Trans-Spinal Direct Current Stimulation for Managing Primary Orthostatic Tremor.

BACKGROUND: Primary orthostatic tremor (POT) is a rare disorder, characterized by 13 to 18 Hz tremor in the legs when standing and is often refractory to medical treatment. Epidural spinal cord stimulation has been proposed as an alternative treatment. However, this approach is invasive, which limits its application. OBJECTIVE: Trans-spinal direct current stimulation (tsDCS) is a non-invasive method to modulate spinal cord circuits. The aim of this proof-of-concept study was to investigate the potential beneficial effect of tsDCS in POT. METHODS: We conducted a double-blind, sham-controlled study in 16 patients with POT. In two separate visits, patients received sham tsDCS first followed by active (either cathodal or anodal) tsDCS. The primary outcome was the change in time in standing position. Secondary outcomes comprised quantitative assessment of tremor, measurement of corticospinal excitability including short-latency afferent inhibition, and clinical global impression-improvement (CGI-I). Measurements were made at baseline, after sham tsDCS, 0-30 min, and 30-60 min after active conditions. RESULTS: Cathodal-tsDCS reduced tremor amplitude and frequency and lowered corticospinal excitability whereas anodal-tsDCS reduced tremor frequency only. CGI-I scores positively correlated with the time in standing position after both active tsDCS conditions. CONCLUSION: A single session of tsDCS can improve instability in POT. This opens a new vista for experimental treatment options using multiple sessions of spinal DC stimulation. © 2021 International Parkinson and Movement Disorder Society.

Unsupervised clustering analysis of data from an online community to identify lupus patient profiles with regards to treatment preferences.

OBJECTIVE: Lupus is a chronic complex autoimmune disease. Non-adherence to treatment can affect patient outcomes. Considering patients' preferences into medical decisions may increase acceptance to their medication. The PREFERLUP study used unsupervised clustering analysis to identify profiles of patients with similar treatment preferences in an online community of French lupus patients. METHODS: An online survey was conducted in adult lupus patients from the Carenity community between August 2018 and April 2019. Multiple Correspondence Analysis (MCA) was used with three unsupervised clustering methods (hierarchical, kmeans and partitioning around medoids). Several indicators (measure of connectivity, Dunn index and Silhouette width) were used to select the best clustering algorithm and choose the number of clusters. RESULTS: The 268 participants were mostly female (96%), with a mean age of 44.3 years 83% fulfilled the American College of Rheumatology (ACR) self-reported diagnostic criteria for systemic lupus erythematosus. Overall, the preferred route of administration was oral (62%) and the most important feature of an ideal drug was a low risk of side-effects (32%). Hierarchical clustering identified three clusters. Cluster 1 (59%) comprised patients with few comorbidities and a poor ability to identify oncoming flares; 84% of these patients desired oral treatments with limited side-effects. Cluster 2 (13%) comprised younger patients, who had already participated in a clinical trial, were willing to use implants and valued the compatibility of treatments with pregnancy. Cluster 3 (28%) comprised patients with a longer lupus duration, poorer control of the disease and more comorbidities; these patients mainly valued implants and injections and expected a reduction of corticosteroid intake. CONCLUSIONS: Different profiles of lupus patients were identified according to their drug preferences. These clusters could help physicians tailor their therapeutic proposals to take into account individual patient preferences, which could have a positive impact on treatment acceptance and then adherence. The study highlights the value of data acquired directly from patient communities.

Effects of Global Postural Reeducation on gait kinematics in parkinsonian patients: a pilot randomized three-dimensional motion analysis study.

The Global Postural Reeducation (GPR) method is a physical therapy based on the stretching of antigravity muscle chains with the parallel enhancement of the basal tone of antagonistic muscles addressed to improve static and dynamic stability. Through a three-dimensional motion analysis (3DMA) system, our study aims to investigate whether in Parkinson's disease (PD) patients a GPR program results in a more physiological gait pattern. The kinematic parameters of gait of twenty subjects with clinically diagnosed PD were calculated. The patients were randomly assigned to a study (10 or control (10) group. All subjects underwent neurological and 3DMA assessments at entry time (t 0), at 4 weeks (t 1, end of GPR program), and at 8 and 12 weeks (t 2 and t 3, follow-up evaluation). The study group underwent a four-week GPR program, three times a week, for 40 min individual sessions. Kinematic gait parameters of thigh (T), knee (K) and ankle (A) and UPDRS-III scores were evaluated. At the end of the GPR program, we observed an improvement of the kinematic gait pattern, documented by the increase in KΔc and TΔc values that respectively express the flexion amplitude of knee and thigh. The amelioration was persistent at follow-up assessments, with a parallel enhancement in clinical parameters. GPR intervention shows a long-term efficacy on gait pattern in PD patients. Furthermore, we validated 3DMA as a valuable tool to study the kinematics of gait thus refining the understanding of the effects of specific rehabilitation programs.

Patient Preferences for Treatment Attributes in Inflammatory Bowel Disease: Results From a Large Survey Across Seven European Countries Using a Discrete Choice Experiment.

BACKGROUND: Inflammatory bowel disease requires long-term treatment; therefore, understanding patient preferences is important in aiding informed treatment decision making. This study explored patients' preferences for treatment attributes of available inflammatory bowel disease therapies. METHODS: Adult patients from 7 European countries who self-reported previous/current treatment for Crohn's disease (CD) or ulcerative colitis (UC) participated in an online survey via the Carenity platform. In a discrete choice experiment, the relative importance of treatment attributes for CD and UC was estimated using conditional logit models. Latent class analysis was conducted to estimate heterogeneous treatment preferences based on patient profiles. Patients' perspectives and preferences regarding their quality of life were assessed. RESULTS: Across 686 completed survey responses (CD, n = 360; UC, n = 326), the mean patient age was 48 and 50 years, respectively. Patients with CD ranked route of administration as the most important attribute (attribute importance: 32%), preferring subcutaneous over intravenous treatment (P < .001). Patients with UC ranked route of administration and frequency of serious adverse events as the most important attributes (attribute importance: 31% and 23%, respectively), preferring oral (P < .001) and subcutaneous (P < .001) over intravenous treatment and treatment that minimized the risk of serious adverse events (P < .001) or mild adverse events (P < .01). Latent class analyses confirmed the impact of patients' sociodemographic profile on their preferences. All patients prioritized general well-being, energy level, and daily activities as the most important aspects for improvement through treatment. CONCLUSIONS: Patient preferences for treatment attributes varied among patients with CD or UC, highlighting the importance of personalized care and shared decision making to maximize treatment benefits.

This study explored patients' preferences for treatment attributes in Crohn's disease or ulcerative colitis, such as subcutaneous/intravenous drug administration and adverse effects. Patients' preferences highlighted the importance of personalized care and shared decision making to maximize treatment benefits.

Patient Perspectives on Value Dimensions of Lung Cancer Care: Cross-sectional Web-Based Survey.

