- Email: [email protected]
carbidopa intestinal gel
Parkinsonism and Related Disorders xxx (2017) 1e3
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Correspondence
Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel
Keywords: Parkinson's disease Levodopa/carbidopa intestinal gel Swallowing Nutrition Dysphagia Percutaneous endoscopic gastrostomy
1. Introduction Levodopa/carbidopa intestinal gel (LCIG) is delivered continuously to the small intestine by an intrajejunal extension tube (jtube) placed through a percutaneous endoscopic gastrostomy (PEG) [1]. While j-tube delivers LCIG, the PEG tube is not used although theoretically it might be utilized for enteral nutrition in patients with dysphagia. Here, we describe the successful use of PEG-J tube for enteral feeding in two patients with Parkinson's disease (PD) also treated with LCIG. 2. Case reports Patient 1 is a 73-year-old male with PD for 20 years. He underwent bilateral subthalamic deep brain stimulation (DBS) at age 60 with improvement of motor fluctuations and dyskinesias. Eight years later, the electrodes were removed due to hardware-related infection, which resulted in significant worsening of motor symptoms, unresponsive to unilateral pedunculopontine DBS. Due to severe dysphagia, he underwent PEG (20 Fr) placement for enteral feeding at age 72. One year later, as a result of severe motor fluctuations, the 9 Fr-jejunal extension used for LCIG delivery was inserted through the second lumen of the PEG (Fig. 1). LCIG therapy was started with remarkable clinical improvement. Enteral nutrition was administered three to four times during the day and continuously overnight. The levodopa equivalent daily dose (LEDD) [2] prior to LCIG was 2695 mg/day and was slowly increased to 3188 mg/day within six months. He continued enteral feeding and LCIG with benefit until he developed pneumonia and died at age 75 (final LEDD of 3628 mg/day). During the follow-up period, PEG-J was changed once, after 12 months, and there were no device related complications. Patient 2 is a 79-year-old male with PD for 17 years. He underwent bilateral motor cortex stimulation at age 73 with slight improvement of motor symptoms. Two years later, he suffered
from aspiration pneumonia requiring hospitalization and antibiotic treatments. In light of both severe dysphagia with signs of malnutrition and unpredictable motor fluctuations, he underwent PEG-J placement for LCIG infusion. Concomitantly, we used the gastric port for 24-h infusion of enteral nutrition (Fig. 1). Before LCIG treatment LEDD was 2296 mg/day, reduced to 1936 mg/day within six months. LCIG produced an overall clinical improvement including swallowing function. After two years, due to the progressive increase of oral caloric intake, enteral feeding was reduced and administered continuously and exclusively overnight. Four years after LCIG initiation, LEDD was 2718 mg/day. During the follow-up period, PEG-J was changed twice, after 24 and 36 months; there were no device related complications.
3. Discussion Dysphagia is common in PD patients and increases the risk of aspiration pneumonia, which is a major cause of death in PD. These two cases show that e although off-label e PEG-J used for LCIG treatment can also be a viable route for enteral nutrition in PD patients with dysphagia, and e off-label too e existing PEGs primarily used for enteral nutrition can be adapted to deliver LCIG. An important issue for enteral feeding through the gastric port is the reduction of its lumen caliber due to the presence of the j-tube. In our patients there were no device-related complications, in particular PEG-J was replaced at rates similar to those reported in a recent Italian multicenter survey [3], ruling out the hypothesis of a faster deterioration of PEG-J with enteral feeding. Another issue is the impact of enteral feeding on the efficacy of LCIG treatment, as the continuous infusion of nutrition could interfere with levodopa absorption by competing with amino-acid carriers at the level of enterocytes and blood-brain barrier [4]. Patient 1 underwent a significant increase of LEDD after LCIG, possibly related to the poor control of PD-related symptoms. Conversely, patient 2 underwent a LEDD reduction after LCIG. Continuous administration of nutrition overnight and LCIG during the day might represent a strategy to avoid the interaction between levodopa and nutrition in patients who experience worsening of motor symptoms with continuous enteral feeding. On the other hand, levodopa might interfere with the absorption of B vitamins, delivered as part of enteral nutrition [5]. Hence, serial clinicalelectrophysiological evaluations are mandatory in these patients, given the possible risk of peripheral neuropathy, and continuous administration of nutrition overnight might be evaluated to minimize the interaction between levodopa and vitamins absorption. In conclusion, our experience emphasizes a potential advantage of PEG-J to guarantee both nutrition and management of PD
http://dx.doi.org/10.1016/j.parkreldis.2017.06.015 1353-8020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015
2
Correspondence / Parkinsonism and Related Disorders xxx (2017) 1e3
Fig. 1. Left panel: the jejunal extension used for LCIG delivery was inserted through the second lumen of the PEG; the first lumen was already used for enteral nutrition. Right panel: the PEG-J currently used for LCIG continuous infusion has two ports: a jejunal port (9 Fr) used for LCIG and a gastric port (20 Fr) that is not usually utilized but it is here used for continuous infusion of enteral nutrition.
