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wearing off Parkinsonism

Ken Ikeda, Takehisa Hirayama, Takanori Takazawa, Kiyokazu Kawabe, Yasuo Iwasaki
Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients...
2016: Internal Medicine
Chiara Baston, Manuela Contin, Giovanna Calandra Buonaura, Pietro Cortelli, Mauro Ursino
Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system...
2016: Frontiers in Human Neuroscience
Yuki Yasutaka, Shinsuke Fujioka, Hirotomo Shibaguchi, Osamu Imakyure, Atsushi Washiyama, Yoshio Tsuboi, Koujiro Futagami
Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital...
June 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
Tuhin Virmani, Sirinan Tazan, Pietro Mazzoni, Blair Ford, Paul E Greene
BACKGROUND: The modulation of levodopa transport across the blood brain barrier by large neutral amino acids is well documented. Protein limitation and protein redistribution diets may improve motor fluctuations in patients with Parkinson's disease but the pharmacokinetics and pharmacodynamics of levodopa and amino acids are highly variable. METHODS: Clinical records of 1037 Parkinson's disease patients were analyzed to determine the proportion of patients with motor fluctuations related to protein interaction with levodopa...
2016: J Clin Mov Disord
Philippe Huot, Susan H Fox, Jonathan M Brotchie
Striatal dopamine deficiency is the core feature of the pathology of Parkinson's disease (PD), and dopamine replacement with l-3,4-dihydroxyphenylalanine (l-DOPA) is the mainstay of PD treatment. Unfortunately, chronic l-DOPA administration is marred by the emergence of dyskinesia and wearing-off. Alternatives to l-DOPA for alleviation of parkinsonism are of interest, although none can match the efficacy of l-DOPA to date. Catechol-O-methyltransferase and monoamine oxidase inhibitors are currently used to alleviate wearing-off, but they do not increase "on-time" without exacerbating dyskinesia...
June 2016: Journal of Pharmacology and Experimental Therapeutics
Dhanya Vijayakumar, Joseph Jankovic
Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. Levodopa-induced dyskinesia (LID) is one of the main types of drug-induced dyskinesia, occurring in patients with Parkinson's disease (PD) who have been treated with levodopa for long time, but this side effect may be encountered even within a few weeks or months after initiation of levodopa therapy. Based on the temporal pattern in relationship to levodopa dosing, LIDs are divided into "peak-dose dyskinesia," "diphasic dyskinesia," and "wearing off" or "off-period" dyskinesia, of which peak-dose dyskinesia is the most common, followed by off-period, and then diphasic dyskinesia...
May 2016: Drugs
Dhanya Vijayakumar, Joseph Jankovic
Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. The main types of drug-induced dyskinesias include levodopa-induced dyskinesia (LID) in patients with Parkinson's disease and tardive syndrome (TS), typically present in patients with psychiatric or gastrointenstinal disorders treated with dopamine receptor blocking drugs, also referred to as neuroleptics. Besides preventive measures (i.e., avoiding the use of the offending drugs), general treatment strategies include slow taper of the offending agent and use of dopamine-depleting agents like tetrabenazine...
May 2016: Drugs
Marina Picillo, Raffaele Palladino, Marcello Moccia, Roberto Erro, Marianna Amboni, Carmine Vitale, Paolo Barone, Maria Teresa Pellecchia
INTRODUCTION: In Parkinson's disease (PD), non motor symptoms can fluctuate either along or irrespective to motor on/off phenomena. Prospective studies suggest that higher motor scores and levodopa dosage, younger age at onset and female gender represent risk factors for motor fluctuations' development. Yet, the predictors of development of non motor fluctuations (NMF) are less clear. In this prospective study, we aimed to assess the relationship between NMF and gender along with other potential risk factors...
June 2016: Parkinsonism & related Disorders
Rohit Dhall, David L Kreitzman
Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease...
April 5, 2016: Neurology
Marc Morissette, Nicolas Morin, Laurent Grégoire, Alex Rajput, Ali H Rajput, Thérèse Di Paolo
L-DOPA-induced dyskinesias (LID) appear in the majority of Parkinson's disease (PD) patients. Nicotinic acetylcholine (nACh) receptor-mediated signaling has been implicated in PD and LID and modulation of brain α7 nACh receptors might be a potential therapeutic target for PD. This study used [(125)I]α-Bungarotoxin autoradiography to investigate α7 nACh receptors in LID in post-mortem brains from PD patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4)...
June 1, 2016: Biochemical Pharmacology
Morad Elshehabi, Katrin S Maier, Sandra E Hasmann, Susanne Nussbaum, Heinz Herbst, Tanja Heger, Daniela Berg, Markus A Hobert, Walter Maetzler
BACKGROUND: In Parkinson's disease (PD), the effects of dopaminergic medication on straight walking and turning were mainly investigated under single tasking (ST) conditions. However, multitasking situations are considered more daily relevant. METHODS: Thirty-nine early-to-moderate PD patients performed the following standardized ST and dual tasks as fast as possible for 1 min during On- and Off-medication while wearing inertial sensors: straight walking and turning, checking boxes, and subtracting serial 7s...
