Editorial

Since the first description of the "shaking palsy" by James Parkinson in 1817, 1 our knowledge and understanding of Parkinson's disease (PD) has been evolving.2 The degeneration of dopamine neurons in the substantia nigra leads to the primary motor symptoms of PD, although changes throughout the brain have been reported, accounting for both motor and nonmotor symptoms (NMS) of the disease.3 The pathogenesis of the loss of dopamine neurons remains unclear and studies have reported both genetic and environmental risk factors.4 To date, the majority of treatments for PD have focused on the fact that degeneration of the dopaminergic nigrostriatal pathways results in the loss of motor control and replenishing dopamine would reverse, at least temporarily, the symptoms of PD. 5 Dopamine replacement therapy with levodopa results in significant clinical improvement and remains the mainstay for treating the motor deficits related to PD. 6 However, levodopa can lead to motor complications including dyskinesia and motor fluctuations, such as the re-emergence of motor symptoms at the end of the levodopa dosing window (wearing off), unpredictable loss of symptom control, and dose failures.The short half-life of levodopa produces a pulsatile stimulation of striatal dopamine receptors, which has been hypothesized to contribute to the occurrence of levodopa-induced motor complications.2,6 Furthermore, observation of the tonic firing of dopaminergic neurons in animal studies suggested that continuous dopaminergic stimulation may better control the symptoms of PD without the development of motor complications.7 The discovery of the dopaminergic receptors involved in striatal motor control led to the development of more specific dopamine agonists for the treatment of PD.Due to their longer half-life, dopamine agonists have been shown to reduce the occurrence of levodopa-induced motor fluctuations and dyskinesia.2,8 Dopamine agonists are divided into ergot-derived and non-ergot-derived agents.The first dopamine agonists to become available, the ergot agonists, include bromocriptine, cabergoline, pergolide, and lisuride.The non-ergot-derived dopamine agonists include pramipexole, ropinirole, rotigotine, and apomorphine.Due to the risk of fibrotic valvular heart disease with ergot agonists, they have largely been replaced by the nonergot agonists that have not been reported to cause these problems.9 Managing the motor symptoms associated with PD continues to be the primary focus of treatment; however, NMS can cause significant disability and are often underrecognized and undertreated.10 The NMS of PD include sleep and mood disorders, pain, autonomic dysfunction, and cognitive abnormalities.11 Nearly all PD patients report NMS, the most common of which include fatigue (58%), anxiety, (56%), leg Dr Lyons has received consulting fees from Adamas, St Jude Medical, and Teva Neuroscience.