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.     

STN vs. Pallidal Stimulation in Parkinson Disease: Improvement With Experience and Better Patient Selection

Objectives. This is a prospective study to determine the outcomes of subthalamic nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at our institution. Materials and Methods. We studied a total of 39 patients — 29 with STN and 10 with GPi DBS over a period of up to 6 years. Mean ages in the two groups were similar (59 and 60 years, respectively) and disease duration prior to implantation was similar (9.6 and 11.7 years, respectively). Unified Parkinson Disease Rating Scale (UPDRS) was recorded preoperatively and at follow‐up (at least at 6‐month intervals). Medications also were recorded, and each patient's levodopa equivalent units (LEU) were calculated. Results were analyzed using a paired Student's t‐test. Results. LEU reduced significantly (p < 0.05) in the STN group (5.7 to 3.7) but not the GPi group. Both targets significantly improved part 3 and part 4 scores of the UPDRS but GPi DBS did not improve part 2 scores (activities of daily living). STN DBS had much better outcome on the motor “off” scores of the UPDRS, whereas GPi only improved tremor. A comparison of the “earliest 10” and “most recent 10” STN patients showed a significant improvement in outcome in the most recent cases. Conclusions. In our group, STN was more effective for alleviating the symptoms of Parkinson disease, even in older patients with significant dyskinesias. Better patient selection and greater experience have led to more improvement in the more recent 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     

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.     

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.     

Multi-target strategy for Parkinsonian patients: the role of deep brain stimulation in the centromedian-parafascicularis complex

The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the basal ganglia and is recently regaining its position has a putative neurosurgical target for Parkinsonian syndromes. The multi-target approach we have encouraged since the late nineties has allowed the combined implantation of a standard target (the subthalamic nucleus-STN or the internal pallidus-GPi) plus an innovative one (CM/Pf) in well-identified Parkinson's disease (PD) patients; hence, it is possible to study, in the same PD patients, the specific target-mediated effects on different clinical signs. Here, we focus on the potential usefulness of implanting the CM/Pf complex when required in the management of contra-lateral tremor (resistant to standard deep brain stimulation-DBS - in STN - , n=2) and disabling involuntary movements, partially responsive to GPi-DBS (n=6). When considering global UPDRS scores, CM/Pf-DBS ameliorate extra-pyramidal symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very powerfully on tremor and contributes to the long-term management of l-Dopa-induced involuntary movements. The lack of cognitive deficits and psychic impairment associated with the improvement of their quality of life, in our small cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and attractive area for surgical treatment of advanced PD, possibly affecting not only motor but also associative functions.     

Gait disturbance and deep brain stimulation

Gait disturbance, one of the axial symptoms, is caused by various disorders, including basal ganglia disease. Deep brain stimulation (DBS) has widened the spectrum of therapeutic options for patients with gait disturbance due to Parkinson disease and dystonia. In gait disturbance caused by basal ganglia disease, the main targets of DBS are the subthalamic nucleus (STN) and globus pallidus internus (GPi). STN DBS is more than GPi DBS effective for treating levodopa-responsive parkinsonian symptoms, including gait disturbance. GPi DBS is effective for the treatment of primary segmental or generalized dystonia. The pedunculopontine tegmental nucleus (PPN), which is involved in locomotion, is one of the new targets for treating gait disturbance in Parkinson disease. We review DBS in the treatment of gait disturbance due to Parkinson disease and dystonia.     

Subthalamic nucleus and globus pallidus interna influence firing of tonically active neurons in the primate striatum through different mechanisms

Both the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are major targets for neuromodulation therapy for movement disorders. An example of such a therapy is deep brain stimulation (DBS). The striatum is the primary target for pharmacological treatment of these disorders. To further our understanding of both the functional relationships among motor nuclei and the mechanisms of therapies for movement disorders, it is important to clarify how changing the neuronal activity of one target, either by medication or by artificial electrical stimulation, affects the other connected nuclei. To investigate this point, we recorded single‐unit activity from tonically active neurons (TANs), which are putative cholinergic interneurons in the striatum, of healthy monkeys (Macaca fuscata) during electrical stimulation of the STN or GPi. Both STN stimulation and GPi stimulation reduced the TAN spike rate. Local infusion of a D2 receptor antagonist in the striatum blocked the reduction in spike rate induced by STN stimulation but not that induced by GPi stimulation. Further, STN stimulation induced phasic dopamine release in the striatum as revealed by in vivo fast‐scan cyclic voltammetry. These results suggest the presence of multiple, strong functional relationships among the STN, GPi, and striatum that have different pathways and imply distinct therapeutic mechanisms for STN‐ and GPi‐DBS.     

