Levodopa response in long‐term bilateral subthalamic stimulation for Parkinson's disease

Piboolnurak, Panida; Lang, Anthony E.; Lozano, Andrés M.; Miyasaki, Janis; Saint‐Cyr, Jean A.; Poon, Yu‐Yan; Hutchison, William D.; Dostrovsky, Jonathan O.; Moro, Elena

doi:10.1002/mds.21482

Cited by 117 publications

(109 citation statements)

References 32 publications

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“…Cardinal signs of tremor and rigidity were not significantly different between the OFF DBS/OFF medication state 4 to 5 years postsurgery and the OFF medication presurgery [21][22][23][24] but bradykinesia had worsened somewhat. [21][22][23] In contrast, PIGD scores OFF DBS and OFF medication had deteriorated significantly 4 to 5 years after DBS, compared to the pre-DBS OFF medication scores. [21][22][23] Two of these studies tested patients with the stimulator turned off for 10 -12 hours.…”

mentioning

confidence: 77%

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

George¹,

Nutt²,

Burchiel³

et al. 2010

Neurology

273

192

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Objective: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi).Results: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states.Conclusions: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed. Neurology Balance and gait are gradually, and inevitably, impaired as Parkinson disease (PD) progresses, resulting in significant impairment of mobility. Mobility disability is one of the most important causes of diminished quality of life, morbidity, and mortality in patients with PD.1,2 Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or globus pallidus interna (GPi) is an increasingly common therapy for mid-to late-stage PD. With optimized stimulation settings, DBS typically lessens the motor symptoms of tremor, limb rigidity, bradykinesia, and akinesia. However, the long-term effects on balance, locomotion, and speech, often referred to as axial motor signs, are debated.Despite improvements in clinical ratings of PIGD immediately after DBS surgery, patients tend to fall more.3 These seemingly contradictory findings are not altogether surprising given that balance and gait are complex behaviors consisting of many sensorimotor subsystems that may not be fully characterized by the PIGD items in the Unified Parkinson's Disease Rating Scale (UPDRS). So although posture and gait are affected by bradykinesia, rigidity, and to a lesser extent tremor, other sensorimotor systems underlying posture and gait, such as setdependent flexibility, 4 sensory integration, 5 and postural synergies, 6 do not show the same responsiveness to levodopa. Therefore, each subsystem underl...

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mentioning

confidence: 77%

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

George¹,

Nutt²,

Burchiel³

et al. 2010

Neurology

273

192

View full text Add to dashboard Cite

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“…However, comparing the MED-ON/STIM-ON scores with the preoperative MED-ON, a significant improvement was observed only at 1 year; at 11 years, all symptoms except rigidity significantly worsened. A reduced magnitude of the response to levodopa was noticed also for symptoms usually considered drug-responsive, and this could have different explanations: during the follow-up patients were taking a levodopa amount smaller than in the preoperative, and this could affect the response to levodopa challenge [14]; chronic STN-DBS could affect the magnitude of levodopa response, probably due to long-term plastic changes of the dopaminergic system [15]; the quality of levodopa responsiveness deteriorates over time.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

Rizzone

Fasano

Daniele

et al. 2014

Parkinsonism & Related Disorders

161

152

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Background: Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome.Objective: To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres. Methods:Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson's Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded.Results: At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time. Conclusions:Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.

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“…This can mean that assessments in the Off medication and OFF stimulation setting can be associated with much more profound severity of "OFF" symptoms and signs, presumably because of the long duration response to L-dopa replacement that is not seen in the "practically defined "Off" state after a short overnight withdrawal [18]. Therefore it was predicted that OFF-medication assessments in these 3 patients would be a potential source of bias (favouring the exenatide group) and not comparable with previous ratings or with the rest of the cohort.…”

Section: Patients Who Had Undergone Dbsmentioning

confidence: 99%

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Avilés-Olmos

Dickson

Kefalopoulou

et al. 2014

JPD

228

148

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Abstract. Background:Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide. Objective: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication. Methods: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide. Results: Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale.

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Levodopa response in long‐term bilateral subthalamic stimulation for Parkinson's disease

Cited by 117 publications

References 32 publications

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

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