Long-term efficacy of globus pallidus stimulation for the treatment of Parkinson's disease

OBJECTIVE: To determine the long-term efficacy and safety of globus pallidus internus (GPi) stimulation for Parkinson's disease (PD). BACKGROUND: We previously reported 3-month data for 5 patients who underwent GPi stimulation for PD. We now report long-term data on these 5 patients and 4 additional patients. METHODS: Nine PD patients, 5 men and 4 women, with an average age of 49 years and disease duration of 10 years, underwent GPi stimulation. Six patients had staged bilateral implants and 3 patients had unilateral implants. The mean follow-up was 48.5 months. All patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and completed 2-day diaries before and after surgery. RESULTS: There was a 21% improvement in UPDRS Part II (activities of daily living; ADL) scores and a 37% improvement in UPDRS Part III (motor) scores when the longest follow-up in the 'stimulation-on/medication-off' state was compared to the 'medication-off' state at baseline. The UPDRS Part II (ADL) scores improved by 30% and the UPDRS Part III (motor) scores improved by 39% when the longest follow-up in the 'stimulation-on/mediation-on' state was compared to the 'medication-on' state at baseline. As measured by patient diaries, 'on' time increased from 25 to 59% and 'on with dyskinesia' decreased from 42 to 15%. Surgical- and device-related complications included transient hemiparesis in the operating room, postoperative seizures, and implantable pulse generator and lead problems. There were seven device-related events requiring additional surgical procedures. CONCLUSIONS: GPi stimulation continues to be effective for the long-term treatment of the disabling symptoms of PD; however, the physician and patient should be aware that device-related problems are not uncommon and additional surgery may be necessary.     

The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease: a positron emission tomography study

OBJECT: The aim of this study was to estimate the impact of stereotactic pallidal surgery on the binding potential of dopamine D2 receptors in patients with advanced Parkinson disease (PD). METHODS: Six patients with advanced PD (three men and three women; mean age 56.7 +/- 9.8 years, Hoehn and Yahr stage 3.3 +/- 1.1/3.9 +/- 1.2 [on/off scores], mean +/- standard deviation) underwent stereotactic pallidal surgery. One underwent right posteroventral pallidotomy (PVP), one received left PVP, three were treated with deep brain stimulation (DBS) of the left globus pallidus internus (GPi), and one with bilateral DBS of the GPi. The binding potential of the dopamine D2 receptors of these patients was determined before and after surgery by using positron emission tomography scanning with 11C-nemonapride and it was compared with the value in eight healthy volunteers. The authors also examined whether changes in the D2 receptor binding potential were correlated with the clinical outcome. The clinical symptoms, especially those in the off state, were significantly improved after surgery. Preoperatively, the D2 receptor binding potential in the putamen was elevated by 27% (p < 0.01) and that in the thalamus was 29% lower than that in controls (p < 0.01). The D2 receptor binding potential in the putamen and thalamus returned to control levels after surgery. The preoperative level of the D2 receptor binding potential in the anterior cingulate cortex was comparable to that of controls, but it declined significantly after surgery, whereas the D2 receptor binding potential in other regions of both hemispheres showed no significant changes after surgery. Although the D2 receptor binding potential did not correlate with the Hoehn and Yahr stage, the Schwab and England score, or the Unified PD Rating Scale (UPDRS) score, a positive correlation was seen between the percent improvement rate of the total UPDRS score in the off state and the percentage change of the D2 receptor binding potential in the putamen (r = 0.773, p = 0.0417 according to the Pearson linear correlation). CONCLUSIONS: The altered dopamine D2 receptor binding potential in the putamen might play a crucial role in clinical improvement after PVP or DBS of the GPi in advanced PD.     

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.     

CSF Neurotransmitter metabolites in comatose head injury patients during changes in their clinical state

Summary The main metabolites of noradrenaline, serotonin, and dopanine, methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA), respectively, were assessed in CSF samples of patients in coma after severe head injury, the first days after the accident and again after an improvement (13 patients) or deterioration (7 patients) in their clinical state, evaluated by the score on the Glasgow Coma Scale.Improvement was accompanied by significant decreases in HVA and 5HIAA. In the patients who deteriorated, the levels of the three metabolites remained high.The results show that the increased turnover of CNS neurotransmitters in severe head injury normalizes during recovery. The use of noradrenaline, dopamine, and serotonin antagonists in brain injury experimental models may clarify the role of the increased biogenic amine turnover in the processes that lead to recovery. We propose relevant pharmacological intervention influencing neurotransmission in severe head injury.     

