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wearing off Parkinsonism

Luxi Wang, Nian Xiong, Jinsha Huang, Shiyi Guo, Ling Liu, Chao Han, Guoxin Zhang, Haiyang Jiang, Kai Ma, Yun Xia, Xiaoyun Xu, Jie Li, Jing Y Liu, Tao Wang
Levodopa is considered to be the most effective symptomatic drug for Parkinson's disease (PD). As the disease progresses, however, the patients are likely to experience a reduced response to levodopa and develop motor fluctuations (i.e., end-of-dose wearing off and unpredictable "on-off"). Protein-rich diets and elevated plasma concentrations of large neutral amino acids have been proved to impair the therapeutic effect of levodopa by reducing its absorption and influx into the brain. On the other hand, the protein-restricted diets including low-protein diet (LPD), protein-redistribution diet (PRD) and PRD with use of low-protein products can all improve the efficacy of levodopa in patients with motor fluctuations...
2017: Frontiers in Aging Neuroscience
Jongkyu Park, Younsoo Kim, Jinyoung Youn, Phil H Lee, Young H Sohn, Seoung B Koh, Jee-Young Lee, Jong S Baik, Jin W Cho
BACKGROUND: Levodopa bioavailability is enhanced by adding entacapone. However, the optimal dose of levodopa while transitioning to levodopa/carbidopa/entacapone (LCE) in Parkinson's disease (PD) during the wearing-off period is unclear. AIMS: The relative therapeutic efficacy and safety of different doses of levodopa were assessed when transitioning to the LCE combination for optimizing combined levodopa therapy. MATERIALS AND METHODS: A randomized, multicenter, double-arm, open-label study was conducted in Korea...
July 2017: Neurology India
Dolores Vilas, Rubén Fernández-Santiago, Elena Sanchez-Rodriguez, Luis J Azcona, Meritxell Santos-Montes, Pilar Casquero, Lucía Argandoña, Eduardo Tolosa, Coro Paisán-Ruiz
Common genetic variability in the ACMSD gene has been associated with increased risk for Parkinson's disease (PD) but ACMSD mutations in clinical cases of PD have so far not been described. We report a 74-year-old man with sporadic PD who developed tremor in his right hand and slowness. On examination, moderate rigidity, asymmetric bradykinesia, and bilateral action tremor were present. He was started on levodopa with significant improvement. Two years later, he developed wearing off phenomena. The genetic study in the patient identified a novel ACMSD mutation resulting in p...
June 30, 2017: Journal of Parkinson's Disease
Qin Xiao, Yiwei Qian, Jiujiang Liu, Shaoqing Xu, Xiaodong Yang
BACKGROUND: Recent studies have found that the functional catechol-O-methyltransferase (COMT) gene may be associated with the susceptibility to and pharmacotherapy of Parkinson's disease (PD). In this case-control study, we investigated the most common functional COMT gene haplotypes that had been shown to influence COMT enzymatic activity and the association of the single and combined COMT haplotypes with clinical symptoms and pharmacotherapy in Chinese patients with PD. METHODS: One hundred forty-three patients with idiopathic PD and 157 healthy individuals were enrolled in this study...
2017: Translational Neurodegeneration
Tetsuya Maeda, Yasushi Shimo, Shih-Wei Chiu, Takuhiro Yamaguchi, Kenichi Kashihara, Yoshio Tsuboi, Masahiro Nomoto, Nobutaka Hattori, Hirohisa Watanabe, Hidemoto Saiki
INTRODUCTION: We aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD). METHODS: A total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8)...
May 2017: Parkinsonism & related Disorders
Ramón Cacabelos
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects...
March 4, 2017: International Journal of Molecular Sciences
Tatsuya Ueno, Megumi Sasaki, Haruo Nishijima, Yukihisa Funamizu, Tomoya Kon, Rie Haga, Akira Arai, Chieko Suzuki, Jin-Ichi Nunomura, Masayuki Baba, Masahiko Tomiyama
The efficacy of LSVT-BIG for advanced Parkinson's disease (PD) patients with wearing off remains to be determined. Therefore, we evaluated whether LSVT-BIG improves motor disability in eight PD patients with wearing off. Unified Parkinson's Disease Rating Scale (UPDRS) scores, daily off time, and mobility assessments were evaluated during the "on" time before and after the LSVT-BIG course. LSVT-BIG significantly improved UPDRS III scores at 4 weeks and UPDRS II scores in the "off" state at 12 weeks, with no changes in the other measures...
