Subthalamic Nucleus Deep Brain Stimulation as Rescue Therapy for Levodopa Carbidopa Intestinal Gel–Associated Biphasic‐Like Dyskinesias

Abstract

We read with interest the report by Mulroy et al about the patient with Parkinson’s disease (PD) who developed troublesome dyskinesias while on levodopa carbidopa intestinal gel (LCIG) that were successfully treated by adding deep brain stimulation (DBS) of the globus pallidus pars interna (Gpi). “Biphasic-like” dyskinesias have been described by our group as a potential complication of LCIG therapy. We agree with Mulroy et al that such dyskinesias reflect the combination of disease progression and LCIG. Indeed, a significant amount of our patients had a previous history of typical biphasic dyskinesias while on oral therapy. The pathogenesis of biphasic dyskinesias is still not fully elucidated. In fact, although they might be associated with a low or end-of-dose levodopa plasmatic concentration—thus explaining the sustained presentation in patients on underdosed LCIG—not all cases can be explained in pharmacokinetic terms. Intriguingly, pharmacodynamic hypotheses—such as a more widespread dopaminergic degeneration also involving D1 receptors—have been advocated to explain the pathogenesis of biphasic dyskinesias. Herein we report a 59-year-old man with a 20-year history of PD who developed biphasic-like dyskinesias while on LCIG. This patient was successfully treated by adding DBS of the subthalamic nucleus (STN). Prior to LCIG, his levodopa equivalent daily dose was 1150 mg/day. Because of the presence of severe motor fluctuations, he received LCIG in 2017 (levodopa equivalent daily dose [LEDD] of 1326 mg/day). A few weeks after LCIG, he developed biphasic-like dyskinesias, which we tried to manage with multiple strategies for several months, unsuccessfully. Thus, STN DBS was added. In contrast with a similar case and similarly to Mulroy et al, LCIG therapy was continued with a slight LEDD reduction (1232 mg/day). The combination of STN DBS and LCIG led to the improvement of motor fluctuations and a sustained remission of dyskinesias (Video 1). LCIG should be the best strategy to treat biphasic dyskinesias, but all of