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Effectiveness of Foot Reflexology (FR) on the pain intensity in Parkinson's disease (PD) compared with Sham Massage (SM). Monocentric, longitudinal, prospective, double-blind, randomized controlled trial. Randomization with a random number generator in the R software. Fixed-sized block randomization of 3 implemented into Clinsight. Idiopathic PD patients with chronic pain (Visual Analogue Scale (VAS)≥4) were recruited from the Toulouse University Hospital between the 14th of April 2021 and the 25th of May 2025. Four one-hour long FR or SM sessions three weeks apart with the same specialized FR researcher. Pain intensity change measured by the mean VAS before and after full completed interventions. The difference was compared between group using a Wilcoxon Mann Witney test. Exploratory outcome: brain functional connectivity. 30 PD patients were randomized and analyzed. Interventions were delivered as planned for all patients. Clinical variables did not significantly differed between FR and SM groups. Mean VAS decreased by -12.3 mm ± 15.2 in FR group (n = 15) and -17.9 mm ± 29.4 in SM group (n = 15). Analyses did not reveal any significant difference between the FR and SM groups (p-value = 0.88). There are different patterns in connectivity changes in the medial pain system between responders (at least 30% pain reduction) and non-responders to both therapies. There were no adverse events. FR is not more effective than SM in relieving chronic pain in PD. The differences in connectivity patterns within the medial pain pathway may underlie the response to tactile stimulation (FR and SM). ClinicalTrials.gov NCT04705207.

Background Multiple system atrophy (MSA) is characterized by progressive autonomic/motor dysfunction, but robust biomarkers do not exist. Electrochemical skin conductance (ESC) provides a noninvasive measure of sudomotor function, but its longitudinal predictive value and prognostic relevance in MSA remain insufficiently studied. We aimed to comprehensively evaluate ESC in a large longitudinal cohort. Methods We analyzed 175 patients with MSA followed for a mean of 4.2 ± 2.1 years. Disease severity was assessed using UMSARS Parts 1 and 2, COMPASS31, SCOPA‐AUT, and orthostatic blood pressure (BP) measurements. Hand and foot ESC were measured using Sudoscan. Cross‐sectional and longitudinal associations were examined using linear mixed‐effects models, repeated‐measures correlations, and grouped 10‐fold cross‐validation. Mortality predictors were assessed with time‐varying Cox proportional hazards models. Results ESC was strongly inversely associated with UMSARS 1 and 2 (β = −0.58 to −0.65; r = −0.67 to −0.75; all p < 0.0001), whereas associations with orthostatic BP, autonomic symptom scales, and disease duration were weaker or inconsistent. ESC declined significantly over time (feet −6.88 ± 0.60 μS/year; hands −5.41 ± 0.46 μS/year; both p < 0.001), paralleling UMSARS progression. ESC outperformed orthostatic BP drops in predicting UMSARS scores in mixed‐effects models and cross‐validation. Higher ESC independently predicted lower mortality, while higher UMSARS scores and greater orthostatic BP drops predicted increased risk. Median survival was 46.2 months. Conclusions ESC is a sensitive biomarker of disease severity, progression, and survival in MSA, substantially outperforming orthostatic BP measures. Its simplicity and prognostic value support incorporation into routine monitoring and clinical trials. In a longitudinal cohort of 175 patients with multiple system atrophy followed for 4.2 years, electrochemical skin conductance (ESC) was strongly associated with disease severity (UMSARS), declined significantly over time, and independently predicted survival. ESC outperformed orthostatic blood pressure drops in tracking progression and predicting clinical outcomes. These findings support ESC as a simple, noninvasive biomarker for monitoring disease progression and as a candidate endpoint for clinical trials.

Background Spinocerebellar ataxia 27B is the most common genetic late onset cerebellar ataxia (LOCA). However, it commonly overlaps with other genetic LOCA as with the cerebellar form of multiple system atrophy (MSA-C). Objectives To pinpoint which clinical signs and symptoms best discriminate between FGF14  + from FGF14  − patients at symptoms’ onset. Methods Twenty SCA27B (≥ 250 GAA repeat expansion) patients were retrospectively matched by gender and age at disease onset with 20 negative FGF14 (−) LOCA patients and with 20 MSA-C patients. Clinical features were ranked based on their contribution towards distinguishing between the groups (feature importance ranking). Results SCA27B patients had significantly higher rates of episodic symptoms, cerebellar oculomotor signs, dysdiadochokinesia, and alcohol intolerance than LOCA- FGF14  − ataxia patients. The lack of autonomic symptoms and MRI signs in SCA27B patients were the most discriminating features from MSA-C. An AUC of 0.87 was obtained if using the “top 3 clinical features model” (episodic symptoms, cerebellar oculomotor signs and dysdiadochokinesia) to distinguish SCAB27 from LCOA FGF14  − . Regarding MRI findings, no significant differences were found between SCA27B and FGF14  − patients, while a positive hot cross buns sign and the presence of brainstem atrophy were key distinguishing features between SCA27B from MSA-C patients ( p  < 0.005). Conclusion Our pilot case–control study contributes to the identification of early clinical symptoms to differentiate SCA27B to LOCA patients including FGF14 - and MSA-C ones. From a feature perspective, while clinical features are crucial, identifying surrogate biomarkers—such as ocular or gait parameters—could aid in the early diagnosis and follow-up of SCA27B patients.

