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Parkinson Disease: HELP
Articles from Taiwan
Based on 436 articles published since 2008

These are the 436 published articles about Parkinson Disease that originated from Taiwan during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18
1 Editorial Behavioural and Cognitive Changes in Lewy Body Dementias. 2018

Kung, Woon-Man / Ho, Ying-Jui / Yoshizawa, Hiroshi / Matsuo, Shinro / Wei, Cheng-Yu. ·Department of Exercise and Health Promotion, College of Education, Chinese Culture University, Taipei, Taiwan. · Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. · Department of Surgery, School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan. · Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan. · Department of Neurology, Neurological Institute, Tokyo Women's Medical University, Kawadacho, Shinjuku, Tokyo, Japan. · Department of Nuclear Medicine, Kanazawa University Hospital, Takaramachi, Kanazawa, Japan. · Department of Neurology, Chang Bing Show Chwan Memorial Hospital, Changhua County, Taiwan. ·Behav Neurol · Pubmed #30534208.

ABSTRACT: -- No abstract --

2 Editorial Commentary: chromaffin cell plasticity in stress, inflammation, development, and disease. 2012

Kao, Lung-Sen. ·Department of Life Sciences and Institute of Genome Sciences, Brain Research Center, National Yang-Ming University, Taipei, Taiwan. lskao@ym.edu.tw ·J Mol Neurosci · Pubmed #22618601.

ABSTRACT: -- No abstract --

3 Review Non-steroidal anti-inflammatory drugs and risk of Parkinson's disease in the elderly population: a meta-analysis. 2019

Poly, Tahmina Nasrin / Islam, Md Mohaimenul Rubel / Yang, Hsuan-Chia / Li, Yu-Chuan Jack. ·Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. · International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan. · Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. jack@tmu.edu.tw. · International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan. jack@tmu.edu.tw. · Department of Dermatology, Wan Fang Hospital, Taipei, Taiwan. jack@tmu.edu.tw. · TMU Research Center of Cancer Translational Medicine, Taipei, Taiwan. jack@tmu.edu.tw. ·Eur J Clin Pharmacol · Pubmed #30280208.

ABSTRACT: PURPOSE: Several studies have explored the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the extent to which NSAIDs may increase or decrease the risk of PD remains unresolved. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between NSAID use and PD risk in the elderly population. METHODS: The electronic databases such as PubMed, EMBASE, Scopus, Google Scholar, and Web of Science were used to search the relevant articles published between January 1990 and December 2017. Large (n ≥ 1000) observational design studies with a follow-up at least 1 year were considered. Two authors independently extracted information from the included studies. Random effect model was used to calculate risk ratios (RRs) with 95% confidence interval (Cl). RESULTS: A total of 17 studies with 2,498,258 participants and nearly 14,713 PD patients were included in the final analysis. The overall pooled RR of PD was 0.95 (95%CI 0.860-1.048) with significant heterogeneity (I CONCLUSION: Despite the neuroprotective potential of NSAIDs demonstrated in some experimental studies, our findings suggest that there is no association between NSAIDs and the risk of Parkinson disease at the population level. Until further evidence is established, clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.

4 Review Neuroprotective Role of Phytochemicals. 2018

Velmurugan, Bharath Kumar / Rathinasamy, Baskaran / Lohanathan, Bharathi Priya / Thiyagarajan, Varadharajan / Weng, Ching-Feng. ·Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam. bharath.kumar.velmurugan@tdtu.edu.vn. · Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan. rathinabaski@gmail.com. · Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 10617, Taiwan. bharathi.log@gmail.com. · Department of Pathology, Anatomy and Cell biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. varadha86@gmail.com. · Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan. cfweng@gms.ndhu.edu.tw. ·Molecules · Pubmed #30262792.

ABSTRACT: Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer's disease (AD) and Parkinson's disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more extensive investigation needs to be conducted for reducing the progression of AD and PD.

