Nonmotor fluctuations in Parkinson's disease: frequent and disabling

OBJECTIVE: To assess the frequency and disability caused by nonmotor fluctuations (NMF) in PD. METHODS: A structured questionnaire was administered to 50 patients with PD with motor fluctuations (MF), focused on 54 nonmotor symptoms classified in three subgroups: 26 dysautonomic, 21 cognitive and psychiatric, and seven pain/sensory NMF. The link between each NMF and the motor state was determined. Patients were asked to grade their disability from 0 (no disability) to 4 (maximum discomfort) and to specify which kind of fluctuation subgroup (motor or nonmotor) was the most incapacitating. A statistical analysis was performed to determine the frequency of each NMF and to determine whether the level of disability resulting from NMF could be correlated to the main characteristics of the population. RESULTS: All patients had had at least one type of NMF, most of which were associated with the "off" state. Anxiety (66%), drenching sweats (64%), slowness of thinking (58%), fatigue (56%), and akathisia (54%) were the most frequent NMF. Some symptoms such as anxiety or dyspnea correlated with a greater level of disability. The total number of NMF was found to be correlated with the motor disability. Incapacity resulting from the dysautonomic fluctuations was also significantly correlated with levodopa treatment. Surprisingly, 28% of the patients stated that NMF involved a greater degree of disability than MF. CONCLUSION: Nonmotor fluctuations are frequent and debilitating in PD.     

Non-motor fluctuations in Parkinson's disease

Nonmotor fluctuations (NMF) in Parkinson's disease are nonmotor symptoms that occur in coincidence with motor fluctuations or independently. Long under-assessed, NMF are now recognized as frequent and sometimes involving a greater degree of disability than motor fluctuations. They can be classified in three categories: dysautonomic, cognitive/psychiatric and sensory/pain. Recognition of these nonmotor fluctuations as part of Parkinson's disease has important implications. Some symptoms such as dyspnea, chest pain, or abdominal pains can mimic cardiac or gastrointestinal emergencies. The underlying pathogenic mechanisms of NMF are not well known. The dopaminergic system is probably involved via modulation of other systems (serotoninergic, adrenergic) since NMF usually respond to dopaminergic treatment. Subthalamic nucleus deep brain stimulation alleviates NMF-- particularly sensory, dysautonomic and cognitive fluctuations--while psychic fluctuations respond less consistently to this treatment. The development of new instruments that enable a comprehensive and precocious assessment of NMF is important for optimized management of advanced Parkinson's disease.     

Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials are limited. OBJECTIVE: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD. DESIGN: This study represents the combined results from our previously published, randomized, blinded, parallel-group pilot study and additional patients enrolled in our single-center extension study. SETTING: Oregon Health and Science University in Portland.Patients Twenty-three patients with idiopathic PD, levodopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Patients and evaluating clinicians were blinded to stimulation site. All patients were tested preoperatively while taking and not taking medications and after 3, 6, and 12 months of DBS. MAIN OUTCOME MEASURES: Postoperatively, response of symptoms to DBS, medication, and combined medication and DBS was evaluated. Twenty patients (10 in the GPi group and 10 in the STN group) completed 12-month follow-up. RESULTS: Off-medication Unified Parkinson's Disease Rating Scale motor scores were improved after 12 months of both GPi and STN stimulation (39% vs 48%). Bradykinesia tended to improve more with STN than GPi stimulation. No improvement in on-medication function was observed in either group. Levodopa dose was reduced by 38% in STN stimulation patients compared with 3% in GPi stimulation patients (P = .08). Dyskinesia was reduced by stimulation at both GPi and STN (89% vs 62%). Cognitive and behavioral complications were observed only in combination with STN stimulation. CONCLUSION: Stimulation of either the GPi or STN improves many features of advanced PD. It is premature to exclude GPi as an appropriate target for DBS in patients with advanced disease.     

Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not.

