Levodopa/carbidopa intestinal gel infusion long‐term therapy in advanced Parkinson’s disease

Background: Infusion of levodopa/carbidopa intestinal gel (Duodopa^®; Abbott) was introduced in Sweden in 1991 as an experimental treatment in advanced Parkinson’s disease and obtained EU approval in 2004. There is compelling evidence for short‐term use of this treatment; however, long‐term data are scarce. Methods: A retrospective review of medical records was performed. The primary objective was to assess the duration of treatment for all Swedish patients starting long‐term levodopa/carbidopa gel therapy between January 1991 and June 2008. Secondary aims were to study demographics, treatment with anti‐Parkinson’s disease drugs and other concomitant medications, and reasons for discontinuation of levodopa/carbidopa gel. Results: Of 150 identified patients, 135 were included in the study. On average, patients were 49 years at diagnosis of Parkinson’s disease and 63 years when infusion therapy was initiated. The median treatment time on infusion was 3.4 years (range, 0–16 years). The restricted mean treatment time was nearly 8 years; 81 patients were still on treatment at the end of the study. Levodopa was used as monotherapy in a majority of patients. Dosage of the drug was stable over time. Thirty‐one patients discontinued infusion prior to the cutoff date and 23 patients died. Device‐related problems were the most common reason for discontinuation. Patients were more likely to discontinue infusion therapy before 2000. The year of infusion initiation was significantly earlier in the dropout group compared with a matched group of continuing patients. Conclusions: Levodopa/carbidopa intestinal gel infusion is a long‐term treatment alternative in patients with advanced Parkinson’s disease.     

Economic burden of Parkinson’s disease in Singapore

Background: This study was carried out to evaluate the economic burden of Parkinson’s disease (PD) and factors independently associated with individual components of total cost in Singapore. Methods: A consecutive sample of 195 patients with PD (mean age: 68.2, men: 51.8%) attending a tertiary neuroscience clinic were identified and interviewed using standardized questionnaires including a financial burden questionnaire, two Health Related Quality of Life (HRQoL) questionnaires and the Beck Depression Inventory questionnaire. Results: Annual total cost of PD from a societal perspective was SGD11345 (USD10129) per patient, with direct cost accounted for 38.5% and indirect cost 61.5%. The main cost components for direct medical cost, direct non‐medical cost, and indirect cost was pharmacotherapy (50.4%), home care (76.1%), and productivity loss (97.9%), respectively. In multiple linear regression analysis, higher education, younger age and longer duration of PD were associated with higher total cost. Conclusions: Parkinson’s disease exerts a considerable burden on patients, health care system and society in Singapore. As productivity loss accounts for a large share of the economic burden imposed by PD, treatments and health care programmes with potential for returning patients to higher productivity are urgently needed.     

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

Santos‐García D, Sanjurjo LF, Macías M, Llaneza M, Carpintero P, de la Fuente‐Fernández R. 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.
Acta Neurol Scand: 2012: 125: 187–191.
© 2011 John Wiley & Sons A/S. Background – 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. Methods – 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. Results – 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. Conclusions– 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.     

Quality of life,caregiver burden and insurance in patients with Parkinson’s disease in Germany

Background: German health politicians claim that maintenance and thus quality of life (QoL) of patients with chronic disease do not differ between the various healthcare insurance systems in Germany. Patient organizations i.e. the Deutsche Parkinson Vereinigung for patients with Parkinson’s disease (PD), physicians, patients themselves and their carers controversially discuss this opinion making by politicians. Methods: We performed a survey to analyse the relations between QoL, insurance, disability and caregiver burden in 2603 patients with PD and their carers. Results: Insurance with private reimbursement provides a significant better self‐reported patient disability and QoL according to the various employed rating instruments in patients with PD. Government employees with PD, who have additional private insurance, demand for significant shorter intervals of care giving by their carers. In general, caregiver burden did not significantly differ between patients with PD of the different healthcare insurance systems. Conclusion: At least in Germany, obligatory medical insurance with associated state regulation of health care is inferior to private reimbursement insurance in various domains of QoL.     

Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease,and in comparison to healthy controls

Hariz G‐M, Forsgren L. Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease, and in comparison to healthy controls.
Acta Neurol Scand: 2011: 123: 20–27.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson’s disease (PD), according to subtype of disease and compared to healthy controls. Materials and methods – 99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability‐gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL‐taxonomy, SF‐36, and the Parkinson disease questionnaire (PDQ‐39). Results – Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type. Conclusions – Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.     

