P.R. Schuurman

Neuropsychological effects of bilateral STN stimulation in parkinson disease : A controlled study

Objective: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). Methods: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and 36 patients were evaluated 6 months later. At baseline and at follow-up we administered neuropsychological tests of language, memory, visuospatial function, mental speed, and executive functions. A depression rating scale, a quality of life scale, self and proxy ratings of memory and dysexecutive symptoms, and a neuropsychiatric interview were also administered. Results: Six months after surgery, the STN group showed a larger decline than the control group on measures of verbal fluency, color naming, selective attention, and verbal memory. Moreover, the STN group showed a decrease in positive affect, and an increase in emotional lability and cognitive complaints. On the other hand, the STN group showed an increase in quality of life and a slight decrease in depressive symptoms. Nine percent of the STN patients had psychiatric complications (vs 3% of controls). Conclusions: Bilateral subthalamic nucleus stimulation has an adverse effect on executive functions with implications for daily life of the patients and their relatives.

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD A randomized trial

Objective: To compare the efficacy of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson disease (PD) in a randomized, observer-blind, multicenter trial. Methods: Thirty-four patients with advanced PD were randomly assigned to have unilateral pallidotomy or bilateral STN stimulation. The primary outcome was the change from baseline to 6 months in the motor part of the Unified PD Rating Scale (motor UPDRS) in the off phase. Secondary outcomes were parkinsonian symptoms in the on phase (motor UPDRS), dyskinesias (Clinical Dyskinesia Rating Scale and dyskinesias UPDRS), functional status (activities of daily living UPDRS and Schwab and England scale), PD Quality of Life questionnaire, changes in drug treatment, and adverse effects. Results: The off phase motor UPDRS score improved from 46.5 to 37 points in the group of pallidotomy patients and from 51.5 to 26.5 in the STN stimulation patients (p = 0.002). Of the secondary outcome measures, on phase motor UPDRS and dyskinesias UPDRS improved significantly in favor of the STN stimulation patients. Reduction of antiparkinsonian drugs was greater after STN stimulation than after pallidotomy. One patient in each group had a major adverse effect. Conclusions: Bilateral STN stimulation is more effective than unilateral pallidotomy in reducing parkinsonian symptoms in patients with advanced PD.

Deep brain stimulation in addiction: a review of potential brain targets

Deep brain stimulation (DBS) is an adjustable, reversible, non-destructive neurosurgical intervention using implanted electrodes to deliver electrical pulses to areas in the brain. DBS is currently investigated in psychiatry for the treatment of refractory obsessive–compulsive disorder, Tourette syndrome and depressive disorder. Although recent research in both animals and humans has indicated that DBS may be an effective intervention for patients with treatment-refractory addiction, it is not yet entirely clear which brain areas should be targeted. The objective of this review is to provide a systematic overview of the published literature on DBS and addiction and outline the most promising target areas using efficacy and adverse event data from both preclinical and clinical studies. We found 7 animal studies targeting six different brain areas: nucleus accumbens (NAc), subthalamic nucleus (STN), dorsal striatum, lateral habenula, medial prefrontal cortex (mPFC) and hypothalamus, and 11 human studies targeting two different target areas: NAc and STN. Our analysis of the literature suggests that the NAc is currently the most promising DBS target area for patients with treatment-refractory addiction. The mPFC is another promising target, but needs further exploration to establish its suitability for clinical purposes. We conclude the review with a discussion on translational issues in DBS research, medical ethical considerations and recommendations for clinical trials with DBS in patients with addiction.