5 Review REM Sleep Behavior Disorder (RBD) in Dementia with Lewy Bodies (DLB). 2018

Chan, Po-Chi / Lee, Hsun-Hua / Hong, Chien-Tai / Hu, Chaur-Jong / Wu, Dean. ·Department of Neurology, Show Chwan Memorial Hospital, Changhua, Taiwan. · Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan. · Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. · Sleep Center, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan. · Vertigo and Balance Impairment Center, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan. ·Behav Neurol · Pubmed #30018672.

ABSTRACT: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia, with abnormal dream-enacting behavior during the rapid eye movement (REM) sleep. RBD is either idiopathic or secondary to other neurologic disorders and medications. Dementia with Lewy bodies (DLB) is the third most common cause of dementia, and the typical clinical presentation is rapidly progressive cognitive impairment. RBD is one of the core features of DLB and may occur either in advance or simultaneously with the onset of DLB. The association between RBD with DLB is widely studied. Evidences suggest that both DLB and RBD are possibly caused by the shared underlying synucleinopathy. This review article discusses history, clinical manifestations, possible pathophysiologies, and treatment of DLB and RBD and provides the latest updates.

6 Review Neurohealth Properties of 2018

Li, I-Chen / Lee, Li-Ya / Tzeng, Tsai-Teng / Chen, Wan-Ping / Chen, Yen-Po / Shiao, Young-Ju / Chen, Chin-Chu. ·Grape King Bio Ltd, Zhong-Li Dist., Taoyuan City, Taiwan. · Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei City, Taiwan. · Institute of Food Science and Technology, National Taiwan University, Taipei City, Taiwan. · Department of Food Science, Nutrition and Nutraceutical Biotechnology, Shih Chien University, Taipei City, Taiwan. · Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan. ·Behav Neurol · Pubmed #29951133.


7 Review LRRK 2 gene mutations in the pathophysiology of the ROCO domain and therapeutic targets for Parkinson's disease: a review. 2018

Chen, Meng-Ling / Wu, Ruey-Meei. ·Department of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Da-an Dist, Taipei City, 10617, Taiwan. · Department of Neurology, College of Medicine, National Taiwan University Hospital, National Taiwan University, No. 7, Chung-Shan South Road, Zhongzheng Dist, Taipei City, 10002, Taiwan. · Department of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Da-an Dist, Taipei City, 10617, Taiwan. robinwu@ntu.edu.tw. · Department of Neurology, College of Medicine, National Taiwan University Hospital, National Taiwan University, No. 7, Chung-Shan South Road, Zhongzheng Dist, Taipei City, 10002, Taiwan. robinwu@ntu.edu.tw. ·J Biomed Sci · Pubmed #29903014.

ABSTRACT: Parkinson's disease (PD) is the most common movement disorder and manifests as resting tremor, rigidity, bradykinesia, and postural instability. Pathologically, PD is characterized by selective loss of dopaminergic neurons in the substantia nigra and the formation of intracellular inclusions containing α-synuclein and ubiquitin called Lewy bodies. Consequently, a remarkable deficiency of dopamine in the striatum causes progressive disability of motor function. The etiology of PD remains uncertain. Genetic variability in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of sporadic and familial PD. LRRK2 encodes a large protein containing three catalytic and four protein-protein interaction domains. Patients with LRRK2 mutations exhibit a clinical and pathological phenotype indistinguishable from sporadic PD. Recent studies have shown that pathological mutations of LRRK2 can reduce the rate of guanosine triphosphate (GTP) hydrolysis, increase kinase activity and GTP binding activity, and subsequently cause cell death. The process of cell death involves several signaling pathways, including the autophagic-lysosomal pathway, intracellular trafficking, mitochondrial dysfunction, and the ubiquitin-proteasome system. This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches.

