanced Parkinson's disease. The main outcome measure was the likely total health service costs per patient, including preoperative assessment, surgery, and postoperative management over a 5-year period. The preoperative assessment, surgery, and discounted follow-up costs associated with subthalamic nucleus surgery were estimated at approximately UK Pounds 32,526 per patient over 5 years. Almost 70% of these costs are attributable to the initial costs of the equipment and the likely follow-up and replacement costs of the equipment. These costs will be affected mainly by future equipment costs and their replacement period and are relatively insensitive to preoperative assessment staff costs, length of hospital stay after surgery, and imaging costs. This cost estimate should be of use to researchers, health care managers, policy makers, and surgeons working in this area. Providing an estimate of the cost of this new procedure will provide a baseline for tracking future changes in costs and will assist the production of cost-effectiveness estimates.     

Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation.

Pathological gambling (PG) related to dopaminergic treatment in Parkinson's disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syndrome (DDS). We describe a series of PD patients with preoperative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The patients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54 +/- 9 years; levodopa equivalent dose, 1,390 +/- 350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0-48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS-associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly attributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subthalamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment.     

Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinson's disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% ± 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms. © 2009 Movement Disorder Society     

Does subthalamic nucleus deep brain stimulation really improve quality of life in Parkinson's disease?

We investigated the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on quality of life (QOL) in patients with advanced Parkinson's disease, as self-assessed before and after surgery by completing the Parkinson's Disease Questionnaire (PDQ39). In addition to this prospective evaluation, we asked patients postoperatively to evaluate their preoperative QOL. In the prospective assessment, results showed that patients perceived a general improvement of QOL after the STN DBS. However, when evaluated retrospectively, they tended to overestimate their preoperative functioning, therefore obscuring the improvement found prospectively. This observation highlights the impact of the method used on obtained results when assessing the effects of STN DBS.     

Evolution of Parkinson's disease during 4 years of bilateral deep brain stimulation of the subthalamic nucleus.

Patients with advanced Parkinson's disease (PD) and motor complications can obtain significant symptom improvement by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Very little is published, however, about long-term effect and disease evolution during DBS. We performed a 4-year prospective study of the first 22 consecutive patients treated with STN DBS. The patients were evaluated with Unified Parkinson's Disease Rating Scale Part II to VI and a patient diary concerning on-off periods and dyskinesia. Patients were scored before surgery on medication and off medication for 10 to 12 hours and in four conditions 1 and 4 years after surgery: off medication+/-stimulation and on medication+/-stimulation. In advanced PD, a significant reduction of dyskinesia and off periods was present 4 years (90%/67%) after the operation. Total motor function on stimulation alone improved 55% at 4 years, compared with baseline and activities of daily living (42%). On stimulation, significant worsening of axial symptoms and speech was present from 1 to 4 years. To evaluate disease evolution, motor symptoms were assessed off stimulation and medication for 12 hours and were found not to worsen compared with baseline, which is remarkable in an otherwise progressive disorder. Five patients developed dementia. Severe adverse events were not observed.     

Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease.

Among 30 Parkinson's disease patients who received high frequency stimulation of the subthalamic nucleus, 5 developed remarkable disorders of mood or sexual behavior after the implant. We describe 2 men who developed mania and hypersexuality a few days after the implant that lasted for some months and then gradually disappeared spontaneously.     

Expectation and the placebo effect in Parkinson's disease patients with subthalamic nucleus deep brain stimulation.

To determine whether the degree to which a patient with Parkinson's disease expects therapeutic benefit from subthalamic nucleus-deep brain stimulation (STN-DBS) influences the magnitude of his or her improved motor response, 10 patients with idiopathic Parkinson's and bilateral STN-DBS were tested after a 12-hour period off medication and stimulation. Four consecutive UPDRS III scores were performed in the following conditions: (a) stimulation OFF, patient aware; (b) stimulation OFF, patient blind; (c) stimulation ON, patient aware; and (d) stimulation ON, patient blind. Statistical significance (P = 0.0001) was observed when comparing main effect ON versus OFF (mean ON: 32.55; mean OFF: 49.15). When the stimulation was OFF, patients aware of this condition had higher UPDRS motor scores than when they were blinded (mean: 50.7 vs. 47.6). With the stimulation ON, UPDRS motor scores were lower when the patients were aware of the stimulation compared with when they were blinded (mean: 30.6 vs. 34.5). The interaction between these levels was significant (P = 0.049). This variation was important for bradykinesia and was not significant for tremor and rigidity. The authors conclude that the information about the condition of the stimulation enhanced the final clinical effect in opposite directions. The results presented support the role of expectation and placebo effects in STN-DBS in Parkinson's disease patients.     

Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease.

In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico-striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions.     

Deep brain stimulation effects on gait variability in Parkinson's disease

The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on fall risk in patients with Parkinson's disease (PD) currently remain unclear. Although several gait parameters, such as gait speed, have shown improvement with DBS, some studies have reported an increased fall risk following DBS. The purpose of this study was to examine the effect of bilateral DBS on gait variability, a marker of fall risk. The gait of 13 patients with idiopathic PD was analyzed to determine the influence of DBS, levodopa and both therapies together. Following treatment with both levodopa and STN DBS, subjects displayed improved gait speed, reduced gait variability (enhanced stability), and lower Unified Parkinson's Disease Rating Scale (UPDRS) scores. Although UPDRS scores improved with STN DBS alone, parallel improvements were not seen for gait variability. These findings suggest that different mechanisms may contribute to performance on UPDRS motor testing and gait stability in response to DBS. © 2009 Movement Disorder Society