2017: Parkinson's Disease
Alberto J Espay, Fernando L Pagan, Benjamin L Walter, John C Morgan, Lawrence W Elmer, Cheryl H Waters, Pinky Agarwal, Rohit Dhall, William G Ondo, Kevin J Klos, Dee E Silver
PURPOSE OF REVIEW: To help clinicians optimize the conversion of a patient's Parkinson disease pharmacotherapy from immediate-release carbidopa/levodopa (IR CD/LD) to an extended-release formulation (ER CD/LD). RECENT FINDINGS: Eleven movement disorders specialists achieved consensus positions on the modification of trial-based conversion guidelines to suit individual patients in clinical practice. SUMMARY: Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected...
February 2017: Neurology. Clinical Practice
Shinji Matsunaga, Taro Kishi, Nakao Iwata
BACKGROUND: There is uncertainty about the efficacy and tolerability of zonisamide for Parkinson's disease (PD). OBJECTIVE: We performed a meta-analysis of zonisamide treatment in PD patients who received antiparkinson drugs such as levodopa. METHODS: The primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, wearing-off time, and discontinuation rate due to all causes. Secondary outcome measures were UPDRS total and subscale scores; discontinuation rates due to adverse events, inefficacy, and death; and individual adverse events...
2017: Journal of Alzheimer's Disease: JAD
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Parkinson's disease (PD) is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD...
November 2016: Neural Regeneration Research
Yoshikuni Mizuno, Satoe Shimoda, Hideki Origasa
We report a long-term treatment of Parkinson's disease in out-patient clinics. The patients with Parkinson's disease were evaluated at the time of clinic visit from September 1st, 2015 to February 29th, 2016. Total number of the patients was 498. The age at the evaluation was 69.9 ± 9.3 years and the age of onset was 60.2 ± 11.3. Hoehn and Yahr severity was 3.28 ± 0.94 in patients who were from 16 to 20 years (n = 53) and 3.00 ± 0.86 in patients from 21 years or more (n = 38) from the onset of the disease to the evaluation...
January 16, 2017: Journal of Neural Transmission
Anthony H V Schapira, Susan H Fox, Robert A Hauser, Joseph Jankovic, Wolfgang H Jost, Christopher Kenney, Jaime Kulisevsky, Rajesh Pahwa, Werner Poewe, Ravi Anand
Importance: Although levodopa remains the most effective oral pharmacotherapy for Parkinson disease (PD), its use is often limited by wearing off effect and dyskinesias. Management of such complications continues to be a significant challenge. Objective: To investigate the efficacy and safety of safinamide (an oral aminoamide derivative with dopaminergic and nondopaminergic actions) in levodopa-treated patients with motor fluctuations. Design, Setting, and Participants: From March 5, 2009, through February 23, 2012, patients from academic PD care centers were randomized (1:1 ratio) to receive double-blind adjunctive safinamide or placebo for 24 weeks...
February 1, 2017: JAMA Neurology
Giovanni Mostile, Alessandra Nicoletti, Valeria Dibilio, Antonina Luca, Loredana Raciti, Giorgia Sciacca, Calogero Edoardo Cicero, Rosario Vasta, Giulia Donzuso, Donatella Contrafatto, Mario Zappia
OBJECTIVE: To evaluate the severity of wearing-off and dyskinesia in patients with complicated Parkinson disease (PD) after switching L-dopa oral therapy from a "pulsatile" administration, consisting in intermittent multiple daily small doses of the drug, to a "pulse" administration, consisting in standard oral doses given at specific interdose intervals. METHODS: Thirty-four PD patients with motor complications were monitored twice with standardized waking day motor status evaluations using the Unified Parkinson Disease Rating Scale-Motor Examination (UPDRS-ME) and the Abnormal Involuntary Movement Scale (AIMS) after switching L-dopa administration modality from "pulsatile" to "pulse...
January 2017: Clinical Neuropharmacology
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: Journal of Clinical Movement Disorders
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
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