BackgroundThe objective was to compare different definitions of remission and low disease activity (LDA) in patients with psoriatic arthritis (PsA), based on both patients’ and physicians’ perspectives.MethodsIn ReFlap (Remission/Flare in PsA; NCT03119805), adults with physician-confirmed PsA and >2 years of disease duration in 14 countries were included. Remission was defined as very low disease activity (VLDA), Disease Activity index for PSoriatic Arthritis (DAPSA) ≤4, and physician-perceived and patient-perceived remission (specific question yes/no), and LDA as minimal disease activity (MDA), DAPSA <14, and physician-perceived and patient-perceived LDA. Frequencies of these definitions, their agreement (prevalence-adjusted kappa), and sensitivity and specificity versus patient-defined status were assessed cross-sectionally.ResultsOf 410 patients, the mean age (SD) was 53.9 (12.5) years, 50.7% were male, disease duration was 11.2 (8.2) years, 56.8% were on biologics, and remission/LDA was frequently attained: respectively, for remission from 12.4% (VLDA) to 36.1% (physician-perceived remission), and for LDA from 25.4% (MDA) to 43.9% (patient-perceived LDA). Thus, patient-perceived remission/LDA was frequent (65.4%). Agreement between patient-perceived remission/LDA and composite scores was moderate to good (kappa range, 0.12–0.65). When patient-perceived remission or LDA status is used as reference, DAPSA-defined remission/LDA and VLDA/MDA had a sensitivity of 73.1% and 51.5%, respectively, and a specificity of 76.8% and 88.0%, respectively. Physician-perceived remission/LDA using a single question was frequent (67.6%) but performed poorly against other definitions.ConclusionIn this unselected population, remission/LDA was frequently attained. VLDA/MDA was a more stringent definition than DAPSA-based remission/LDA. DAPSA-based remission/LDA performed better than VLDA/MDA to detect patient-defined remission or remission/LDA. Further studies of long-term outcomes are needed.

BackgroundPrevious studies suggested that the 2-step approach of Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is accurate in stratifying patients with MASLD on the risk of liver-related events (LREs). This study aimed to assess whether prognostic performance was affected in specific patient subpopulations.MethodsThe VCTE-Prognosis study included patients with MASLD who had undergone VCTE examination across 16 centers in Asia, Europe, and the US with follow-up for clinical events. Patients were classified into different subpopulations, which included patients with and without diabetes, elevated alanine transaminase (ALT) levels, obesity, obesity and ≥1 additional CMRF, and patients with ≥2 CMRFs. The integrated time-dependent area under the receiver operating characteristic curve (itAUROC) of LREs over 5 years was used as the primary measure of discriminatory power.ResultsWe included 12,950 patients (mean age 52 years old, 41% female) with MASLD and available FIB-4 and LSM. The itAUROC of the 2-step approach in all patients was 0.832, with 248 (1.9%) patients developing LREs at a median follow-up of 47 months. Of the at-risk populations, patients with obesity, obesity and ≥1 CMRF, ≥2 CMRFs, and elevated ALT levels had an itAUROC of >0.8 (IDDF2025-ABS-0022 figures 1 and 2). In these respective subpopulations, 141 (1.8%), 137 (1.9%), 209 (2.0%), and 55 (1.6%) patients developed LREs. Patients with diabetes had a lower itAUROC of 0.797, with 158 (3.0%) patients developing LREs. For the other subpopulations, obese patients with no additional CMRFs and patients with <2 CMRFs had a comparatively lower itAUROC (0.617 and 0.660, respectively). All subpopulations had a consistent trend of increasing cumulative incidence of LREs as risk increased (IDDF2025-ABS-0022 figure 3).Abstract IDDF2025-ABS-0022 Figure 1Abstract IDDF2025-ABS-0022 Figure 2Abstract IDDF2025-ABS-0022 Figure 3ConclusionsThe 2-step approach remains accurate for classifying different risk of LREs in at-risk patients with MASLD. The relatively low itAUROCs in non-at-risk patients confirm EASL and AGA guidelines for targeting at-risk patients using the 2-step algorithm. However, these comparatively lower itAUROCs should be interpreted with caution due to the smaller subpopulation size and number of LREs.