Surgical targets in Psychiatric disorders. From movement to emotions

Deep brain stimulation (DBS) for psychiatric disorders refractory to conventional treatments are currently been performed based on the knowledge obtained in the motor disorder surgery and mainly in Parkinson's disease. Depression, obsessive-compulsive disorder (OCD) and Tourette syndrome, all of them are cortico-striato-thalamo-cortical pathological process involved in the limbic loop of the basal ganglia. This review describes the different targets in these pathological neuro-psychiatric disorders. For OCD there are currently two targets, ventral striatum (VS) Accumbens nucleus (Nacc) and the subthalamic nucleus (STN). In refractory depression the subgenual area (25 Brodmann area) and VS/Nacc. For Tourette syndrome the ventralis oralis internus and centromedianum/parafascicularis of the thalamus (Voi and CM/Pf) and the internal part of the globus pallidus (GPi). Currently there are no specific surgical target for each pathological disorder because clinical results reported are very similar after stimulation surgery. In other point, a selected surgical target also may improve different pathologies.     

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.     

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.     

Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials are limited. OBJECTIVE: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD. DESIGN: This study represents the combined results from our previously published, randomized, blinded, parallel-group pilot study and additional patients enrolled in our single-center extension study. SETTING: Oregon Health and Science University in Portland.Patients Twenty-three patients with idiopathic PD, levodopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Patients and evaluating clinicians were blinded to stimulation site. All patients were tested preoperatively while taking and not taking medications and after 3, 6, and 12 months of DBS. MAIN OUTCOME MEASURES: Postoperatively, response of symptoms to DBS, medication, and combined medication and DBS was evaluated. Twenty patients (10 in the GPi group and 10 in the STN group) completed 12-month follow-up. RESULTS: Off-medication Unified Parkinson's Disease Rating Scale motor scores were improved after 12 months of both GPi and STN stimulation (39% vs 48%). Bradykinesia tended to improve more with STN than GPi stimulation. No improvement in on-medication function was observed in either group. Levodopa dose was reduced by 38% in STN stimulation patients compared with 3% in GPi stimulation patients (P = .08). Dyskinesia was reduced by stimulation at both GPi and STN (89% vs 62%). Cognitive and behavioral complications were observed only in combination with STN stimulation. CONCLUSION: Stimulation of either the GPi or STN improves many features of advanced PD. It is premature to exclude GPi as an appropriate target for DBS in patients with advanced disease.     

The persistent effects of unilateral pallidal and subthalamic deep brain stimulation on force control in advanced Parkinson's patients

The persistent effects of unilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus (STN) on specific movement parameters produced by Parkinson's disease (PD) patients are poorly understood. The aim of this study was to determine the effects of unilateral GPi and STN DBS on the force-producing capabilities of PD patients during maximal efforts and functional bimanual dexterity. Clinical and biomechanical data were collected from 14 unilaterally implanted patients (GPi=7; STN=7), at least 13 months post-DBS surgery, during On and Off stimulation in the absence of medication. Unilateral DBS of either location produced a 33% improvement in UPDRS motor scores. Significant gains in maximum force production were present in both limbs during unimanual efforts. The greatest increase in maximum force, for both limbs, was under bimanual conditions. Force in the contralateral limb increased more than 30% during bimanual efforts while ipsilateral force increased by 25%. Unilateral DBS improved grasping force control and consistency of digit placement during the performance of a bimanual dexterity task. The clinical and biomechanical data indicate that unilateral DBS of GPi or STN results in persistent improvements in the control and coordination of grasping forces during maximal efforts and functional dexterous actions. Unilateral DBS implantation of either site should be considered an option for those patients in which bilateral procedures are contraindicated.     

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.     

Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson's disease: which target?

