Deep brain stimulation in Parkinson's disease: bilateral implantation of globus pallidus and subthalamic nucleus

AIM: Deep brain stimulation (DBS) of subthalamic nucleus (STN) and of the pars interna of globus pallidus (GPi) is used to improve Parkinsonian symptoms and attenuate levodopa-induced motor complications in Parkinson's disease (PD). What are the physiological effect of DBS and the best anatomical structure to stimulate are still not completely clear. In this way we could evaluate the clinical effects of simultaneous stimulation of STN and GPi as well as the isolated stimulation of each target. METHODS: The stereotactic methods used to localise STN and GPi were based on non-telemetric ventriculography, with 3P Maranello or Leksell Stereotactic System. The effects of DBS have been assessed in 13 cases of PD, immediately after (30 minutes) the stimulation has turned on and during chronic stimulation (weeks or months). RESULTS: Most of the studies have been conducted on patients with STN implantation, and these studies reported relevant improvement in motor function and relatively low rate of complication. CONCLUSION: The large experience of ablative surgery associate with the DBS experience of some group worldwide indicate that GPi is a possible and very promising target for the management of Parkinsonian symptoms. Our patients demonstrate in acute and chronic evaluation, the best clinical results with contemporary activation of DBS in both targets.     

Parkinson’s disease: Surgical options

Opinion statement Surgical therapy for Parkinson’s disease (PD) has been a treatment option for over 100 years. Advances in the knowledge of basal ganglia physiology and in techniques of stereotactic neurosurgery and neuroimaging have allowed more accurate placement of lesions or “brain pacemakers” in the sensorimotor regions of target nuclei. This, in turn, has led to improved efficacy with fewer complications than in the past. Currently, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is the preferred option (and is approved by the US Food and Drug Administration) for the surgical treatment of PD. The most important predictors for outcome for DBS for PD are patient selection and electrode location. Patients should have a documented preoperative improvement from dopaminergic medication of at least 30% in the patient’s Unified Parkinson’s Disease Rating Scale motor disability scores. A levodopa challenge may be needed to document the best “on” state. Dementia or active cognitive decline must be excluded. Active psychiatric disease should be treated preoperatively. Patients should be motivated, with good support systems, and committed to the postoperative management of DBS therapy. Deep brain stimulation should be considered when the patient begins to experience dyskinesia and on-off fluctuations despite optimal medical therapy. Deep brain stimulation is not a good option at the final stages of the disease because of the increased incidence of dementia and severe comorbidity. The DBS electrode should be placed in the sensorimotor region of the GPi or STN. Subthalamic nucleus and GPi DBS can improve all motor aspects of PD, as well as predictable “on” time, without dyskinesia or fluctuations. On average, STN DBS results in a greater reduction of dopaminergic medication compared with GPi DBS. Because of the smaller size of the target region, the pulse generator battery life is longer with STN then with GPi DBS. Deep brain stimulation programming is a skill that is readily learned and may be required of all neurologists in the future. Emerging surgical therapies are restorative, and they aim to replace or regenerate degenerating dopaminergic neurons. These include embryonic mesencephalic tissue transplantation, human embryonic stem cell transplantation, and gene-derived methods of intracerebral implantation of growth factors and dopamineproducing cell lines. It will be important to determine whether DBS, if performed before the onset of motor response complications to medical therapy, may prevent this stage of disease altogether or delay it for a significant period of time. The same question applies to the future with restorative therapy.     

Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease

OBJECT: The authors compared the effects of deep brain stimulation (DBS) in the globus pallidus internus (GPi) with those in the subthalamic nucleus (STN) in patients with Parkinson disease (PD) in whom electrodes had been bilaterally implanted in both targets. METHODS: Eight of 14 patients with advanced PD in whom electrodes had been implanted bilaterally in both the GPi and STN for DBS were selected on the basis of optimal DBS effects and were studied 2 months postsurgery in off- and on-stimulus conditions and after at least 1 month of pharmacological withdrawal. Subcutaneous administration of an apomorphine test dose (0.04 mg/kg) was also performed in both conditions. Compared with the off status, the results showed less reduction in the Unified PD Rating Scale Section III scores during DBS in the GPi (43.1%) than during DBS of the STN (54.5%) or DBS of both the STN and GPi (57.1%). The difference between the effects of DBS in the GPi compared with that in the STN or simultaneous DBS was statistically significant (p < 0.01). In contrast, no statistical difference was found between DBS in the STN and simultaneous DBS in the STN and GPi (p < 0.9). The improvement induced by adding apomorphine administration to DBS was similar in all three stimulus modalities. The abnormal involuntary movements (AIMs) induced by apomorphine were almost abolished by DBS of the GPi, but were not affected by stimulation of the STN. The simultaneous stimulation of STN and GPi produced both antiparkinsonian and anti-AIM effects. CONCLUSIONS: The improvement of parkinsonian symptoms during stimulation of the GPi, STN, and both nuclei simultaneously may indicate a similar DBS mechanism for both nuclei in inducing antiparkinsonian effects, although STN is more effective. The antidyskinetic effects produced only by DBS of the GPi, with or without STN, may indicate different mechanisms for the antidyskinetic and antiparkinsonian activity related to DBS of the GPi or an additional mechanism in the GPi. These findings indicate that implantation of double electrodes for DBS should not be proposed as a routine procedure, but could be considered as a possible subsequent choice if electrode implantation for DBS of the STN does not control AIMs.     

