Tolerability of non-ergot oral and transdermal dopamine agonists in younger and older Parkinson's disease patients: an European multicentre survey.

In older patients with Parkinson's disease (PD), the use of dopamine agonists (DA) has been limited due to uncertainties related to their tolerability in spite of potential gains with the advent of longer acting or transdermal therapies. Comparative real-life data addressing the tolerability of DA therapy across age ranges are currently sparse. This study addressed the tolerability (Shulman criteria, continued intake of DA therapy for at least 6 months) in PD patients across several European centres treated with long-acting and transdermal DA (Rotigotine skin patch, Ropinirole extended release, or Pramipexole prolonged release) as part of routine clinical care in younger and older PD patients. A medical record-based retrospective data capture and clinical interview-based follow-up survey of patients initiating or initiated on DA treatment (short and long acting) in a real-life setting. 425 cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37), 31.5% older age (≥ 75 years of age)]. Tolerability was above 90% irrespective of age, with no significant differences between younger and older patients. Based on our findings, we suggest that long-acting/transdermal DA are tolerated in non-demented older patients, as well as in younger patients, however, with lower daily dose in older patients.

[Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) for assessment of non-motor symptoms in dystonia : Intercultural adaptation in the German language]. / Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) zur Erhebung nichtmotorischer Symptome bei Dystonie : Interkulturelle Adaptation in deutscher Sprache.

BACKGROUND: Non-motor symptoms (NMS) in patients with dystonia have a relevant impact on health-related quality of life; however, a comprehensive easy to use NMS assessment tool for clinical bedside use is currently not available. OBJECTIVE: The validated German version of the dystonia non-motor symptoms questionnaire (DNMSQuest) for assessing NMS in craniocervical dystonia is presented. METHODS: The DNMSQuest in the German language was developed based on internationally recognized standards for intercultural adaptation of self-completed patient questionnaires. Translation of the original English questionnaire into the German language as well as back translation to English was carried out independently by four bilingual specialists in neurological movement disorders. In each case a consensus version accepted by each translator was created by another neurologist. The back translated English version was compared with the original English questionnaire for relevant linguistic and content discrepancies by a neurologist who was significantly involved in the development of the original questionnaire. The final German version was used in 130 patients with cervical dystonia and 48 healthy controls in an international, multicenter validation study. RESULTS: An interculturally adapted validated version of the DNMSQuest in the German and English languages was developed for rapid bedside assessment and evaluation of NMS in cervical dystonia. CONCLUSION: The DNMSQuest successfully bridges the current gap of a validated disease-specific, patient self-administered, short, comprehensive questionnaire for NMS assessment in routine clinical practice in craniocervical dystonia. It is envisaged that this tool will be useful for the clinical practice and trials.

First comprehensive tool for screening pain in Parkinson's disease: the King's Parkinson's Disease Pain Questionnaire.

BACKGROUND AND PURPOSE: Pain is highly prevalent in Parkinson's disease (PD), impacting patients' ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. METHODS: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test-retest) and diagnostic performance of the questionnaire were analysed. RESULTS: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS  = 0.80) but weak or moderate with other pain assessments. Test-retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS  = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%-98.3%. CONCLUSIONS: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes.

Workforce participation and activities in Parkinson's disease patients receiving device-aided therapy.

OBJECTIVES: Many countries have an aging population, and it is thus likely that Parkinson's disease (PD) will become an increasing health problem. It is important to ensure this group can use their resources in the best way possible, including remaining in the work market. This study aimed to investigate workforce participation and daily activities among patients with PD receiving device-aided therapy to provide new knowledge that may be used to inform decisions about these therapy options. MATERIALS AND METHODS: This was a retrospective, descriptive quantitative pilot study, including 67 patients with PD from 3 centers in Sweden and Denmark. Included patients were younger than 67 years at the time of introduction of device-aided therapy. Eligible patients were identified by the Swedish national Parkinson patient registry or by the treating neurologist. Quantitative interviews were made by telephone. RESULTS: A majority of the patients could perform the same, or more, amount of activities approximately 5 years after the introduction of device-aided therapy. A small number of patients receiving deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG) were able to increase their work capacity within 1 year of initiating device-aided therapy and a remarkably high share could still work at the end-point of this study, approximately 15 years since the diagnosis of PD. CONCLUSIONS: Device-aided therapy may sustain or increase daily activities and workforce participation in patients with PD who have not yet reached retirement age. There is need for prospective studies, both quantitative and qualitative, to confirm these results.

