Showing papers by "William G. Ondo published in 2010"
TL;DR: The most frequently nondeclared symptoms of Parkinson's disease patients were delusions, daytime sleepiness, intense and vivid dreams, and dizziness, and in many, appropriate treatments for undeclared NMS were started only after these were recognised following completion of NMSQuest.
Abstract: The nonmotor symptoms (NMS) of Parkinson's disease (PD) are less well recognised and can be more troublesome to patients and carers than classical motor features. NMS are frequently missed during routine consultations and such under-recognition may have implications on quality of care given that many NMS are treatable. To determine the proportion of patients not declaring NMS to healthcare professional (HCP) as assessed by self completion of the NMS questionnaire (NMSQuest), a validated, self-completing questionnaire with 30 items. Multicentre international study. The data was collected from PD patients across all age groups and stages attending outpatient clinics in specialist and care of the elderly settings. 242 patients recruited and undeclared NMS ranged from 31.8% (diplopia) to 65.2% (delusions). The most frequently nondeclared symptoms were delusions, daytime sleepiness, intense and vivid dreams, and dizziness. In many, appropriate treatments for undeclared NMS were started only after these were recognised following completion of NMSQuest. NMS of PD are frequently undeclared at routine hospital consultation and may be related to the fact that patients often do not link these symptoms with PD or may be too embarrassed to discuss these. Use of NMSQuest allows patients to flag symptoms which may be otherwise undeclared and remain untreated when potential treatments exist.
335 citations
TL;DR: Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms and co‐primary efficacy parameters decreased from baseline to end of maintenance.
Abstract: This randomized, double-blinded, placebo-controlled trial (NCT00135993) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome (RLS) over a 6-month maintenance period. A total of 505 eligible participants with moderate to severe RLS (IRLS sum score >or= 15) were randomly assigned to five groups to receive either placebo or rotigotine (0.5, 1, 2, or 3 mg/24 hr) delivered by once-daily transdermal patch (fixed-dose regimen). The two co-primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions (CGI-1) score. On both primary measures, 2 and 3 mg/24 hr rotigotine was superior to placebo (P < 0.001). Adjusted treatment differences to placebo for the IRLS sum score were -4.5 (95% CI: -6.9, -2.2) for 2 mg/24 hr rotigotine, -5.2 (95% CI: -7.5, -2.9) for 3 mg/24 hr rotigotine, and for CGI item 1 -0.65 (95% CI: -1.0, -0.3) and -0.9 (95% CI: -1.3, -0.5) for the 2 and 3 mg/24 hr doses, respectively. Skin reactions (27%) and known dopaminergic side effects such as nausea (18.1%) and headache (11.6%) were mostly mild or moderate in rotigotine subjects. Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms. Treatment efficacy was maintained throughout the 6-month double-blind period.
105 citations
TL;DR: Melanoma prevalence appears to be higher in patients with PD than in the general population, and despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in Patients with PD.
Abstract: Objective To evaluate the possible association of Parkinson disease (PD) and melanoma in North America. Design, Setting, and Patients Thirty-one centers enrolled patients with idiopathic PD. At visit 1, a neurologist obtained a medical history. At visit 2, a dermatologist recorded melanoma risk factors, performed a whole-body examination, and performed a biopsy of lesions suggestive of melanoma for evaluation by a central dermatopathology laboratory. We compared overall prevalence of melanoma with prevalence calculated from the US Surveillance Epidemiology and End Results (SEER) cancer database and the American Academy of Dermatology skin cancer screening programs. Results A total of 2106 patients (mean [SD] age, 68.6 [10.6] years; duration of PD, 7.1 [5.7] years) completed the study. Most (84.8%) had received levodopa. Dermatology examinations revealed 346 pigmented lesions; dermatopathological findings confirmed 20 in situ melanomas (0.9%) and 4 invasive melanomas (0.2%). In addition, histories revealed 68 prior melanomas (3.2%). Prevalence (5-year limited duration) of invasive malignant melanoma in the US cohort of patients with PD (n = 1692) was 2.24-fold higher (95% confidence interval, 1.21-4.17) than expected in age- and sex-matched populations in the US SEER database. Age- or sex-adjusted relative risk of any melanoma for US patients was more than 7 times that expected from confirmed cases in American Academy of Dermatology skin cancer screening programs. Conclusions Melanoma prevalence appears to be higher in patients with PD than in the general population. Despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in patients with PD.
99 citations
TL;DR: Iron dextran can dramatically improve refractory RLS but results are inconsistent and not predicted by patient demographics, and may be superior to other IV iron preparations.
66 citations
TL;DR: Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.
Abstract: This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.
30 citations
29 citations
TL;DR: This small pilot study did not show significant group differences favoring OD C/L; however, larger studies may be justified, and individual patients may benefit.
