Device–assisted therapy for Parkinson disease : Deep brain stimulation and levodopa–carbidopa intestinal gel therapy

Abstract

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms, such as akinesia, rigidity, and tremor, as well as non–motor symptoms. On initiation of treatment for PD, the medication response for motor symptoms is high, which is known as the “honeymoon period.” However, as the disease progresses, motor complications such as wearing–off and dyskinesia appear, and modulation of oral medications and control of medication timing are required. Thereafter, these symptoms may become unstable and difficult to manage despite intensive drug adjustments. Device–assisted therapy, such as deep brain stimulation (DBS) and levodopa–carbidopa intestinal gel therapy (LCIG), is available to manage these drug–resistant motor complications. DBS improves motor symptoms by regulating the functional neural networks and modulating hyperactive neurotransmission. Therefore, the suitable cases for its indication are limited to those with sufficient dopa–responsiveness and minimal impairment of the non–dopaminergic system, such as absence of dementia or psychiatric symptoms. A commonly targeted nucleus in DBS implantation for PD is the subthalamic nucleus (STN). STN–DBS has a drug–reducing effect in addition to the effects on motor symptoms. DBS targeted at the globus pallidus internus has a strong inhibitory effect on dyskinesia, and the ventral intermediate nucleus of the thalamus–targeted DBS has a strong therapeutic effect on medication–refractory intractable tremor. These DBS targets are chosen based on the patients' condition. LCIG delivers drugs continuously to the gastrointestinal tract so that the absorption profile and therapeutic effect could be kept constant without fluctuations. Different from DBS, LCIG requires daily management and careful attention to drug storage. The benefits obtained from these device–assisted therapies depend also on each patient's condition. It is important to fully understand the details of each treatment including benefits, adverse effects, and applications. Furthermore, the treatment goals should be defined along with the appropriate treatment selection.