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in Parkinson's disease: one year follow-up of a randomised observer-blind multi centre trial

BACKGROUND: To investigate whether STN stimulation is more efficacious than unilateral pallidotomy in advanced Parkinson's disease (PD) one year after surgery. METHOD: Thirty-four patients with advanced PD were randomly assigned to unilateral pallidotomy or bilateral STN stimulation. Outcome measures were parkinsonian symptoms in off and on phases (UPDRS 3), dyskinesias, functional status, Parkinson's disease quality of life questionnaire, the effects on separate symptoms, timed tests, patient diaries, dopaminergic drugs changes, adverse effects, and global outcome scale. Patients were assessed before surgery, six months and one year after surgery. The primary outcome measure was the off phase UPDRS 3 at six months follow-up. FINDINGS: The off phase UPDRS 3 score improved from 46.5 to 32 points in the pallidotomy patients and from 51.5 to 24 in the STN stimulation patients (p = 0.002). On phase UPDRS 3 and off phase Schwab and England functional scale improved significantly in favour of the STN stimulation patients. Dopaminergic drugs reduction was larger in the STN group although the difference between the treatment groups was not significant. One patient in each group had a major adverse effect. CONCLUSIONS: Bilateral STN stimulation is more efficacious than unilateral pallidotomy in advanced PD up to one year after surgery.     

Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor

Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson's disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6-12 months after surgery. The mean voltage 1 week postoperatively was 1. 45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.     

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in Parkinson’s disease: one year follow-up of a randomised observer-blind multi centre trial

Summary Background. To investigate whether STN stimulation is more efficacious than unilateral pallidotomy in advanced Parkinson’s disease (PD) one year after surgery. Method. Thirty-four patients with advanced PD were randomly assigned to unilateral pallidotomy or bilateral STN stimulation. Outcome measures were parkinsonian symptoms in off and on phases (UPDRS 3), dyskinesias, functional status, Parkinson’s disease quality of life questionnaire, the effects on separate symptoms, timed tests, patient diaries, dopaminergic drugs changes, adverse effects, and global outcome scale. Patients were assessed before surgery, six months and one year after surgery. The primary outcome measure was the off phase UPDRS 3 at six months follow-up. Findings. The off phase UPDRS 3 score improved from 46.5 to 32 points in the pallidotomy patients and from 51.5 to 24 in the STN stimulation patients (p = 0.002). On phase UPDRS 3 and off phase Schwab and England functional scale improved significantly in favour of the STN stimulation patients. Dopaminergic drugs reduction was larger in the STN group although the difference between the treatment groups was not significant. One patient in each group had a major adverse effect. Conclusions. Bilateral STN stimulation is more efficacious than unilateral pallidotomy in advanced PD up to one year after surgery.     

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.     

Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release

OBJECTIVE: The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson's disease (PD). The mechanism by which electrical stimulation of the STN ameliorates symptoms of PD remains unknown. One consistent aspect of STN stimulation is the ability to reduce the dosage of dopaminergic medications; sometimes they can be eliminated altogether. Furthermore, nigrostriatal projection axons are apposed to the dorsal surface of the STN and are likely affected by the application of current in this region. We sought to determine whether STN stimulation could release endogenous striatal dopamine. METHODS: Five patients with PD, who had previously undergone surgical implantation of bilateral STN stimulators, underwent [(11)C]raclopride positron emission tomographic scanning. l-dopa was withheld for 12 hours, and both stimulators were turned off 9 hours before scanning. We assayed for striatal dopamine release by measuring radioligand displacement as a consequence of turning on the right STN stimulator after 45 minutes of a 90-minute [(11)C]raclopride infusion. Patients were evaluated with the motor section of the Unified Parkinson's Disease Rating Scale before and after the studies. RESULTS: Comparisons between the right and left striata, before and after right STN stimulation, demonstrated no significant differences in [(11)C]raclopride binding, despite significant improvements in Unified Parkinson's Disease Rating Scale motor scores with unilateral stimulation (mean improvement, 26.0 +/- 16.4%; P < 0.05). This finding was also noted when the striatum was partitioned into dorsal and ventral caudate and putamen and the four regions were analyzed separately. CONCLUSION: Our results suggest that STN stimulation does not mediate its anti-PD effects via the release of dopamine, as assessed with [(11)C]raclopride displacement.     

Progression of Parkinson's disease following thalamic deep brain stimulation for tremor

We assessed the long-term effect of thalamic deep brain stimulation (DBS) on motor symptoms and progression of Parkinson's disease (PD) in PD patients treated for resting and postural/action tremor. Thalamic DBS was performed in 17 patients with treatment-resistant resting and postural/action tremor. Nine patients were available for follow-up examination a mean of 5.5 years after surgery. Three had tremor-dominant PD. DBS produced marked improvement in resting and postural/action tremor in target upper extremity in all 9 patients, which persisted unchanged at the time of the last follow-up visit 5.5 years after surgery. PD severity with DBS 'on' and 'off' 1 year after surgery was compared to PD severity at the last follow-up visit using UPDRS (Unified Parkinson's Disease Rating Scale) III motor scores and individual motor item subscores. Patients were tested while on medication. There was no significant worsening of tremor, rigidity, speech, postural stability, gait, or axial bradykinesia with DBS either on or off at the last follow-up visit compared to the 12-month visit. UPDRS III motor scores were unchanged. However, global assessment of PD progression and increased mean L-dopa dose and L-dopa equivalent daily dose at the time of last follow-up visit indicated that a progression of PD had occurred.     