8 Review The Role of Gene Editing in Neurodegenerative Diseases. 2018

Fan, Hueng-Chuen / Chi, Ching-Shiang / Lee, Yih-Jing / Tsai, Jeng-Dau / Lin, Shinn-Zong / Harn, Horng-Jyh. ·1 Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan. · 2 Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan. · 3 Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan. · 4 School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. · 5 School of Medicine, Chung Shan Medical University, Taichung, Taiwan. · 6 Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. · 7 Bioinnovation Center, Tzu Chi Foundation, Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan. · 8 Bioinnovation Center, Tzu Chi Foundation, Department of Pathology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan. ·Cell Transplant · Pubmed #29766738.

ABSTRACT: Neurodegenerative diseases (NDs), at least including Alzheimer's, Huntington's, and Parkinson's diseases, have become the most dreaded maladies because there are no precise diagnostic tools or definite treatments for these debilitating diseases. The increased prevalence and a substantial impact on the social-economic and medical care of NDs propel governments to develop policies to counteract the impact. Although the etiologies of NDs are still unknown, growing evidence suggests that genetic, cellular, and circuit alternations may cause the generation of abnormal misfolded proteins, which uncontrolledly accumulate to damage and eventually overwhelm the protein-disposal mechanisms of these neurons, leading to a common pathological feature of NDs. If the functions and the connectivity can be restored, alterations and accumulated damages may improve. The gene-editing tools including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats-associated nucleases (CRISPR/CAS) have emerged as a novel tool not only for generating specific ND animal models for interrogating the mechanisms and screening potential drugs against NDs but also for the editing sequence-specific genes to help patients with NDs to regain function and connectivity. This review introduces the clinical manifestations of three distinct NDs and the applications of the gene-editing technology on these debilitating diseases.

9 Review Exosomes and Stem Cells in Degenerative Disease Diagnosis and Therapy. 2018

Chang, Yu-Hsun / Wu, Kung-Chi / Harn, Horng-Jyh / Lin, Shinn-Zong / Ding, Dah-Ching. ·1 Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. · 2 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. · 3 Department of Orthopedics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. · 4 Department of Pathology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. · 5 Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. · 6 Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. ·Cell Transplant · Pubmed #29692195.

ABSTRACT: Stroke can cause death and disability, resulting in a huge burden on society. Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor dysfunction. Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage destruction and osteophyte formation in the joints. Stem cell therapy may provide a biological treatment alternative to traditional pharmacological therapy. Mesenchymal stem cells (MSCs) are preferred because of their differentiation ability and possible derivation from many adult tissues. In addition, the paracrine effects of MSCs play crucial anti-inflammatory and immunosuppressive roles in immune cells. Extracellular vesicles (EVs) are vital mediators of cell-to-cell communication. Exosomes contain various molecules such as microRNA (miRNA), which mediates biological functions through gene regulation. Therefore, exosomes carrying miRNA or other molecules can enhance the therapeutic effects of MSC transplantation. MSC-derived exosomes have been investigated in various animal models representing stroke, PD, and OA. Exosomes are a subtype of EVs. This review article focuses on the mechanism and therapeutic potential of MSC-derived exosomes in stroke, PD, and OA in basic and clinical aspects.

10 Review Atypical presentation of dopa-responsive dystonia in Taiwan. 2018

Weng, Yi Ching / Wang, Chun Chieh / Wu, Yih Ru. ·Department of Neurology Chang Gung Memorial Hospital Chang-Gung University College of Medicine Taipei Taiwan. ·Brain Behav · Pubmed #29484265.

