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Dyskinesias during levodopa–carbidopa intestinal gel (LCIG) infusion: Management inclinical practice
Parkinsonism and Related Disorders xxx (2015) 1e2
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice The continuous levodopaecarbidopa intestinal gel (LCIG) infusion is a valid alternative for motor control in advanced Parkinson's disease (PD). It has been demonstrated to improve motor fluctuation with a global increase in ON-time, generally without the outbreak of troublesome hyperkinesias [1]. However both peakdose and biphasic dyskinesias are observed in patients undergoing LCIG treatment. Here is reported our experience with a PD patient, whose LCIG treatment was challenged by the outbreak of peculiar dyskinesiasfollowingthe PEG-J-tube bedtime flushing. A 73 yearsold woman was affected by advanced PD with motor fluctuations. Because of her extreme susceptibility to develop dyskinesias even with very small doses of levodopa (otherwise defined as “brittle response” [2]), the maximum acceptable oral treatment was of 475 mg fractionated in 9 small doses a day. APEG-J was inserted and LCIG therapy was started in order to obtain a lower and more stable therapeutic regimen. A significant reduction of the OFFperiods and of the dyskinesias were obtained through a LCIG titration of the morning dose to1.5 ml (30 mg of levodopa), of the continuous dose to 1.0 ml (20 mg) per hour per 16 h a day (total dose of 350 mg) and of the extra-doses to 1.0 ml (20 mg). Nevertheless, at the end of the daily treatment, the mandatory operation of flushing the PEG-J-tube after pump disconnection [3] resulted in stereotypical violent peak-dose choreo-dystonic hyperkinesias that required patient protections to prevent disastrous falls. The tube cleaning led to the immediate delivery of the 3 ml (60 mg) of levodopa-gel contained in the device. Unfortunately the patient was highly sensitive to levodopa; so much that extra-doses have to be set at 1 ml (20 mg) per dose. LCIG pump turning off may result in biphasic dyskinesias due to the incipient discontinuation of the levodopa effect; in this case the simple interruption of the infusion did not lead to any dyskinesia contrary to what was observed after bedtime tube cleaning. In fact through the flushing the patient received extra 60 mg of levodopa gel, that is three times the dose needed to overcome OFF-period, resulting in violent peak-dose dyskinesias. Levodopa gel is contained in a reservoir bag inside a hard plastic cassette. A used reservoir bag was cleaned out from residual gel through a solution of diluted ethyl alcohol delivered through a syringe connected to the cassette tube, and later rinsed with room temperature tap water. Then, the cassette was connected to the tube and the water was administered at usual maintenance dose (1 ml/h), so that it could slowly push the column of levodopa gel contained in the tube. After 3 h, water completely replaced the gel in the tube, and cleaning operations could be easily performed without the risk of delivering a high bolus of levodopa
and, consequently, without dyskinesias. The infusion time necessary to completely replace the gel in the PEG-J-tube with water can be easily calculated as follow: PEG-J-tube volume (3 ml) ÷ maintenance velocity (in our case 1 ml per hour). In this way, it is possible to determine the exact time when the original cassette should be substituted with the water-filled one; eventually, at bedtime the tube might be flushed without complications. The suggested procedure may represent a reliable solution for a previously unmet need in LCIG management. However, since it is not approved by medical authorities further studies are needed to validate the technique. As in this case, ordinary procedures (e.g. tube washout) have to be suited on patient features (e.g. levodopa sensitivity and brittle response); otherwise they may become problematic, undermining patient's and caregiver's compliance. Sharing technical tips would be useful to the movement disorder specialist in gain expertise and avoid unnecessary LCIG patient dropout. Funding sources and conflict of interest None. Financial disclosures None. Author roles All authors contributed equally to the project.
Acknowledgment None.
References [1] Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, et al., LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopacarbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014;13: 141e9. [2] Martinez-Ramirez D, Giugni J, Vedam-Mai V, Shukla AW, Malaty IA, McFarland NR, et al. The “brittle response” to Parkinson's disease medications: characterization and response to deep brain stimulation. PLoS One 2014;9: e94856.
http://dx.doi.org/10.1016/j.parkreldis.2014.12.023 1353-8020/© 2015 Published by Elsevier Ltd.
Please cite this article in press as: Melgari J-M, et al., Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice, Parkinsonism and Related Disorders (2015), http://dx.doi.org/10.1016/j.parkreldis.2014.12.023
2
Letter to the Editor / Parkinsonism and Related Disorders xxx (2015) 1e2
[3] Pedersen SW, Clausen J, Gregerslund MM. Practical guidance on how to handle levodopa/carbidopa intestinal gel therapy of advanced PD in a movement disorder clinic. Open Neurol J 2012;6:37e50.
