New strategies in motor parkinsonism

A satisfactory motor control can be achieved for many years in Parkinson's disease (PD). Clinical management is more complex when disease progresses and occurrence of motor fluctuations and dyskinesias negatively impacts on patients' quality of life. Mobility depends increasingly on levodopa peripheral bioavailability. Medical strategies consist of raising the number of levodopa administrations and the association with COMT inhibitors, entacapone or the more potent tolcapone. MAO-B inhibitors rasagiline or selegiline can be also added. When these options fail, achievement of motor control requires more complex therapeutic strategies: continuous infusion of dopaminergic drugs or neuromodulation with deep brain stimulation (DBS). Apomorphine is a dopamine agonist that can provide motor benefit similar to dopamine, but its use is limited by compliance, local skin reactions at the site of injection and risk of psychiatric adverse events, particularly when round-the-clock administration is used. DBS of the subthalamic nucleus is very effective but feasible only for a small number of patients mostly because of age constraints. Continuous duodenal infusion of levodopa/carbidopa allows replacement of oral therapy resulting in marked improvement of quality of life and activities of daily living. Interestingly, this procedure produces a satisfactory therapeutic response that is paralleled by a reduction in dyskinesia severity.