ABSTRACT: The typical clinical presentation of dopa-responsive dystonia, which is also called Segawa disease, is a young age of onset, with predominance in females, diurnal fluctuation of lower limb dystonia, and fair response to low-dose levodopa. This disease has both autosomal dominant and autosomal recessive inheritance. Autosomal dominant Segawa disease is caused by

11 Review Point-of-Care Devices Using Disease Biomarkers To Diagnose Neurodegenerative Disorders. 2018

Wei, Ting-Yen / Fu, Yun / Chang, Kuo-Hsuan / Lin, Kun-Ju / Lu, Yu-Jen / Cheng, Chao-Min. ·Interdisciplinary Program of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan; These authors contributed equally. · Department of Dermatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 33305, Taiwan; These authors contributed equally. · Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan. · Animal Molecular Imaging Center and Department of Nuclear Medicine, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 33305, Taiwan. · Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan. Electronic address: luyj@cgmh.org.tw. · Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: chaomin@mx.nthu.edu.tw. ·Trends Biotechnol · Pubmed #29242004.

ABSTRACT: Neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are highly prevalent and immensely destructive to the health and well-being of individuals and their families across the globe. Neurodegenerative diseases are characterized by the gradual loss of neural tissue in the central nervous system. Clearly, early diagnosis of the onset of neurodegeneration is vital and beneficial. Current diagnostic methods rely heavily on symptoms or autopsy results, thus overlooking early diagnosis, the only opportunity for amelioration. However, appropriately selected and used biomarker diagnostics provide a solution. This article reviews the development and application of biomarker-related diagnostics for neurodegenerative disease with specific recommendations for point-of-care (POC) methodology. These advantageous approaches may offer a solution to existing obstacles and limitations to neurodegenerative disease treatment.

12 Review Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review. 2018

Thevathasan, Wesley / Debu, Bettina / Aziz, Tipu / Bloem, Bastiaan R / Blahak, Christian / Butson, Christopher / Czernecki, Virginie / Foltynie, Thomas / Fraix, Valerie / Grabli, David / Joint, Carole / Lozano, Andres M / Okun, Michael S / Ostrem, Jill / Pavese, Nicola / Schrader, Christoph / Tai, Chun-Hwei / Krauss, Joachim K / Moro, Elena / Anonymous621156. ·Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia and the Bionics Institute of Australia, Melbourne, Australia. · Movement Disorders Center, Division of Neurology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble Alpes University, Grenoble, France. · Department of Neurosurgery, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Heidelberg, Germany. · Department of Bioengineering, Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, USA. · Department of Neurology, Institut de Cerveau et de la Moelle épinière, Sorbonne Universités, University Pierre-and-Marie-Curie (UPMC) Université, Paris, France. · Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, United Kingdom. · Department of Neurology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtière University Hospital, Paris, France. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders, Gainesville, Florida, USA. · Department of Neurology, UCSF Movement Disorder and Neuromodulation Center, University of California, San Francisco, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience, University of Aarhus, Aarhus, Denmark. · Department of Neurology, Hannover Medical School, Hannover, Germany. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Neurosurgery, Hannover Medical School, Hannover, Germany. ·Mov Disord · Pubmed #28960543.

ABSTRACT: Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

13 Review A New Treatment Strategy for Parkinson's Disease through the Gut-Brain Axis: The Glucagon-Like Peptide-1 Receptor Pathway. 2017

Kim, Dong Seok / Choi, Ho-Il / Wang, Yun / Luo, Yu / Hoffer, Barry J / Greig, Nigel H. ·1 Peptron Inc., Yuseong-gu, Daejeon, Republic of Korea. · 2 Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. · 3 Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. · 4 Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. ·Cell Transplant · Pubmed #29113464.

ABSTRACT: Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based antidiabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut-brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase-4 inhibitors. Recently, the first open label clinical study of exenatide, a long-acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double-blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative diseases are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut-brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.

14 Review Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review. 2017

Chen, Ying-Fa / Chang, Yung-Yee / Lan, Min-Yu / Chen, Pei-Lung / Lin, Chin-Hsien. ·Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. · Center for Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. · Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan. · Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan. · Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan. chlin@ntu.edu.tw. · Department of Neurology, National Taiwan University Hospital, Taipei, 100, Taiwan. chlin@ntu.edu.tw. ·BMC Neurol · Pubmed #28985717.