Predictors of cognitive and psychosocial outcome after STN DBS in Parkinson's Disease

Objective To find predictors of cognitive decline and quality of life 1 year after bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinsons disease (PD). Methods A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery. A control group of 40 PD patients was included to control for effects of repeated testing and disease progression. The authors determined individual changes in cognition, mood and quality of life using a statistical method that controls for multiple comparisons, and performed logistic regression analyses to assess predictors of cognitive changes and quality of life. Results 12 months after surgery, the improvement in motor function was 41% (Unified Parkinsons Disease Rating Scale Part 3 score in off). The STN group showed a large improvement in quality of life compared with the control group (Cohen d=0.9). At the individual level, 32% (95% CI 22 to 40) of the STN group showed a substantial improvement in quality of life. 36% (95% CI 27 to 46) of the STN patients showed a profile of cognitive decline compared with the control group. Mood improved in 16 STN patients and declined in 16 subjects. Impaired attention, advanced age and a low l-dopa response at baseline predicted cognitive decline, whereas a high l-dopa response at baseline predicted an improvement in quality of life. Postoperative decrease in dopaminergic medication was not related to cognitive decline. Conclusions STN DBS improves quality of life. However, a profile of cognitive decline can be found in a significant number of patients. l-dopa response, age and attention at baseline are predictors of cognitive and psychosocial outcome.

Directional steering: A novel approach to deep brain stimulation.

Objective: The aim of this study was to investigate whether directional steering through a novel 32-contact electrode is safe and can modulate the thresholds for beneficial and side effects of stimulation. Methods: The study is a single-center, performance and safety study. Double-blind intraoperative evaluations of the thresholds for therapeutic benefit and for side effects were performed in 8 patients with Parkinson disease while stimulating in randomized order in spherical mode and in 4 different steering modes with the 32-contact electrode, and in monopolar mode with a commercial electrode. In addition, simultaneous recordings of local field potentials through all 32 contacts were performed. Results: There were no adverse events related to the experimental device. For 13 of 15 side effects (87%), the threshold could be increased by ≥1 mA while steering in at least one direction in comparison to conventional spherical stimulation, thereby increasing the therapeutic window by up to 1.5 mA. Recording local field potentials through all 32 electrode contacts yielded spatiotemporal information on pathologic neuronal activity. Conclusions: Controlled steering of current through the brain may improve the effectiveness of deep brain stimulation (DBS), allow for novel applications, and provide a tool to better explore pathophysiologic activity in the brain. Classification of evidence: This study provides Class IV evidence that for patients with Parkinson disease, steering DBS current is well tolerated, increases the threshold for side effects, and may improve the therapeutic window of subthalamic nucleus DBS as compared with current standard spherical stimulation.

A comparison of neuropsychological effects of thalamotomy and thalamic stimulation

Objective: The neuropsychological effects of thalamotomy and thalamic stimulation in patients with severe drug-resistant tremor due to PD, essential tremor (ET), or MS were compared in a randomized trial. Methods: Complete neuropsychological evaluations at baseline and 6 months after surgery were obtained in 62 patients who underwent thalamotomy (n = 32: 21 PD, 6 ET, 5 MS) or thalamic stimulation (n = 30: 19 PD, 7 ET, 4 MS). Results: Six months after thalamotomy, a decline was seen in the scores of the Stroop Color-Word Test, with the exception of the interference score. In the thalamic stimulation group, no significant changes were found on any of the cognitive tests. Age, diagnosis, disease severity, and baseline cognitive status were not correlated to cognitive changes. A difference in score changes between right- and left-sided surgery was found in verbal fluency and Stroop Test scores after both thalamotomy and thalamic stimulation. Conclusions: Both thalamotomy and thalamic stimulation are associated with a minimal overall risk of cognitive deterioration. Verbal fluency decreased after both left-sided thalamotomy and thalamic stimulation.

New actigraph for long-term tremor recording

A new method of movement analysis is validated, allowing an actigraph to discriminate tremor from other movements and store duration and intensity measures of both movement types. For algorithm optimization, wrist acceleration was recorded in nine controls and nine Parkinsons disease patients, while simultaneously rating their observed tremor minute by minute on item 20 of the Unified Parkinsons Disease Rating Scale. An optimization procedure to minimize false positives in controls while maximizing tremor detection in patients resulted in false positive tremor classification in 2.4% ± 2.5% of the movement time of control subjects (range, 0%–7%), while providing tremor classification in 82.1% ± 15.4% of the movement time in patients (range, 55%–100%), correlating r = 0.93 with their averaged observed tremor score. A second, generalizability study showed that application of the optimized algorithm resulted in accurate classification of 71% ± 14% of the observed tremor time (range, 46%–90%) in another 9 patients and in a false positive classification in only 0.5% ± 0.8% of the time in another 10 controls (range, 0%–2.4%). The commercial availability of this actigraph now for the first time makes it possible to investigate tremor fluctuations over several weeks. An example is given of how long‐term monitoring can be of use in evaluation of symptom management.