Hyperhomocysteinemia recurrence in levodopa‐treated Parkinson’s disease patients

Background: Patients with Parkinson’s disease (PD) and chronically treated with L‐DOPA exhibit, in a percentage of 10–30%, supra‐physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper‐homocysteinemic PD patients, the time of hyper‐tHcy recurrence after discontinuation of 1‐month folate supplementation given to normalize plasma tHcy levels. Methods: Plasma tHcy, cobalamin and folate were assayed before and after 1‐month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 ± 6.9 years) stabilized on a mean L‐DOPA dose of 509.4 ± 312.1 mg/day. Results: After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2‐month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper‐tHcy. Conclusions: One‐month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper‐homocysteinemic PD patients. Following folate discontinuation, hyper‐tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper‐homocysteinemic patients with PD.     

Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

Background: Subthalamic nucleus deep brain stimulation (STN DBS) and continuous dopaminergic infusions (jejunal levodopa or subcutaneous apomorphine) are indicated in complicated Parkinson’s disease (PD), although it remains unsettled how they compare to each other. Methods: We investigated the daytime motor condition in patients with advanced PD under monotherapy with jejunal levodopa, subcutaneous apomorphine, or STN DBS and also measured the motor changes produced by an additional standard morning dose of levodopa. Motor performance was assessed with the UPDRS‐III, hand taps, the AIMS dyskinesia score and patients’ diaries. Outcome measures were time to best motor ‘on’ after start of morning treatment, daytime variability of motor condition, motor scores. Results: The time to ‘on’ was longest in the jejunal levodopa group. DBS and jejunal levodopa treatments produced stable motor conditions without appreciable ‘off’ episodes. Continuous apomorphine infusion was associated with the worst motor scores (UPDRS‐III and taps) and the most frequent off‐states. Jejunal levodopa infusion was associated with the highest AIMS scores. Addition of a levodopa dose produced shortening of time to ‘on’ and a transient motor improvement in the jejunal levodopa group without increase in dyskinesias; in the DBS and apomorphine groups, there was an increase in dyskinesias without changes in UPDRS‐III or taps. Conclusions: STN DBS provided adequate trade‐off between motor improvement and dyskinesia control, although dyskinesias could be elicited by adding oral levodopa. Jejunal levodopa infusion produced adequate motor improvement with slow time to ‘on’ and moderate dyskinesias. Apomorphine infusion produced insufficient motor control and negligible dyskinesias.     

Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion

Objective – To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. Methods – Of 18 patients completing a 6‐week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire‐39 (PDQ‐39). Results – During the trial and follow‐up, major diurnal fluctuations were observed, especially for hyperkinesia, ‘off’ time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, ‘off’ time and ability to walk, with improved outcomes with PDQ‐39. Conclusions – Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient’s QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.     

Longitudinal study of the socioeconomic burden of Parkinson’s disease in Germany

Objective: To determine the health economic burden on patients with Parkinson’s disease (PD) in Germany over a 12‐month observation period and provide a comprehensive analysis of cost‐driving factors. Methods and patients: Patients with PD (n = 145) were recruited from two clinical departments, two office‐based neurologists and 12 GPs. Clinical evaluations were performed at baseline, 3, 6 and 12 months. Disease severity was measured using the Unified Parkinson’s Disease Rating Scale (UPDRS). Cost data were assessed based on a patient diary and via personal structured interviews at the respective time‐points. Costs were calculated from the societal perspective (2009 €). Cost‐driving factors were identified by multivariate regression analysis. Results: Mean annual costs totalled €20 095 per patient. Amongst direct costs, the highest expenditures (€13 158) were for drugs (€3526) and inpatient care including nursing homes (€3789). Indirect costs accounted for 34.5% (€6937) of total costs. Costs of home care provided by family accounted for 20% of direct costs. Cost‐driving factors were identified for total costs (UPDRS, fluctuations, dyskinesia and younger age), direct costs (UPDRS, fluctuations), patient expenditures (UPDRS, depression) and drug costs (younger age). Conclusion: Parkinson’s disease has a chronic course with growing disability and considerable socioeconomic burden. Disease progression leads to an increasing number of patients who require costly institutionalized care. Home care is a major factor influencing patients’ families. Healthcare programmes aimed at reducing the burden of PD on society and individuals should consider cost‐driving factors of PD.     