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.     

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.     

The role of sigma-receptors in levodopa-induced dyskinesia in patients with advanced Parkinson disease: a positron emission tomography study

OBJECT: Levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD) mimics acute dystonic reactions induced by antipsychotic agents, possibly mediated by sigma-receptors; however, there are few reports in which the relationship between sigma-receptors and LID in advanced PD is investigated. The binding potential of cerebellar sigma-receptors before and after a pallidal surgery for dyskinesia in patients with advanced PD is assessed. METHODS: Six patients with advanced PD (male/female ratio 3:3, age 56.7 +/- 9.8 years) underwent stereotactic pallidal surgery (two posteroventral pallidotomy procedures and four deep brain stimulation of the globus pallidus internus, including one bilateral case). Clinical features of patients with PD were assessed using Hoehn and Yahr (H & Y) stages, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Life Scale (S & E). The LID was evaluated by LID severity score. The binding potential of cerebellar sigma-receptors was determined before and after the surgery by 11C-nemonapride positron emission tomoraphy, a specific radioligand for sigma-receptors in the cerebellum. All clinical scores, especially the LID severity score, were dramatically improved after the surgery (p < 0.05). Preoperatively, contralateral cerebellar binding potential was significantly elevated (p < 0.01), and it was reduced after the surgery, but it was still higher than that of healthy volunteers (p < 0.05). The ipsilateral cerebellar binding potential remained unchanged after the surgery. The level of binding potential did not correlate with H & Y stage, UPDRS, or S & E score, but a strong positive correlation was seen between the binding potential and the preoperative LID severity score when the patients were receiving medication (r = 0.893, p < 0.05). CONCLUSIONS: Cerebellar sigma-receptors may potentially involve the genesis of LID in advanced PD.     

Effects of anterodorsal pallidal stimulation on gait freezing (Kinesia paradoxa) in Parkinson's disease

The results of a double-blind evaluation of the effects of internal globus pallidus (GPi) stimulation in 7 patients with advanced Parkinson's disease are summarized. The evaluation was performed 6-8 months after surgery while the patients were on medication with an optimal dose and schedule. The stimulation was turned off for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during their daytime activity were recorded as the on-period and off-period scores, respectively. A significant reduction in the total score on part III of the Unified Parkinson's Disease Rating Scale was induced by GPi stimulation at the off-period (-57%) as well as the on-period (-36%). Clinically important improvement was also achieved in severe gait freezing (kinesia paradoxa) in 2 patients when stimulation was applied to the anterodorsal portion of the GPi. Such an effect was observed during unilateral stimulation of the right side alone.     

Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up

OBJECT: Bilateral subthalamic nucleus (STN) stimulation is increasingly used in patients with advanced Parkinson disease (PD). This study was performed to evaluate the long-term efficacy and safety of bilateral STN stimulation in cases of PD. METHODS: The authors performed a prospective, open-label study in patients with PD who underwent bilateral STN stimulation. The authors compared motor scores and activities of daily living (ADL) scores based on the Unified PD Rating Scale (UPDRS) obtained before surgery while patients were in the medication-off state with scores obtained at follow-up evaluations of these patients while in the medication-off/stimulator-on state. Data contained in patient diaries were also compared. Thirty-three patients with PD were evaluated 12 months postoperatively and 19 were evaluated at a mean follow-up time of 28 months. A comparison between UPDRS scores obtained in patients in the medication-off/stimulator-on state and those obtained when patients were in the baseline medication-off state showed a 27% improvement in ADL scores and a 28% improvement in motor scores after surgery. There was a 57% reduction in the use of levodopa-equivalent medication doses. The percentage of the waking day that patients were in the medication-on state increased from 38 to 72%. Surgical complications included seizures (three patients), confusion (five patients), hemiballismus (one patient), and visual disturbance (one patient). Stimulation-related adverse effects were mild. Device-related events included nine lead replacements, seven lead revisions, six extension replacements, and 12 implantable pulse generator (IPG) replacements; one IPG was cleaned and one IPG was placed in a pocket because of the presence of a shunt. CONCLUSIONS: Bilateral STN simulation is associated with a significant improvement in the motor features of PD. Device-related events were common in the first 20 patients who underwent surgery, often requiring repeated surgeries.     

Lesion volume and clinical outcome in stereotactic pallidotomy and thalamotomy.

