Assessment of an Objective Method of Dyskinesia Measurement in Parkinson's Disease.

BACKGROUND: The goal of this study was to validate an objective method of measuring levodopa induced dyskinesia in Parkinson's disease (PD). METHODS: To characterize agreement between the clinician-based measure and a force plate, we assessed dyskinesia in PD subjects participating in a randomized and blinded clinical trial of an adenosine A2A anatagonist. Convergent validity and intra-class correlations were evaluated between the objective force plate measure and clinician assessments. RESULTS: All measures correlated across time and detected differences in treatments. CONCLUSION: Our results indicate that objective measure from a force plate is in scale agreement with clinical ratings of dyskinesia severity, indicating it as a reliable method to measure LID objectively but with greater resolution to detect changes in LID.

A randomized, controlled pilot study of the effects of vitamin D supplementation on balance in Parkinson's disease: Does age matter?

OBJECTIVES: To explore if short term, high dose vitamin D supplementation is safe and improves balance in persons with Parkinson's disease (PD). METHODS: A pilot randomized, double-blind intervention trial to measure the effects of 16 weeks of high dose vitamin D (10,000 IU/day) on balance as well as other motor and non-motor features of PD. We measured balance, gait, strength, falls, cognition, mood, PD severity, and quality of life before and after 16 weeks of high dose vitamin D supplementation or placebo. All participants also received 1000 mg calcium once daily. RESULTS: Fifty-one randomized participants completed sixteen weeks of high dose vitamin D supplementation or placebo. The intervention resulted in a rise in serum concentrations of vitamin D (25-OH) (30.2 ng/ml to 61.1 ng/ml) and was well tolerated with no serious adverse events. Serum vitamin D (25-OH) levels rose steadily and did not suggest a leveling off at the end of the 16 weeks. There was not an improvement in the primary endpoint, balance as measured by the Sensory Organization Test (p = 0.43). A post hoc analysis examining treatment effects in younger (ages 52-66) versus older (ages 67-86) participants found a significant improvement in the SOT of 10.6 points in the younger half of the cohort (p = 0.012). CONCLUSIONS: Short term, high dose vitamin D supplementation appears safe in persons with PD, but did not significantly improve balance as measured with the Sensory Organization Test in this pilot study population. A post hoc analysis suggests that vitamin D may have potential for improving balance in a younger population with PD. High dose vitamin D supplementation in PD needs further study especially in light of new research suggesting that mega doses and even moderate doses (as low as 4000IU a day) may increase falls in an older populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01119131.

The use of acetazolamide during pregnancy in intracranial hypertension patients.

BACKGROUND: Acetazolamide is the mainstay of medical therapy for idiopathic intracranial hypertension (IIH). Its use in pregnant women has not been recommended because of reported teratogenic effects in rodents and rabbits. However, the safety of acetazolamide use during human pregnancy remains unclear. We report the pregnancy and offspring outcomes in women with intracranial hypertension (IH) treated with acetazolamide during pregnancy. METHODS: Data were collected through questionnaires sent to patients with IH and their physicians. The questionnaires focused on IH diagnosis, obstetric history and outcomes, and pediatric outcomes. RESULTS: A total of 101 women with IH were consented (total of 158 pregnancies) and acetazolamide usage before 13 weeks of gestation was reported in 50 pregnancies. The risk of spontaneous abortion was similar to the control group and no major complication was identified in the offspring of women treated with acetazolamide. CONCLUSION: There is no convincing evidence for an adverse effect for acetazolamide use in human pregnancy, even when prescribed prior to the 13th week of gestation. While the liberal use of acetazolamide should be avoided during pregnancy, this medication should remain a treatment option in pregnant women when clinically indicated.

Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease.

OBJECTIVE: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability. BACKGROUND: Falling due to postural instability is a significant problem in advancing PD, and is minimally impacted by dopaminergic therapy. Anticholinergic medications increase falling in the elderly. Further, CNS cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine augmentation may reduce frequent falling in subjects with PD. METHODS: We enrolled 23 subjects with PD who reported falling or nearly falling more than 2 times per week. In a randomized, placebo-controlled, crossover design, subjects were given 6 weeks of donepezil or placebo with a 3-week washout between phases. The primary outcomes were daily falls and near falls reported on postcards. Secondary outcomes included scores on the Activities of Balance Confidence Scale, Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental State Examination, and the motor section of the Unified Parkinson's Disease Rating Scale. RESULTS: Fall frequency per day on placebo was 0.25 ± 0.08 (SEM) compared with 0.13 ± 0.03 on donepezil (p < 0.05). The frequency of near falls was not significantly different between phases. The secondary outcomes did not differ; however, there was a trend to improvement on the subject-completed Global Impression of Change scale. CONCLUSIONS: Subjects with PD fell approximately half as often during the 6 weeks on donepezil than on placebo. Larger trials of cholinergic augmentation are warranted in subjects with PD with frequent falls. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that donepezil (maximum 10 mg per day) significantly reduced the number of falls in patients with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day, SEM = 0.08, p = 0.049).

Objective measurement of dyskinesia in Parkinson's disease using a force plate.

Clinical investigation of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is limited because of lack of objective measurements and no consensus on use of a standard measuring tool. Currently, clinical trials use subject-completed diaries of dyskinesia throughout the day or investigator-administered clinical rating scales. An objective and valid method of measuring LID would reduce bias, variability, and decrease the time and number needed in trials of potential anti-dyskinetic agents. We have investigated using a force plate under standing subjects, which records movement of the center of pressure (CoP) to quantify LID over a levodopa (L-dopa) cycle. Twenty-two PD subjects (15 with LID, 7 without LID) admitted to an inpatient research facility had their PD meds withheld overnight, followed by a 2 hours intravenous L-dopa infusion the next day. The root mean squared of the velocity in the anterior-posterior direction (RMSV) derived from an analysis of the CoP, and, the modified Abnormal Involuntary Movement Scale (mAIMS) were performed repeatedly for 6 hours, initially as subjects were OFF before the infusion, through infusion until OFF again. There was a high correlation between the area under the curve (AUC) of the mAIMS and the RMSV within and between subjects. As a measure of LID, RMSV had excellent validity and reliability between subjects, and using a force plate was feasible. Sensitivity to changes in LID was initially demonstrated but should be repeated. Thus, CoP recordings on a force plate can objectively quantify LID in PD and may be very useful in clinical trials or other investigations of dyskinesia.