Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease

CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating parkinsonian symptoms even to the extent to permit levodopa withdrawal. OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN: Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS: Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were evaluated in off-medication and on-medication conditions. Dopaminergic drug dosages were reduced after surgery, aiming for complete withdrawal. Six months after surgery, patients were reeavaluated in off- and on-medication conditions, with the stimulation turned on and off. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the off-medication condition improved by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by 65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All results reached significance (P<.001). Stimulation of the STN achieved antiparkinsonian effect similar to that of treatment with levodopa. No life-threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation safely improves all parkinsonian symptoms, decreases or eliminates the need for levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal of levodopa is feasible with this technique and the overall motor effect of STN stimulation is quantitatively comparable to that obtained with levodopa.     

Variance in effects of subthalamic nucleus stimulation]

Chronic stimulation of subthalamus nucleus (STN) is effective in treating severe motor fluctuation and levodopa induced dyskinesia as well as parkinsonian motor symptoms. The improvement of peak-dose/diphasic dyskinesias of STN stimulation is considered to be due to the decrease in the daily dosage of antiparkinsonian drugs. However one report pointed out that STN stimulation improved directly levodopa induced dyskinesia. Moreover the timing of the improvement for levodopa induced dyskinesia is not yet obvious. In the present study, we have assessed variance in the latency of improvement of levodopa induced dyskinesia due to STN stimulation. In addition, we would clarify an issue which cite of STN stimulation improved parkinsonian symptoms and motor complication (motor dyskinesias and motor fluctuation). We have studied seven patients diagnosed with advanced idiopathic Parkinson's disease with motor fluctuations and levodopa induced dyskinesias. Before and after the implantation of stimulating electrode, patients were assessed by the Unified Parkinson's Disease Rating Scale and % 'OFF' motor state. The dosage of the antiparkinsonian medication was not modified for one month prior to implantation. Following implantation, dosage of the medication and strength of stimulation was adjusted, if necessary. Symptoms of motor fluctuation and dyskinesia improved in all patients six month after surgery. The mean off-time duration and dyskinesia disability improved compared with presurgical conditions. However, the time course of the improvement of dyskinesias was not the same among patients. Contralateral limb dyskinesias in three patients improved immediately after the stimulation without modification of medication. In contrast, the stimulation worsened contralateral limb dyskinesias in other three patients immediately following the surgery. In two of the three patients, dyskinesias gradually improved within one month after surgery without reducing the dosage of medication. Dyskinesias of the other patient improved following a reduction in the dosage of medication one month after the surgery. Improvement of parkinsonian symptoms of the patients with longer latency of stimulation effect for dyskinesias was better than that of the patients with shorter latency. Stimulation cite of the former group appeared to locate more central than that of the latter group. Latency and strength of the effects of STN stimulation are variable.     

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.     

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

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

Unilateral subthalamic stimulation for early-stage Parkinson's disease]

According to evidenced-based criteria, surgical treatment with subthalamic stimulation is indicated for advanced Parkinson's disease with severe motor complications. Currently, the treatment is indicated for patients in whom medical treatment has failed even if the patient is still in an early stage. This study investigated the efficacy and safety of unilateral subthalamic stimulation for patients with early-stage Parkinson's disease. We evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab England ADL score before and 6 months after this treatment in 6 patients with early-stage Parkinson's disease demonstrating predominantly unilateral parkinsonian symptoms. We implanted a stimulation electrode (model 3387 or 3389) unilaterally on the side showing dominate symptoms, using both MRI and electrophysiological guidance. Six months after the beginning of stimulation, the UPDRS motor score without medication was improved by 64% and the Schwab England ADL score was improved by 23%. There were no adverse events except for asymptomatic intra-ventricular hemorrhage in one patient. Unilateral subthalamic stimulation is a useful treatment for patients with early-stage Parkinson's disease showing predominantly unilateral parkinsonian symptoms. However, long-term results of subthalamic stimulation for early-stage patients remain unclear.     

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease

Objective To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD). Methods 36 consecutive patients with idiopathic Parkinson’s disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson’s Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions. Results At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients. Conclusions Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.     

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     

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

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

Psychiatric Symptoms and Subthalamic Nucleus Stimulation in Parkinson's Disease. A Retrospective Study in Our Japanese Patients

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty‐five patients underwent bilateral STN stimulation. Pre‐ and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab‐England (S‐E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug‐induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients’ psychiatric symptoms. Postoperative S‐E score showed a significant improvement compared to the pretreatment baseline in both of “on” and “off” medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S‐E score in “on” state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in “off” state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug‐induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.     

Subthalamic stimulation in Parkinson disease: intraoperative predictive factors

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced forms of Parkinson disease. Postoperative improvement of motor parkinsonian disability is known to depend on patient selection and surgical targeting. OBJECTIVE: To determine which clinical and electrophysiological variables evaluated during the operation predict the postoperative clinical outcome of patients with Parkinson disease treated by bilateral high-frequency stimulation of the STN. METHODS: Intraoperative clinical and electrophysiological data obtained in 41 patients with Parkinson disease who underwent bilateral implantation of electrodes for STN stimulation were correlated with the improvement in parkinsonian disability assessed 6 months after the operation. RESULTS: The extent of STN neuronal activity recorded along the trajectory of the therapeutic electrode had no effect on the postoperative clinical outcome. The intraoperative improvement in segmental akinesia, but not rigidity, was predictive of the postoperative improvement in parkinsonian motor disability and reduction in daily levodopa-equivalent dosage. Parkinsonian motor disability scores assessed after surgery were lower in patients with intraoperative stimulation-induced dyskinesias than in those without stimulation-induced dyskinesias. CONCLUSION: The improvement of segmental akinesia and the observation of dyskinesias provoked by stimulation during the operation predict the best postoperative effects of bilateral STN stimulation on parkinsonian motor disability.     

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.     

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.     

Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine

OBJECTIVES: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication. METHODS: Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off. RESULTS: Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p<0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p<0.05). Total daily apomorphine dose was reduced by 68.9% (p<0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination. CONCLUSIONS: In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.     

Staged unilateral versus bilateral subthalamic nucleus stimulator implantation in Parkinson disease.

In 17 consecutive patients with Parkinson disease (PD), bilateral subthalamic nucleus (STN) stimulators were implanted during staged surgeries. The Unified Parkinson Disease Rating Scale (UPDRS) and the Dyskinesia Disability Scale were completed both off and on medication prior to any surgery and also OFF and ON stimulation after each surgery. On-medication UPDRS activities of daily living (ADL) and motor examination scores changed little with unilateral or bilateral stimulation. Off-medication UPDRS motor examination scores improved to similar degrees after each staged STN electrode implantation. Most of the improvements in off-medication ADL scores, dyskinesia scores, complications of therapy, and medication dose reduction occurred after unilateral STN stimulation with smaller improvements after the second operation.     

Bilateral subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease. Five years' personal experience

Background and purposeThe objective of the study was to assess bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with advanced Parkinson disease (PD).Material and methodsThe study population included 5 patients with bilateral STN DBS who completed a 5-year postoperative follow-up period. In all patients electrodes (Model 3387 or 3389) were stereotactically bilaterally inserted into the STN using a Leksell stereotactic G frame. The clinical rating tests included Unified Parkinson's Disease Rating Scale (UPDRS) and two motor-timed tests derived from CAPIT (rapid movements between two points and stand-walk-sit test). All patients were assessed in off and on condition before implantation and 1, 3 and 5 years in medication on and off condition and stimulation on condition and stimulation off condition. To compare preoperative to postoperative UPDRS scores, only mean values and standard deviations are presented because of the small study population.ResultsThe stimulation effect was noted in the off state, resulting in a 59% improvement in motor scores of UPDRS at 5-year follow-up, when compared to preoperative scores. In the on state the stimulation improved motor scores by 17%. At 5-year follow-up, reduction of daily levodopa dose was 50%.ConclusionsBilateral STN DBS is an effective and safe treatment for patients with advanced PD. Bilateral STN DBS contributes to improvement of parkinsonian symptoms in the off state and levodopa-induced dyskinesia. This can be correlated with a 50% reduction of daily levodopa dose 5 years postoperatively.     

Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.

Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on levodopa-induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2-hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinson's Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa-induced dyskinesias by 50%without any loss of the anti-parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.     