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B‐STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory‐deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B‐STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N_subset = 23; P < 0.001 for both); (3) B‐STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B‐STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003). © 2006 Movement Disorder Society     

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease

Background: The objective of this study was to investigate 24‐month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). Methods: In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN‐DBS, we examined the Non‐motor Symptom Scale, Non‐Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire‐8, Scales for Outcomes in Parkinson's Disease‐motor examination, ‐activities of daily living, and ‐complications, and levodopa‐equivalent daily dose preoperatively and at 5 and 24‐month of follow‐up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated‐measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24‐month follow‐up were calculated for all outcomes. Results: The Non‐motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5‐month follow‐up. From 5 to 24‐month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24‐month follow‐up, significant improvements were observed for the Non‐motor Symptom Scale (small effect), Scales for Outcomes in PD‐motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease‐complications and levodopa‐equivalent daily dose showed large effects. Non‐motor Symptom Scale change scores from baseline to 24‐month follow‐up correlated significantly with Parkinson's Disease Questionnaire‐8, Scales for Outcomes in Parkinson's Disease‐activities of daily living, and ‐motor complications change scores. Conclusions: This study provides evidence of beneficial effects of bilateral STN‐DBS on nonmotor symptoms at 24‐month follow‐up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society     

Speed effects of deep brain stimulation for Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) accelerates reaction time (RT) in patients with Parkinson's disease (PD), particularly in tasks in which decisions on the response side have to be made. This might indicate that DBS speeds up both motor and nonmotor operations. Therefore, we studied the extent to which modifications of different processing streams could explain changes of RT under subthalamic DBS. Ten PD patients on‐DBS and off‐DBS and 10 healthy subjects performed a choice‐response task (CRT), requiring either right or left finger button presses. At the same time, EEG recordings were performed, so that RTs could be assessed together with lateralized readiness potentials (LRP), indicative of movement preparation. Additionally, an oddball task (OT) was run, in which right finger responses to target stimuli were recorded along with cognitive P300 responses. Generally, PD patients off‐DBS had longer RTs than controls. Subthalamic DBS accelerated RT only in CRT. This could largely be explained by analog shortenings of LRP. No DBS‐dependent changes were identified in OT, neither on the level of RT nor on the level of P300 latencies. It follows that RT accelerations under DBS of the STN are predominantly due to effects on the timing of motor instead of nonmotor processes. This starting point explains why DBS gains of response speed are low in tasks in which reactions are initiated from an advanced level of movement preparation (as in OT), and high whenever motor responses have to be raised from scratch (as in CRT). © 2010 Movement Disorder Society     

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.     

Long‐term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease

We report the 5 to 6 year follow‐up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty‐five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross‐over double‐blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off‐ and on‐medication states with and without stimulation, activities of daily living (ADL), anti‐PD medications, and dyskinesias. In double‐blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off‐stimulation, regardless of the sequence of stimulation. In open assessment, both STN‐ and GPi‐DBS significantly improved the off‐medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti‐PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long‐term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN‐DBS patients and fewer adverse events in the GPi‐DBS group. © 2010 Movement Disorder Society     

Deep brain stimulation and medication for parkinsonian tremor during secondary tasks.

This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS.     

Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease

To examine the effects of levodopa (L ‐dopa) and deep brain stimulation of the subthalamic nucleus (STN‐DBS) on sensory symptoms and signs in Parkinson's disease (PD). Seventeen patients with PD were included. (1) Presence of sensory symptoms and (2) effects of L ‐dopa and STN‐DBS on sensory symptoms and signs [assessed by quantitative sensory testing (QST)] were examined 6 months after starting STN‐DBS. In addition, in 12 of these patients, presence of sensory symptoms prior and post STN‐DBS was compared. Pain was most frequently nociceptive. In about 30–40%, pain and sensory symptoms were associated with PD motor symptoms. In most of these cases, pain responded to L ‐dopa. Intensity of pain was reduced post STN‐DBS compared to pre STN‐DBS. L ‐Dopa had no influence on detection thresholds, whereas STN‐DBS improved thermal detection thresholds. However, thermal and mechanical pain thresholds were uninfluenced by L ‐dopa or STN‐DBS. Although some patients reported an improvement of pain with STN‐DBS or L ‐dopa, objectively pain sensitivity as assessed by QST was not altered by STN‐DBS or L ‐dopa suggesting that there is no evidence for a direct modulation of central pain processing by L ‐dopa or STN‐DBS. © 2010 Movement Disorder Society     

Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

Effect of deep brain stimulation of the subthalamic nucleus on non-motor fluctuations in Parkinson's disease: Two-year' follow-up

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkinson's disease (PD) but its effect on non-motor fluctuations (NMF) is not well known. In this study we assess the efficacy of STN-DBS on NMF two years after surgery.MethodsAutonomic, cognitive, psychiatric and sensory NMF in 20 patients were evaluated using a questionnaire designed to assess the frequency and severity of the NMF preoperatively and after two years of follow-up. The UPDRS scale was used for assessing the motor state.ResultsCompared with the preoperative situation, STN-DBS at 2 years of follow-up was associated with a significant reduction in the number and severity of autonomic and psychiatric NMF in the “off” state (without medication), and in the severity of sensory NMF, which were not observed in the “on” state (with medication). A cross-sectional analysis at the two-year time-point of the four possible motor conditions (combining medication and stimulation) showed a reduction in the total number of NMF and in the severity of autonomic and sensory NMF after switching on the stimulation in the “on” state. Improvement of the UPDRS-motor score was correlated with a reduction in the severity but not in the frequency of NMF. A worsening of motor function after suppressing stimulation in the “off” state was not paralleled by a worsening of NMF.ConclusionAfter two years of follow-up, STN-DBS in the “off” medication was associated with a reduction in the frequency and severity of NMF. These results will need to be confirmed in controlled studies.     

Chronic subthalamic deep brain stimulation improves pain in Parkinson disease

Background   

Pain is a well recognized feature of Parkinson disease (PD). Like motor fluctuations, pain in PD may fluctuate as ‘non-motor fluctuations’. Subthalamic deep brain stimulation (STN DBS) is an established treatment for motor fluctuations in PD. However, the effect of STN DBS on the pain in PD is only partially investigated.     

Relationship of clinical efficacy to postmortem-determined anatomic subthalamic stimulation in Parkinson syndrome

OBJECTIVE/BACKGROUND: Patients with medically refractory Parkinson's disease (PD) obtain significant clinical benefit from subthalamic nucleus (STN) stimulation. The degree to which a successful outcome relates to the anatomic location of the stimulating electrode has not yet been clearly established. Many studies have attempted to correlate the clinical result with the electrode location using postoperative magnetic resonance imaging (MRI) and there have been a few that used autopsy-determined locations. In this report, we describe long-term clinical follow-up in a patient with autopsy-determined electrode tip anatomic location. METHODS: A 67-year-old patient with a 27-year history of idiopathic PD complicated by disabling motor fluctuations and dopaminergic dyskinesias underwent bilateral STN deep brain stimulation (DBS). He was prospectively followed in a long-term clinical protocol until his death 40 months after electrode placement. Postoperative magnetic resonance (MR) imaging and postmortem studies of this patient's brain were performed to localize DBS tip locations. RESULTS: STN stimulation produced improvement of the patient's motor fluctuations, dyskinesias and clinical motor performance, especially appendicular tremors, rigidity and bradykinesia. MRI showed the electrode tips to be within 2 mm of the intended target. Postmortem brain analysis identified the right DBS tip location at the dorsomedial edge of the STN, with the left electrode in the vicinity (but not within) the STN. Chronic DBS elicited minor reactive changes were confined to the immediate vicinity of the electrode tracks. The pathological analysis demonstrated numerous cortical Lewy bodies and degenerative encephalopathy, establishing the diagnosis of transitional type diffuse Lewy body disease (DLBD) rather than simple PD. CONCLUSION: This patient obtained clinical benefit from STN stimulation typical of that seen for most PD patients. Both the MR analysis and the autopsy demonstrated electrode placement at or outside the boundaries of the STN, suggesting that that clinical efficacy may not depend on electrode location within the central region of the STN.     

双侧丘脑底核电刺激对帕金森病患者脑局部糖代谢的影响

目的 研究双侧丘脑底核(subthalamic nucleus,STN)慢性电刺激术(deep brain stimulation,DBS)对晚期帕金森病(Parkinson's disease,PD)患者静止期脑局部糖代谢的影响,并探讨其作用机制。方法 对5例进行双侧STN的DBS治疗的晚期帕金森病患者,分别在术前以及术后1个月电刺激条件下,进行静止期18F-脱氧葡萄糖(FDG)/PET检查和UPDRS运动评分,并通过SPM99统计学软件进行数据分析,比较STN的DBS治疗对脑内代谢的影响。结果 双侧STN的DBS治疗使PD患者临床症状明显改善,同时脑局部糖代谢也发生了明显变化:双侧豆状核、脑干(中脑、脑桥)、双侧顶枕部、运动前区(BA6)及扣带回的脑代谢增加,双侧前额叶底部海马的脑代谢明显减少(P<0.05)。结论 双侧STN的DBS治疗可能通过兴奋STN轴突的方式,使其投射区域的基底上行和下行通路以及相应的皮层高级中枢的代谢改善,从而使PD患者的临床症状改善。     

