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.
Summary Background Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone–naloxone ...for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment. Methods This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investigator's opinion to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day; in the extension, all patients started on oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day. The primary outcome was mean change in severity of symptoms according to the International RLS Study Group severity rating scale sum score at 12 weeks. This study is registered with ClinicalTrials.gov (number NCT01112644 ) and with EudraCT (number 2009-011107-23). Findings We screened 495 patients, of whom 306 were randomly assigned and 276 included in the primary analysis (132 to prolonged release oxycodone–naloxone vs 144 to placebo). 197 patients participated in the open-label extension. Mean International RLS Study Group rating scale sum score at randomisation was 31·6 (SD 4·5); mean change after 12 weeks was −16·5 (SD 11·3) in the prolonged release oxycodone–naloxone group and −9·4 (SD 10·9) in the placebo group (mean difference between groups at 12 weeks 8·15, 95% CI 5·46–10·85; p<0·0001). After the extension phase, mean sum score was 9·7 (SD 7·8). Treatment-related adverse events occurred in 109 of 150 (73%) patients in the prolonged release oxycodone–naloxone group and 66 of 154 (43%) in the placebo group during the double-blind phase; during the extension phase, 112 of 197 (57%) had treatment-related adverse events. Five of 306 (2%) patients had serious treatment-related adverse events when taking prolonged release oxycodone–naloxone (vomiting with concurrent duodenal ulcer, constipation, subileus, ileus, acute flank pain). Interpretation Prolonged release oxycodone–naloxone was efficacious for short-term treatment of patients with severe restless legs syndrome inadequately controlled with previous treatment and the safety profile was as expected. Our study also provides evidence of open-label long-term efficacy of this treatment. Opioids can be used to treat patients with severe restless legs syndrome who have had no benefit with first-line drugs. Funding Mundipharma Research.
Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole‐exome sequencing could be an efficient approach to genetic ...testing in PD. To evaluate its performance in early‐onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD. Variants in validated and candidate disease genes and risk factors for PD and atypical Parkinson syndromes were annotated, followed by further analysis for selected variants. We detected pathogenic variants in Mendelian genes in 6.25% of cases and high‐impact risk factor variants in GBA in 5% of cases, resulting in overall maximum diagnostic yield of 11.25%. One individual was compound heterozygous for variants affecting canonical splice sites in VPS13C, confirming the causal role of protein‐truncating variants in this gene linked to autosomal‐recessive early‐onset PD. Despite the low diagnostic yield of exome sequencing in sporadic early‐onset PD, the confirmation of the recently discovered VPS13C gene highlights its advantage over using predefined gene panels.
Restless legs syndrome (RLS) is one of the most common neurological disorders. It describes an irresistible urge to move the legs, mostly manifested in the evening and at night, which can lead to ...severe sleep disturbance. As part of the European Brain Council (EBC)‐led Value‐of‐Treatment project, this study aimed at capturing the socioeconomic impact of RLS related to the inadequate diagnosis and treatment across different European healthcare settings. The economic burden of RLS was estimated using the published EBC framework of analysis in three separate European Union healthcare systems (France, Germany, and Italy). The RLS care pathway was mapped to identify the unmet needs of patients. Based on specific patient stories, the economic impact of correctly diagnosing RLS and changing between inadequate and target treatment was calculated using appropriate scenario analysis. RLS proved to be a significant personal and social burden, when epidemiological data, high prevalence of RLS, and its need for treatment are combined. By looking at the savings emerging from the provision of optimal care management (timely and correct diagnosis, evidence‐based therapy, avoidance of therapy‐related complications such as augmentation), the authors foresee substantial economic savings with the achievement of adequate diagnosis and treatment of RLS. Education about RLS is urgently needed for all subspecialties involved in RLS patient care as well as the general public. Equally important, the search for new causal treatment strategies should be intensified to reduce suffering and substantial societal cost.