fluctuations. The current PEG-J used for LCIG is not designed for enteral feeding, therefore devices featuring ports with different calibers may be of value in the future.
Documentation of author roles Francesco Bove: substantial contributions to the acquisition of data; drafting the article; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Anna Rita Bentivoglio: substantial contributions to the analysis and interpretation of data, revising the article critically for important intellectual content, final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Taline Naranian: substantial contributions to the acquisition of data; drafting the article; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Alfonso Fasano: substantial contributions to the conception and design of the study; revising the article critically for important intellectual content; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
Funding None related to this study.
Conflict of interest Francesco Bove declare no conflict of interest. Anna Rita Bentivoglio received research funding and speaker's honoraria by Chiesi Pharmaceuticals, Merz, Allergan, Ipsen, Medtronic, Abbvie. Taline Naranian received speaker's honoraria by Abbvie. Alfonso Fasano received grant support from Weston Foundation, McLaughlin Centre, the University of Toronto and the Michael J. Fox Foundation; he received speaking honoraria from Abbvie, Medtronic, Boston Scientific, Chiesi, Ipsen, UCB pharma and Novartis; he received royalty for “Disorders of Movement” book by Springer; he is in an advisory board for Abbvie, Boston Scientific and Ipsen Canada, and provided consultancies and experted testimony for Medtronic, Boston Scientific and Abbvie.
References [1] C.W. Olanow, K. Kieburtz, P. Odin, A.J. Espay, D.G. Standaert, H.H. Fernandez, A. Vanagunas, A.A. Othman, K.L. Widnell, W.Z. Robieson, Y. Pritchett, K. Chatamra, J. Benesh, R.A. Lenz, A. Antonini, LCIG Horizon Study Group, Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, doubleblind, double-dummy study, Lancet Neurol. 13 (2014) 141e149. [2] C.L. Tomlinson, R. Stowe, S. Patel, C. Rick, R. Gray, C.E. Clarke, Systematic review of levodopa dose equivalency reporting in Parkinson's disease, Mov. Disord. 25 (2010) 2649e2653. [3] M. Sensi, G. Cossu, F. Mancini, M. Pilleri, M. Zibetti, N. Modugno, N. Modugno, R. Quatrale, F. Tamma, A. Antonini, Italian Levodopa Carbidopa Intestinal Gel Working Group, Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with longterm follow-up, Park. Relat. Disord. 38 (2017) 90e92. [4] M.K. Cooper, D.G. Brock, C.M. McDaniel, Interaction between levodopa and enteral nutrition, Ann. Pharmacother. 42 (2008) 439e442. [5] A. Merola, A. Romagnolo, M. Zibetti, A. Bernardini, D. Cocito, L. Lopiano, Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a longterm prospective assessment, Eur. J. Neurol. 23 (2016) 501e509.