Mobility device use in people with Parkinson's disease: A 3-year follow-up study.

OBJECTIVES: This study aimed to investigate how the use and perceived unmet need of mobility devices (MD) in people with Parkinson's disease (PD) evolve over a 3-year period. METHODS: The study reports baseline assessments (n = 255) and comparisons for participants with complete data at baseline and the 3-year follow-up (n = 165). Structured questions addressed the use and perceived unmet need of various MDs indoor and outdoor (eg, canes, wheeled walkers, and manual and powered wheelchairs). McNemar tests were used to investigate differences over time. RESULTS: In the total sample at baseline, 30% and 52% of the participants reported using MDs indoors and outdoors, respectively. Among those with complete data also at the 3-year follow-up, the proportion of participants using MDs increased significantly (P < .001) from 22% to 40% for indoors and from 48% to 66% for outdoors, with transition of MD toward more assistive potential (ie, wheeled walker and manual wheelchair). Wheeled walkers were the most commonly used MD indoors as well as outdoors on both occasions. Among the users of multiple MDs, the most common combination was cane and wheeled walker on both occasions. The proportion of participants who reported a perceived unmet need of MDs was 5% at baseline, whereas it was 21%, 3 years later. CONCLUSIONS: The use and perceived unmet need of MDs in people with PD increase over time. There is a need for addressing MDs at clinical follow-ups of people with PD, with continuous attention in primary health care and municipality contexts.

[King's Parkinson's disease pain scale : Intercultural adaptation in the German language]. / King's Parkinson's Disease Pain Scale : Interkulturelle Adaption in deutscher Sprache.

BACKGROUND: Pain is a frequent symptom of idiopathic Parkinson's disease and has a substantial impact on quality of life. The King's Parkinson's disease pain scale (KPPS) has become internationally established and is an English-language, standardized, reliable and valid scale for evaluation of pain in idiopathic Parkinson's disease. This article presents a validated version in German. METHOD: The German translation was adapted interculturally and developed using an internationally recognized procedure in consultation with the authors of the original publication. The primary text was first translated by two bilingual neuroscientists independently of one another. Thereafter, the two versions were collated to generate a consensus version, which was accepted by the translators and preliminarily trialled with 10 patients. Hereafter, the German version was re-translated back into English by two other neurologists, again independently of one another, and a final consensus was agreed on using these versions. This English version was then compared with the original text by all of the translators, a process which entailed as many linguistic modifications to the German version as the translators considered necessary to generate a linguistically acceptable German version that was as similar as possible to the original English version. After this test text had been subsequently approved by the authors, the German text was applied to 50 patients in two hospitals, and reviewed as to its practicability and comprehensibility. RESULTS: This work led to the successful creation of an inter-culturally adapted and linguistically validated German version of the KPPS. DISCUSSION: The German version presented here is a useful scare for recording and quantifying pain in empirical studies, as well as in clinical practice.

Algorithms for the treatment of motor problems in Parkinson's disease.

Several different strategies are effective for medical treatment of motor problems in Parkinson's disease (PD). Many guidelines and evidence-based reviews are available, but there is no documentation or consensus in favor of just one treatment strategy. This review presents two algorithms that may be helpful when deciding how to treat a PD patient at various stages of the disease. The first algorithm suggests one way to treat PD from the first onset of motor symptoms. It is largely based on treatment recommendations from the Scandinavian countries and Germany. The other algorithm is meant as assistance for choosing among the different device-aided treatments for advanced PD. There is not sufficient comparative data to recommend one particular line of treatment, neither in early PD nor in advanced disease with motor complications. Individualized treatment is needed for each patient. The current algorithms only represent an alternative for aiding treatment decisions.

