Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life

Abstract

Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open-label observational study, we report the effects of intrajejunal levodopa/carbidopa gel infusion on NMS in PD based on standard assessments utilizing the nonmotor symptoms scale (NMSS) along with the unified Parkinson's disease rating scale (UPDRS 3 motor and 4 complications) and quality of life (QoL) using the Parkinson's disease questionnaire (PDQ-8). Twenty-two advanced PD patients (mean age 58.6 years, duration of disease 15.3 years) were followed for 6 months. A statistically significant beneficial effect was shown in six of the nine domains of the NMSS: cardiovascular, sleep/fatigue, attention/memory, gastrointestinal, urinary, and miscellaneous (including pain and dribbling) and for the total score of this scale (NMSST) paralleling improvement of motor symptoms (UPDRS 3 motor and 4 complications in "best on" state) and dyskinesias/motor fluctuations. In addition, significant improvements were found using the Parkinson's disease sleep scale (PDSS) and the PDQ-8 (QoL). The improvement in PDQ-8 scores correlated highly significantly with the changes in NMSST, whereas a moderately strong correlation was observed with UPDRS changes. This is the first demonstration that a levodopa-based continuous dopaminergic stimulation is beneficial for NMS and health-related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias.

Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease

“…37,48 Non-motor symptoms are likely to significantly affect QoL and several such symptoms were improved by LCIG in a six-month study. 41 Cognitive function was reported to be improved in two patients, two to 24 months after the introduction of LCIG, possibly related to increased 'on' time. 49 In an interview with 25 patients, of whom the majority had been using infusion for more than two years, 76 % agreed completely that their QoL was improved with infusion as compared to before.…”

“…12,13,[35][36][37][38][39][40][41][42][43][44][45][46] Most studies so far have focused on motor symptoms. The general finding is that LCIG provides more time in motor states near normal performance and less time in 'off' and dyskinetic states as compared to conventional optimised therapy.…”

Levodopa/Carbidopa Intestinal Gel for Treatment of Advanced Parkinson’s Disease: An Update on the Effects of Cognitive Functions

“…Similarly, another retrospective study [66] showed the safety and tolerability of 24-h infusion of LCIG on 21 advanced PD patients with severe night-time disability, the drop-out rate from treatment due to worsening of cognitive/neuropsychiatric symptoms being <5%. Sanchez Castaneda et al [67] described the marked improvement of cognitive functions after switching oral therapy to LCIG infusion in two patients with PD with cognitive impairment, and Honig and coworkers [68] demonstrated the significant beneficial effect of LCIG on NMS, in particular attention and memory, in an observational study on 22 advanced PD patients monitored for 6 months. Finally, Zibetti and collaborators [69] performed a prospective study on 25 patients treated with LCIG for 3 years.…”

Continuous dopaminergic delivery to minimize motor complications in Parkinson’s disease

“…With a constant infusion rate of the levodopa-carbidopa gel during the waking hours, smooth plasma levodopa levels, and therefore, more continuous stimulation of striatal dopamine receptors can be achieved. This has been shown to be a successful strategy to minimize motor fluctuations and dyskinesias in advanced PD patients, in addition to providing a more consistent clinical benefit [42,61] and enhanced quality of life (QoL) [62,63].…”