Dyskinesias induced by subthalamotomy in Parkinson's disease are unresponsive to amantadine

BACKGROUND: Dyskinesias are a transient but severe complication of subthalamotomy in some patients. PATIENTS AND METHODS: Three patients with Parkinson's disease undergoing bilateral micro-recording guided surgery of the subthalamic nucleus (STN) are described; deep brain stimulation (DBS) was used in one case, and subthalamotomy in the other two. Prior to surgery, levodopa induced dyskinesia had improved (< or = 50%) under treatment with amantadine (400 mg/day, po) in all three patients. The patient treated with DBS developed severe dyskinesia a few days after discharge and began self medication with amantadine but showed no improvement. This suggested a possible lack of response to amantadine for treatment of dyskinesias induced by surgery of the STN. RESULTS: Both patients treated with bilateral subthalamotomy developed unilateral choreoballistic movements immediately after surgery, despite not taking levodopa (L-dopa). Patients were scored using the dyskinesia scale and started treatment with 400 mg amantadine (po) for 4 days within the first postoperative week with no effect on dyskinesia score or its phenomenology. Amantadine was therefore discontinued. One month after surgery both patients were free of involuntary movements with an improvement of about 60% in the "off" state UPDRS motor score. Six month follow up showed maintained antiparkinsonian benefit, without need for levodopa treatment and complete absence of dyskinesia. CONCLUSION: The present findings suggest that: (i) amantadine probably exerts its anti-dyskinetic effect by acting on the "indirect" pathway; (ii) the pathophysiological mechanisms of subthalamotomy induced dyskinesias may differ from those involved in L-dopa induced dyskinesias; (iii) dyskinesias induced by STN surgery resolve spontaneously as compensatory mechanisms develop.     

Pallidal stimulation in advanced Parkinson's patients with contraindications for subthalamic stimulation

The aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa‐resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45–70), mean disease duration of 12.5 ± 4.3 years (range, 7–20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off‐dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off‐dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6‐month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa‐resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients. © 2010 Movement Disorder Society     

Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery

Before the introduction of high frequency stimulation of the subthalamic nucleus (STN), many disabled tremor dominant parkinsonian patients underwent lesioning or chronic electrical stimulation of the thalamus. We studied the effects of STN stimulation in patients with previous ventral intermediate nucleus (VIM) surgery whose motor state worsened. Fifteen parkinsonian patients were included in this study: nine with unilateral and two with bilateral VIM stimulation, three with unilateral thalamotomy, and one with both unilateral thalamotomy and contralateral VIM stimulation. The clinical evaluation consisted of a formal motor assessment using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests encompassing a 50 point frontal scale, the Mattis Dementia Rating Scale, and the Beck Depression Inventory. The first surgical procedure was performed a mean (SD) of 8 (5) years after the onset of disease. STN implantation was carried out 10 (4) years later, and duration of follow up after beginning STN stimulation was 24 (20) months. The UPDRS motor score, tremor score, difficulties in performance of activities of daily living, and levodopa equivalent daily dose significantly decreased after STN stimulation. Neither axial symptoms nor neuropsychological status significantly worsened after the implantation of the STN electrodes. The parkinsonian motor state is greatly improved by bilateral STN stimulation even in patients with previous thalamic surgery, and STN stimulation is more effective than VIM stimulation in tremor dominant parkinsonian patients.     

Bilateral subthalamic stimulation effects on oral force control in Parkinson's disease

Dysarthria in Parkinson's disease (PD) consists of articulatory, phonatory and respiratory impairment. Bilateral subthalamic nucleus (STN) stimulation greatly improves motor disability, but its long-term effect on speech within a large group of patients has not been precisely evaluated. The aim of this study was to determine the effect of bilateral STN stimulation on oral force control in PD. We measured forces of the upper lip, lower lip and tongue in twenty-six PD patients treated with bilateral STN stimulation. Measurements of the articulatory organ force, as well as a motor evaluation using the Unified Parkinson's Disease Rating Scale (UPDRS), were made with and without STN stimulation. Maximal voluntary force (MVF), reaction time (RT), movement time (MT), imprecision of the peak force (PF) and the hold phase (HP) were all improved with STN stimulation during the articulatory force task, as well as the motor examination scores of the UPDRS. It seems that the beneficial STN stimulation-induced effect on articulatory forces persisted whatever the duration of post-surgical follow-up. However, dysarthria evaluated by the UPDRS was worse in two subgroups of patients with a one to two year and three to five year post-surgical follow-up, in comparison with a subgroup of patients with a three month follow-up. STN stimulation has a beneficial long-term effect on the articulatory organs involved in speech production, and this indicates that parkinsonian dysarthria is associated, at least in part, with an alteration in STN neuronal activity. Nevertheless, to confirm the persistence of the beneficial effect of STN stimulation on parkinsonian dysarthria, a longitudinal evaluation is still needed. Received: 2 January 2002, Received in revised form: 27 August 2002, Accepted: 3 September 2002 Correspondence to S. Pinto