Improvements in nocturnal symptoms with ropinirole prolonged release in patients with advanced Parkinson’s disease

Background: The 24‐week, double‐blind Efficacy and Safety Evaluation in PD–Adjunct (EASE‐PD Adjunct) study randomized patients with advanced Parkinson’s disease (PD) suboptimally controlled with levodopa to once‐daily placebo or adjunctive ropinirole prolonged release (2–24 mg/day). We investigated the effect of ropinirole prolonged release on nocturnal symptoms in these patients. Methods: Total and grouped item PD Sleep Scale (PDSS) scores were analyzed post hoc in patients with baseline PDSS total scores ≤ 100 (troublesome nocturnal symptoms) and >100. Results: Baseline PDSS total score was ≤ 100 in 93 of 198 (47%) and 89 of 189 (47%) patients receiving ropinirole prolonged release and placebo, respectively; this subgroup displayed evidence at baseline of greater daily awake ‘off’ time, reduced night‐time sleep and worse quality of life, than the PDSS >100 subgroup. Significant improvements with ropinirole prolonged release versus placebo in PDSS score from baseline to Week 24 last observation carried forward were observed for those with baseline PDSS ≤ 100 [adjusted mean treatment difference 9.0 (95% CI: 2.76, 15.33; P = 0.0051)], but not >100. The PDSS ≤ 100 subgroup demonstrated treatment benefits for PDSS groupings of motor symptoms on waking and global quality of sleep. Changes in daytime sleepiness were similar between treatment groups. The PDSS >100 subgroup demonstrated significant treatment benefit for global quality of sleep. The unadjusted odds ratio for a positive response with ropinirole prolonged release relative to placebo, for the PDSS ≤ 100 subgroup, was 2.90 (95% CI: 1.42, 5.95, P = 0.004). Conclusions: Once‐daily ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD not optimally controlled with levodopa who suffer troublesome nocturnal disturbance.     

Prevalence of Parkinson’s disease in Korea

The prevalence of neurodegenerative disorders is not well documented in Korea. We assessed the prevalence of Parkinson's disease in an elderly population in a newly industrialized city in a rural region. Subjects for this study were randomly selected from a community-based cohort study. The sample in the cohort represented approximately 1.3% (4700) of 362 625 adults (age>18 years) listed in the city register in 1998. Among this group, 4218 subjects (1086 subjects aged>60 years) agreed to be interviewed and underwent a physical examination and neuropsychological tests administered by a neurologist and neuropsychologist. All participants were examined. Participants who had bradykinesia and at least one other possible cardinal sign of parkinsonism at the neurologic screening, and those who reported that they had Parkinson's disease, or were taking antiparkinsonian drugs were identified. In our study, 16 subjects showed evidence of Parkinson's disease. The prevalence in this population was 0.37%. Prevalence increased with age, and prevalence was 1.47% for those aged older than 60 years. Postural instability and gait disturbance were more common in the older age group. The results of neuropsychological tests were as follows: (1) only two subjects had low scores (<20) in the Korea-version mini-mental status examination; (2) seven subjects scored 0.5, one subject scored 2 and the other eight subjects scored 0 in the clinical dementia rating. The results of our prevalence study are similar to those of studies carried out in Western countries. Age is a risk factor for Parkinson's disease in Korea.     

Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women

Background and purpose: The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low‐dose and high‐dose patients with Parkinson’s disease (PD) in a university hospital. Methods: Patients with ≥ 1 and ≥ 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006–2007 were examined to select a low‐dose group (≤ 400 mg levodopa daily, n = 21) and a high‐dose group (≥ 1200 mg daily, n = 26) with at least 5 years of PD duration. Results: In total, 33 534 levodopa users with ≥ 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses ≥ 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low‐dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. Conclusions: We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low‐dose patients but increases in high‐dose patients.     

Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease

Mateo I, Infante J, Sánchez‐Juan P, García‐Gorostiaga I, Rodríguez‐Rodríguez E, Vázquez‐Higuera JL, Berciano J, Combarros O. Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 136–138.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase‐1 (HO‐1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up‐regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO‐1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO‐1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO‐1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO‐1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO‐1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO‐1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.