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Movement Disorders Parkinson’s Disease Morning Akinesia and the Potential Role of Gastroparesis – Managing Delayed Onset of First Daily Dose of Oral Levodopa in Patients with Parkinson’s Disease Stuart H Isaacson 1 and K Ray Chaudhuri 2 1. Associate Professor, Florida International University, Herbert Wertheim College School of Medicine, Miami; Director, Parkinson’s Disease and Movement Disorders Center of Boca Raton; Research Director, Marcus Neuroscience Institute, Boca Raton Regional Hospital, Florida, US; 2. Professor of Neurology/Movement Disorders and Director, National Parkinson Foundation Centre of Excellence, Department of Neurology, King’s College Hospital; Kings Health Partners, London, UK Abstract In patients with Parkinson’s disease (PD), motor and non-motor symptoms are frequent during OFF periods, especially when the next levodopa dose has a delayed onset of action (delayed ON). Delayed ON of the first daily dose of levodopa is known as morning akinesia, which can significantly affect quality of life and impair daily activities. Morning akinesia can occur due to a delay in gastric emptying, impaired intestinal absorption, pharmacodynamic effects or other mechanisms. Gastroparesis is common in patients with PD and can cause gastrointestinal symptoms, delayed ON and morning akinesia. Alternative delivery of dopaminergic therapy by a non-oral route may be useful in patients with PD and gastroparesis. Subcutaneous apomorphine injection is used by patients with PD in the OFF state to decrease time-to-ON. An ongoing study is investigating its use for morning akinesia, as well as the frequency of delayed gastric emptying in these patients. Keywords Parkinson’s disease, motor complications, akinesia, delayed ON, gastroparesis, levodopa, apomorphine Disclosure: Stuart H Isaacson has received honoraria for CME activities, research grants and/or consultant and promotional speaker fees from: Abbvie, Acadia, Adamas, Addex, Allergan, Allon, AstraZeneca, Biotie, Britannia, Chelsea, Civitas, Eisai, GE, GSK, Impax, Ipsen, Kyowa, Lilly, Merck Schering-Plough, Medtronics, Merz, Michael J Fox Foundation, Novartis, Neurocrine, National Institutes of Health (NIH), Novartis, Orion, Parkinson Study Group, Phytopharm, Purdue, Roche, Santhera, Serono, Shire, Teva, UCB and US World Meds. K Ray Chaudhuri has been a consultant for Abbott, BI, Britannia, GSK, Medtronic, Mundipharma and UCB, has received grants/research support from Abbott, BI and UCB and has received honoraria from Abbott, BI, Britannia, GSK, Medtronic, Mundipharma and UCB. Acknowledgements: Editorial assistance was provided by Helen Lawn Associates, supported by Britannia Pharmaceuticals Ltd. Received: 7 October 2013 Accepted: 11 November 2013 Citation: European Neurological Review, 2013;8(2):82–4 Correspondence: Stuart H Isaacson, Parkinson’s Disease and Movement Disorders Center of Boca Raton, 951 NW 13th St Suite 5E, Boca Raton, FL 33486, US. E: isaacson@ParkinsonsCenter.org Support: The publication of this article was supported by Britannia Pharmaceuticals Ltd. The views and opinions expressed are those of the authors and not necessarily those of Britannia Pharmaceuticals Ltd. This article reviews the potential role of delayed gastric emptying in patients with Parkinson’s disease (PD) and morning akinesia. This can result in impaired motor function and impairment of a range of non- motor functions, as shown in a recently reported early morning OFF study. 1 Morning akinesia can have a significant impact on quality of life (QoL) and delay a patient’s ability to carry out their normal daily activities. 2 Treatment strategies for morning akinesia remain suboptimal. Gastrointestinal (GI) dysfunction (including gastroparesis) is a common feature of PD. Gastroparesis can occur throughout the disease duration, and in some cases may even precede diagnosis. 3,4 GI symptoms of gastroparesis not only impair patients’ QoL but can also impact the onset of oral levodopa, by delaying its delivery to the small intestine where it is absorbed. 5,6 Delayed ON and Morning Akinesia in Parkinson’s Disease Patients In PD, motor symptoms reflect severe degeneration of nigrostriatal dopaminergic pathways with intracellular aggregation of synuclein 82 (i.e. Lewy bodies). 7 Non-motor symptoms are often poorly understood and inadequately treated, but are thought to arise from more diffuse involvement of the central, autonomic and enteric nervous systems. 8 Widespread involvement of the GI system is common in PD, with synuclein and Lewy bodies demonstrated throughout the enteric nervous system, including within myenteric neurons. The treatment of PD motor symptoms relies on oral levodopa, which must be emptied from the stomach and absorbed in the proximal small intestine. Gastroparesis causes delayed gastric emptying of levodopa with a delay in its delivery to the duodenum, resulting in the clinical phenomenon of delayed ON after a levodopa dose. 9 Initially, the therapeutic effect of each levodopa dose is rapid, reliable and sustained (onset around 20 minutes and a long duration response). However, after several years of levodopa treatment, the long duration response becomes replaced by a short duration response, and OFF periods emerge. 10,11 While OFF periods can be treated with several adjunctive medications, delayed onset of the next levodopa dose can significantly increase OFF period duration. 11 © TOUC H ME D IC A L ME D IA 2013