As part of the European Brain Council (EBC)‐led Value‐of‐Treatment (VoT) Project, this study aimed at capturing the socio‐economic impact of RLS related to the inadequate diagnosis and treatment across different European healthcare settings. RLS proved to be a significant personal and social burden, when including epidemiological data and high prevalence of RLS and its need for treatment. By looking at the savings emerging from the provision of optimal care management, the authors foresee substantial economic savings with the achievement of adequate diagnosis and treatment of RLS.
Pain is one of the most common and troublesome non‐motor symptoms of Parkinson's disease (PD). It can appear at any time during the disease and is often present before diagnosis. However, there is ...little or no consensus on its definition. An expert group of clinicians with relevant research experience met to review the existing evidence and to identify gaps in our understanding leading towards AUTHOR: ’understanding towards’ has been changed to ’understanding leading towards‘. Please check and confirm that this is appropriate an optimized therapy of pain in PD. Key findings from epidemiologic, neurophysiologic, neuroimaging and clinical studies are reviewed. In each case, the evidence base is limited by wide variations in the definitions of pain applied, study methodologies and populations evaluated. Disease‐related and medical conditions trigger spontaneous pain in patients with PD, which is then abnormally processed and results in painful manifestations in specific body parts. Dopaminergic medications, such as rotigotine, as well as opiate analgesics, such as oxycodone, have shown positive results but future studies with more detailed pain characterization at inclusion are warranted.
Abstract Background Transcutaneous spinal direct current stimulation (tsDCS) is a new non-invasive technique to modulate spinal cord activity. The pathophysiological concept of primary RLS proposes ...increased spinal excitability. Objective This pilot study used tsDCS to reduce pathologically enhanced spinal excitability in RLS patients and to thereby ameliorate clinical symptoms. Methods 20 patients with idiopathic RLS and 14 healthy subjects participated in this double-blinded, placebo-controlled study. All participants received one session of cathodal, anodal and sham stimulation of the thoracic spinal cord for 15 min (2.5 mA) each, in randomized order during their symptomatic phase in the evening. The soleus Hoffmann-reflex with Hmax/Mmax-ratio and seven different H2/H1-ratios (of two H-reflex responses to double stimuli) were measured. The RLS symptoms were assessed by a visual analogue scale (VAS). All parameters were measured before and twice after tsDCS. Results RLS patients showed increased H2/H1-ratios during their symptomatic phase in the evening. Application of anodal stimulation led to a decreased H2/H1-ratio for 0.2 and 0.3 s interstimulus intervals in patients. Furthermore, application of anodal and cathodal stimulation led to a reduction in restless legs symptoms on the VAS, whereas application of sham stimulation had no effects on either the VAS or on the H2/H1-ratio in patients. VAS changes did not correlate with changes of H2/H1-ratios. Conclusions This is the first tsDCS study in idiopathic RLS, which resulted in short-lasting clinical improvement. Furthermore, our results support the pathophysiological concept of spinal cord hyperexcitability in primary RLS and provide the basis for a new non-pharmacological treatment tool.
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.
The differential diagnosis of Parkinson syndromes remains a major challenge. Quantitative MR imaging can aid in this classification, but it is unclear which of the proposed techniques is best suited ...for this task. We, therefore, conducted a head-to-head study with different quantitative MR imaging measurements in patients with IPS, MSA-type Parkinson, PSP, and healthy elderly controls.
Thirty-one patients and 13 controls underwent a comprehensive quantitative MR imaging protocol including R2*-, R2- and R1-mapping, magnetization transfer, and DTI with manual region-of-interest measurements in basal ganglia regions. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction and an ROC.
The best separation of MSA from IPS in patients and controls could be achieved with R2*-mapping in the PU, with an ROC AUC of ≤0.96, resulting in a sensitivity of 77.8% (with a specificity 100%). MD was increased in patients with PSP compared with controls and to a lesser extent compared with those with IPS and MSA in the SN.
Among the applied quantitative MR imaging methods, R2*-mapping seems to have the best predictive power to separate patients with MSA from those with IPS, and DTI for identifying PSP.
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