In clinical trials for patients with Parkinson's disease (PD) with motor fluctuations, efficacy is generally ascribed to an intervention if motor function is significantly improved or if "off" time is significantly reduced. However, we have argued that patients might not be improved if off time is reduced only to the extent that unwanted dyskinesia is increased. Therefore, a home diary should include an assessment of dyskinesia to provide an accurate reflection of clinical status over a period of time. We undertook two studies to develop a home diary to assess functional status in patients with PD with motor fluctuations and dyskinesia. In both studies, patients concurrently completed a test and a reference diary. In Study I, we evaluated the impact of different severities of dyskinesia on patient-defined functional status. There were 1,149 evaluable half-hour time periods from 24 patients; 94.3% of off time was considered "bad" time and 90.2% of "on" time without dyskinesia, 72.6% of on time with mild dyskinesia, 43.0% of on time with moderate dyskinesia, and 15.2% of on time with severe dyskinesia was considered "good" time. In Study II, we evaluated a new home diary designed to separate dyskinesia that had a negative impact on patient-defined functional status from dyskinesia that did not. There were 816 evaluable time periods from 17 patients; 84.9% of off time and 89.9% of on time with troublesome dyskinesia was considered bad time while 85.5% of on time without dyskinesia and 93.8% of on time with nontroublesome dyskinesia was considered good time. With this diary (Diary II), the effect of an intervention can be expressed as the change in off time and the change in on time with troublesome dyskinesia (bad time). The sum can be used as an outcome variable and compared to baseline or across groups. In evaluating the efficacy of an intervention, assessment of change in off time and change in on time with troublesome dyskinesia provides a more accurate reflection of clinical response than change in off time alone.

Abstract-Background: Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. Methods: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August 2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. Results and Conclusions: Propranolol and primidone reduce limb tremor (Level A). Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective in reducing limb tremor (Level B). Limited studies suggest that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness, hoarseness, and swallowing difficulties may occur in the treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure carries a small risk of major complications. Some adverse events from DBS may resolve with time or with adjustment of stimulator settings. There is insufficient evidence regarding the surgical treatment of head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional prospective, double-blind, placebo-controlled trials are needed to better determine the efficacy and side effects of pharmacologic and surgical treatments of ET.