Changes in cognitive‐emotional and physiological symptoms of depression following STN‐DBS for the treatment of Parkinson’s disease

Background and purpose: Subthalamic nucleus deep brain stimulation (STN‐DBS) has been shown to have beneficial effects on the motor features of Parkinson’s disease (PD), but its impact on non‐motor symptoms, most notably mood, has not been fully explored. Methods: In the first study to independently compare the emotional‐cognitive and somatic/physiological symptoms of depression, we examined mood differences in 17 bilateral STN‐DBS and 22 matched non‐surgical PD patients at baseline and 6 months. Results: The STN‐DBS group reported higher levels of depression at baseline with significant endorsement of physical symptomatology. Postoperatively, no significant between‐group differences in physical symptoms of depression were found. In contrast, a significant group by time interaction for cognitive‐emotional symptoms of depression was found, with the STN‐DBS group reporting an increase in psychological symptoms of distress. The STN‐DBS group also reported an increase in anxiety following surgery. The suicide rate of 5% found in our study is consistent with other postoperative studies in PD. The impact of changes in levodopa and psychotropic medication are also explored. Conclusions: Preliminary results suggest that the motor improvement often observed in patients with PD following bilateral STN‐DBS may be partially offset by an increase in affective‐cognitive symptoms of depression.     

Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease

A higher than expected frequency of suicide has been reported among patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) for advanced Parkinson's disease (PD). We conducted a retrospective survey of 200 patients with PD who underwent STN DBS. Two patients (1%) committed suicide and four (2%) attempted suicide, despite clear motor improvements. Suicidal patients did not differ from non-suicidal patients with respect to age, disease duration or preoperative depressive and cognitive status. Suicidal behaviour was associated with postoperative depression and/or altered impulse regulation. Suicidal behaviour is a potential hazard of STN DBS, calling for careful preoperative assessment and close postoperative psychiatric and behavioural follow-up.     

OFF-off rebound dyskinesia in subthalamic nucleus deep brain stimulation of Parkinson's disease.

A 61-year-old man with Parkinson's disease (PD), motor fluctuations, and dyskinesias underwent bilateral implantation of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). One month after surgery, DBS was optimized to bilateral monopolar settings at the most proximal electrode just superior to the STN, which improved motor fluctuations and dyskinesias. At several postoperative evaluations off medications overnight, both stimulators were turned off and within 60 seconds he developed severe dyskinesias. When the stimulators were turned back on, the dyskinesias soon resolved. This article is a first report of a unique pattern of rebound-type dyskinesia that occurred in the off medication state produced by stopping STN DBS.     

Chronic inhibition of the subthalamic nucleus in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a popular treatment option for patients suffering from severe Parkinson's disease (PD). Yet the long-term outcome of subthalamic DBS is unknown. A total of 27 patients suffering from severe PD underwent bilateral stereotactic implantation of high-frequency stimulators in the STN. Before surgery and at least annually after surgery they were examined with the Unified Parkinson's Disease Rating Scale (UPDRS). This study presents the results of a mean 30 months (range 23 to 55) follow-up of these patients. We found stable and significant off medication improvement of motor function by DBS (between 40% and 44% in the UPDRS part III). While on medication there was no significant change in the motor function by DBS. UPDRS part III worsened gradually during the follow-up period, suggesting disease progression. Thirty months postsurgery the UPDRS part II (ADL) was still improved by 17%. There was a lasting decrease in fluctuations by more than 50%, and dyskinesias were reduced by about 70%. Freezing was reduced significantly from 2.2 in the UPDRS part II to 1.2 at the endpoint. The daily levodopa-equivalent dose was reduced by 39% at 12 months and by 30% at 30 months after STN stimulator implantation. Subthalamic DBS improves sustainable motor function in patients with severe Parkinson's disease and leads to a lasting reduction of medication. Limitations of this procedure were found for disturbances of speech and swallowing.