The latest evidence on target selection in deep brain stimulation for Parkinson’s disease

Deep brain stimulation (DBS) is one of the most promising neuromodulatory techniques to gain momentum over the last 20 years, with significant evidence showing the benefit of DBS for Parkinson’s disease (PD). However, many questions still exist pertaining to the optimal placement of stimulation contacts. This paper aims to review the latest and most relevant studies evaluating subthalamic nucleus (STN) and globus pallidus interna (GPi) stimulation. Additionally, it aims to shine a light on several of the lesser-known targets with mounting evidence of efficacy. Referenced literature for the main body of the article was gathered from Medline and PubMed databases. Results were limited to “full text”, “English language” and publications from 1999 onwards. Case reports were excluded. The current evidence irrefutably demonstrates the benefits of both STN and GPi DBS on Unified Parkinson’s Disease Rating Scale (UPDRS) III motor scores, with very similar outcomes seen after 1–2 years. Currently, it appears the greatest differences lie in the associated adverse effects. STN DBS was associated with a greater reduction in dopamine replacement therapy, but also appeared to have more negative effects on speech and mood. Meanwhile, in regards to alternative targets, the pedunculopontine nucleus has shown promising improvement in axial symptoms, while the ventral intermediate nucleus has demonstrated significant efficacy at suppressing tremor, and the caudal zona incerta may be superior to the STN and GPi in improving UPDRS-III scores. Due to the complexity of Parkinson’s disease, an individual disease profile must be determined in a patient-by-patient fashion such that appropriate targets can be selected accordingly.     

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease

Evidente VGH, Premkumar AP, Adler CH, Caviness JN, Driver‐Dunckley E, Lyons MK. Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 211–214.
© 2010 John Wiley & Sons A/S. Objective – To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson’s disease (PD). Materials and methods – Records of 12 patients with PD who underwent GPi‐DBS at our institution from 2002 to 2008 were matched by pre‐operative PD medication doses and pre‐operative motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores to 12 cases of STN‐DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). Results – GPi and STN groups had similar mean pre‐operative LEDs and motor UPDRS scores. At 6 months post‐DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post‐operative ‘medication off/stimulation on’ motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). Conclusions – We conclude that in disease‐matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.     

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     

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson’s disease

Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat Parkinson’s disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory and electrode to treat patients with tremor-dominant PD, yet outcome data for this procedure remains sparse. Our objective is to determine the safety and efficacy of combination STN-VIM DBS. We conducted a single-center retrospective case series of all patients who underwent combined STN-VIM DBS. Demographic, perioperative, and outcome data, including Unified Parkinson Disease Rating Scale-III (UPDRS) and tremor scores (OFF-medication), and levodopa equivalent daily dose (LEDD), were collected and analyzed. Nineteen patients underwent this procedure. Patients were 89% male and 11% female, with a mean age of 63.6 years. Mean preoperative UPDRS was 24.1, and LEDD was 811.8. At a mean follow-up of 33.8 months, UPDRS and LEDD decreased by an average of 9.2 (38.2%) and 326.3 (40.2%), respectively. Tremor scores decreased by 4.9 (59.0%), and 58% were able to decrease total medication burden. One patient developed transient left-sided weakness, yielding a complication rate of 5.3%. Combined targeting of STN and VIM thalamus via a single frontal trajectory for tremor-dominant Parkinson’s Disease results in similar UPDRS outcomes to STN DBS and improved control of tremor symptoms. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.     

Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus

While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center. Patients underwent motor, mood, verbal fluency and QoL (Parkinson disease questionnaire: PDQ-39) measures before and 6 months following surgery. Groups experienced motor and mood improvements that did not differ by target. Patients with STN DBS evidenced a slight decrement on letter fluency. On average, all patients endorsed better overall QoL after surgery. However, despite similar motor and mood improvements, GPi patients improved more than STN patients (38 vs. 14%, respectively; P = 0.03). Patients reported better QoL on subscales of mobility, activities of daily living (ADLs), emotional well-being, stigma, cognition and discomfort, but not on those of social support and communication. Improvements on the mobility, ADLs, stigma and social support subscales were greater amongst GPi patients. In regression analyses, only depression changes independently predicted changes in overall QoL as well as emotional well-being and social support changes. Within the STN group only, declining category fluency scores correlated with poorer QoL on the communication subscale. Unilateral DBS in both STN and GPi improved QoL overall and in disparate domains 6 months after surgery. Patients receiving GPi DBS reported greater improvements that cannot be explained by differential mood or motor effects; however, verbal fluency changes may have partially contributed to lesser QoL improvements amongst STN patients.     

Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease

Objectives. Traditional deep brain stimulation (DBS) at the subthalamic nucleus (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very disabling l ‐dopa–induced abnormal involuntary movements (AIMs) and axial signs are slightly affected, suggesting that we target less conventional targets. Our candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar thalamic complex (Pf or CM), given its extensive functional links with basal ganglia nuclei. Materials and Methods. The routine utilization of our innovative stereotactic apparatus allows us to implant, at the same time, both the CM‐Pf complex together with the GPi in six Parkinson disease patients. Both intraoperative and postoperative neurophysiologic assessments helped us recognize functional subregions while optimizing implantation of electrodes. Unified Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were carefully blindly evaluated for each condition. Results. A significant amelioration of UPDRS scores was achieved by simultaneous activation of both targets. CM‐Pf activation was only slightly effective in reducing rigidity and akinesia, but more efficacious on freezing. Not surprisingly, AIMs were peculiarly decreased by the activation of the permanent electro‐catheter in the posteroventral GPi. Conclusions. These findings confirm that, in selected patients, it is conceivable to target structures other than the conventional STN in order to maximize clinical benefit.     

Bilateral Implantation in Globus Pallidus Internus and in Subthalamic Nucleus in Parkinson's Disease

Introduction . Deep brain stimulation (DBS) of the 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) (DBS for PD study group, 2001). It is still not clear what the best anatomic structures to stimulate are or what the physiologic effects of DBS are. Most of the studies regarding DBS for parkinsonian symptoms have been conducted in patients with STN implantation, and these studies reported significant improvement in motor function with a relatively low rate of complication. The large experience of ablative surgery associated with the DBS experience of some groups worldwide indicate that GPi is a possible and very promising target for the management of parkinsonian symptoms. Surgical procedures have become safer and it is now possible, in selected cases, to target both structures in the same patient by means of the stereotactic system, “3P Maranello” (CLS‐SRL, Italy). Using this system we were able to evaluate the clinical effects of simultaneous stimulation of both STN and GPi as well as evaluate the effects of isolated stimulation of each target. As it is known that there is a high intersubject variability of DBS, it seems relevant to test all different combinations of DBS in the same patient. Methods . We assessed the effects of DBS in 13 cases of PD, immediately after (30 min) stimulation and during chronic stimulation (weeks or months). Patients fell into two groups. The first (n = 7) responded to both GPi and STN stimulation equally. The second group (n = 6) was preferentially stimulated with only one target (STN = 5, GPi = 1). Results . There was a good reduction in levodopa treatment following surgery. Most patients remained were chronically treated with bilateral stimulation of both targets. Conclusion . We conclude that DBS of STN and GPi was effective, with most patients treated chronically with both targets stimulated.     

Deep Brain Stimulation for Early-Stage Parkinson’s Disease: An Illustrative Case

Objectives: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective intervention in advanced Parkinson's disease (PD), but its efficacy and safety in early PD are unknown. We are conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN‐DBS. Materials and Methods: Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra are collected at implantation. The Unified Parkinson's Disease Rating Scale Motor Subscale (UPDRS‐III) is administered in the ON and OFF states semi‐annually and neuropsychological function and quality of life are assessed annually. We describe a 54‐year‐old man with a two‐year history of PD who was randomized to DBS + ODT and followed for two years. Results: The subject showed a lower STN to substantia nigra ratio of neuronal activity than advanced PD patients, and higher firing rate than non‐PD patients. The subject's total UPDRS and UPDRS‐III scores improved during the two‐year follow‐up, while his OFF UPDRS‐III score and levodopa equivalent daily dose increased. Quality of life, verbal fluency, and verbal learning improved. He did not experience any serious adverse events. Conclusions: This report details the first successful application of bilateral STN‐DBS for early‐stage PD during a clinical trial.     

Multicenter study on deep brain stimulation in Parkinson's disease: An independent assessment of reported adverse events at 4 years

Ongoing adverse events (AEs) at 4‐years postsurgery in 69 patients with advanced Parkinson′s disease (PD) who received deep brain stimulation (DBS) of the subthalamic nucleus (STN) (n = 49) or the internal globus pallidus (GPi) (n = 20), in the framework of a subset of eight centers of a multicenter study, were analyzed by an independent ad hoc committee. At baseline, the patients' age, sex, disease duration, and clinical condition were virtually identical, as was the duration of follow‐up. There were 64 AEs reported in 53% of STN DBS patients and eight AEs reported in 35% of GPi DBS patients. Most of the AEs were not deemed severe and were reported to be present “both with and without stimulation.” The majority of the AEs affected patients' cognitive, psychiatric and behavioral status, as well as speech, gait, and balance, and most of these AEs occurred in STN DBS patients. When comparing patients who exhibited AEs with those who did not, it was found that in the STN DBS group, the patients with AEs had a longer disease duration, as well as more gait disorders and psychiatric disturbances at baseline. © 2007 Movement Disorder Society     