Long-term outcomes of bilateral subthalamic nucleus stimulation in patients with advanced Parkinson's disease

BACKGROUND: In patients with advanced Parkinson's disease (PD), deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to improve motor function and decrease medication requirements in the short term. However, the long-term benefits of DBS are not yet established. OBJECTIVE: It was the aim of this study to evaluate long-term outcomes of patients with PD treated with bilateral DBS of the STN. DESIGN AND METHODS: Thirty-three subjects who had bilateral STN DBS were followed prospectively after surgery. We evaluated subjects, using the Unified Parkinson's Disease Rating Scale (UPDRS), preoperatively, 12 months after surgery and at a long-term follow-up visit. Ratings were performed on and off dopaminergic medications. We compared postoperative UPDRS scores, dyskinesia ratings and medication dosages with preoperative values. RESULTS: Twenty-seven subjects had evaluations beyond 18 months (median 33.7 months). Total UPDRS scores in the 'medication-off' state were improved by 37% (p < 0.001) at 12 months and 17.7% (p = 0.0051) at the long-term evaluation. Medication-off state UPDRS part III scores were significantly improved at both 1 year and at the last evaluation (37.6 and 29.3%; p < 0.001). Dopaminergic medication requirements were decreased by 35.3% (p < 0.001) during the first postoperative year and remained below preoperative levels at the long-term evaluation. Average duration of 'off' time remained decreased by about 40% at both 1 year and at the time of last evaluation. Subjects had a sustained reduction in dyskinesia severity (88.6% at 1 year and 68.8% at last evaluation). CONCLUSIONS: In this cohort of subjects with advanced PD, bilateral STN stimulation improved 'off' medication motor function, reduced time spent in the medication-off state and reduced medication requirements for up to 4 years after surgery. We conclude that STN DBS is an effective long-term therapy for selected patients with advanced PD.     

Weight Change after Globus Pallidus Internus or Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease and Dystonia

Background: Weight gain has been described in Parkinson's disease (PD) patients after subthalamic nucleus (STN) deep brain stimulation (DBS). Objectives: We examined change in weight following DBS in both PD and dystonia patients to further investigate the role of disease and brain target (STN or globus pallidus internus, GPi) specificity. Methods: Data was retrospectively collected on 61 PD DBS patients (STN n = 31 or GPi n = 30) and on 36 dystonia DBS patients (STN n = 9 and GPi n = 27) before and after surgery. Annual change in body mass index (BMI) was evaluated with nonparametric tests between groups and multiple quantile regression. Results: PD patients treated with STN DBS had a small increase in median BMI while those with GPi had a small decrease in BMI. Dystonia patients treated with STN DBS had a greater increase in BMI per year compared to those treated with GPi DBS. Multivariable regression analyses for each disease showed little difference between targets in weight gain in those with PD, but STN target was strongly associated with weight gain in dystonia patients (STN vs. GPi, +7.99 kg, p = 0.012). Conclusions: Our results support previous reports of weight gain after DBS in PD. This is the first report to suggest a target-specific increase in weight following STN DBS in dystonia patients.     

Deep Brain Stimulation for Parkinson’s Disease: Recent Trends and Future Direction

To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson’s disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed.     

Effect of subthalamic stimulation on mood state in Parkinson's disease: evaluation of previous facts and problems

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinson's disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7-76%, 2-33.3%, and 4.2-8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.     

Does deep brain stimulation improve lower urinary tract symptoms in Parkinson's disease?

Aims

To investigate whether deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or the subthalamic nucleus (STN) improve lower urinary tract symptoms (LUTS) in advanced Parkinson's disease (PD).

Methods

An exploratory post‐hoc analysis was performed of specific LUTS items of questionnaires used in a randomized clinical trial with 128 patients (NSTAPS study). First, we compared scores on LUTS items at baseline and 12 months for the GPi DBS and STN DBS group separately. Second, we divided the group by sex, instead of DBS location; to assess a possible gender associated influence of anatomical and pathophysiological differences, again comparing scores at baseline and 12 months. Third, we reported on Foley‐catheter use at baseline and after 12 months.

Results

Urinary incontinence and frequency improved after both GPi DBS and STN DBS at 12 months, postoperatively, but this was only statistically significant for the STN DBS group (P = 0.004). The improvements after DBS were present in both men (P = 0.01) and women (P = 0.05). Nocturia and urinary incontinence did not improve significantly after any type of DBS, irrespective of sex. At 12 months, none of the patients had a Foley‐catheter.

Conclusions

Urinary incontinence and frequency significantly improved after STN DBS treatment in male and female patients with PD. Nocturia and nighttime incontinence due to parkinsonism did not improve after DBS, irrespective of gender.     

Effect of subthalamic stimulation on mood state in Parkinson’s disease: evaluation of previous facts and problems

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinsons disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7–76%, 2–33.3%, and 4.2–8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.     

Unilateral deep brain stimulation of the subthalamic nucleus for Parkinson disease

OBJECT: The object of this study was to assess the results of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for management of advanced Parkinson disease (PD). METHODS: A clinical series of 24 patients (mean age 71 years, range 56-80 years) with medically intractable PD, who were undergoing unilateral magnetic resonance imaging-targeted, electrophysiologically guided STN DBS, completed a battery of qualitative and quantitative outcome measures preoperatively (baseline) and postoperatively, using a modified Core Assessment Program for Intracerebral Transplantations protocol. The mean follow-up period was 9 months. Statistically significant improvement was observed in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and scores for axial motor features (19%), contralateral tremor (88%), rigidity (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's Disease Quality of Life questionnaire score (15%) in the on-stimulation state compared with baseline. Ipsilateral symptoms improved by approximately 15% or less. Performance on the Purdue pegboard test improved in the contralateral hand in the on-stimulation state compared with the off-stimulation state (38%, p < 0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018). Neuropsychological tests revealed an improvement in mental flexibility and a trend toward reduced letter fluency. There were no permanent surgical complications. Of the 16 participants with symmetrical disease, five required implantation of the DBS unit on the second side. CONCLUSIONS: Unilateral STN DBS is an effective and safe treatment for selected patients with advanced PD. Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as well as quality of life, reduces requirements for medication, and possibly enhances mental flexibility. This method of surgical treatment may be associated with a reduced risk and may provide an alternative to bilateral STN DBS for PD, especially in older patients or patients with asymmetry of parkinsonism.     

Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism

Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.     

Direct effect of subthalamic nucleus stimulation on levodopa-induced peak-dose dyskinesia in patients with Parkinson's disease

We examined the direct effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on levodopa-induced peak-dose dyskinesia in 45 patients with Parkinson's disease (PD) without reducing the levodopa dosage during the early period after surgery. In 8 patients (18%), the dyskinesia was quickly attenuated by bipolar stimulation in an experimental trial (5 min) with the contacts placed within the area above the STN. In contrast, bipolar stimulation using contacts placed within the STN itself tended to provoke or exacerbate the dyskinesia, indicating that dyskinesia could be inhibited by stimulation of the areas above the STN rather than the STN itself. In an attempt to control the cardinal symptoms of PD and dyskinesia at the same time, we employed bipolar stimulation with a longer interpolar distance as a therapeutic procedure (2 weeks), using contacts within the STN as a cathode and contacts within the area above the STN as an anode. Bilateral STN-DBS significantly attenuated the dyskinesia as evaluated by the dyskinesia severity rating scale (p < 0.05). In 24 patients (53%), almost complete control of the dyskinesia was observed. The contacts used as an anode in these patients were located more dorsally compared to those of the remaining patients, suggesting again that the dyskinesia was inhibited by stimulation of the areas above the STN rather than the STN itself. In the area above the STN, pallidothalamic, pallidosubthalamic and subthalamopallidal fibers are densely distributed. It appears that stimulation of these fibers may cause effects similar to thalamic or pallidal DBS and therefore inhibit peak-dose dyskinesia. Bipolar STN-DBS with contacts placed within the area above the STN as an anode appears to represent a useful option for controlling both the cardinal symptoms of PD and peak-dose dyskinesia at the same time.     

