1.: Levodopa-carbidopa intestinal gel infusion improves motor performance and quality of life in patients with advanced Parkinson’s disease

Abstract

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from the largest case series in an Australian movement disorder center at Westmead Hospital. An open-label, 12 months prospective study (Clinicaltrials.gov identifier: NCT00335153) of treatment with LCIG in patients with advanced Parkinson's disease was conducted. Patients with motor fluctuations despite optimal pharmacological treatment were included. Patients were given a16 hour daily infusion of LCIG for mean of 22±10 months. Minnesota Impulse Disorders Interview (MIDI), complications, the total levodopa daily equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) part III, daily hours "off", daily hours "on" without dyskinesia, daily total hours "on" and pre-existing psychiatric diagnosis or impulse control disorder (ICD) was collected at baseline, 3, 6 and 12 months. The study was approved by the Human Research Ethic Committee at Western Sydney Area Health Service. Fifteen patients participated. Mean improvement in UPDRS part III was 37±11%. Mean daily "off" period reduced from 6.3±2 to 1.9±2 hours; total daily "on" time increased from 10.2±3 to 13.7±2 hours; "on" period without dyskinesia increased from 4.5±3 to 7.5±5 hours; 39-item Parkinson's Disease Questionnaire Summary Index improved by 32.5±35%. The most common adverse event was peripheral neuropathy secondary to vitamin B12±vitamin B6 deficiency (67%), local tube problems (60%), impulse control disorder (47%), and stoma infection (30%). No patient had stoma bleeding or peritonitis. All patients with impulse control disorder had a past psychiatric diagnosis and a higher daily levodopa intake at 6 months of LCIG infusion. Intraduodenal LCIG improves motor performance, quality of life and daily "on" period. Our rate of intestinal tube problem or infection was similar to reported literature. Prior to and during duodenal LCIG infusion, clinicians should monitor for peripheral neuropathy and vitamin B12 and B6 deficiency, as supplementation can reverse peripheral neuropathy. Our study suggests that an increased daily levodopa dose compared to baseline is associated with a later development of impulse control disorders, but larger sample studies are needed to confirm this finding.