Federica Scrascia Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Jean-Marc Melgari* Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Neurology, Treviglio Hospital, Treviglio, Bergamo, Italy
Neurology, Treviglio Hospital, Treviglio, Bergamo, Italy Gaetano Salomone, Lazzaro di Biase, Massimo Marano Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Vincenzo Di Lazzaro Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy *
Corresponding author. Tel.: þ39 06 225411220; fax: þ39 06 225411955. E-mail address: [email protected] (J.-M. Melgari). 27 October 2014
Please cite this article in press as: Melgari J-M, et al., Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice, Parkinsonism and Related Disorders (2015), http://dx.doi.org/10.1016/j.parkreldis.2014.12.023
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice The continuous levodopaecarbidopa intestinal gel (LCIG) infusion is a valid alternative for motor control in advanced Parkinson's disease (PD). It has been demonstrated to improve motor fluctuation with a global increase in ON-time, generally without the outbreak of troublesome hyperkinesias [1]. However both peakdose and biphasic dyskinesias are observed in patients undergoing LCIG treatment. Here is reported our experience with a PD patient, whose LCIG treatment was challenged by the outbreak of peculiar dyskinesiasfollowingthe PEG-J-tube bedtime flushing. A 73 yearsold woman was affected by advanced PD with motor fluctuations. Because of her extreme susceptibility to develop dyskinesias even with very small doses of levodopa (otherwise defined as “brittle response” [2]), the maximum acceptable oral treatment was of 475 mg fractionated in 9 small doses a day. APEG-J was inserted and LCIG therapy was started in order to obtain a lower and more stable therapeutic regimen. A significant reduction of the OFFperiods and of the dyskinesias were obtained through a LCIG titration of the morning dose to1.5 ml (30 mg of levodopa), of the continuous dose to 1.0 ml (20 mg) per hour per 16 h a day (total dose of 350 mg) and of the extra-doses to 1.0 ml (20 mg). Nevertheless, at the end of the daily treatment, the mandatory operation of flushing the PEG-J-tube after pump disconnection [3] resulted in stereotypical violent peak-dose choreo-dystonic hyperkinesias that required patient protections to prevent disastrous falls. The tube cleaning led to the immediate delivery of the 3 ml (60 mg) of levodopa-gel contained in the device. Unfortunately the patient was highly sensitive to levodopa; so much that extra-doses have to be set at 1 ml (20 mg) per dose. LCIG pump turning off may result in biphasic dyskinesias due to the incipient discontinuation of the levodopa effect; in this case the simple interruption of the infusion did not lead to any dyskinesia contrary to what was observed after bedtime tube cleaning. In fact through the flushing the patient received extra 60 mg of levodopa gel, that is three times the dose needed to overcome OFF-period, resulting in violent peak-dose dyskinesias. Levodopa gel is contained in a reservoir bag inside a hard plastic cassette. A used reservoir bag was cleaned out from residual gel through a solution of diluted ethyl alcohol delivered through a syringe connected to the cassette tube, and later rinsed with room temperature tap water. Then, the cassette was connected to the tube and the water was administered at usual maintenance dose (1 ml/h), so that it could slowly push the column of levodopa gel contained in the tube. After 3 h, water completely replaced the gel in the tube, and cleaning operations could be easily performed without the risk of delivering a high bolus of levodopa
and, consequently, without dyskinesias. The infusion time necessary to completely replace the gel in the PEG-J-tube with water can be easily calculated as follow: PEG-J-tube volume (3 ml) ÷ maintenance velocity (in our case 1 ml per hour). In this way, it is possible to determine the exact time when the original cassette should be substituted with the water-filled one; eventually, at bedtime the tube might be flushed without complications. The suggested procedure may represent a reliable solution for a previously unmet need in LCIG management. However, since it is not approved by medical authorities further studies are needed to validate the technique. As in this case, ordinary procedures (e.g. tube washout) have to be suited on patient features (e.g. levodopa sensitivity and brittle response); otherwise they may become problematic, undermining patient's and caregiver's compliance. Sharing technical tips would be useful to the movement disorder specialist in gain expertise and avoid unnecessary LCIG patient dropout. Funding sources and conflict of interest None. Financial disclosures None. Author roles All authors contributed equally to the project.
Acknowledgment None.
References [1] Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, et al., LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopacarbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014;13: 141e9. [2] Martinez-Ramirez D, Giugni J, Vedam-Mai V, Shukla AW, Malaty IA, McFarland NR, et al. The “brittle response” to Parkinson's disease medications: characterization and response to deep brain stimulation. PLoS One 2014;9: e94856.
http://dx.doi.org/10.1016/j.parkreldis.2014.12.023 1353-8020/© 2015 Published by Elsevier Ltd.
Please cite this article in press as: Melgari J-M, et al., Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice, Parkinsonism and Related Disorders (2015), http://dx.doi.org/10.1016/j.parkreldis.2014.12.023
2
Letter to the Editor / Parkinsonism and Related Disorders xxx (2015) 1e2
[3] Pedersen SW, Clausen J, Gregerslund MM. Practical guidance on how to handle levodopa/carbidopa intestinal gel therapy of advanced PD in a movement disorder clinic. Open Neurol J 2012;6:37e50.
Federica Scrascia Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Jean-Marc Melgari* Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Neurology, Treviglio Hospital, Treviglio, Bergamo, Italy
Neurology, Treviglio Hospital, Treviglio, Bergamo, Italy Gaetano Salomone, Lazzaro di Biase, Massimo Marano Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
Vincenzo Di Lazzaro Institute of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy *
Corresponding author. Tel.: þ39 06 225411220; fax: þ39 06 225411955. E-mail address: [email protected] (J.-M. Melgari). 27 October 2014
Please cite this article in press as: Melgari J-M, et al., Dyskinesias during levodopaecarbidopa intestinal gel (LCIG) infusion: Management inclinical practice, Parkinsonism and Related Disorders (2015), http://dx.doi.org/10.1016/j.parkreldis.2014.12.023