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Intrajejunal Levodopa Infusion in Advanced Parkinson's Disease

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Intrajejunal Levodopa Infusion in Advanced Parkinson's Disease European Review for Medical and Pharmacological Sciences 2012; 16: 79-89 Intrajejunal levodopa infusion in advanced Parkinson’s disease: long-term effects on motor and non-motor symptoms and impact on patient’s and caregiver’s quality of life A. FASANO1,2, L. RICCIARDI1,3, F. LENA4, A.R. BENTIVOGLIO1, N. MODUGNO4 1Department of Neurology, School of Medicine, Catholic University of the Sacred Heart, Rome (Italy) 2Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Rome (Italy) 3Department of Neurosciences, Psychiatry and Anesthesiologic Sciences, University of Messina, Messina (Italy) 4Neuromed Institute, Pozzilli (IS) (Italy) Abstract. – Background: Continuous in- Conclusions: CIILG is an effective treatment fusion of intrajejunal levodopa/carbidopa gel option for patients with advanced PD over the (CIILG) for advanced Parkinson’s disease (PD) long-term period as it may improve both the mo- has been proved to be beneficial on motor com- tor complications and the psychiatric side ef- plications, non-motor symptoms and quality of fects caused by other dopaminergic therapies. life in the short-term follow-up. Key Words: Aim of this two-center, retrospective, open-la- bel study was to evaluate the long-term effect of Non-motor symptoms, Intrajejunal levodopa, CIILG on patients’ condition and caregivers’ Parkinson’s disease, Quality of life, Caregiver. quality of life. Materials and Methods: The assessments (performed at baseline and at latest follow-up available after CIILG) included: the unified PD rating scale (UPDRS I-IV), the non-motor symp- toms scale (NMSS), the PD questionnaire (PDQ- 8), the PD sleep scale (PDSS), and a battery as- Introduction sessing the cognitive and psychiatric status as well as caregiver’s quality of life. Medications Only recently non-motor symptoms (NMS) of were expressed as levodopa equivalent daily Parkinson’s disease (PD) have been well recog- dose (LEDD). nized as important features of the disease, receiv- Results: 14 advanced PD patients (age: ing greater attention than in the past1,2. NMS can 67.0±11.5 years, disease duration: 12.9±4.8 years) were followed for 24.9±14.4 months after be present in every stage of the disease and can CIILG. Total LEDD was unchanged at follow-up, be even more troublesome than the classical mo- however therapy was globally simplified by re- tor parkinsonian symptoms as they contribute to ducing dopamine agonists (DAs). A statistically disability and to the worsening of quality of life significant beneficial effect was shown on motor (QoL) of both patients and caregivers. Moreover, complications while the severity of motor symp- several studies have shown that NMS have great toms did not change over time. A significant im- significance when analysed in terms of institu- provement of depressive symptoms and psychi- 3,4 atric side effects caused by DAs was detected. tionalisation rates and health economics . Sleep quality and diurnal somnolence ameliorat- NMS are directly related to the widespread ed as revealed by the significant reduction of dopaminergic and non-dopaminergic neurode- PDDS. Caregivers’ stress and patients’ quality of generation associated with PD1. Therefore, they life were not significantly improved. However, play an important role especially in the advanced when categorized according to their outcome, stages of the disease. Advanced PD is not only patients with improvement of motor condition and functionality gained an improvement of an economic issue but it also leads to important quality of life. Apart from the severity of motor social consequences. In fact, as any chronic dis- impairment at baseline, no other predicting fac- ease, PD may impair the QoL and social func- tors were detected. tioning of caregivers and their entire family5. Corresponding Author: Alfonso Fasano, MD, Ph.D.; e-mail: [email protected] 79 A. Fasano, L. Ricciardi, F. Lena, A.R. Bentivoglio, N. Modugno Continuous intrajejunal infusion of levodopa/ those patients with severe nocturnal akinesia lim- carbidopa gel (CIILG – Duodopa®, Abbott Prod- iting sleep (Table I). Patients gave informed con- ucts GmbH) is a novel strategy for the treatment sent before undergoing CIILG procedures. of motor complications in advanced PD as it pro- vides more stable levodopa plasma concentra- Assessments and Analysis tions compared to oral therapy6. Several clinical All the assessments were completed at base- studies have shown that CIILG reduces off time line before the initiation of CIILG and at the lat- and dyskinesia severity and duration in advanced est available follow-up (Table I). Clinical and de- PD7-9. More recent studies have also addressed mographical data were collected