BACKGROUND: While the lung cancer (LC) treatment landscape has rapidly evolved in recent years, easing symptom burden and treatment side effects remain central considerations in disease control. OBJECTIVE: The aim of this study was to assess the relative importance of dimensions of LC care to patients, and to explore the disease burden, including socioeconomic aspects not commonly covered in patient-reported outcomes instruments. METHODS: A questionnaire was sent to patients with LC and their caregivers to rate the value of a diverse set of quality of life dimensions in care, to evaluate communication between health care professionals (HCPs) and patients, and to explore the economic impact on respondents. The survey included questions on the dimensions of care covered by patient-reported outcomes instruments for quality-of-life evaluation (Functional Assessment of Cancer Therapy-Lung scale, EQ-5D, the European Organization for Research and Treatment of Cancer's Core Quality of Life questionnaire, and the European Organization for Research and Treatment of Cancer's Core Quality of Life in lung cancer 13-item questionnaire), as well as the International Consortium for Health Outcomes Measurement (ICHOM) standard set of patient-centered outcomes for LC. The survey respondents were participants on Carenity's patient community platform, living either in France, the United Kingdom, Germany, Italy, or Spain. RESULTS: The survey included 150 respondents (115 patients and 35 caregivers). "Physical well-being" and "end-of-life care" (median scores of 9.6, IQR 7.7-10, and 9.7, IQR 8.0-10, on a 10-point scale) were rated highest among the different value dimensions assessed. "Physical well-being and functioning" was the dimension most frequently discussed with health care professionals (82/150, 55%), while only (17/100, 17%) reported discussing "end-of-life care." After diagnosis, 43% (49/112) of patients younger than 65 years stopped working. Among respondents who indicated their monthly household income before and after diagnosis, 55% (38/69) reported a loss of income. CONCLUSIONS: Our results showed the relevance of a broad range of aspects of care for the quality of life of patients with LC. End-of-life care was the dimension of care rated highest by patients with LC, irrespective of stage at diagnosis; however, this aspect is least frequently discussed with HCPs. The results also highlight the considerable socioeconomic impact of the disease, despite insurance coverage of direct costs.

Patient knowledge of gut microbiota and acceptability of fecal microbiota transplantation in various diseases.

BACKGROUND: Fecal microbiota transplantation (FMT) is now evaluated in various diseases. However, large-scale population treatment may encounter feasibility issues in terms of acceptance. We aim to evaluate patient knowledge of gut microbiota and the acceptability of FMT in various diseases. METHODS: Patients of Carenity's French online community were invited by email to participate in a questionnaire. The following parameters were assessed: patient's principal illness and duration, demographic data, therapeutics, dietary habits, knowledge of gut microbiota, probiotics and FMT, and its acceptability. KEY RESULTS: In total, 877 patients participated in the online questionnaire: 156 with inflammatory bowel disease (17.8%), 127 with rheumatoid arthritis (14.5%), 222 with ankylosing spondylitis (25.3%), 52 with lupus (5.9%), 64 with psoriasis (7.3%), 61 with obesity (7%), and 195 with type 2 diabetes (22.2%). Characteristics of participating patients were similar to those of the entire cohort (n = 23084). Overall, 47.1% (n = 413/877) of patients knew what the microbiota is with no difference among diseases. Knowledge was reported to be developed by patients themselves (203/413; 49.2%) without involving a healthcare professional. If proposed by a healthcare professional, 37.2% (326/877) reported being interested or very interested in undergoing FMT. Factors associated with good acceptability of FMT were the male sex (OR: 1.63, CI95% [1.14 to 2.32]), previous knowledge of FMT (OR: 4.16, CI95% [2.92 to 5.96]), and previous knowledge of gut microbiota (OR: 1.54, CI95% [1.05 to 2.24]). CONCLUSION AND INFERENCES: Knowledge of gut microbiota is still limited in patients' communities and mainly developed by patients themselves, impacting FMT acceptability.

Patient perception of burden of disease and treatment preferences in non-small cell lung cancer: Results from a European survey.

OBJECTIVES: To understand European non-small cell lung cancer (NSCLC) patients' perceptions of disease burden, treatment, and future expectations of treatment and care. MATERIALS AND METHODS: A 32-item online survey was conducted on a sample of NSCLC patients across Europe. Descriptive statistics were used to analyse the data. Results were presented by disease stage (I-III vs. IV). RESULTS: NSCLC patients (N = 292) from 10 countries responded. Most patients resided in France, Spain, Italy, Germany and UK, with 16 patients from five other countries. Patients' knowledge of biomarker testing was limited (23% of 376 responses indicated no knowledge). Patients reported fear (stage I-III: 40%, stage IV: 27%), anxiety (stage I-III: 44%, stage IV: 33%) and depression (stage I-III: 24%, stage IV: 20%), but also hope (stage I-III: 57%, stage IV: 59%). Professional status was majorly impacted for 43% of stage I-III patients and 58% stage IV patients. Household finances were impacted for âˆ¼70% of all patients. Oral treatment was preferred (60%), and respondents understood dosing schedules (stage I-III: 82%, stage IV: 97%) remembering to take medications (stage I-III: 82%, stage IV: 87%). Most respondents were willing to take more pills, but some indicated that this would be difficult. CONCLUSION: Approximately half of the patients in this survey were aware of clinical trial options, but most lacked information about their molecular tumor profile, making it difficult for patients to engage in discussions about their care. The results also suggest that NSCLC patients have significant information and support needs, especially in the areas of emotional and financial burden. Action is needed to address these burdens associated with NSCLC. Furthermore, patients should be provided with the information needed to actively participate in treatment decisions.

