Duodenal Levodopa Infusion Research Articles

PEG-J replacement for duodenal levodopa infusion in Parkinson\u2019s disease patients: a retrospective study

BackgroundReducing percutaneous endoscopic gastrostomies with jejunal extension tubes (PEG-J) related complications is vital to the long-term preservation of duodenal levodopa infusion (DLI) in advanced Parkinson’s disease (APD). Here, we provide data on the frequency of complications for both the standard “pull” and the non-endoscopic, radiologic assisted, “push” replacement PEG-J techniques in APD.MethodsWe retrospectively identified all patients treated with DLI from October 2009 to January 2020 at the Movement Disorders Center. Patients features and demographics, PEG-J procedures, causes for any discontinuation, reported complications and mortality were collected. In this cohort, PEG-J replacements were performed using the standard “pull” procedure or the radiologic assisted “push” method. Descriptive statistical analysis, t-test and paired t-test with False Discovery Rate correction was performed.ResultsThis retrospective study included 30 APD patients [median age 72 ± 5.6 years; mean disease duration 17.2 + 5.7 years]. Mean treatment duration was 35.6 (30.6) months. Overall, 156 PEG-J procedures were performed, and Nineteen patients (63.3%) had a total of 185 reported complications, 85 of which were peristomal complications. 17 (56.6%) underwent 100 replacement procedures due to complications. The most commonly reported complication for replacement was J-tube dislocation (36%). One patient discontinued treatment after 6 months, due to peripheral neuropathy. Six patients died for causes not related to DLI. PEG-J replacements performed with the “push” method had a higher turnover (5.6 vs. 7.6 mo.), but fewer reported complications (67 vs. 75%).ConclusionThe overall rate of complications was lower for “push” technique. This result might have been due to a higher replacement turnover that acted as a protective factor.

Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review.

Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results. Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature. Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans. Infusion of LCIG reduced "off" time, increased "on" time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited. The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.

Causes of withdrawal of duodenal levodopa infusion in advanced Parkinson disease.

We performed a real-life observation of patients with Parkinson disease (PD) who received duodenal levodopa infusion (DLI) to determine which adverse events caused treatment discontinuation and when such events occurred. All consecutive patients with PD treated at the Carlo Besta Neurological Institute were included. The patients were evaluated at baseline and after DLI at regular intervals. Their motor condition was assessed and adverse events were recorded. Thirty-five patients with PD (15 men and 20 women) were included. They received DLI implants between October 2007 and September 2013. Four patients died of causes unrelated to the procedure. At the end of the study, 21 patients (60%) were still on treatment. DLI provided efficacious motor control in all patients. Discontinuation was most frequently caused by device- or infusion-related adverse events. Ten patients of the remaining 31 discontinued DLI. There were 2 main causes of withdrawal: stoma infection (4 patients), and worsening of dyskinesias not manageable with infusion reduction (3 patients). In most patients, discontinuations occurred during the first year after implant. Risk of discontinuation was related to age at implant, but no other demographic or clinical variables. We identified 2 main causes leading to DLI withdrawal during the first year postimplant and suggest adopting measures to prevent such occurrences. Elderly patients are at higher risk of treatment discontinuation.

Effect and safety of duodenal levodopa infusion in advanced Parkinson’s disease: a retrospective multicenter outcome assessment in patient routine care

Duodenal levodopa infusion represents an effective strategy to manage motor and non-motor complications in patients with advanced Parkinson's disease (PD). However, most published clinical series regard small numbers of patients and do not exceed 1 year follow-up. In this multi-national observational cohort study conducted in seven specialised PD clinics and university hospitals we assessed long-term safety and outcome of chronic treatment with intra-duodenal levodopa infusions in a large population of patients with advanced PD. The starting population consisted of 98 treated patients (safety population). We report clinical outcomes of 73 patients with subsequent efficacy assessment(s) (efficacy population) over a follow-up period up to 2 years. Follow-up periods and collection of clinical observations varied based on individual routine care program. At last follow-up there was a significant (p ≤ 0.05) reduction in duration of "Off" periods as well as dyskinesia duration and severity that was associated with an improvement of quality of life. Twenty three patients (25.3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8). The mean duration for last value reported after baseline (LV) was 608 ± 292 days (median: 697 days). Our results demonstrate significant and sustained benefit over a long observation period in motor complications and in quality of life following a change from oral pulsatile to continuous levodopa delivery. The relatively large number of withdrawals reflects the current use of duodenal levodopa infusion in very advanced PD patients.

Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome

ObjectiveDopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and...

Recurrent pancreatitis as a rare complication of duodenal levodopa infusion treatment

Recurrent pancreatitis as a rare complication of duodenal levodopa infusion treatment

Long-term duodenal levodopa infusion in Parkinson’s disease: a 3-year motor and cognitive follow-up study

Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson's disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients' quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its' impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients' QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.

Experience with duodenal levodopa infusion in advanced Parkinson's disease in our hospital

BackgroundContinuous levodopa delivery by enteral infusion is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesia in advanced Parkinson's disease (PD).PurposeThe objective was to...

Patients receiving duodenal levodopa infusion are at risk of vitamin B12 deficiency

Parkinson disease: Patients receiving duodenal levodopa infusion are at risk of vitamin B 12 deficiency

Effect of duodenal levodopa infusion on blood pressure and sweating

Non-motor symptoms are a major contributor to quality of life in patients with advanced Parkinson's disease (PD). Duodenal levodopa infusion (DLI) has been shown to alleviate motor fluctuations, but data on its possible effect on non-motor symptoms are scarce. The aim of the study was to assess the effect of DLI on blood pressure (BP), sweating, and non-motor symptoms. We evaluated prospectively and open-label nine male patients with advanced PD (age 68.5±6.2years) treated with DLI because of daily motor fluctuations. Patients were evaluated using orthostatic test, sweating and skin temperature measurements, Unified Parkinson's Disease Rating Scale (UPDRS), Non-motor Symptom Scale (NMSS), and PDQ-39 before and after 2months of treatment. Orthostatic BP drop worsened after 1week of DLI compared with oral medication (24.1 vs 11.9mmHg, P=0.011) and remained significant after 2months of treatment. UPDRS motor scores improved significantly in 2months compared with baseline (25 vs 19, P<0.01). Sweating or skin temperatures did not change. Several domains in NMSS (sleep/fatigue, gastrointestinal symptoms, sweating) and PDQ-39 (mobility, bodily discomfort, communication) improved significantly. BP should be monitored during initiation of DLI because of the risk of orthostatic hypotension. Our results indicate that DLI improves both motor and non-motor symptoms in patients with advanced PD.

Polyneuropathy while on duodenal levodopa infusion in Parkinson’s disease patients: we must be alert

Some reports have emerged describing the occurrence of Guillain-Barré syndrome and polyneuropathy related to vitamin B(12) deficiency in some patients with Parkinson's disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B(12) deficiency while on treatment with duodenal levodopa infusion, review other cases reported in the literature, discuss potential etiologic factors, and suggest a possible algorithm for the management and prevention of this complication. One case of Guillain-Barré syndrome and at least 12 cases of polyneuropathy related to vitamin B(12) deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B(12) levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of L: -dopa, abnormal L: -dopa absorption, and direct neurotoxicity of L: -dopa at high doses. Vitamin B(12) supplementation may need to be considered in PD patients on duodenal levodopa infusion therapy. Vitamin B(12) deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest. We must be alert.

Duodenal levodopa/carbidopa infusion therapy in patients with advanced Parkinson’s disease leads to improvement in caregivers’ stress and burden

Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson's disease (PD). However, the impact of DLI on caregivers' stress and burden has not been reported. We evaluated prospectively open-label seven advanced PD patients (65.7 ± 9.6 years, 71.4% men) treated with DLI. Schwab & England Activities of Daily Living Scale (ADLS), 39-item Parkinson's disease QoL Questionnaire Summary Index score (PDQ-39SI), Zarit Caregiver Burden Interview (ZCBI), and Caregiver Strain Index (CSI) were used. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 31.4 ± 7.9 months (range, 23-42). In patients, mean ± SD ADLS was increased from 50 ± 8.2 to 80 ± 11.6 (P = 0.014), and mean ± SD PDQ-39SI was decreased from 53.7 ± 11.9 to 33.6 ± 12.8 (P = 0.018). In caregivers, ZCBI decreased from 43 ± 13.3 to 20.7 ± 12.1 (P = 0.018) and CSI from 6.3 ± 2.5 to 1.6 ± 0.9 (P = 0.018). At baseline, 57.1% of caregivers reported moderate to severe burden (ZCBI 41-88) compared to 28.6% at the end of the follow-up (P = 0.015); at that time, no caregiver reported high level of stress (CSI ≥ 7) compared to 57.1% at baseline (P = 0.046). There were significant correlations between ZCBI and CSI improvement (r = 0.813, P = 0.026), ZCBI and PDQ-39SI (r = 0.875, P = 0.01), and ZCBI and ADLS (r = 0.813, P = 0.026). Duodenal levodopa infusion-related clinical improvement in patients with advanced PD leads to substantial reductions in caregivers' stress and burden.