2016: Frontiers in Aging Neuroscience
Yasuhiro Nagashima, Tomoyoshi Kondo, Mayumi Sakata, Jinsoo Koh, Hidefumi Ito
Mucuna pruriens is a levodopa-containing legume and its favorable effects on motor complications in Parkinson disease patients have been reported. The aim of this study was to investigate the effects of another legume, soybeans, on the pharmacokinetics and metabolism of levodopa. Seven parkinsonian patients with the wearing-off phenomenon and dyskinesia and five healthy volunteers participated in this study. We conducted a crossover study of the clinical effects on the participants before and after taking either levodopa (100mg)/carbidopa (10mg) only (LD/CD) or levodopa/carbidopa with 11 g of ground soybeans (LD/CD/soy)...
February 15, 2016: Journal of the Neurological Sciences
P K Chattha, P E Greene, Ritesh A Ramdhani
Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson's disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes. We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state...
2015: Journal of Clinical Movement Disorders
Asako Yoritaka, Jiro Fukae, Taku Hatano, Eisei Oda, Nobutaka Hattori
Objective Many studies on the cost of Parkinson disease (PD) have been published; however, there are limited studies pertaining to this issue in Asia. This study looks to assess the direct medical costs of patients with PD at a university hospital in Japan by calculating the average monthly direct medical costs of PD patients from July to December 2008. Methods We enrolled 724 consecutive patients (411 women and 313 men) with PD who were registered in Japan's "Specified Disease Treatment Research Program" and obtained data on the total direct medical costs of all patients...
2016: Internal Medicine
Matthias Löhle, Julia Mende, Martin Wolz, Bettina Beuthien-Baumann, Liane Oehme, Jörg van den Hoff, Jörg Kotzerke, Heinz Reichmann, Alexander Storch
OBJECTIVE: To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson disease (PD) for the onset of later motor complications. METHODS: This retrospective, observer-blinded cohort study followed up 31 patients with early PD who completed quantitative (18)F-dopa PET imaging to measure striatal (18)F-dopa uptake (Kocc) and effective distribution volume ratio (EDVR) as the inverse of dopamine turnover prior to antiparkinsonian treatment...
January 19, 2016: Neurology
George DeMaagd, Ashok Philip
Parkinson's motor complications include wearing-off, a delayed or absent response to carbidopa/levodopa therapy, freezing of gait, dyskinesias, and dystonias. Treatment may include medication adjustments, such as increased dopaminergic stimulation.
November 2015: P & T: a Peer-reviewed Journal for Formulary Management
Masahiro Nomoto, Shin-ichiro Kubo, Masahiro Nagai, Tatsuo Yamada, Akira Tamaoka, Yoshio Tsuboi, Nobutaka Hattori
OBJECTIVES: This study is the first controlled trial to evaluate the efficacy and safety of subcutaneous apomorphine in Japanese patients with advanced Parkinson disease. METHODS: A phase II, multicenter, randomized, double-blind, parallel-group trial was undertaken in 16 patients with advanced Parkinson disease with wearing-off phenomenon to compare subcutaneous apomorphine versus placebo. The maintenance dose of apomorphine (1-6 mg per dose), determined individually for each patient by titration, was additionally administered 3 times at 2-hour intervals in the multiple-dose phase in which pharmacokinetics was evaluated...
November 2015: Clinical Neuropharmacology
Keisuke Suzuki, Masayuki Miyamoto, Tomoyuki Miyamoto, Koichi Hirata
Sleep disturbances are important nonmotor symptoms in Parkinson's disease (PD) that are associated with a negative impact on quality of life. Restless legs syndrome (RLS), which is characterized by an urge to move the legs accompanied by abnormal leg sensations, can coexist with PD, although the pathophysiology of these disorders appears to be different. RLS and PD both respond favorably to dopaminergic treatment, and several investigators have reported a significant relationship between RLS and PD. Sensory symptoms, pain, motor restlessness, akathisia, and the wearing-off phenomenon observed in PD should be differentiated from RLS...
2015: Parkinson's Disease
Kei Watanabe, Toru Hirano, Keiichi Katsumi, Masayuki Ohashi, Atsushi Ishikawa, Ryoko Koike, Naoto Endo, Masatoyo Nishizawa, Takayoshi Shimohata
BACKGROUND: The aim of this study was to determine the exacerbating factors of chronic low back pain (LBP) and strategic points against LBP in patients with Parkinson's disease (PD). METHODS: Forty-four consecutive PD patients complaining of LBP were included. Clinical characteristics of PD and LBP, spinal musculoskeletal condition, and clinical health status were evaluated. RESULTS: Patient age at PD and LBP onset was contiguous, and LBP time period was mainly described as constant or upon waking up...
December 2015: International Orthopaedics
Tomoko Oeda, Atsushi Umemura, Yuko Mori, Satoshi Tomita, Masayuki Kohsaka, Kwiyoung Park, Kimiko Inoue, Harutoshi Fujimura, Hiroshi Hasegawa, Hiroshi Sugiyama, Hideyuki Sawada
Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined...
December 2015: Neurobiology of Aging
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