Abstract: Levodopa use in fluctuating Parkinson's disease (PD) is complicated by an inconsistent and prolonged onset to clinical improvement. An orally dissolved carbidopa/levodopa (OD C/L) preparation (Parcopa UCB Pharma) is available in the United States. This offers potential advantages to shorten the duration from ingestion to clinical improvement. Surprisingly, this has never been clinically assessed. We tested 20 patients with fluctuating PD and a Unified Parkinson's Disease Rating Scale (UPDRS) "off" motor score of ≥ 25 in a 2-day, single-dose, double-blind, double-dummy, crossover study. Patients arrived in the morning in the practically defined "off" state and were randomly assigned to receive identical doses of either oral C/L and OD placebo or OD C/L and oral C/L placebo on 1st day and the reverse combination on a 2nd day. After training, patients underwent bilateral hand tapping at baseline and every 5 minutes for 60 minutes after dose ingestion. Stride length (SL) was recorded at 5-minute intervals with an ambulatory gait monitor. Patients identified their subjective latency to "on" and noted drug preferences and adverse events. They also underwent a UPDRS motor examination at baseline and 60 minutes after dose. Twenty subjects [15 male, age 68.7 (9.7), PD duration 13.4 (6.8)] completed. There were no significant group differences in tapping speed, subjective time to "on," latency of increased SL, or overall preference. However, all trends did favor OD C/L. Adverse events were similar. This small pilot study did not show significant group differences favoring OD C/L; however, larger studies may be justified, and individual patients may benefit.
24 citations
TL;DR: Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome pharmacokinetic limitations of the drug and is generally well tolerated and is useful in the treatment of RLS.
Abstract: Restless legs syndrome (RLS) is a common sleep-related neurological disorder that is characterized by the urge to move, worsening at rest, improvement with activity, and worsening in the evening and night. Dopamine agonists are usually the first-line therapy. Other agents including benzodiazepines, narcotics, and anticonvulsants have been used to treat RLS. Gabapentin has been shown to improve RLS in a small number of clinical studies, but is limited by its short half-life and variable bioavailability. Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome these pharmacokinetic limitations. In vitro and in vivo studies have demonstrated that gabapentin enacarbil has improved absorption, bioavailability and pharmacokinetics compared with gabapentin. Phase II and III studies have demonstrated that gabapentin enacarbil is generally well tolerated and is useful in the treatment of RLS.
22 citations
TL;DR: Essential tremor is a common movement disorder with clinical features that manifest with both motor (tremor and balance disorders) and non-motor symptoms and several new agents including 1-octanol, pregabalin and sodium oxybate are currently under investigation.
Abstract: Essential tremor (ET) is a common movement disorder with clinical features that manifest with both motor (tremor and balance disorders) and non-motor (such as mild cognitive deficits and hearing loss) symptoms. The diagnosis of ET is based on the presence of an action tremor of greater severity than enhanced physiological tremor, without other identifiable causes. Patients with ET experience a decrease in the performance of their motor skills and social activities, and a decline in their quality of life. The pathophysiology of ET is still not clear. Pharmacotherapy for ET is indicated if the disease interferes with the patient's quality of life. Propranolol, a nonselective β-adrenergic receptor antagonist, and primidone, an antiepileptic, remain the standard treatments for ET. However, studies show that several other agents, including topiramate, gabapentin and zonisamide, might also be beneficial. Local injections of botulinum toxins and surgical interventions such as thalamic deep brain stimulation play a role as alternative options when pharmacological treatment is not satisfactory. Several new agents including 1-octanol, pregabalin and sodium oxybate are currently under investigation.
20 citations
TL;DR: MLE has minimal long term clinical effect except for possibly allowing for lower DBS settings, including amplitude and pulse width, trended to be mildly lower in those with a marked MLE.
11 citations
01 Dec 2010
TL;DR: Drug-induced movement disorders remain a common and under-recognized problem and blockade of the dopaminergic system results in multiple syndromes, which include tardive dyskinesia, acute dystonic reactions, akathisia, drug-induced parkinsonism and neuroleptic malignant syndrome.
Abstract: Drug-induced movement disorders remain a common and under-recognized problem. Blockade of the dopaminergic system results in multiple syndromes and will be the main focus of this discussion. These syndromes are often referred to as extrapyramidal side effects (EPSE) and include tardive dyskinesia, acute dystonic reactions, akathisia, drug-induced parkinsonism and neuroleptic malignant syndrome (Figure 6.1). Serotonin syndrome and drug-induced tremor are also briefly discussed.
TL;DR: The results support the pathological evidence that dopamine stores and release are not deficient in RLS and suggest that histamine release, which is markedly inhibited by TBZ, does not worsen RLS despite marked exacerbation of RLS with histamine blocking medications.
TL;DR: A56-YEAR-old chInese woman presented to the authors' clinic at age 46 years with a 2-year history of progressive instability and impaired manual dexterity.
Abstract: A56-YEAR-OLD CHInese woman presented to our clinic at age 46 years with a 2-year history of progressive instability and impairedmanualdexterity.Herphysical examination revealed broad