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Alleviating Interdose Trough Disability Could Prolong Levadopa's Effects in Parkinson's

Deep brain stimulation reduces motor fluctuations in Parkinson's disease by decreasing drug-off disability, not by altering levodopa pharmacodynamics.

This finding suggests that reducing interdose trough disability could be an alternative way of prolonging the effects of each dose of levodopa so as to reduce motor fluctuations, report United States neurologists.

Patients had reported that deep brain stimulation reduced levodopa-induced motor fluctuations and dyskinesia throughout the day, the researchers report. However, this had not been quantified. Nor was it known how deep brain stimulation modified the response to levodopa.

The neurologists, at Oregon Health Sciences University, Portland, Oregon, and University of Kansas, Kansas City, US, studied 12 patients 12 to 33 months after surgery. Six of these patients were studied with bilateral globus pallidus interna electrodes and six with bilateral subthalamic nucleus electrodes.

Patients were monitored hourly throughout two waking days with their usual oral medications -- one day with deep brain stimulation on and one day with it off.

Both patients and nurse raters were blinded to the status of the deep brain stimulation.

Likewise, the effects of a two-hour levodopa infusion were examined with deep brain stimulation on for one day and off for one day and, again, under double-blind conditions.

The time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores and dyskinesia scores.

It was found that deep brain stimulation 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. Deep brain stimulation increased the drug-off tapping speed, but did not affect peak response or duration of response to levodopa.

The study was not powered to detect differences between globus pallidus interna and subthalamic nucleus stimulation. The only difference that approached significance was that globus pallidus interna reduced peak dyskinesia while subthalamic nucleus tended to increase it.
Neurology 2001;57:1835-1842. "Interactions between deep brain stimulation and levodopa in Parkinson's disease"

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