Postoperative lesion volume and clinical outcome were assessed in 19 Parkinson's disease (PD) patients who received posteroventral pallidotomy, and in 14 essential tremor (ET) patients who received ventrolateral thalamotomy. Before and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Inner and total lesion volumes were determined with postoperative MR imaging and three-dimensional data segmentation. Lesion volumes were compared to percent improvement in UPDRS and FTM scores, using Spearman's rank-order correlation test. No rank-order correlations were found between lesion volume and clinical improvement in either the PD or the ET patients. In performing stereotactic surgery for movement disorders, any lesion volume within a prescribed range may be equally effective in relieving symptoms associated with PD or ET.     

Neuronal activity in GP and Vim of parkinsonian patients and clinical changes of tremor through surgical interventions

Microrecordings were performed during pallidotomy and thalamotomy for Parkinson's disease (PD). Neuronal activity in globus pallidus (GP) was in general agreement with previous studies of human and primate models of PD. Neuronal activity, where frequency of tremor appeared to oscillate independently from peripheral input, was encountered in GPi. In contrast, neuronal activity in Vim regarding frequency of firing also correlated with tremor and was passively driven by kinesthetic stimuli with a somatotopic arrangement. Pallidal lesions based on microrecording induced relative reductions of tremor, while small Vim lesions immediately alleviated tremor. Basal ganglia pathology due to dopamine depletion could generate oscillatory neuronal activity in GPi, which may cause tremor. However, peripheral feedback to the motor cortex via Vim is also significant for tremorgenesis, because Vim may be an excitatory driving source for motor cortical neurons. Thus, a Vim lesion could reduce excitability of the motor cortical neurons and abolish tremor.     

Deep brain stimulation for Parkinson’s disease: how to select candidates for pallidal or subthalamic stimulation

Chronic deep brain stimulation therapy has the reversibility, selectivity and adjustability needed to achieve an adequate effect, so that it represents an ideal tool for functional neurosurgery designed to treat parkinsonian symptoms. Some kinds of chronic stimulation have become an alternative to lesion-making surgery, supported by the fact that high-frequency stimulation induces quite a small area of inactivity around the stimulating electrode compared with the lesions induced with a lesionmaker, and stimulation directed at a particular target exerts more specific effects on particular symptoms of Parkinson’s disease (PD). Thus, whenever stimulation therapy is to be applied to patients, an effective stimulation target must be selected depending on the nature of the symptom to be improved. For example, ventral intermediate nucleus (VIM) thalamic stimulation is able to stop tremor completely, but has no appreciable effects on other symptoms. Bilateral globus pallidum interna (GPi) stimulation and subthalamic nucleus (STN) stimulation have been applied to reduce the pathological inhibitory effects on the thalamocortical circuit from the GPi and/or the substantia nigra pars reticular nucleus (SNr), which produces the final output of the basal ganglia circuits. However, there is still controversy about both the indications for and the role of GPi versus STN stimulation. This article presents a review of recent reports that describe follow-up results and double-blind studies on the signs for relief of each type of parkinsonian symptom, following GPi or STN stimulation. It also includes a discussion of how further research should be organized in order to identify whether GPi or STN stimulation exerts the greatest effect on particular kinds of parkinsonian symptoms.     

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 for Parkinson's disease: how to select candidates for pallidal or subthalamic stimulation

Chronic deep brain stimulation therapy has the reversibility, selectivity and adjustability needed to achieve an adequate effect, so that it represents an ideal tool for functional neurosurgery designed to treat parkinsonian symptoms. Some kinds of chronic stimulation have become an alternative to lesion-making surgery, supported by the fact that high-frequency stimulation induces quite a small area of inactivity around the stimulating electrode compared with the lesions induced with a lesion-maker, and stimulation directed at a particular target exerts more specific effects on particular symptoms of Parkinson's disease (PD). Thus, whenever stimulation therapy is to be applied to patients, an effective stimulation target must be selected depending on the nature of the symptom to be improved. For example, ventral intermediate nucleus (VIM) thalamic stimulation is able to stop tremor completely, but has no appreciable effects on other symptoms. Bilateral globus pallidum interna (GPi) stimulation and subthalamic nucleus (STN) stimulation have been applied to reduce the pathological inhibitory effects on the thalamocortical circuit from the GPi and/or the substantia nigra pars reticular nucleus (SNr), which produces the final output of the basal ganglia circuits. However, there is still controversy about both the indications for and the role of GPi versus STN stimulation. This article presents a review of recent reports that describe follow-up results and double-blind studies on the signs for relief of each type of parkinsonian symptom, following GPi or STN stimulation. It also includes a discussion of how further research should be organized in order to identify whether GPi or STN stimulation exerts the greatest effect on particular kinds of parkinsonian symptoms.