Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.
High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.
We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time.
advise on prognosis and subsequent symptomatic therapy.Our case shows that in a case of intermittent exercise-induced focal cramps, the possibility of an atypical presentation of PD should be kept in mind. In the absence of the cardinal physical signs of PD, detection of dopaminergic neurodegeneration by dopamine transporter SPECT would provide support for dopamine replacement therapy.
Article abstract-The authors studied the effect of bilateral subthalamic nucleus stimulation on levodopa-induced dyskinesias in 24 consecutive parkinsonian patients with disabling dyskinesias. The improvement in the three subtypes of levodopa-induced dyskinesias was significant from the third postoperative month and was mainly due to the decrease in the daily dose of levodopa allowed by the stimulation-induced improvement in the motor score. NEUROLOGY 2000;55:1921-1923 A few years after beginning levodopa treatment, many patients with idiopathic PD develop motor fluctuations and levodopa-induced dyskinesias (LID), which may be more disabling than parkinsonism, especially in patients with young-onset PD. Chronic stimulation of the subthalamic nucleus (STN) is effective in treating parkinsonian motor symptoms and can be suggested to patients with severe motor fluctuations.1 Operating on the STN might theoretically be harmful to LID. Hemiballism can be induced by spontaneous lesions of the STN and by experimental high frequency stimulation of the STN in patients with PD as well. 2 We investigated the effect of STN stimulation on different types of LID in parkinsonian patients.Patients and methods. Twenty-four consecutive patients-12 men and 12 women-with severe PD and motor complications were bilaterally operated. The characteristics of these patients are summarized in table 1. The neurosurgical procedure has been described. 1Clinical evaluation was based on the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol and was performed after a 12-hour withdrawal of antiparkinsonian drugs.3 Patients were assessed twice before surgery and 3 and 12 months after the operation in "off "-drug and "on"-drug conditions, using Unified PD Rating Scale (UPDRS) motor scores and the dyskinesia duration and disability items of the UPDRS part IV. Levodopa-induced dyskinesias were evaluated during a levodopa challenge using the same suprathreshold dose as preoperatively.4 "Off "-period dystonia, onset-of-dose, and peak-dose dyskinesias were assessed separately using three scales encompassing the face, neck, and the four limbs, each scored from zero to four proportionally to severity. 5 The conditions of evaluation were not randomized and onset-of-dose dyskinesia was evaluated in "off "-stimulation condition at least 30 minutes after the neurostimulator was switched off. The patients were blinded but not the examiner. Results are presented as mean Ϯ SD values. The data were analyzed by analysis of variance for repeated measures, and by the paired t-test and the Wilcoxon signed-rank test when required. Results.Results are presented in table 2 and the figure. STN stimulation significantly reduced the UPDRS motor score. In the "off "-drug condition, the UPDRS motor scores decreased from 54.4 Ϯ 13.1 before surgery to 45.8 Ϯ 19.7 and 49.3 Ϯ 17.9 in the "off "-stimulation condition and to 18.3 Ϯ 12.3 and 18.2 Ϯ 8.8 in the "on"-stimulation condition at 3-and 12-month follow-ups, respectively. In the "on"-drug condition t...
Eight patients with advanced PD received a unilateral STN DBS. The UPDRS III off drug-on DBS was improved by a mean 44%. Dyskinesias were ameliorated. Levodopa daily dose was reduced. Three patients required the implantation of the second electrode. Unilateral DBS may be efficacious in some patients with advanced PD.
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