Levodopa/Carbidopa Intestinal Gel Long‐Term Outcome in Parkinson's Disease: Focus on Dyskinesia

Abstract

Background Background: Levodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD). Objective Objective: To identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients. Methods Methods: PD patients were assessed for clinical and therapeutic variables, before LCIG treatment (T0) and at last outpatient visit (T1). Subgroups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment. Results Results: We included 53 PD patients. After a mean of 51.7 AE 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at T1 (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at T1 (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at T1 (sum of the items 32 and 33: P = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration. Conclusion Conclusion: Dyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients.

Continuous 24-h Levodopa-Carbidopa Intestinal Gel Infusion After a Levodopa Holiday Suppressed Refractory Dyskinesia Despite Increasing Levodopa Dose

“…However, even after LCIG treatment initiation, it may be difficult to control levodopa-induced dyskinesia (LID), especially in females. 1 Several studies have reported that 24-h LCIG improves disabling dyskinesia, freezing of gait, night-time akinesia, and sleep quality unresponsive to 16-h LCIG. 2,3 Herein, we report the case of a patient in whom disabling dyskinesia of the trunk and neck was completely ameliorated by 24-h LCIG treatment.…”

“…Continuous delivery of levodopa–carbidopa intestinal gel (LCIG) to the jejunum can improve the symptoms of advanced levodopa-responsive Parkinson’s disease (PD) by allowing continuous dopamine stimulation. However, even after LCIG treatment initiation, it may be difficult to control levodopa-induced dyskinesia (LID), especially in females [ 1 ]. Several studies have reported that 24-h LCIG improves disabling dyskinesia, freezing of gait, night-time akinesia, and sleep quality unresponsive to 16-h LCIG [ 2 , 3 ].…”

The effect and mechanism of low intensity focused ultrasound in the treatment of Parkinson's disease

“…LIFUS has become an area of intense interest in many research fields (Lee, Fomenko, & Lozano, 2019). Currently available surgical treatment for PD, including deep brain stimulation (DBS) (Miocinovic et al, 2020), levodopa-carbidopa intestinal gel treatments (Fabbri et al, 2020), the HIFU-mediated burning of the thalamus (Bauer et al, 2014), and other treatments, are highly invasive. LIFUS has facilitated achievements in tumor treatment (Son et al, 2020), stem cell research (Liu, Ullah, Concepcion, Dahl, & Thakor, 2020), neurological research (Karmacharya et al, 2015;Yang et al, 2020) and many other fields.…”

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

“…6 These observations, together with further recent hints, might indicate that a patient undergoing LCIG should be informed about the possibility that LCIG could fail to completely control involuntary movements. 7 We now have some evidence that adding DBS might avoid such discontinuation and guarantee a synergistic effect on the motor complications experienced by some patients with advanced PD.…”