Camera-based objective measures of Parkinson's disease gait features

OBJECTIVE: Parkinson's disease is a common, age-related, neurodegenerative disease, affecting gait and other motor functions. Technological developments in consumer imaging are starting to provide high-quality, affordable tools for home-based diagnosis and monitoring. This pilot study aims to investigate whether a consumer depth camera can capture changes in gait features of Parkinson's patients. The dataset consisted of 19 patients (tested in both a practically defined OFF phase and ON phase) and 8 controls, who performed the "Timed-Up-and-Go" test multiple times while being recorded with the Microsoft Kinect V2 sensor. Camera-derived features were step length, average walking speed and mediolateral sway. Motor signs were assessed clinically using the Movement Disorder Society Unified Parkinson's Disease Rating Scale. RESULTS: We found significant group differences between patients and controls for step length and average walking speed, showing the ability to detect Parkinson's features. However, there were no differences between the ON and OFF medication state, so further developments are needed to allow for detection of small intra-individual changes in symptom severity

‘We don’t know for sure’: discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations

Pre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors’ communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of counselors discussing a multigene panel with a simulated patient were videotaped. Simulated patients represented a counselee who had had multiple cancer types, according to a script. Before and afterwards, counselors completed a survey. Counselors’ uncertainty expressions, initiating and the framing of expressions, and their verbal responses to scripted uncertainties of the simulated patient were coded by two researchers independently. Coding was done according to a pre-developed coding scheme using The Observer XT software for observational analysis. Additionally, the degree of SDM was assessed by two observers. Correlation and regression analyses were performed to assess associations of communicated uncertainties, responses and the extent of SDM, with counselors’ background characteristics. In total, twenty-nine counselors, including clinical geneticists, genetic counselors, physician assistants-in-training, residents and interns, participated of whom working experience varied between 0 and 25 years. Counselors expressed uncertainties mainly regarding scientific topics (94%) and on their own initiative (95%). Most expressions were framed directly (77%), e.g. We don’t know, and were emotionally neutral (59%; without a positive/negative value). Counselors mainly responded to uncertainties of the simulated patient by explicitly referring to the uncertainty (69%), without providing space for further disclosure (66%). More experienced counselors provided less space to further disclose uncertainty (p < 0.02), and clinical geneticists scored lower on SDM compared with o

Towards a prescription for exercise for persons with Parkinson’s disease

Contains fulltext : 224758.pdf (publisher's version ) (Open Access)Radboud University, 30 oktober 2020Promotor : Bloem, B.R. Co-promotores : Post, B., Vries-Farrouh, N.M. d

Risk of aneurysm rupture at intracranial arterial bifurcations.

Item does not contain fulltextBACKGROUND: Aneurysms on the posterior circulation, most commonly located at the basilar top, have a higher risk of rupture than aneurysms on the anterior circulation. If hemodynamic shear stress, which has its maximum impact at the distal carina of bifurcations, explains the higher rupture rate of basilar top aneurysms, aneurysms at the top of the carotid artery should have similar rupture rates given their geometrical similarities. AIM: Our purpose was to compare rupture risks of carotid and basilar artery bifurcation aneurysms. METHODS: We included studies from Medline and Embase searches and compared proportions of ruptured and unruptured aneurysms at the basilar and carotid bifurcation with the assumption that carotid aneurysms are twice as prevalent based on the presence of 2 carotid and 1 basilar artery bifurcation on the circle of Willis. Results: Of all unruptured aneurysms, 8.3% were located on the basilar and 6.0% on the carotid bifurcation; 8.0% of all ruptured aneurysms were located on the basilar and 4.3% on the carotid bifurcation. Subsequently the ratios of carotid versus basilar aneurysms were 0.72 for unruptured and 0.55 for ruptured aneurysms, instead of the expected 2.0. CONCLUSIONS: Aneurysms are less frequently located on the carotid than on the basilar artery bifurcation. The proportion of ruptured carotid aneurysms is smaller than that of unruptured carotid aneurysms, suggesting a lower rupture risk for aneurysms at the carotid artery bifurcation. The anatomical geometry of the bifurcations and concomitant hemodynamic stress are considered an unlikely explanation for the higher risk of posterior circulation aneurysms

Design of the Park-in-Shape study: a phase II double blind randomized controlled trial evaluating the effects of exercise on motor and non-motor symptoms in Parkinson's disease

Contains fulltext : 154960.pdf (publisher's version ) (Open Access)BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. METHODS/DESIGN: The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. DISCUSSION: This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. TRIAL REGISTRATION: Dutch trial register NTR4743.12 p

