Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact on quality of life, and treatments.

Levodopa is the most effective agent to alleviate motor dysfunction in Parkinson's disease but its long-term use is associated with the development of dyskinesias. Although the pathogenic processes behind the development of levodopa-induced dyskinesias are still being elucidated, it appears that chronic administration of this short-lived agent results in nonphysiologic pulsatile stimulation of striatal neurons and abnormal firing patterns in the basal ganglia. Dyskinesias have been associated with decreased quality of life, and a number of methodologies to evaluate severity of dyskinesias are now available. Strategies to avoid, reduce, or eliminate dyskinesias include providing more continuous dopaminergic stimulation, administering an antidyskinetic agent, and surgery. Several new compounds that may provide an antidyskinetic effect are also under investigation.

Duration of disease does not equally influence all aspects of quality of life in Parkinson's disease.

Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinson's disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n=302), self-reported HRQoL on the Parkinson's Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5years of diagnosis, those within 6-10years of diagnosis, and those greater than 11years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1-5years and 6-10year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses.

Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial.

IMPORTANCE: Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTS: The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. INTERVENTIONS: Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. MAIN OUTCOMES AND MEASURES: The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. CONCLUSIONS AND RELEVANCE: Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00833690.

Feasibility of clinical hypnosis for the treatment of Parkinson's disease: a case study.

Parkinson's disease is a severe neurodegenerative disorder with a prevalence rate of approximately 1.6% in elderly Americans. This case study reports on a 51-year-old male Parkinson's patient who received 3 weekly sessions of a hypnosis intervention, as well as instruction in self-hypnosis. Actigraphy was used to assess rest-tremor severity. Results revealed a 94% reduction in rest tremors following treatment. Self-reported levels of anxiety, depression, sleep quality, pain, stiffness, libido, and quality of life also showed improvements. The patient reported a high level of satisfaction with treatment. These findings suggest clinical hypnosis is potentially feasible and beneficial treatment for some Parkinson's symptoms. Further investigation with diverse samples and an ambulatory monitoring device is warranted.

Management of essential tremor.

Essential tremor (ET) is the most prevalent tremor syndrome. It commonly affects the hands, head, voice, and other body parts. Appropriate management begins with correct diagnosis. Primidone and propranolol are the first-line medications for the treatment for ET, but several other medications may also provide benefit. In patients with medically refractory tremor, alternative therapies, including surgery or injections of botulinum toxin, may be considered.