Interactions between deep brain stimulation and levodopa in Parkinson's disease

John Nutt, S. L. Rufener, Julie Carter, Valerie Anderson, R. Pahwa, John Hammerstad, Kim Burchiel

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. Background: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. Methods: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and I day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. Results: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. Conclusion: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.

Original languageEnglish (US)
Pages (from-to)1835-1842
Number of pages8
JournalNeurology
Volume57
Issue number10
StatePublished - Nov 27 2001

Fingerprint

Deep Brain Stimulation
Levodopa
Parkinson Disease
Dyskinesias
Subthalamic Nucleus
Globus Pallidus
Tremor
Electrodes
Parkinsonian Disorders
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Interactions between deep brain stimulation and levodopa in Parkinson's disease. / Nutt, John; Rufener, S. L.; Carter, Julie; Anderson, Valerie; Pahwa, R.; Hammerstad, John; Burchiel, Kim.

In: Neurology, Vol. 57, No. 10, 27.11.2001, p. 1835-1842.

Research output: Contribution to journalArticle

Nutt, J, Rufener, SL, Carter, J, Anderson, V, Pahwa, R, Hammerstad, J & Burchiel, K 2001, 'Interactions between deep brain stimulation and levodopa in Parkinson's disease', Neurology, vol. 57, no. 10, pp. 1835-1842.
Nutt J, Rufener SL, Carter J, Anderson V, Pahwa R, Hammerstad J et al. Interactions between deep brain stimulation and levodopa in Parkinson's disease. Neurology. 2001 Nov 27;57(10):1835-1842.
Nutt, John ; Rufener, S. L. ; Carter, Julie ; Anderson, Valerie ; Pahwa, R. ; Hammerstad, John ; Burchiel, Kim. / Interactions between deep brain stimulation and levodopa in Parkinson's disease. In: Neurology. 2001 ; Vol. 57, No. 10. pp. 1835-1842.
@article{a6996509479941d9966b4414bc3f9fe5,
title = "Interactions between deep brain stimulation and levodopa in Parkinson's disease",
abstract = "Objective: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. Background: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. Methods: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and I day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. Results: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. Conclusion: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.",
author = "John Nutt and Rufener, {S. L.} and Julie Carter and Valerie Anderson and R. Pahwa and John Hammerstad and Kim Burchiel",
year = "2001",
month = "11",
day = "27",
language = "English (US)",
volume = "57",
pages = "1835--1842",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Interactions between deep brain stimulation and levodopa in Parkinson's disease

AU - Nutt, John

AU - Rufener, S. L.

AU - Carter, Julie

AU - Anderson, Valerie

AU - Pahwa, R.

AU - Hammerstad, John

AU - Burchiel, Kim

PY - 2001/11/27

Y1 - 2001/11/27

N2 - Objective: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. Background: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. Methods: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and I day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. Results: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. Conclusion: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.

AB - Objective: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. Background: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. Methods: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and I day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. Results: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. Conclusion: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.

UR - http://www.scopus.com/inward/record.url?scp=0035960647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035960647&partnerID=8YFLogxK

M3 - Article

C2 - 11723273

AN - SCOPUS:0035960647

VL - 57

SP - 1835

EP - 1842

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -