developing objective measures of levodopa induced dyskinesia: (study 1)

Conditions: Dyskinesias; Movement Disorders; Parkinson Disease

Summary: the ultimate goal of this proposal is to reduce dyskinesia in parkinson's disease (pd) patients. dyskinesias are abnormal movements, often caused by the standard treatment for pd symptoms, levodopa. in this study, we will test if biochemical devices are equal to the clinical rating system in measuring dyskinesias.

levodopa induced dyskinesia (lid) is a major problem associated with chronic use of levodopa (ld) for symptomatic treatment of parkinson's disease (pd). ld remains our most potent therapy and nearly all pd patients will use it. a substantial portion of them will experience lid, with the impact ranging from non-interfering to severely disabling. the objective of this study is to develop reliable and sensitive objective measures of lid that will quantify muscular control and postural stability in subjects with dyskinesia. while the "gold standard" of measuring lid is the subjective rs, we will determine if objective biochemical devices will equal the reliability and validity of crs. we hypothesize that force plate technology quantifies postural sway movements best, and pinch-grip will best quantify muscle overflow force during voluntary movements. we will compare two biomechanical devices and a traditional clinical rating scale (crs). once biomechanical instrument measures lid in the setting of voluntary muscle activity, the other acquires lid data related to postural sway.. a cross-section of ld-treated patients with and without clinically apparent dyskinesia will be used to assess the measures. 32 subjects will be invited to participate, 24 with pd and 8 age-matched controls (likely unaffected spouses) without neurologic disease. of the pd patients 7 will have no clinically apparent dyskinesia, 7 will have mild dyskinesia and 7 with moderate to severe dyskinesia will be recruited (3 additional subjects are included to account for missing data or drop-outs). they will comfortably stand with their feet placed in a preset marked stance on the force plate either with or without a mental task and pick up a pinch-grip device multiple times. testing will be done in the effective motor "on" and "off" states to establish validity and reliability of instrument data, as these states often reflect the usual clinical experience of patients. the second method for rating dyskinesia will be the clinical rating scale. subjects will be rated while standing on the force plate during both mental task and non-mental task conditions. all subjects will undergo this testing. healthy subjects will undergo this testing three times during one visit. subjects with pd will be admitted overnight, and have seven testing periods which will vary in the number of times the procedures will be done. inpatient subjects will also receive 1mg/kg/hr or 1.5mg/kg/hr of intravenous levodopa depending on their everyday usage of levodopa or levodopa equivalent medications for 2 hours (9am - 11am) with carbidopa 25 mg po at 8am, 10am and noon to prevent nausea.

Eligibility criteria:
inclusion criteria: * clinical diagnosis of probable idiopathic parkinson's disease or no neurologic disease (no disease for controls only) * at least 21 years of age * mini mental status exam score\>=25 exclusion criteria: * evidence of psychosis (hallucinations or delusions) by history * any unstable medical condition * currently using dopamine blocking medication * currently taking anticoagulants or mao inhibitors

Keywords: dyskinesia levodopa movement disorders parkinson disease