Staged bilateral deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease

Background  Several investigators have described the efficacy and safety of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of Parkinson’s disease (PD). Some patients who underwent unilateral STN DBS required additional surgery on the contralateral side because the unilateral treatment was insufficient. The goal of this study was to assess the efficacy and safety of staged bilateral STN DBS compared to the simultaneous bilateral procedure. Methods  Ten patients with medically intractable PD underwent staged bilateral STN DBS, and 12 patients underwent a simultaneous bilateral procedure. Clinical assessments were performed preoperatively and 6 months after the last surgery using the Unified Parkinson’s Disease Rating Scale (UPDRS), motor and activity of daily living (ADL) subscores, and Hoehn and Yahr stages. Findings  Both the staged and simultaneous groups experienced significant improvement in the UPDRS motor and ADL scores, and the Hoehn and Yahr stages. There were no statistical differences between the two groups in the percent improvement in UPDRS scores. The rate of adverse events in the staged group (20%) was less than that of the simultaneous group (42%), although the difference was not statistically significant. Conclusions  Both the staged bilateral STN DBS and the simultaneous bilateral procedure are effective and safe treatment options, but the staged bilateral procedure may be regarded as the preferred choice for the treatment of some patients. No financial support was received for this research. The findings presented herein have not been previously published.     

Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety

OBJECT: Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. METHODS: In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. CONCLUSIONS: This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.     

Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients.

OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.     

Effects of bilateral subthalamic nucleus stimulation on sleep, daytime sleepiness, and early morning dystonia in patients with Parkinson disease

OBJECT: The aim of this study was to assess the long-term effects of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) on sleep, daytime sleepiness, and early morning dystonia and to evaluate the relationship between total sleep time and motor function. METHODS: Patients who had undergone bilateral STN DBS and a follow-up evaluation of 6 months (89 patients), 12 months (83 patients), and 24 months (43 patients) were included in this study. The patients were preoperatively assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) in the medication-on and -off conditions, and they completed patient diaries. A subset of patients also completed the Epworth Sleepiness Scale. These assessments were repeated postoperatively with stimulation. The UPDRS activities of daily living (ADL) and motor scores as well as total sleep hours were significantly improved at 6, 12, and 24 months poststimulation and with no medication compared with baseline values. Increased sleep time was significantly correlated with improvements in bradykinesia but not with tremor or rigidity. Patient-reported sleep problems and early morning dystonia were reduced after STN DBS. Antiparkinsonian medications were significantly reduced after STN DBS; however, there were no changes in excessive daytime sleepiness 6, 12, or 24 months after surgery. CONCLUSIONS: Bilateral STN DBS increased total sleep time and reduced patient-reported sleep problems and early morning dystonia for up to 24 months posttreatment. These changes in sleep were related to improvements in functioning, specifically those affected by bradykinesia. Despite significant reductions in antiparkinsonian medications, STN DBS did not reduce excessive daytime sleepiness.     

Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes

OBJECT: Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. METHODS: This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = -0.02). CONCLUSIONS: In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.     

Results of chronic subthalamic nucleus stimulation for Parkinson's disease: a 1-year follow-up study

BACKGROUND: Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson's disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS. METHODS: Thirty-eight patients have undergone surgery for advanced PD since 1996. They include 12 females and 26 males with a mean age of 55.6 years. The mean stage on the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes (Medtronic DBS 31389) were stereotactically implanted into the STN bilaterally. Targeting was performed using computerized tomography (CT) scans and ventriculography (VG). After 4 days of external stimulation, permanent neurostimulators were implanted. Patients were evaluated preoperatively and 1, 6, and 12 months postoperatively. Evaluations were performed in defined on and off states using the Unified Parkinson's Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr Scale, the dyskinesia scale, and the Activities of Daily Living (ADL) Scale. RESULTS: Significant improvement of all motor symptoms was found in all patients (UPDRS motor score 32/48 preoperatively versus 15/30 at 12-month follow-up, p < 0.001). Daily off-times were reduced by 35%. Dyskinesias also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3 at 12 months follow-up). Postoperative L-dopa medication was adjusted (mean reduction: 53%). Complications occurred in two patients (5%) who developed infections, leading to system removal. Systems were replaced after 6 months. Two patients (5%) had a permanent worsening of a previously known depressive state and developed progressive dementia. CONCLUSIONS: TN stimulation is a relatively safe procedure for treating advanced PD. The possibility of readjusting the stimulation parameters postoperatively improves the therapeutic outcome and reduces side effects in comparison to ablative methods.     

Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.