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Tuesday, August 3, 2010


( The article is in Two parts forwarded by Dr. Sephy Philip. It has a lot of valuable information)

Managing Parkinson's 'Wearing-Off' Symptoms - Part I
"Wearing off" is the term Parkinson patients use for the distressing symptoms they experience when their anti-Parkinson medication stops working, until the next dose arrives. Here's the first of two articles about wearing off, written from the patient's perspective. It describes wearing off - the symptoms, and the effects.
Early Diagnosis and Optimized Treatment are Key
Three to four hours after taking his drug treatment for Parkinson's disease (PD), Tom - who has had PD for the past nine years - gets a tremor in his right hand that gradually affects the rest of his body.
Doctors call Tom's problem 'wearing-off'. It happens because the effects of his drugs literally 'wear off' and his symptoms of PD reappear.
What causes wearing-off?
'Wearing-off' occurs as the duration of effect of one of the most commonly used drugs to treat PD - levodopa - diminishes over time as the disease progresses.
People with PD have reduced levels of dopamine - a chemical messenger in the brain that is involved in coordinating nerve and muscle cells to control movement and activities such as walking and talking. When dopamine drops beyond a certain level, symptoms of PD emerge, including tremor, muscle rigidity and problems with movement (especially slowness) known as motor symptoms and also some non-motor symptoms like anxiety.
The treatment of PD is based on topping up dopamine levels with levodopa - which is converted into dopamine in the brain. Levodopa is a short-acting drug, which means that each dose only provides additional dopamine for a few hours. During the first few years of treatment, because the brain still provides relatively high levels of dopamine, little additional dopamine is needed to keep symptoms at bay and most people have sustained improvement in symptoms with three doses of levodopa each day.
Unfortunately, as PD progresses the number of nerve cells producing and storing dopamine in the brain falls. With less brain dopamine available, a dose of levodopa that initially removed symptoms for four hours may not provide enough dopamine to maintain full control of symptoms until the next dose. The benefit of levodopa literally 'wears off' before it is time for the next dose.
1 The effect of each dose of levodopa lasts for progressively shorter periods of time, and symptoms of PD reappear. These symptoms then typically improve 15-45 minutes after taking your next dose of PD medication.
Many people call the time when their drugs are controlling their PD symptoms their 'on time' and the time when they are suffering from wearing-off their 'off time.'
For people who prefer to think in pictures, here is a diagram explaining what happens to levodopa levels in the body over a day:

How common is wearing-off?
Tom, aged 35, is far from alone in suffering from wearing-off. It was thought that around one-third to one-half of people developed 'wearing-off' after approximately five years of levodopa therapy. But recent research studies have revealed that it can happen earlier - with one out of three patients developing 'wearing-off' within one to two years of starting to take levodopa.
What are the symptoms of wearing-off?
The way in which wearing-off affects people is very variable. Tom tends to have tremor as a symptom of wearing-off. But Marian, aged 54, who has had PD for 10 years, finds his main problem is stiffness and being unable to begin movements.
Many people find their motor (movement) symptoms - such as tremor, rigidity or slowness of movement (technically termed bradykinesia) return during wearing-off. But wearing-off symptoms can be much more subtle problems not associated with movement (non-motor symptoms), including anxiety, fatigue, changes in mood, difficulty in thinking clearly, restlessness, sweating and increased salivation (when your mouth produces too much saliva).
"In a research study, we found the most common wearing-off symptom was tremor, followed by slowness," explained Professor Robert Hauser, who is Professor of Neurology, Pharmacology and Experimental Therapeutics at the University of South Florida, Tampa, USA. "The commonest non-motor symptom of wearing-off was anxiety."
The initial manifestation of wearing-off may be quite subtle. "Many people find they just don't feel as well as they did when they first start to suffer from wearing-off," added Professor Fabrizio Stocchi, Professor of Neurology, Institute of Neurology IRCCS, Meuromed, Rome, Italy.
Symptoms of wearing-off - An overview

What is the effect of wearing-off?
Research has shown that many people find the loss of energy during their 'off time' particularly disabling. It can be difficult to go about their normal activities - including walking or working - when they are suffering from wearing-off. Marian finds it hard to do ordinary things like getting out of his car when he is wearing-off.
Tom plans his day around his wearing-off time - to ensure that he does not have to do anything when it might occur. "When I am wearing-off, there is sometimes little I can do. Sometimes, I just sit and do nothing until my next dose of medication kicks in."
This is the first of two articles. To read the second one, see first link below.
Susan J. Mayor, BSc, MSc, PhD, is a freelance medical writer based in London.

1. Levodopa in Parkinson's disease: mechanisms of action and pathophysiology of late failure. W. Poewe, G. Wenning, In: Jankovic, Tolosa eds, Parkinson's disease and movement disorders, 2002, vol. 8, pp. 104--1152. Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson's disease. JAMA 2000; 284: 1931-1938; Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann Neurol 1997; 42: 747-755.

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