Website Edition: June/July 2009

Editor's Choice Article and Review

Movement Disorders
Volume 24 Issue 7, Pages 993-1000
Published Online February 27, 2009

Patient profile, indications, efficacy and safety of duodenal levodopa infusion in advanced Parkinson's disease
David Devos, MD, PhD, for the French DUODOPA Study Group

Abstract

The studies of duodenal infusion of a levodopa on small groups of parkinsonian patients have reported beneficial effects on motor complications. However, little is known about the patient profile and indications for duodenal levodopa infusion. The purpose of this study is to exhaustively investigate the clinical characteristics of the population and indication, efficacy and tolerability of duodenal levodopa infusion in natural care settings. Of the 102 patients treated with duodenal levodopa infusion since 2003, 91 were enrolled in a multicentre retrospective study. The mean age was 72.7 years, with average disease duration of 17 years. Patients were at advanced stage: 91% had gait disorders, 65% had visual hallucinations, and 50% were demented (MMSE: 23). Duodenal levodopa infusion was the last line of treatment for motor complications in 98% of the patients, due to failure of or contraindication for apomorphine pump and neurosurgical treatments. Long-term treatment was observed by 73% of the population. Of these, >90% reported an improvement in motor fluctuations, quality of life, and autonomy. There were few severe adverse events. Technical problems were commonplace. Duodenal levodopa infusion seems to be an effective last-line therapy for motor complications in Parkinson's disease. Hence, technical improvements and earlier introduction should be considered.

© 2009 Movement Disorder Society

Received: 7 October 2008; Revised: 17 November 2008; Accepted: 8 December 2008

Read article: HTML or PDF PDF file

Review by Angelo Antonini, MD

Download podcast audio file

Management of motor complications in advanced Parkinson's disease is often unsatisfactory while conventional therapies can only marginally control dyskinesia and wearing off. Deep brain stimulation is efficacious but its application is limited mainly by age constrains. Infusional therapies particularly with duodenal levodopa represent potentially a good alternative for many patients. However, current experience is limited since the European Medicines Agency (EMEA) approved this procedure only four years ago while a trial is underway for reimbursement in North America.

Available clinical studies have demonstrated that duodenal levodopa infusion is associated with significantly better outcome compared to conventional treatment regarding global functioning, ability to walk, "off" time and most importantly dyskinesia. This is achieved without significant changes to the total daily levodopa dose but rather by a modification in its administration pattern (from pulstile to continuous). Pharmacological adverse events profile of duodenal is similar to that observed with oral levodopa although problems like dislocation of the intestinal tube or related to the percutaneous gastrostomy are not uncommon. Effects involve also non-motor symptoms that were associated with improvements in quality of life (PDQ-8). Nonetheless, clinical characteristics of suitable patients and indication are still debated.

In a recent issue of the Movement Disorders Journal Devos and his colleagues of the French Duodopa Study Group reported their experience from 102 PD patients who were treated with duodopa in France since 2003. Ninety-one patients from 24 centers were enrolled in a retrospective study. Treated patients (mean age was 72.7 with average disease duration of 17 years) were at advanced stage: 91% had gait disorders, 65% had visual hallucinations and 50% were demented. Duodenal levodopa infusion was last line treatment for motor complications in 98% of the patients, due to failure of or contraindication for apomorphine pump and neurosurgical treatments. Consistently with other studies more than 90% reported an improvement in motor fluctuations and experienced a higher quality of life and more autonomy. Adverse events (2.2% of psychosis induction and 4.3% of peritonitis) but technical problems were frequent.

While these results are important since represent the first report of experience in a large number of non-selected clinical neurology centers. Main weakness is that observations were also sampled at different time points from infusion initiation. Moreover, given the retrospective nature of these assessments and the use of questionnaire for data collection, this was not ideal to assess safety. Nonetheless the finding of significant clinical benefit in these patients led the authors to conclude that earlier introduction should be considered.

While the main indication for duodenal levodopa infusion remains control of motor complications inadequately managed by oral therapy, results from another study reently published online in MDJ indicate that non-motor symptoms might also be part of the indication for levodopa-based continuous dopaminergic stimulation.

References:
Nyholm D et al Neurology 2005
Antonini A et al Mov Disord 2007
Devos et al Mov Disord 2009
Honig H et al Mov Disord 2009

Angelo Antonini
Parkinson Institute Milan, Italy

Angelo AntoniniAbout Angelo Antonini, MD
Professor Antonini was born in Foligno (Perugia, Italy) on August 2, 1961.
From 1980 to 1986 he studied medicine at the University "La Sapienza" in Rome, Italy
In October 1986 graduated in Medicine with honors discussing a thesis on: Continuous subcutaneous lisuride infusion in patients with Parkinson's disease promoted by Professor Alessandro Agnoli.
From 1986 to 1990 he trained in Neurology at the Neurology Department of the University "La Sapienza" in Rome, Italy.
In November 1990 he was boarded in Neurology with honors and discussed a thesis on: Dopamine D2 receptor density in healthy subjects and patients with Parkinson's disease measured with PET and the tracer [11C]raclopride promoted by Professor Alessandro Agnoli.
From November 1990 to June 1991 he was a visiting fellow at the PET Department Paul Scherrer Institute, Villigen, Switzerland on a grant of the Italian National Council of Research.
In July 1991 he started a Ph.D. program in Neuroradiology at the Paul Scherrer Institute, Villigen, Switzerland under the supervision of Professor Klaus Leenders.
In February 1994 he discussed his Ph.D. thesis in Neuroradiology at the University Hospital in Zurich, Switzerland entitled: Dopamine D2 receptors and T2 relaxation time in Parkinson's disease. A study with PET and Magnetic Resonance Imaging (MRI) promoted by Professor A.Valavanis.
From March 1994 to September 1995 he worked as research assistant in neurology and neuroimaging at the Paul Scherrer Institute and University Hospital of Zurich under the direction of Professor K.L. Leenders.
In October 1995 he joined the Neuroimaging laboratories at the Department of Neurology of North Shore University Hospital in NY, USA directed by Professor D. Eidelberg.
Starting November 1995 he was promoted Assistant Professor of Neurology at the New York University, NY, USA In 1995 he received the first award from the National Parkinson Foundation for "young researchers in Parkinson's disease". In 1996 he was awarded the Junior Faculty Award 1996/97 from United Parkinson Foundation and Parkinson's Disease Foundation for his research in the field of Parkinson's disease.
In November 1997 he joined the Parkinson Institute in Milan, Italy. He is now medical coordinator for Information Technology and Clinical Research at the Department of Neuroscience of the Hospital "Istituti Clinici di Perfezionamento" in Milan, Italy. He is also aggregate Professor of Neurology at the University of Milan-Bicocca.
During his academic career Dr. Antonini has published over 150 peer-reviewed full manuscripts, over 200 abstracts and several book chapters. He has also been applicant and principal investigator in several grants both in Switzerland and in the USA. He serves as reviewer for the main neurology journals and for the Editorial Board of Movement Disorders.