Deep brain stimulation (DBS) is an accepted therapy for people with Parkinson's disease (PD) motor symptoms that are refractory to pharmacologic therapy. Standard DBS targets are globus pallidus interna (GPi) and subthalamic nucleus (STN). The pedunculopontine nucleus (PPN) is being investigated as a novel target. Which target provides the best outcomes is unknown. The utility of GPi and STN as targets has been confirmed in numerous studies, including randomized comparisons of GPi DBS and STN DBS that demonstrated no difference in motor outcomes. DBS at either site improves appendicular motor symptoms, but beneficial effects on axial manifestations of PD such as postural instability or gait dysfunction (PIGD) are less apparent. PPN has been introduced as a DBS target due to failure of GPi and STN DBS to improve PIGD. Small observational studies indicate improved PIGD with PPN DBS, but small blinded trials show only subjective reduction in falls with no other impact on PIGD or other PD manifestations. No single DBS target is superior to the others. Each target offers relative advantages. Further studies are needed to better define the roles of each target, particularly PPN. Choice of target should be individualized according to providers' preferences and patients' needs.     

Different cerebral cortical areas influence the effect of subthalamic nucleus stimulation on parkinsonian motor deficits and freezing of gait.

Inconsistent response in freezing of gait (FOG) with levodopa treatment or STN DBS makes the pathogenesis difficult to understand. We studied brain areas associated with the expression of STN DBS effect on parkinsonian motor deficits and FOG. Ten Parkinson's disease patients with typical FOG were included. One month before STN DBS, we performed [(18)F]-deoxyglucose PET scans and measured the UPDRS motor and modified FOG (mFOG) scores during levodopa off and on periods. At two months after STN DBS, same rating scores were measured. The percentage improvement of mFOG and UPDRS motor scores by STN DBS during levodopa off period was calculated. We searched for brain areas in which glucose metabolism correlated with the improvement of mFOG and UPDRS motor scores by DBS. During levodopa off period, STN DBS improved the UPDRS motor scores by 32.3% and the mFOG scores by 56.6%. There was no correlation between the improvements of both scores. The improvement of UPDRS motor score by DBS correlated with the metabolic activities of rostral supplementary motor area (Brodmann's area 8; BA8), anterior cingulate cortex (BA32), and prefrontal cortex (BA9). On the other hand, there was a positive correlation between the improvement of mFOG score by DBS and the metabolic activity of the parietal, occipital, and temporal sensory association cortices. In conclusion, dysfunction of different cerebral cortical areas limits the beneficial effects of DBS on parkinsonian motor deficits and FOG.     

Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.     

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.     

Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

Background: Subthalamic nucleus deep brain stimulation (STN DBS) and continuous dopaminergic infusions (jejunal levodopa or subcutaneous apomorphine) are indicated in complicated Parkinson’s disease (PD), although it remains unsettled how they compare to each other. Methods: We investigated the daytime motor condition in patients with advanced PD under monotherapy with jejunal levodopa, subcutaneous apomorphine, or STN DBS and also measured the motor changes produced by an additional standard morning dose of levodopa. Motor performance was assessed with the UPDRS‐III, hand taps, the AIMS dyskinesia score and patients’ diaries. Outcome measures were time to best motor ‘on’ after start of morning treatment, daytime variability of motor condition, motor scores. Results: The time to ‘on’ was longest in the jejunal levodopa group. DBS and jejunal levodopa treatments produced stable motor conditions without appreciable ‘off’ episodes. Continuous apomorphine infusion was associated with the worst motor scores (UPDRS‐III and taps) and the most frequent off‐states. Jejunal levodopa infusion was associated with the highest AIMS scores. Addition of a levodopa dose produced shortening of time to ‘on’ and a transient motor improvement in the jejunal levodopa group without increase in dyskinesias; in the DBS and apomorphine groups, there was an increase in dyskinesias without changes in UPDRS‐III or taps. Conclusions: STN DBS provided adequate trade‐off between motor improvement and dyskinesia control, although dyskinesias could be elicited by adding oral levodopa. Jejunal levodopa infusion produced adequate motor improvement with slow time to ‘on’ and moderate dyskinesias. Apomorphine infusion produced insufficient motor control and negligible dyskinesias.     

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