Factors associated with life satisfaction in Parkinson's disease.

OBJECTIVES: To identify factors associated with life satisfaction (LS) in people with Parkinson's disease (PD), including a specific focus on those with late-stage PD. MATERIAL AND METHODS: The study included 251 persons with PD (median age 70 years; PD duration 8 years). Analyses involved the total sample and a subsample with late-stage PD, that is Hoehn and Yahr stages IV and V (n=62). LS was assessed with item 1 of the Life Satisfaction Questionnaire (LiSat-11). Simple logistic regression analyses were performed for both the total sample and for the subsample with late-stage PD. For the total sample, a multivariable logistic regression analysis was also performed. RESULTS: In the total sample, 12 of the 20 independent variables were significantly associated with LS: need of help with ADL; walking difficulties; number of non-motor symptoms (NMS); fatigue; depressive symptoms; general self-efficacy; motor symptoms; pain; PD severity; freezing episodes; gender (woman); and fluctuations. When controlling for age and gender in the multivariable logistic regression model, depressive symptoms were negatively associated with high LS and general self-efficacy was positively associated with high LS. In late-stage PD, simple logistic regression analyses (controlling for age and gender) identified the following factors as associated with LS: number of NMS, general self-efficacy, walking difficulties and fatigue. CONCLUSIONS: This study provides new knowledge on factors associated with LS in a PD sample, including those with late-stage PD. As the ultimate goal for PD care should be improvement in LS, the results have direct clinical implication.

Workforce unavailability in Parkinson's disease.

OBJECTIVES: Individuals with Parkinson's disease (PD) become unavailable in the workforce earlier than comparable members of the general population. This may result in significant social insurance expenses, but as workforce participation can be a source for social interaction and a vital part of the personal identity, there are likely to be personal implications extending far beyond the economic aspects. This study aimed to identify aspects that may contribute to workforce unavailability in people with PD. MATERIALS & METHODS: This was a cross-sectional registry study using data from the Swedish national quality registry for PD and included persons with PD in Skåne County, Sweden who were younger than 65 years. Variables were selected from the registry based on earlier studies and clinical experience and were tested for association with unavailability in the workforce: first in a series of simple regression analyses and then in a multiple logistic regression analysis. RESULTS: A total of 99 persons with PD-of whom 59 were available and 40 were unavailable in the workforce-were included in the study. Age (OR per year: 1.47, 95% CI: 1.18-1.85; P < 0.01) and anxiety (OR: 6.81, 95% CI: 1.20-38.67; P = 0.03) were significant contributing factors for unavailability in the workforce. CONCLUSIONS: Based on the findings in this exploratory study, anxiety-a potentially modifiable factor-and age may be contributing factors for workforce unavailability in PD. However, prospective studies are warranted to confirm the findings and the causation of the association between anxiety and workforce unavailability needs to be clarified.

A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short- and long-acting dopamine agonists.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short- or long-acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care. METHODS: A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short- and long-acting, and transdermal) across a broad range of disease stages and age groups was performed. RESULTS: Four hundred and twenty-five cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; P < 0.05) compared with any other assessed DAs except for prolonged release PPX (PPX-PR). The rate of ICDs for PPX-PR (6.6%) was significantly lower than for immediate release PPX (PPX-IR) (19.0%; P < 0.05). Discontinuation rates of DA therapy due to ICDs were low. CONCLUSION: Our data suggest a relatively low rate of ICDs with long-acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.

Improvement of dyskinesias with L-dopa infusion in advanced Parkinson's disease.