Progressive multifocal leukoencephalopathy in an immunocompetent patient

Contains fulltext : 165751.pdf (publisher's version ) (Open Access)Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, is typically diagnosed in immunocompromised persons. Here, we describe the diagnostic challenge of PML in an apparently immunocompetent patient. Thorough analyses, including cytokine release assays and whole exome sequencing, revealed a deficit in the antiviral interferon gamma production capacity of this patient and compound heterozygous mutations in BCL-2-associated athanogene 3. Interestingly, both factors are associated with reduced expression of John Cunningham virus T-antigen, a protein that plays a key role in viral replication in infected cells. After validation in other patients, our findings may contribute to novel insights into the etiology and possibly treatment of PML

Investigation on the formation of tungsten carbide in tungsten-containing diamond like carbon coatings

A series of tungsten-containing diamond-like carbon (Me-DLC) coatings have been produced by unbalanced magnetron sputtering using a Hauzer HTC-1000 production PVD system. Sputtering from WC targets has been used to form W-C:H coatings. The metal to carbon ratio has been varied to study changes in the metal carbide formation and distribution within the amorphous hydrocarbons (a-C:H) matrix. The difference in the formation of the metal carbide is then linked to changes in the mechanical and tribological properties of the coatings. Detailed high-resolution cross-section TEM has been carried out to analyze the microstructure of the coatings. By changing the amount of a-C:H in the W-C:H coatings, the coefficient of friction could be varied between 0.129 and 0.312. The hardness was found to vary between 8 and 27.5 GPa by using different acetylene gas flows. It was observed that all coatings did have a pronounced multilayered structure.

Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson's disease: A double-blind, randomised controlled trial

Contains fulltext : 207798pos.pdf (postprint version ) (Open Access)Background: High-intensity aerobic exercise might attenuate the symptoms of Parkinson's disease, but high-quality evidence is scarce. Moreover, long-term adherence remains challenging. We aimed to evaluate the effectiveness of aerobic exercise-gamified and delivered at home, to promote adherence-on relieving motor symptoms in patients with Parkinson's disease with mild disease severity who were on common treatment regimes. Methods: In this single-centre, double-blind, randomised controlled trial (Park-in-Shape), we recruited sedentary patients with Parkinson's disease from the outpatient clinic at Radboudumc, Nijmegen, Netherlands. Patients were made aware of the study either by their treating neurologist or via information in the waiting room. Patients could also contact the study team via social media. We included patients aged 30-75 years with a Hoehn and Yahr stage of 2 or lower, who were on stable dopaminergic medication. Patients were randomly assigned (in a 1:1 ratio) to either aerobic exercise done on a stationary home-trainer (aerobic intervention group) or stretching (active control group) by means of a web-based system with minimisation for sex and medication status (treated or untreated) and permuted blocks of varying sizes of more than two (unknown to study personnel). Patients were only aware of the content of their assigned programme. Assessors were unaware of group assignments. Both interventions were home based, requiring 30-45 min training three times per week for 6 months. Both groups received a motivational app and remote supervision. Home trainers were enhanced with virtual reality software and real-life videos providing a so-called exergaming experience (ie, exercise enhanced by gamified elements). The primary outcome was the between-group difference in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor section at 6 months, tested during the off state (>/=12 h after last dopaminergic medication). The analysis was done on an intention-to-treat basis in patients who completed the follow-up assessment, regardless of whether they completed the assigned intervention. Patients reported adverse events directly to their coach and also after the 6-month visit retrospectively. A between-group difference of 3.5 points or more was deemed a-priori clinically relevant. The study is concluded and registered with the Dutch Trial Registry, NTR4743. Findings: Between Feb 2, 2015, and Oct 27, 2017, 139 patients were assessed for eligibility in person, of whom 130 were randomly assigned to either the aerobic intervention group (n=65) or the active control group (n=65). Data from 125 (96%) patients were available for the primary analysis; five patients were lost to follow-up (four in the intervention group; one in the control group). 20 patients (ten in each group) did not complete their assigned programme. The off-state MDS-UPDRS motor score revealed a between-group difference of 4.2 points (95% CI 1.6-6.9, p=0.0020) in favour of aerobic exercise (mean 1.3 points [SE 1.8] in the intervention group and 5.6 points [SE 1.9] for the control group). 11 patients had potentially related adverse events (seven [11%] in the intervention group, four [6%] in the control group) and seven had unrelated serious adverse events (three in the intervention group [vestibilar disorder, vasovagal collapse, knee injury during gardening that required surgery; 6%], four in the control group [supraventricular tachycardia, hip fracture, fall related injury, severe dyskinesias after suprathreshold dose levodopa in a patient with deep brain stimulation; 7%]). Interpretation: Aerobic exercise can be done at home by patients with Parkinson's disease with mild disease severity and it attenuates off-state motor signs. Future studies should establish long-term effectiveness and possible disease-modifying effects. Funding: Netherlands Organization for Health Research and Development.11 p