The Movement Disorder Society Evidence‐Based Medicine Review Update: Treatments for the motor symptoms of Parkinson's disease

The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised to likely efficacious as symptomatic adjunct therapy. This evidence-based medicine review updates the field and highlights gaps for research.

Long-term exposure to duodenal levodopa/carbidopa infusion therapy improves quality of life in relation especially to mobility, activities of daily living, and emotional well-being

Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson's disease (PD). However, in which aspects improve the patients their QoL has been poorly documented. We evaluated 39-item Parkinson's disease Quality of Life Questionnaire Summary Index score (PDQ-39SI) changes analyzing its different domains in nine patients with advanced PD treated with DLI. All the patients (64.7 ± 11.1 years, 55.5% men) improved PDQ-39SI 6 months after beginning with DLI (29.7 ± 8.6, P = 0.008) and after median duration infusion of 25.3 ± 8.8 months (34.8 ± 11.2, P = 0.008) compared with baseline (55.6 ± 11.5). All domains except social support improved significantly at 6 months. Mobility (P = 0.012), activities of daily living (P = 0.015), and emotional well-being (P = 0.008) improved significantly at the end of the follow-up. DLI improves QoL in patients with advanced PD after short- and long-term exposure. Whereas all domains except social support improve after 6 months under DLI, only mobility, activities of daily living and emotional well-being improve significantly after long-term exposure to DLI.

Complexity of Motor Response to Different Doses of Duodenal Levodopa Infusion in Parkinson Disease

The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion. A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes. Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias. Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.

Serum vitamin B12 and folate levels in Parkinson's disease patients treated with duodenal levodopa infusion

Serum vitamin B₁₂ and folate levels in Parkinson's disease patients treated with duodenal levodopa infusion

A Pharmacokinetic-Pharmacodynamic Model for Duodenal Levodopa Infusion

The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of a levodopa/carbidopa gel (Duodopa) to examine pharmacological properties of this treatment. The modeling involved pooling data from 3 studies (on advanced Parkinson disease) and fixing some parameters to values found in literature. The first study involved 12 patients studied on 3 occasions each and was previously published. The second study involved 3 patients on 2 occasions. A bolus dose was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function on a 7-point treatment response scale ranging from "very off" to "very hyperkinetic") were collected until the clinical effect returned to baseline. The third study involved 5 patients on 3 occasions receiving 5 different dose levels. Different structural models were evaluated using the nonlinear mixed-effects modeling program NONMEM VI. Population mean parameter values, and interindividual, interoccasion, and residual variabilities were estimated. Absorption of the levodopa/carbidopa gel can be adequately described with first-order absorption with bioavailability and lag time. Estimated population parameter values were a mean absorption time of 28.5 minutes, a lag time of 2.9 minutes, and a bioavailability of 88%. The pharmacodynamic model for motor ratings had the following population values: a half-life of effect delay of 21 minutes, a concentration at 50% effect of 1.55 mg/L, an Emax of 2.39 U on the treatment response scale, and a sigmoidicity of the Emax function of 11.6. For the typical unmedicated subject, it will take 51.4 minutes until the peak levodopa effect is reached after a bolus dose. This delay is, like the magnitude of the effect, highly variable in this patient group. The residual error magnitudes of 20% for levodopa concentrations and 0.92 U (SD) for motor ratings indicate that the models developed provide predictions of a relevant quality. The developed model may be a first step toward model-guided treatment individualization of duodenal infusion of levodopa.

P2.158 Duodenal levodopa infusion improves motor symptoms and quality of life in advanced Parkinson disease: report of nine patients

P2.158 Duodenal levodopa infusion improves motor symptoms and quality of life in advanced Parkinson disease: report of nine patients

P1.229 Improvement of motor and non-motor symptoms after switching from oral therapy to continuous duodenal levodopa infusion in advanced Parkinson's disease

P1.229 Improvement of motor and non-motor symptoms after switching from oral therapy to continuous duodenal levodopa infusion in advanced Parkinson's disease

Suicide following duodenal levodopa infusion for Parkinson's disease

Suicide following duodenal levodopa infusion for Parkinson's disease