OBJECTIVES: We wanted to investigate whether continuous intrajejunal levodopa-carbidopa intestinal gel (LCIG) therapy has an antidyskinetic effect in patients with Parkinson's disease (PD) and troublesome dyskinesias. We also sought to examine the effect of LCIG therapy on motor function and health-related quality of life (HRQoL). MATERIALS AND METHODS: This open-label pilot study used a single group pre-post design with follow-up at 6 months. Nine patients with PD who reported to spend at least 3 h per day in on with troublesome dyskinesia were included. The patients were examined at baseline using clinical and self-assessment measures and then switched from peroral/transdermal pharmacotherapy to LCIG therapy. Data collection was repeated 6 months after the pharmaceutical intervention. Nonparametric statistical methods were used for data analyses. RESULTS: The mean time spent in on with troublesome dyskinesia per day after 6 months of LCIG therapy decreased by 47% (P < 0.05). This observation was paralleled by a 112% increase in mean time spent in on without troublesome dyskinesia (P < 0.01). Patient self-assessment of dyskinesia intensity on the visual analog scale displayed a 90% reduction of mean dyskinesia intensity (P < 0.01) and patients also exhibited less dyskinesia during standardized levodopa tests. Furthermore, we noted improvements in motor function and HRQoL. CONCLUSIONS: In this pilot study, we found indications that LCIG therapy has a substantial antidyskinetic effect and could be an alternative also for PD patients with dyskinesias as a major symptom. However, further studies with blinded evaluation and larger numbers of patients are warranted to confirm the findings.

[Practical Use of the Levodopa Pump]. / Praktische Anwendung der Levodopa-Pumpe.

Patients with advanced Parkinson's disease and motor complications undergoing optimized oral therapy can significantly benefit from continuous intrajejunal levodopa/carbidopa infusion applied by means of a medication pump. However, this requires a correctly positioned PEG-J tube and finely adjusted pump settings. Although this method is a routine procedure in specialist centers, no standard procedure has been defined up to now. For this reason, an expert recommendation regarding the practical application has been developed in order to standardize the procedure and facilitate patient access to this treatment option.

King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation.

Pain is a key unmet need and a major aspect of non-motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross-sectional, open, multicenter, one-point-in-time evaluation with retest study of the first PD-specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy-eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29-85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non-PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser-Mayer-Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item-total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD-Motor, Non-Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD.

Effect and safety of duodenal levodopa infusion in advanced Parkinson's disease: a retrospective multicenter outcome assessment in patient routine care.

Duodenal levodopa infusion represents an effective strategy to manage motor and non-motor complications in patients with advanced Parkinson's disease (PD). However, most published clinical series regard small numbers of patients and do not exceed 1 year follow-up. In this multi-national observational cohort study conducted in seven specialised PD clinics and university hospitals we assessed long-term safety and outcome of chronic treatment with intra-duodenal levodopa infusions in a large population of patients with advanced PD. The starting population consisted of 98 treated patients (safety population). We report clinical outcomes of 73 patients with subsequent efficacy assessment(s) (efficacy population) over a follow-up period up to 2 years. Follow-up periods and collection of clinical observations varied based on individual routine care program. At last follow-up there was a significant (p ≤ 0.05) reduction in duration of "Off" periods as well as dyskinesia duration and severity that was associated with an improvement of quality of life. Twenty three patients (25.3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8). The mean duration for last value reported after baseline (LV) was 608 ± 292 days (median: 697 days). Our results demonstrate significant and sustained benefit over a long observation period in motor complications and in quality of life following a change from oral pulsatile to continuous levodopa delivery. The relatively large number of withdrawals reflects the current use of duodenal levodopa infusion in very advanced PD patients.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

Duration of L-dopa and dopamine agonist monotherapy in Parkinson's disease.