Corrigendum: Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

[This corrects the article DOI: 10.3389/fneur.2020.00388.].

Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

Background: Botulinum toxin-A (BoNT-A) injections are first-line treatment for adult spasticity. Prior patient surveys have reported that BoNT-A treatment improves quality of life but that symptoms usually recur before the next injection. We aimed to explore, in-depth, patient perceptions of the impact of spasticity and the waning of BoNT-A therapeutic effects. Methods: An internet-based survey was conducted through Carenity, an online patient community, from May to September 2019 in France, Germany, Italy, UK and USA. Eligible respondents were adult patients with spasticity due to stroke, traumatic brain injury (TBI) or spinal cord injury (SCI) who had ≥2 previous BoNT-A injections. Results: Two hundred and ten respondents (mean 47.2 years) met screening criteria and had their responses analyzed. Overall, 43% of respondents had spasticity due to stroke, 30% due to TBI and 27% due to SCI. The mean [95% CI] injection frequency for spasticity management was 3.6 [3.4-3.7] injections/year. Respondents described the time profile of their response to BoNT-A. The mean reported onset of therapeutic effect was 12.9 [12.1-13.7] days and the mean time to peak effect was 5.0 [4.7-5.4] weeks. Symptom re-emergence between injections was common (83%); the time from injection to symptom re-emergence was 89.4 [86.3-92.4] days. Muscle spasms usually re-emerge first (64%), followed by muscle stiffness or rigidity (40%), and limb pain (20%). Over half (52%) of respondents said they had lost their self-confidence, 46% experienced depression and 41% experienced a lack of sleep due to their spasticity symptoms in the past 12 months. Following a report of symptom re-emergence, the most common management approaches were to add adjunctive treatments (36%), increase the BoNT-A dose (28%), and wait for the next injection (26%). Seventy two percentage of respondents said they would like a longer lasting BoNT-A treatment. Conclusions: Patients with spasticity can expect a characteristic profile of BoNT-A effects, namely time lag to onset and peak effect followed by a gradual decline in the symptomatic benefits. Symptom re-emergence is common and has significant impact on quality of life. Greater patient/clinician awareness of this therapeutic profile should lead to better level of overall satisfaction with treatment, informed therapeutic discussions and treatment schedule planning.

Decreasing subthalamic deep brain stimulation frequency reverses cognitive interference during gait initiation in Parkinson's disease.

OBJECTIVE: Freezing of gait (FOG) represents a major burden for Parkinson's disease (PD) patients. High-frequency (130-Hz) subthalamic deep-brain-stimulation (STN-DBS) has been reported to aggravate FOG whereas lowering the frequency to 60-80 Hz improves FOG. To further understand the effects of STN-DBS on FOG, we assessed the effects of 80-Hz and 130-Hz STN-DBS on gait initiation performance, in relation to motor and executive function processing. METHODS: Gait initiation was recorded in 19 PD patients and 20 controls, combined or not with a cognitive interference task with a modified Stroop paradigm. PD patients were recorded before surgery with and without dopaminergic treatment, and after surgery with 80-Hz and 130-Hz STN-DBS in a randomised double-blind crossover study. RESULTS: In the absence of cognitive interference, PD patients exhibited significant gait initiation improvement with dopaminergic treatment, 80-Hz and 130-Hz STN-DBS. Nine patients performed the cognitive interference task. With 130-Hz STN-DBS, all gait initiation parameters were significantly degraded, whereas the cognitive interference task induced no major changes before surgery and with 80-Hz STN-DBS, as in controls. CONCLUSIONS: High-frequency STN-DBS leads to an inability to simultaneously process motor and cognitive information while this ability seems preserved with low-frequency STN-DBS. SIGNIFICANCE: This study supports the potential benefit of 80-Hz STN-DBS on FOG.