ABSTRACT: BACKGROUND: Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). CASE PRESENTATION: A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient's mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. CONCLUSIONS: This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.

15 Review Effectiveness of physical activity on patients with depression and Parkinson's disease: A systematic review. 2017

Wu, Pei-Ling / Lee, Megan / Huang, Tzu-Ting. ·Graduate Institute of Clinical Medical Sciences, Nursing, Chang Gung University, Tao-Yuan, Taiwan. · Department of biochemistry, University of Washington, Seattle, WA, United States of America. · Healthy Aging Research Center School of Nursing, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. · Department of Neurology (Dementia Center), Chang Gung Memorial Hospital Linkou Medical Center, Tao-Yuan, Taiwan. ·PLoS One · Pubmed #28749970.

ABSTRACT: AIM: In this paper we aimed to systematically review the literature on physical activity's effect on depressive symptoms in Parkinson disease. BACKGROUND: Depression is a common symptom of Parkinson's disease and is associated with increased disability, rapid progression of motor symptoms, mortality, and adverse effects on Quality of Life. DESIGN: A systematic review of primary research was undertaken and conducted according to the Preferred Reporting Items for Systematic Reviews. DATA SOURCES: Databases Scopus, Psycho-info, CINAHL, PubMed, and ProQuest Cochrance were searched from January 2006 to June 2017. The language was restricted to English. REVIEW METHODS: Abstracts were screened and reviewed against the eligibility criteria (participants' mean age were ≥ 60 with PD, PA interventions, depression as one of outcome variables, and Randomized Control Trail or quasi-experimental design). Two reviewers appraised the quality of the data extracted. The modified Jadad scale assessed the quality of the methodology of the published papers. RESULTS: The database search yielded 769 abstracts, 11 of which were included in this review and awarded scores ranging from 3 to 8 (Scale scores range from 0 to 8 points, higher scores indicated better quality) by the raters. These 11 studies included 342 patients and executed 17 kinds of physical activity programs. Results of this review show empirical evidence to support the efficacy of physical activity for the population with Parkinson's disease. Aerobic training exercise significantly improved the participants' scores on the Unified Parkinson's Disease Rating Scale, the Beck Depression Inventory, and the Quality of Life of the patients. Qigong improved scores in UPDRS-III and decreased incidences of multiple non-motor symptoms and depression. Furthermore, a balance-training program, such as Tai Chi, can improve postural stability and Quality of Life. CONCLUSIONS: Physical activity may assuage the degeneration of motor skills and depression as well as increase the Quality of Life of Parkinson's disease patients, with aerobic training producing the best results. These findings suggest that physical activity, notably aerobic training, could be a good exercise strategy for patients with Parkinson's disease.

16 Review Ultrasound targeted CNS gene delivery for Parkinson's disease treatment. 2017

Fan, Ching-Hsiang / Lin, Chung-Yin / Liu, Hao-Li / Yeh, Chih-Kuang. ·Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. · Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan 333, Taiwan. · Department of Electrical Engineering, Chang-Gung University, Taoyuan 333, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan. Electronic address: haoliliu@mail.cgu.edu.tw. · Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. Electronic address: ckyeh@mx.nthu.edu.tw. ·J Control Release · Pubmed #28690161.

ABSTRACT: Parkinson's disease (PD) is a potent neurodegenerative disease in which a progressive loss of dopaminergic neurons eventually produces a loss of movement control and other symptoms. To date, in addition to pharmacological, non-pharmacological, and neurosurgical therapies, gene delivery has emerged as a potential therapeutic modality for PD. Effective targeted gene delivery is complicated in that gene vectors cannot penetrate the blood-brain barrier (BBB), thus clinical tests must rely on invasive intracerebral gene vector injection. Burst low-pressure focused ultrasound exposure with microbubbles has been demonstrated to noninvasively target and temporally open the BBB, opening new opportunities to transport large molecule substances into the brain for central nervous system (CNS) disease treatment, and raising the potential for noninvasive gene delivery for PD treatment. This paper reviews the underlying mechanism and current progress for focused ultrasound induced CNS gene delivery, and summarizes potential directions for further ultrasound-medicated PD gene therapy.