The expected duration of initial antiparkinson monotherapy before the need for supplementation is not clearly defined for routine practice. The aim of this study was to define the length of L-dopa (L-3, 4-dihydrophenylalanine) and dopamine agonist monotherapy. The duration of monotherapy and discontinuation rates were investigated in a natural observational setting by plotting Kaplan-Meier survival curves. Out of 345 patients, 180 (52.2%) received L-dopa and 165 (47.8%) received a dopamine agonist as initial monotherapy. Half of the patients starting L-dopa received supplementary therapy with- in 3.6 years (95% confidence interval, 3.2-4.6), significantly longer than for dopamine agonist monotherapy (half required a second agent at 2.3 years [2.0-2.9]; P = 0.00017). Discontinuation of L-dopa therapy was 1%. Dopamine agonists were stopped (due to side-effects like impulse control disorders [6%], somnolence [4%] and light-headedness [3%]) in 20% over four years. The duration and tolerability of L-dopa and dopamine agonists as initial Parkinson's disease monotherapy are defined in this study; this may form part of the information exchange with patients.

[Non-motor Symptoms Questionnaire and Scale for Parkinson's disease. Cross-cultural adaptation into the German language]. / Non-motor Symptoms Questionnaire und Scale für das idiopathische Parkinson-Syndrom. Interkulturell adaptierte Versionen in deutscher Sprache.

Idiopathic Parkinson's disease (PD) is a multisytem degenerative disorder. In addition to motor symptoms such as akinesia, rigidity and tremor, various non-motor symptoms occur, which are still insufficiently diagnosed. Moreover, the frequently used scales and scores do not adequately detect these non-motor symptoms. The Non-motor Symptoms Questionnaire (NMSQuest) is an established self-completed patient questionnaire with 30 qualitative questions covering all important non-motor symptoms of PD. The Non-motor Symptoms Scale (NMSScale) is a grade rating scale for estimating the frequency and severity of non-motor symptoms in PD. Since there are only original English versions of both questionnaires available, self-translated versions were frequently used or the questionnaires were not used at all in native German patients. We used international guidelines for cross-cultural adaptation of questionnaires to provide standard versions of both non-motor symptoms questionnaires in the German language.

[Depression in Parkinson's disease--Part 2: Therapy and management]. / Depression beim idiopathischen Parkinson-Syndrom--Teil 2: Therapie und Management.

A good number of different methods and antidepressive agents are now available for the management of depressive symptoms, the efficacy of which has been confirmed by clinical studies. Various approaches--be it medication, electroconvulsive therapy (ECT), psychoeducation and psychotherapy--have also been developed to treat depression in patients with Parkinson's disease. Unfortunately, only a few controlled studies exist for this very specific group of patients. Systematic knowledge of treatment options, however, is lacking. Efficient management of depressive symptoms is absolutely indispensable considering the proven impact of a depression on the patients' quality of life. So far, more than half of the patients afflicted with Parkinson's disease and depression do not receive proper antidepressive therapy. This survey gives an overview on the pharmacological, somatic and psychological procedures of treatment applied in this group of patients, along with useful suggestions.

The late stage of Parkinson's -results of a large multinational study on motor and non-motor complications.

INTRODUCTION: There is little information on the late stages of parkinsonism. METHODS: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. RESULTS: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. CONCLUSION: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.

Clinical risk-benefit assessment of dopamine agonists.

Dopamine agonists (DAs) have proven efficacy as monotherapy in early Parkinson's disease (PD) for preventing motor complications such as dyskinesia and as adjunct therapy as the disease progresses. Further, it is increasingly evident that at least some DAs may provide additional benefits, such as reduction in depressive symptoms and treatment of refractory tremor. Different side-effect profiles have been associated with levodopa and ergot or non-ergot DA treatment, such as sudden onset of sleep, reduced impulse control, hallucination, and cardiovascular fibrosis. This paper discusses the evidence for specific associations between particular treatments and side effects as well as the clinical implications for patient care. Ultimately, the choice depends on the risk-benefit assessment as it applies to the individual patient's clinical profile and the physician's preference.