Step length predicts executive dysfunction in Parkinson's disease: a 3-year prospective study.

Cognition and gait appear to be closely related. The chronological interplay between cognitive decline and gait dysfunction is not fully understood. The aim of the present prospective study is investigating whether the dysfunction of specific gait parameters, during specific task and medication conditions, may predict subsequent cognitive impairment in Parkinson's disease (PD). We evaluated cognition and gait in 39 Parkinsonian patients at an initial assessment and after 3 years. Cognitive performance was evaluated with a neuropsychological battery designed to assess memory, executive/attention, and visuospatial domains. Gait was investigated using a gait analysis system during both the off and on states in the following conditions: (1) normal gait; (2) motor dual task; and (3) cognitive dual task. We used regression models to determine whether gait predicts subsequent cognitive dysfunction. Overall, the cognitive test scores were stable over time with the exception of the executive/attention scores, whereas all gait parameters declined. The step length during the cognitive dual task during the on state at the initial evaluation was the only significant predictor of executive/attention domain dysfunction at follow up. The results were confirmed when executive/attention dysfunction at the initial assessment evaluation was included in the regression model as a covariate. Our longitudinal study offers additional insight into the progression of gait dysfunction, and its chronological relationship with cognitive dysfunction in PD patients. In particular, the present study indicates that step length during a cognitive task when on medication is an independent predictor of future executive/attention decline.

Spatio-temporal and kinematic gait analysis in patients with Frontotemporal dementia and Alzheimer's disease through 3D motion capture.

Alzheimer's disease (AD) and behavioral variant of Frontotemporal Dementia (bvFTD) are characterized respectively by atrophy in the medial temporal lobe with memory loss and prefrontal and anterior temporal degeneration with dysexecutive syndrome. In this study, we hypothesized that specific gait patterns are induced by either frontal or temporal degeneration. To test this hypothesis, we studied the gait pattern in bvFTD (23) and AD (22) patients in single and dual task ("motor" and "cognitive") conditions. To detect subtle alterations, we performed motion analysis estimating both spatio-temporal parameters and joint excursions. In the single task condition, the bvFTD group was more unstable and slower compared to healthy subjects, while only two stability parameters were compromised in the AD group. During the motor dual task, both velocity and stability parameters worsened further in the bvFTD group. In the same experimental conditions, AD patients showed a significantly lower speed and stride length than healthy subjects. During the cognitive dual task, a further impairment of velocity and stability parameters was observed in the bvFTD group. Interestingly, during the cognitive dual task, the gait performance of the AD group markedly deteriorated, as documented by the impairment of more indices of velocity and stability. Finally, the kinematic data of thigh, knee, and ankle were more helpful in revealing gait impairment than the spatio-temporal parameters alone. In conclusion, our data showed that the dysexecutive syndrome induces specific gait alterations. Furthermore, our results suggest that the gait worsens in the AD patients when the cognitive resources are stressed.

Impaired gait kinematics in type 1 Gaucher's Disease.

Type 1 Gaucher's disease (GD1) is traditionally regarded as "non-neurological". Spatiotemporal and kinematic analysis of gait was carried on thirteen GD1 patients and thirteen healthy controls. We identified a previously unknown subclinical reduction of amplitude of movements in GD1. Articular excursion of ankle, knee and hip was reduced during the swing phase of gait (p <  0.0001). Furthermore, the excursion of the knee appeared also significantly more asymmetric in GD1 patients (p = 0.02). Correction for age, BMI and basal walking speed did not modify the significance. Accordingly to the recent observations that GD1 predisposes to Parkinson's disease, the impaired and asymmetric gait kinematics that we observed might be interpreted as a form of extrapyramidal involvement.