17 Review Pain in early-stage Parkinson's disease: Implications from clinical features to pathophysiology mechanisms. 2017

Tseng, Ming-Tsung / Lin, Chin-Hsien. ·Graduate Institute of Brain and Mind Sciences, National Taiwan University, College of Medicine, Taipei, Taiwan. · Department of Neurology, National Taiwan University, College of Medicine, Taipei, Taiwan. Electronic address: chlin@ntu.edu.tw. ·J Formos Med Assoc · Pubmed #28532582.

ABSTRACT: Pain is a common non-motor symptom of Parkinson's disease (PD) that markedly impacts patients' quality of life. Although pain occurs mostly secondary to motor disability of PD, pain may antedate motor symptoms by years. Numerous studies have shown that PD patients manifest altered sensory and pain thresholds compared with control subjects. Although both levodopa and deep brain stimulation improve motor symptoms, there remains no direct correlation between motor improvement and altered pain sensitivity, suggesting that motor symptoms and pain do not necessarily share pathogenetic mechanisms. Whether nociceptive processing is dysfunctional in the early stages of PD, when motor symptoms are not prominent, remains uncertain. In this review, we highlight the evidence for disrupted nociceptive processing in patients with early-stage PD. Painful symptoms and aberrant pain processing in early PD are associated with both central and peripheral deafferentation. Dopamine depletion in selective striatal regions, and the development of Lewy pathology in specific non-dopaminergic subcortical areas, underlie the clinical features of pain at this early disease stage. An increased awareness of pain as an early feature of PD might provide further insights into a mechanism-based approach to sensory system dysregulation in this disease.

18 Review Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia. 2017

Kandiah, Nagaendran / Pai, Ming-Chyi / Senanarong, Vorapun / Looi, Irene / Ampil, Encarnita / Park, Kyung Won / Karanam, Ananda Krishna / Christopher, Stephen. ·Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital. · Duke-NUS, Graduate Medical School, Singapore. · Division of Behavioral Neurology, Department of Neurology. · Alzheimer's Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. · Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. · Clinical Research Centre. · Department of Medicine, Hospital Seberang Jaya, Penang, Malaysia. · Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines. · Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine, Busan, Republic of Korea. · Novartis Healthcare Private Limited, Hyderabad, India. · Novartis (Singapore) Pte. Ltd., Singapore. ·Clin Interv Aging · Pubmed #28458525.

ABSTRACT: Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC, rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

19 Review Tissue transglutaminase (TG2) and mitochondrial function and dysfunction. 2017

Lai, Thung-S / Lin, Cheng-Jui / Wu, Yu-Ting / Wu, Chih-Jen. ·Institute of Biomedical Science, Mackay Medical College, New Taipei City, Taiwan, ROC, lai00002@mmc.edu.tw. · Nephrology/Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, ROC. · Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. ·Front Biosci (Landmark Ed) · Pubmed #28199195.

ABSTRACT: Mitochondria are the cell's power plant to satisfy the energy demands. However, dysfunctional mitochondria can cause overproduction of reactive oxygen species (ROS), oxidative stress, and alteration of calcium homeostasis, which are the hallmarks of mitochondrial diseases. Under prolong oxidative stress, repeated cytosolic calcium elevations even only transiently, can lead to activation of some enzymes. One calcium-activated enzyme with demonstrated pathophysiological important in mitochondrial disease is tissue transglutaminase (TG2). TG2 is known as a post-translational modification (PTM) enzyme that is induced by oxidative stress. Compared to other types of PTMs, the physiological significance of TG2 mediated PTM is just beginning to be understood. Once activated, TG2 can modulate transcription, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TG2's activity not only can modulate the assembly of respiratory chain complexes but can also modulate the transcription of critical genes including PGC-1alpha and cytochrome C that are important for function and biogenesis of mitochondria. Here, we summarize dysfunctional mitochondria in diseases such as in neurodegenerative disorders can modulate TG2's activity and function.  TG2 is also important for normal function of mitochondria.