Deep brain stimulation for camptocormia in dystonia and Parkinson’s disease

Camptocormia, or “bent spine syndrome”, may occur in various movement disorders such as primary dystonia or idiopathic Parkinson’s disease (PD). Although deep brain stimulation (DBS) is an established treatment in refractory primary dystonia and advanced PD, few data are available on the effect of DBS on camptocormia comparing these two conditions. Seven patients (4 with dystonia, 3 with PD; mean age 60.3 years at surgery, range 39–73 years) with camptocormia were included in the study. Five patients underwent bilateral GPi DBS and two patients underwent bilateral STN DBS guided by CT-stereotactic surgery and microelectrode recording. Pre- and postoperative motor assessment included the BFM in the dystonia patients and the UPDRS in the PD patients. Severity of camptocormia was assessed by the BFM subscore for the trunk at the last available follow-up at a mean of 17.3 months (range 9–36 months). There were no surgical complications. In the four patients with dystonia there was a mean improvement of 53% in the BFM motor score (range 41–79%) and of 63% (range 50–67%) in the BFM subscore for the trunk at the last available follow-up (mean 14.3 months, range 9–18 months). In the three patients with camptocormia in PD who underwent bilateral STN DBS (2 patients) or pallidal DBS (1 patient), the PD symptoms improved markedly (mean improvement in the UPDRS motor subscore stimulation on/medication off 55%, range 49–61%), but there was no or only mild improvement of camptocormia in the two patients who underwent STN DBS, and only moderate improvement in the patient with GPi DBS at the last available follow-up (mean 21 months, range 12–36 months). GPi DBS is an effective treatment for camptocormia in dystonia. The response of camptocormia to chronic STN or GPi DBS in PD is more heterogenous. The latter may be due to a variety of causes and needs further clarification.     

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS. © 2010 Movement Disorder Society     

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.     

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.     

GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease

ObjectivesTo compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities.MethodsWe conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32–34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case–control study.ResultsA total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131).ConclusionsThe overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.     

Acute Changes in Mood Induced by Subthalamic Deep Brain Stimulation in Parkinson Disease Are Modulated by Psychiatric Diagnosis

BackgroundDeep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood.ObjectiveThe study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS.MethodsThirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal.ResultsSTN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS.ConclusionsPD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.     

Changes in Glucose Metabolism in Cerebral Cortex and Cerebellum Correlate With Tremor and Rigidity Control by Subthalamic Nucleus Stimulation in Parkinson's Disease: A Positron Emission Tomography Study

Objective. Employing [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control.     

Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease

ObjectiveThe deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5–4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial.Materials and MethodsAttempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures.ResultsTwelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson’s Disease Rating Scale [UPDRS]–IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; p_interaction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire–39 (PDQ-39), and levodopa equivalent daily dose (LEDD).ConclusionsEleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT00282152.     

Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes

ObjectiveWe aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making.MethodsThis single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes.ResultsFor the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes.ConclusionBilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.     

Deep brain stimulation in Parkinson's disease following fetal nigral transplantation

OFF‐period dyskinesias have been reported as a consequence of fetal nigral transplantation for Parkinson's disease. This type of dyskinesias may appear in patients even in the prolonged absence of antiparkinson medication and be aggravated by levodopa. Therefore, pharmacological therapeutic approaches in these patients are limited. Here we report two patients with bilateral fetal nigral grafts in the caudate and putamen subjected to deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN). Clinical assessment was performed according to UPDRS and the clinical dyskinesia rating scale. In both patients, we found significant improvement in OFF‐period symptoms as well as levodopa‐induced dyskinesias. However, only GPi‐DBS led to a significant reduction of OFF‐period dyskinesias whereas STN‐DBS did not influence dyskinesias unrelated to external dopaminergic application. These findings, based on two case reports, highlight the pivotal role of the GPi in mediating dyskinesia‐related neural activity within the basal ganglia loop. © 2008 Movement Disorder Society     

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundEffects on non-motor symptoms, mainly cognitive and psychiatric side effects, could influence the decision for either globus pallidus pars interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD).Objective1) To compare cognitive and psychiatric outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of suicidal ideation, psychiatric diagnoses, social functioning, and marital satisfaction 3 years after DBS.MethodsPatients were randomized to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate between-group differences on the Mattis Dementia Rating Scale (MDRS), neuropsychological tests, and psychiatric questionnaires 3 years after DBS.ResultsEighty-seven patients (68%) completed at least one neuropsychological test after 3 years. No significant between-group differences were found on the MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS. The Mini International Neuropsychiatric Interview did not indicate a substantial number of psychiatric diagnoses after 3 years. Social functioning and marital satisfaction were comparable in both groups.ConclusionsThree years after GPi DBS and STN DBS no pronounced between-group differences on measures of cognitive and psychiatric functioning could be demonstrated. Overall, cognitive and psychiatric outcome 3 years after DBS do not provide a clear direction for clinicians when considering which of these two surgical targets to choose.