Francesco Bove Cattolica del Sacro Cuore, Institute of Neurology, Universita Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy Anna Rita Bentivoglio Cattolica del Sacro Cuore, Institute of Neurology, Universita Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy Don Gnocchi Foundation, Milan, Italy
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015
Correspondence / Parkinsonism and Related Disorders xxx (2017) 1e3
Taline Naranian Morton and Gloria Shulman Movement Disorders Centre and The Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada Alfonso Fasano* Morton and Gloria Shulman Movement Disorders Centre and The Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
3
Krembil Research Institute, Toronto, Ontario, Canada *
Corresponding author. Division of Neurology, University of Toronto, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst St, 7 Mc412, Toronto, ON M5T 2S8, Canada. E-mail address: [email protected] (A. Fasano). 7 May 2017
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Correspondence
Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel
Keywords: Parkinson's disease Levodopa/carbidopa intestinal gel Swallowing Nutrition Dysphagia Percutaneous endoscopic gastrostomy
1. Introduction Levodopa/carbidopa intestinal gel (LCIG) is delivered continuously to the small intestine by an intrajejunal extension tube (jtube) placed through a percutaneous endoscopic gastrostomy (PEG) [1]. While j-tube delivers LCIG, the PEG tube is not used although theoretically it might be utilized for enteral nutrition in patients with dysphagia. Here, we describe the successful use of PEG-J tube for enteral feeding in two patients with Parkinson's disease (PD) also treated with LCIG. 2. Case reports Patient 1 is a 73-year-old male with PD for 20 years. He underwent bilateral subthalamic deep brain stimulation (DBS) at age 60 with improvement of motor fluctuations and dyskinesias. Eight years later, the electrodes were removed due to hardware-related infection, which resulted in significant worsening of motor symptoms, unresponsive to unilateral pedunculopontine DBS. Due to severe dysphagia, he underwent PEG (20 Fr) placement for enteral feeding at age 72. One year later, as a result of severe motor fluctuations, the 9 Fr-jejunal extension used for LCIG delivery was inserted through the second lumen of the PEG (Fig. 1). LCIG therapy was started with remarkable clinical improvement. Enteral nutrition was administered three to four times during the day and continuously overnight. The levodopa equivalent daily dose (LEDD) [2] prior to LCIG was 2695 mg/day and was slowly increased to 3188 mg/day within six months. He continued enteral feeding and LCIG with benefit until he developed pneumonia and died at age 75 (final LEDD of 3628 mg/day). During the follow-up period, PEG-J was changed once, after 12 months, and there were no device related complications. Patient 2 is a 79-year-old male with PD for 17 years. He underwent bilateral motor cortex stimulation at age 73 with slight improvement of motor symptoms. Two years later, he suffered
from aspiration pneumonia requiring hospitalization and antibiotic treatments. In light of both severe dysphagia with signs of malnutrition and unpredictable motor fluctuations, he underwent PEG-J placement for LCIG infusion. Concomitantly, we used the gastric port for 24-h infusion of enteral nutrition (Fig. 1). Before LCIG treatment LEDD was 2296 mg/day, reduced to 1936 mg/day within six months. LCIG produced an overall clinical improvement including swallowing function. After two years, due to the progressive increase of oral caloric intake, enteral feeding was reduced and administered continuously and exclusively overnight. Four years after LCIG initiation, LEDD was 2718 mg/day. During the follow-up period, PEG-J was changed twice, after 24 and 36 months; there were no device related complications.
3. Discussion Dysphagia is common in PD patients and increases the risk of aspiration pneumonia, which is a major cause of death in PD. These two cases show that e although off-label e PEG-J used for LCIG treatment can also be a viable route for enteral nutrition in PD patients with dysphagia, and e off-label too e existing PEGs primarily used for enteral nutrition can be adapted to deliver LCIG. An important issue for enteral feeding through the gastric port is the reduction of its lumen caliber due to the presence of the j-tube. In our patients there were no device-related complications, in particular PEG-J was replaced at rates similar to those reported in a recent Italian multicenter survey [3], ruling out the hypothesis of a faster deterioration of PEG-J with enteral feeding. Another issue is the impact of enteral feeding on the efficacy of LCIG treatment, as the continuous infusion of nutrition could interfere with levodopa absorption by competing with amino-acid carriers at the level of enterocytes and blood-brain barrier [4]. Patient 1 underwent a significant increase of LEDD after LCIG, possibly related to the poor control of PD-related symptoms. Conversely, patient 2 underwent a LEDD reduction after LCIG. Continuous administration of nutrition overnight and LCIG during the day might represent a strategy to avoid the interaction between levodopa and nutrition in patients who experience worsening of motor symptoms with continuous enteral feeding. On the other hand, levodopa might interfere with the absorption of B vitamins, delivered as part of enteral nutrition [5]. Hence, serial clinicalelectrophysiological evaluations are mandatory in these patients, given the possible risk of peripheral neuropathy, and continuous administration of nutrition overnight might be evaluated to minimize the interaction between levodopa and vitamins absorption. In conclusion, our experience emphasizes a potential advantage of PEG-J to guarantee both nutrition and management of PD
http://dx.doi.org/10.1016/j.parkreldis.2017.06.015 1353-8020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015
2
Correspondence / Parkinsonism and Related Disorders xxx (2017) 1e3
Fig. 1. Left panel: the jejunal extension used for LCIG delivery was inserted through the second lumen of the PEG; the first lumen was already used for enteral nutrition. Right panel: the PEG-J currently used for LCIG continuous infusion has two ports: a jejunal port (9 Fr) used for LCIG and a gastric port (20 Fr) that is not usually utilized but it is here used for continuous infusion of enteral nutrition.