and therapy was the effects of CIILG on QoL10 and NMS11, over- expressed in terms of Levodopa Equivalent Daily all showing positive results in the short-term fol- Dose (LEDD)14. Motor condition and complica- low-up. tions (fluctuation and dyskinesias) were investi- Aim of the present study was to evaluate the gated by means of the sections III and IV of the long-term effects of CIILG treatment on motor Unified Parkinson’s Disease Rating Scale (UP- complications, NMS and QoL in a cohort of PD DRS)15, axial motor impairment was assessed by patients. Moreover, we explored the features pos- means of the Gait and Falls Questionnaire sibly predicting the long-term outcome. Finally, (GFQ)16. The assessment of disability, NMS and we addressed the caregiver’s burden related to QoL was carried out by means of the section II the treatment and patients’ clinical condition. of the Unified Parkinson’s Disease Rating Scale (UPDRS)15, the recently developed NMS scale (NMSS)17; the PD sleep scale (PDSS)18; the short form 8-item PD Questionnaire (PDQ-8)19, activi- Materials and Methods ties of daily living (ADL) and instrumental ADL (IADL)20. Cognitive and neuropsychiatric evalua- This was designed as a two-center, retrospec- tions were assessed by means of the section I of tive, open-label study enrolling all the consecu- the UPDRS15, the mini-mental state examination tive patients who have undergone CIILG in the (MMSE)21, Frontal Assessment Battery (FAB)22, period from April 2008 to March 2011. Inclusion the neuropsychiatric inventory (NPI)23. criteria were: a diagnosis of PD according to the Dopamine dysregulation syndrome (DDS), im- UK Brain Bank criteria12; severe motor fluctua- pulse control disorders (ICD) and punding were tions (symptomatic ‘‘off’’ and/or ‘‘on’’ periods recorded using the questionnaire for ICD in PD with troublesome dyskinesias) refractory to ma- (QUIP)24. All patients’ evaluations were per- nipulations of oral medications, rotigotine patch formed in their ‘‘best on’’ state. and/or apomorphine infusion; good levodopa re- Finally, in order to quantify the impact of PD sponsiveness. Exclusion criteria were: other de- and CIIGL on caregiver’s quality of life we asked generative or vascular parkinsonisms; dementia the nearest caregiver (generally the spouse or according to diagnostic and statistical manual of daughter) to fill out the Relative Stress Scale mental disorders (DSM-IV) criteria13; patient’s (RSS), a 15-item scale measuring three compo- refuse and patient’s or caregiver’s inability to nents of stress: personal distress, life upset and handle the pump equipment. negative feelings25. Procedures Statistical Analysis CIILG was performed in keeping with already Data were presented as mean ± standard devi- published methods7-9. Briefly, the patients were ation (SD). Paired Student’s t test was used to hospitalized and switched from their convention- compare pre- and post-CIILG assessments; un- al pharmacotherapy to CIILG gel infusion deliv- paired Student’s t test was used to compare gen- ered by a temporary nasoduodenal tube. Percuta- der-related differences and subgroups of patients neous endoscopic gastrostomy (PEG) with a jeju- categorized according to the improvement of nal tube was then performed under local anesthe- QoL after CIILG. Correlations between continu- sia. Gel infusion dose was then titrated according ous variables were explored by means of Pear- to patient’s need in the days following the hospi- son’s correlation analysis. Statistica 7.0 (StatSoft, talization and during the scheduled follow-up Tulsa, OK, USA) software was used for all statis- visits. The infusion was withdrawn during the tical analyses. All tests were two-sided with a night but it was occasionally kept for 24 hours in level of significance set at p < 0.05. 80 Table I. Demographic and clinical features of the PD patients enrolled in the study. Therapy before CIILG Therapy after CIILG Age Disease Follow-up at Age duration after N. Levodopa N. PD at at CIILG of mg/h Other of ID Gender onset CIILG CIILG (months) Medications pills/day (hours/24h) therapies pills/day 1 F 69 81 11 7 Levodopa/carbidopa 100 mg/25 mg CR; 10 84 (14) Levodopa/carbidopa 3 levodopa/carbidopa/entacapone 100 mg/25 mg/ 100 mg/25 mg CR 200 mg, melevodopa/carbidopa 100 mg/25 mg 2 M 47 54 7 23 Levodopa/carbidopa 200 mg/50 mg CR, 15 86 (24) Amantadine 100 mg, 5 Duodopa levodopa/carbidopa/entacapone 200 mg/50 mg/200 mg, clozapine 100 mg, melevodopa/carbidopa 100 mg/25 mg, tolcapone 100 mg quetiapine 200 mg, ropinirole 8 mg XL 3 M 48 61 13 42 Levodopa/benserazide 100 mg/25 mg HBS, 17 68 (24) Clozapine 100 mg, 6 levodopa/carbidopa 250 mg/25 mg, melevodopa/carbidopa ® for non-motorsymptoms pramipexole 0.7 mg, quetiapine 100 mg, 100 mg/25 mg, quetiapine 200 mg, tolcapone 100 mg tolcapone 100 mg 4 M 74 88 14 30 Entacapone 200 mg, levodopa/
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