20 Review Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders. 2017

Lee, Yun-Tzai C / Hsu, Shang-Te D. ·Institute of Biological Chemistry, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529,Taiwan. China. · Institute of Biological Chemistry, Academia Sinica, 128, Section 2, Academia Road, Aipei, 11529,Taiwan, China. ·Curr Protein Pept Sci · Pubmed #26899237.

ABSTRACT: Parkinson's disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.

21 Review Psychosis in Parkinson's Disease: Epidemiology, Pathophysiology, and Management. 2016

Chang, Anna / Fox, Susan H. ·Morton and Gloria Shulman Movement Disorder Clinic, University of Toronto, Toronto Western Hospital, 7th Floor, McLaughlin Pavilion, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. · Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. · Morton and Gloria Shulman Movement Disorder Clinic, University of Toronto, Toronto Western Hospital, 7th Floor, McLaughlin Pavilion, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. sfox@uhnresearch.ca. ·Drugs · Pubmed #27312429.

ABSTRACT: Psychotic symptoms are common in Parkinson's disease (PD) and are associated with poorer quality of life and increased caregiver burden. PD psychosis is correlated with several factors, such as more advanced disease, cognitive impairment, depression, and sleep disorders. The underlying causes of psychosis in PD thus involve a complex interplay between exogenous (e.g., drugs, intercurrent illnesses) and endogenous (e.g., PD disease pathology) factors. Current theories of the pathophysiology of PD psychosis have come from several neuropathological and neuroimaging studies that implicate pathways involving visual processing and executive function, including temporo-limbic structures and neocortical gray matter with altered neurotransmitter functioning (e.g., dopamine, serotonin, and acetylcholine). Treatment of PD psychosis requires a step-wise process, including initial careful investigation of treatable triggering conditions and a comprehensive evaluation with adjustment of PD medications and/or initiation of specific antipsychotic therapies. Clozapine remains the only recommended drug for the treatment of PD psychosis; however, because of regular blood monitoring, quetiapine is usually first-line therapy, although less efficacious. Emerging studies have focused on agents involving other neurotransmitters, including the serotonin 5-HT2A receptor inverse agonist pimavanserin, cholinesterase inhibitors, and antidepressants and anxiolytics.

22 Review Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma. 2016

Hall, Justin / Prabhakar, Shilpa / Balaj, Leonora / Lai, Charles P / Cerione, Richard A / Breakefield, Xandra O. ·Departments of Chemistry and Chemical Biology and Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA. · Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA. · Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan. · Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA. breakefield@hms.harvard.edu. · Molecular Neurogenetics Unit, Massachusetts General Hospital-East, 13th Street, Building 149, Charlestown, MA, 02129, USA. breakefield@hms.harvard.edu. ·Cell Mol Neurobiol · Pubmed #27017608.

ABSTRACT: Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.

23 Review Dopaminergic drugs in type 2 diabetes and glucose homeostasis. 2016

Lopez Vicchi, Felicitas / Luque, Guillermina Maria / Brie, Belen / Nogueira, Juan Patricio / Garcia Tornadu, Isabel / Becu-Villalobos, Damasia. ·Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina. · Universidad Nacional de Formosa, Facultad de Ciencias de la Salud; Av. Gutnisky 3200-C.P., 3600-Formosa, Argentina. · Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina. Electronic address: dbecu@dna.uba.ar. ·Pharmacol Res · Pubmed #26748034.