fluctuations. The current PEG-J used for LCIG is not designed for enteral feeding, therefore devices featuring ports with different calibers may be of value in the future.
Documentation of author roles Francesco Bove: substantial contributions to the acquisition of data; drafting the article; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Anna Rita Bentivoglio: substantial contributions to the analysis and interpretation of data, revising the article critically for important intellectual content, final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Taline Naranian: substantial contributions to the acquisition of data; drafting the article; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Alfonso Fasano: substantial contributions to the conception and design of the study; revising the article critically for important intellectual content; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
Funding None related to this study.
Conflict of interest Francesco Bove declare no conflict of interest. Anna Rita Bentivoglio received research funding and speaker's honoraria by Chiesi Pharmaceuticals, Merz, Allergan, Ipsen, Medtronic, Abbvie. Taline Naranian received speaker's honoraria by Abbvie. Alfonso Fasano received grant support from Weston Foundation, McLaughlin Centre, the University of Toronto and the Michael J. Fox Foundation; he received speaking honoraria from Abbvie, Medtronic, Boston Scientific, Chiesi, Ipsen, UCB pharma and Novartis; he received royalty for “Disorders of Movement” book by Springer; he is in an advisory board for Abbvie, Boston Scientific and Ipsen Canada, and provided consultancies and experted testimony for Medtronic, Boston Scientific and Abbvie.
References [1] C.W. Olanow, K. Kieburtz, P. Odin, A.J. Espay, D.G. Standaert, H.H. Fernandez, A. Vanagunas, A.A. Othman, K.L. Widnell, W.Z. Robieson, Y. Pritchett, K. Chatamra, J. Benesh, R.A. Lenz, A. Antonini, LCIG Horizon Study Group, Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, doubleblind, double-dummy study, Lancet Neurol. 13 (2014) 141e149. [2] C.L. Tomlinson, R. Stowe, S. Patel, C. Rick, R. Gray, C.E. Clarke, Systematic review of levodopa dose equivalency reporting in Parkinson's disease, Mov. Disord. 25 (2010) 2649e2653. [3] M. Sensi, G. Cossu, F. Mancini, M. Pilleri, M. Zibetti, N. Modugno, N. Modugno, R. Quatrale, F. Tamma, A. Antonini, Italian Levodopa Carbidopa Intestinal Gel Working Group, Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with longterm follow-up, Park. Relat. Disord. 38 (2017) 90e92. [4] M.K. Cooper, D.G. Brock, C.M. McDaniel, Interaction between levodopa and enteral nutrition, Ann. Pharmacother. 42 (2008) 439e442. [5] A. Merola, A. Romagnolo, M. Zibetti, A. Bernardini, D. Cocito, L. Lopiano, Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a longterm prospective assessment, Eur. J. Neurol. 23 (2016) 501e509.
Francesco Bove Cattolica del Sacro Cuore, Institute of Neurology, Universita Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy Anna Rita Bentivoglio Cattolica del Sacro Cuore, Institute of Neurology, Universita Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy Don Gnocchi Foundation, Milan, Italy
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015
Correspondence / Parkinsonism and Related Disorders xxx (2017) 1e3
Taline Naranian Morton and Gloria Shulman Movement Disorders Centre and The Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada Alfonso Fasano* Morton and Gloria Shulman Movement Disorders Centre and The Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
3
Krembil Research Institute, Toronto, Ontario, Canada *
Corresponding author. Division of Neurology, University of Toronto, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst St, 7 Mc412, Toronto, ON M5T 2S8, Canada. E-mail address: [email protected] (A. Fasano). 7 May 2017
Please cite this article in press as: F. Bove, et al.Enteral feeding in Parkinson's patients receiving levodopa/carbidopa intestinal gel, Parkinsonism and Related Disorders (2017), http://dx.doi.org/10.1016/j.parkreldis.2017.06.015