Parkinson’s Disease and Motor Fluctuations

Many important advances for the treatment of Parkinson’s disease (PD) have been made over the past decade, and quality of life has improved for most patients. Nonetheless, motor fluctuations in the form of wearing off with the re-emergence of parkinsonian symptoms and hyperkinetic movements (dyskinesias) often arise as a complication of long-term dopaminergic therapy and can be disabling. Because treatment of motor fluctuations is difficult, clinicians should attempt to prevent them by using low doses of dopaminergic drugs in early PD, targeting functionally relevant symptoms. Instead of levodopa, dopamine agonists, amantadine, and rasagiline can be used with the aim of delaying the onset of motor fluctuations. Once motor fluctuations arise, off time can initially be addressed with more frequent dosing of levodopa. Later, adjunctive therapy with a dopamine agonist, COMT-inhibitor, or MAO-B inhibitor becomes necessary. For treatment of dyskinesias, reduction of the levodopa dose should be the first step. If this is not tolerated because of increased off time, then adjunctive therapy with levodopa-sparing agents should be attempted. The addition of amantadine (the only currently available antidyskinetic drug) is another useful strategy but is often only a temporary solution. Once medical attempts at treating motor fluctuations fail, deep brain stimulation (DBS) can be considered. Careful patient selection and skilled placement of DBS electrodes are important determinants of the surgical outcome.