ABSTRACT: The importance of dopamine in central nervous system function is well known, but its effects on glucose homeostasis and pancreatic β cell function are beginning to be unraveled. Mutant mice lacking dopamine type 2 receptors (D2R) are glucose intolerant and have abnormal insulin secretion. In humans, administration of neuroleptic drugs, which block dopamine receptors, may cause hyperinsulinemia, increased weight gain and glucose intolerance. Conversely, treatment with the dopamine precursor l-DOPA in patients with Parkinson's disease reduces insulin secretion upon oral glucose tolerance test, and bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients as well as in non diabetic obese animals and humans. The actions of dopamine on glucose homeostasis and food intake impact both the autonomic nervous system and the endocrine system. Different central actions of the dopamine system may mediate its metabolic effects such as: (i) regulation of hypothalamic noradrenaline output, (ii) participation in appetite control, and (iii) maintenance of the biological clock in the suprachiasmatic nucleus. On the other hand, dopamine inhibits prolactin, which has metabolic functions; and, at the pancreatic beta cell dopamine D2 receptors inhibit insulin secretion. We review the evidence obtained in animal models and clinical studies that posited dopamine receptors as key elements in glucose homeostasis and ultimately led to the FDA approval of bromocriptine in adults with type 2 diabetes to improve glycemic control. Furthermore, we discuss the metabolic consequences of treatment with neuroleptics which target the D2R, that should be monitored in psychiatric patients to prevent the development in diabetes, weight gain, and hypertriglyceridemia.

24 Review Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1. 2015

Chan, Julie Y H / Chan, Samuel H H. ·Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, ROC. · Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, ROC. Electronic address: shhchan@cgmh.org.tw. ·Pharmacol Ther · Pubmed #26432617.

ABSTRACT: NAD(P)H: quinone oxidoreductase 1. It follows that activation of DJ-1 as a common endogenous antioxidant provides a new strategy against cancer, neurodegeneration and cardiovascular diseases. Since clinical trials on exogenous application of the known antioxidants have basically failed, an alternative approach would logically be to activate the endogenous antioxidants that are already present in the appropriate cellular locale where elevated oxidative stress is the culprit for the disease. At the same time, since oxidative stress is a common denominator among cancer, neurodegeneration and cardiovascular diseases, development of antioxidant therapy should target the reduction in reactive oxygen species. Instead of focusing on disease-oriented therapy, pharmaceutical companies should concentrate on developing agents and dosing schemes for effective activation of the endogenous antioxidants that are associated with a multitude of oxidative stress-related diseases (mechanism-oriented therapy).

25 Review Asian perspectives on the recognition and management of levodopa 'wearing-off' in Parkinson's disease. 2015

Bhidayasiri, Roongroj / Hattori, Nobutaka / Jeon, Beomseok / Chen, Rou-Shayn / Lee, Moon Keen / Bajwa, Jawad A / Mok, Vincent C T / Zhang, Baorong / Syamsudin, Thamrin / Tan, Louis Chew Seng / Jamora, Roland Dominic G / Pisarnpong, Apichart / Poewe, Werner. ·a 1 Chulalongkorn Centre of Excellence for Parkinson's Disease & Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. · b 2 Juntendo University School of Medicine, Tokyo, Japan. · c 3 Seoul National University, Seoul, South Korea. · d 4 Chang Gung Memorial Hospital, Lingkou, Taiwan. · e 5 Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 46150 Petaling Jaya, Selangor, Malaysia. · f 6 National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia. · g 7 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. · h 8 Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. · i 9 National Brain Centre Hospital, Jakarta, Indonesia. · j 10 National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore. · k 11 Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. · l 12 Movement Disorder Service and Section of Neurology, Institute for Neurosciences, St. Luke's Medical Center-Quezon City and Global City, Philippines. · m 13 Department of Neurology, Bangkok Hospital, Bangkok, Thailand. · n 14 Innsbruck Medical University, Innsbruck, Austria. ·Expert Rev Neurother · Pubmed #26390066.

ABSTRACT: Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.