What are motor fluctuations?
Motor fluctuations are the oscillations, or variations, in the control of motor symptoms associated with the long term use of the medication, levodopa. These fluctuations tend to be more prevalent in those with young-onset Parkinson’s (i.e. under the age of 50) and seem to be associated only with levodopa, not with other anti-Parkinsonian medication. It has been estimated that as many as 50% of those who have taken levodopa for five years or more experience fluctuations1.
What causes motor fluctuations?
Initially levodopa generally provides good symptom control, but over a number of years symptoms tend to re-emerge and response to medication is no longer as smooth and predictable as it once was.
A study conducted at the Institute of Neurology in London2 concluded that motor fluctuations are related to disease duration and to the non-physiological stimulation of dopamine receptors induced by long term administration of levodopa.
People with Parkinson’s have reduced levels of dopamine – a chemical messenger in the brain involved in coordinating the nerve cells and muscles which control movement. When dopamine levels drop below a certain point, motor symptoms such as tremor, muscle rigidity and problems with movement (for example, slowness or bradykinesia) are experienced, and some non-motor symptoms such as anxiety and sweating may also emerge.
Some Parkinson’s treatments are based on increasing dopamine levels with levodopa which converts into dopamine in the brain. During the first few years of treatment the brain still provides relatively high levels of dopamine, so only a small additional amount is needed to keep symptoms controlled. This is a short-acting drug, but each dose provides additional dopamine for a few hours and most people have sustained improvement in symptoms with three doses of levodopa each day.
This extra boost of dopamine helps to control Parkinson’s symptoms initially, but as the disease progresses the number of nerve cells producing and storing dopamine in the brain falls and so the ‘buffering’ capacity of neurons in the substantia nigra is dramatically reduced. At this point, the level of dopamine inside the brain is completely dependent on the level of levodopa in the blood, which itself is reliant on the duration of the most recent dose. As the effectiveness of each dose reduces, many people experience fluctuations in motor control.
However, whilst the fluctuations are certainly associated with levodopa, they cannot be entirely attributed to the medication. Fluctuations tend not to be experienced by people taking levodopa and who do not have Parkinson’s. As such, it is thought motor fluctuations are caused by an interaction between this particular disease and the drug.