Morbidity and mortality following pallidotomy in Parkinson’s disease A systematic review

ObjectiveTo study the frequency of morbidity and mortality associated with pallidotomy. MethodThe authors searched the MEDLINE electronic database for pallidotomy articles reported between January 1992 and December 2000. They selected studies by the following criteria: original clinical data, unequivocal description of morbidity and mortality, and unselected consecutive cases. The authors extracted the following data: number of patients, unilateral or bilateral procedures, age, localization technique, follow-up time, number of patients with adverse effects, number of patients with permanent adverse effects (>3 months), types of adverse effects, and mortality. ResultsFor unilateral pallidotomy, 12 prospective studies included 334 patients. Of these patients, 30.2% (95% CI, 25.3 to 35.2) had adverse effects, and 13.8% (95% CI, 10.1 to 17.5) had permanent adverse effects. A symptomatic infarction or hemorrhage occurred in 3.9% (95% CI, 2.1 to 6.6). The mortality rate was 1.2% (95% CI, 0.3 to 3.0). In the series with microelectrode recording, the frequency of adverse effects was 14.4% (95% CI, 4.7 to 24.1) higher and the frequency of stroke was 4.9% (95% CI, 1.4 to 8.4) higher. The most frequent adverse effects were problems with speech (11.1%) and facial paresis (8.4%). For bilateral pallidotomy, five historical cohort studies including 20 patients were available for review. Fourteen patients had an adverse effect, and the most frequent adverse effects were impairments of speech and cognition. ConclusionsThe risk of permanent adverse effects associated with unilateral pallidotomy was 13.8%. A symptomatic infarction or hemorrhage occurred in 3.9% of patients, and the associated mortality rate was 1.2%.

Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study of 32 patients

OBJECTIVES In a randomised trial to study the efficacy of unilateral pallidotomy in patients with advanced Parkinsons disease, patients having pallidotomy within 1 month after randomisation were compared with patients having pallidotomy 6 months after the primary outcome assessment. Of the 37 patients enrolled 32 had a unilateral pallidotomy. The follow up study of these patients is presented to report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural effects; (4) relation between lesion location and outcome; and (5) preoperative patient characteristics predictive for good outcome. METHODS Outcome measures were the motor section of the unified Parkinsons disease rating scale (UPDRS), levodopa induced dyskinesias, disability, quality of life, and a comprehensive neuropsychological assessment. Multivariate logistic regression was used to identify preoperative patient characteristics independently associated with good outcome. RESULTS Off phase assessment showed a reduction in parkinsonism from 49 to 36.5 points on the UPDRS 6 months after surgery. Improvements were also demonstrated for activities of daily living and quality of life. In the on phase dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three patients had major permanent adverse effects. Besides worsening of verbal fluency after left sided surgery, systematic cognitive deterioration was not detected. Patients taking less than 1000 levodopa equivalent units (LEU)/day were more likely to improve. CONCLUSIONS The positive effects of unilateral pallidotomy are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day were most likely to improve.

Deep brain stimulation for dystonia: patient selection and outcomes

In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For some secondary dystonias – like tardive dystonia, myoclonus‐dystonia (M‐D), NBIA (PANK2), the outcome was very good. Only for the primary generalized dystonias, the efficacy of GPi‐DBS has been confirmed in randomised controlled trials. Predictors of outcome are the experience and dedication of the stereotactic team, the selection of patients – the diagnosis and pre‐operative screening – and the quality of the post‐operative care. Predictors of negative outcome are long duration of the disease – with contractures or scoliosis – and concomitant symptoms like spasticity and cerebellar dysfunction. More studies are required to establish the role of GPi‐DBS in the treatment of secondary dystonias.