Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode implants as a treatment for dyskinesia and chronic pain, were evaluated on a series of neurolinguistic functions to determine if the stimulation of the centromedianum nucleus of the thalamus affected language and cognitive processing. Analysis of the data revealed that the stimulation of the left centromedianum nucleus had resulted in a notable facilitatory influence on the processing of language functions; this facilitatory effect was measured in terms of the number of errors produced and the patients' response latency time. The facilitatory effect was also noted to have extended to other language functions. The nature of the facilitation from the stimulation of the left centromedianum nucleus, an extension of the brainstem reticular formation, on language functions is discussed.
Despite the introduction of new medications, motor fluctuations and dyskinesias disable a significant proportion of Parkinson's disease patients. This has lead to renewed interest in stereotactic neurosurgery. A skilled team is needed to ensure that patient assessment and selection, operative technique, intraoperative monitoring, and post-operative management are optimised. High frequency stimulation has similar effects to ablative surgery, and is generally preferred. The clinical effects and possible mechanisms of action of deep brain stimulation of the subthalamic nucleus and globus pallidus are reviewed.
OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET).
METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living.
RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study.
CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.
The effects of subthalamic nucleus deep brain stimulation were studied in 52 consecutive patients (13 over age 70, 15 under age 60, 24 age 60 to 70). All groups had improvement of motor fluctuations and dyskinesia. Patients over age 70 had worsening of Unified Parkinson's Disease Rating Scale motor scores on medication, despite less medication reduction. Their activities of daily living and axial subscores worsened, particularly in those with preoperative gait difficulties.
<b>OBJECTIVE: </b>To evaluate the long term (4 years) efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease.<b>METHODS: </b>We performed a double blind crossover evaluation of the efficacy of DBS of the STN in the "off" medication condition in 10 patients with Parkinson's disease. Assessments included the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor) and two timed tests (arm tapping and walking). Open evaluation of the effect of stimulation in the off and on drug states preoperatively and at 1 and 4 years postoperatively was also conducted. The latter assessment included the UPDRS parts II (activities of daily living) and III (dyskinesia scale and global assessment) as judged by the patient and examiner. The mean amount of levodopa daily dose at base line, 1 year, and 4 years after surgery was compared.<b>RESULTS: </b>A significant (p<0.04) effect of stimulation was observed in the overall group regarding both the UPDRS motor and the timed tests. Open evaluation also showed a significant benefit of STN DBS with respect to preoperative assessment in both the motor and activities of daily living scales, dyskinesia scale, and in global assessment. Levodopa daily dose was reduced by 48% and 50% at 1 and 4 years, respectively. There was no difference between the 1 and 4 years evaluations in any of the parameters evaluated. Complications due to stimulation were minor.<b>CONCLUSIONS: </b>DBS of the STN provides a significant and persistent anti-parkinsonian effect in advanced Parkinson's disease 4 years after surgery.
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.
BACKGROUND: Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown.
METHODS: We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up.
RESULTS: As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide.
CONCLUSIONS: Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.
OBJECT: The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator.
METHODS: Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time. In this cohort the median duration of follow-up review was 24 months (range 12-52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35-50%], p < 0.001) and the motor score decreased by 48% (95% CI 42-55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31-50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27-48%, p < 0.001) at 1 year and 36% (95% CI 25-48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2-72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa.
CONCLUSIONS: In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.
Parkinson's disease is a progressive neurological disorder characterized by rest tremor, bradykinesia, rigidity and postural instability. The cause is unknown, but growing evidence suggests that it may be due to a combination of environmental and genetic factors. Treatment during the early stage of Parkinson's disease has evolved, and evidence suggests that dopamine agonist monotherapy may prevent the response fluctuations that are associated with disease progression. L-dopa therapy, however, remains the most efficacious treatment. Treatment during the advanced stage focuses on improving control of a number of specific clinical problems. Successful management of motor response fluctuations (e.g., "wearing off," on-off fluctuations, nighttime deterioration, early morning deterioration and dyskinesias) and of psychiatric problems is often possible with specific treatment strategies. Surgical treatment is an option for a defined patient population.
Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode implants as a treatment for dyskinesia and chronic pain, were evaluated on a series of neurolinguistic functions to determine if the stimulation of the centromedianum nucleus of the thalamus affected language and cognitive processing. Analysis of the data revealed that the stimulation of the left centromedianum nucleus had resulted in a notable facilitatory influence on the processing of language functions; this facilitatory effect was measured in terms of the number of errors produced and the patients' response latency time. The facilitatory effect was also noted to have extended to other language functions. The nature of the facilitation from the stimulation of the left centromedianum nucleus, an extension of the brainstem reticular formation, on language functions is discussed.
