Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up

Neurological Sciences - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective therapy for the treatment of advanced Parkinson's disease (PD)....     

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease

BackgroundIn Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD.MethodsWe investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17.ResultsAll pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or l-Dopa reduction.ConclusionsSTN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients.     

Deep brain stimulation of the subthalamic nucleus improves intrinsic alertness in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with Parkinson's disease (PD) in the advanced stage. Besides motor improvement, DBS of the STN may also modulate cognitive and attentional functions of the basal ganglia. In our study, 13 patients with PD and bilateral DBS of the STN were assessed with DBS switched on and off by the use of a wide range of neuropsychological tasks. This included reasoning, cognitive flexibility, phonemic and semantic word fluency, verbal and nonverbal short‐term memory, learning, delayed verbal memory recall, and stimulus‐response incompatibility. Special emphasis was put on basic attentional functions, in particular intrinsic and phasic alertness as well as visual search. DBS significantly improved intrinsic alertness, whereas phasic alertness and other neuropsychological domains were not affected. Additionally, the effects on intrinsic alertness were independent of motor improvements by DBS. The findings suggest that DBS modulates the fronto‐parietal network of alertness. © 2009 Movement Disorder Society     

Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's disease

Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off- to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.     

Deep brain stimulation promotes excitation and inhibition in subthalamic nucleus in Parkinson's disease

Subthalamic nucleus single-unit recordings were undertaken before and during pedunculopontine [corrected] nucleus-stimulation at clinically relevant frequency (25 Hz) in six patients with Parkinson's disease. Pedunculopontine [corrected] nucleus stimulation changed the firing activity of almost every subthalamic nucleus cell (44/48) by decreasing the ongoing discharge in bursting subthalamic nucleus neurons (-62.1%) and exciting irregular (+63.2%) and tonic/regular discharges (+20.1%). These conflicting data challenge the definition of pedunculopontine [corrected] nucleus as a new target area for Parkinson's disease. If the modulation of subthalamic nucleus bursting units may corroborate the pedunculopontine [corrected] nucleus therapeutic role, the simultaneous excitatory influence during nonbursty patterns might interfere with a favorable outcome on motor signs. As a result, the implantation of pedunculopontine [corrected] nucleus alone may be hazardous while the association of subthalamic nucleus plus pedunculopontine [corrected] nucleus seems to be reasonable.     

Deep brain stimulation of the subthalamic nucleus improves sense of well-being in Parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short-term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self-reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty-three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better-coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short-term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day-to-day management of patients with deep brain stimulation of the subthalamic nucleus are discussed.     

Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease

To investigate the bilateral effects of unilateral subthalamic nucleus deep brain stimulation (STN-DBS), we prospectively studied 9 consecutive advanced Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months postoperatively with and without dopaminergic medications ('on' and 'off' medication, respectively). Postoperatively, patients were assessed with and without stimulation. We found that, when compared with baseline, the 'off' medication scores of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p = 0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6 months. At 6 months after surgery, the subscore of UPDRS III of body parts contralateral to the DBS implantation had improved by 48% (p = 0.028), and the ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of levodopa was reduced by 15% at 6 months. No patient exhibited permanent side effects. These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism.     

Deep brain stimulation of subthalamic nucleous in Parkinson's disease

We present the preliminary results in patients well selected to be implanted by deep brain stimulation (DBS) for Parkinsons's disease (PD). METHODS: 8 PD patients with disabled tremor, akinetic/bradikinetic and rigidity, in spite of best therapeutic assay with poor response were referred to surgery. It was implanted DBS Itrell 2. Theses patients were evaluated by the following scales: UPDRS, Schwab and England. RESULTS: The preliminary results in 6 months showed significant improvement of motor performance and it is shown by the scores. There were no complications so far with these procedures. CONCLUSION: The preliminary results indicate that DBS is highly effective, with benefit to those patients and it is according to literature.     

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease

BackgroundDespite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions.Patients and methodsInvestigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure.ResultsThe comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex.ConclusionDeep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects.     

Deep brain stimulation of the subthalamic nucleus: clinical effectiveness and safety

The authors report the data relative to the clinical effectiveness of bilateral deep brain stimulation of the subthalamic nucleus in 16 patients with PD 3 months after the surgery. The comparison of the Unified PD Rating Scale scores in the different conditions of medication and stimulation, and the lack of significant surgical complications, confirm the effectiveness and the safety of the subthalamic nucleus deep brain stimulation for the treatment of advanced PD.     

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.     

Contrast sensitivity in Parkinson's disease patients with subthalamic nucleus deep brain stimulation

This study examined whether deep brain stimulation (DBS) would affect the contrast sensitivity (CS) curve in patients with PD. CS was tested in 12 nondemented PD patients treated with bilateral subthalamic nucleus DBS on and off stimulation and medications. Neither stimulation condition (on vs. off) nor medications altered CS performance in this group of patients. However, collapsed across conditions, patients with bipolar stimulation in this study had significantly poorer CS at higher spatial frequencies (12 and 18 cycles per degree) than patients with monopolar stimulation. This suggests that CS deficits in PD may possibly be influenced by DBS polarity and merits further study. © 2009 Movement Disorder Society     

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a therapy approaching evidence-based standards

Journal of Neurology - DBS of the STN is one of the most promising new therapies for the treatment of PD. However – like many other therapies for PD – the present stage of the...     

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic Parkinson's disease: one year follow-up

Summary. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 ± 14.3 to 27.8 ± 5.8, and after 12 months from 49.4 ± 14.1 to 27.1 ± 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 ± 2.47 hours to 1.00 ± 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 ± 2.72 to 14.62 ± 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (± 4.18) to 0.25 (± 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 ± 1.58 hours, p < 0.001; on-periods without: 13.87 ± 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 ± 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation – and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. Received June 25, 1998; accepted February 3, 1999     

Deep brain stimulation for the treatment of Parkinson's disease: subthalamic nucleus versus globus pallidus internus

OBJECTIVES: Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinson's disease who have side effects from drugs. Which is the best target-globus pallidus internus (GPi) or subthalamic nucleus (STN)-is still a matter of discussion. The aim of this prospective study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinson's disease. PATIENTS AND METHODS: Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinson's disease. Presurgery and 3, 6, and 12 months postsurgery patients were scored according to the CAPIT protocol. RESULTS: Stimulation of the STN increased best Schwab and England scale score significantly from 62 before surgery to 81 at 12 months after surgery; GPi stimulation did not have an effect on the Schwab and England scale. Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication. Whereas STN stimulation increased the unified Parkinson's disease rating scale (UPDRS) motor score, GPi stimulation did not have a significant effect. Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively. CONCLUSION: Stimulation of the GPi reduces medication side effects, which leads to a better drug tolerance. There was no direct improvement of bradykinesia or tremor by GPi stimulation. Stimulation of the STN ameliorated all parkinsonian symptoms. Daily drug intake was reduced by STN stimulation. The STN is the target of choice for treating patients with severe Parkinson's disease who have side effects from drugs.     

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a therapy approaching evidence-based standards

DBS of the STN is one of the most promising new therapies for the treatment of PD. However - like many other therapies for PD - the present stage of the scientific assessment does not yet suffice the rigid criteria of evidence-based medicine. Further studies should specifically address the questions of efficacy and side effects as well as the impact on quality of life.     

Addiction in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation

In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinson's disease, therefore, does not constitute an obstacle to high‐frequency STN stimulation, and this treatment may even cure the addiction. © 2005 Movement Disorder Society