A Wearable Proprioceptive Stabilizer (Equistasi®) for Rehabilitation of Postural Instability in Parkinson’s Disease: A Phase II Randomized Double-Blind, Double-Dummy, Controlled Study

<div><p>Background</p><p>Muscle spindles endings are extremely sensitive to externally applied vibrations, and under such circumstances they convey proprioceptive inflows to the central nervous system that modulate the spinal reflexes excitability or the muscle responses elicited by postural perturbations. The aim of this pilot study is to test the feasibility and effectiveness of a balance training program in association with a wearable proprioceptive stabilizer (Equistasi) that emits focal mechanical vibrations in patients with PD.</p><p>Methods</p><p>Forty patients with PD were randomly divided in two groups wearing an active or inactive device. All the patients received a 2-month intensive program of balance training. Assessments were performed at baseline, after the rehabilitation period (T1), and two more months after (T2). Posturographic measures were used as primary endpoint; secondary measures of outcome included the number of falls and several clinical scales for balance and quality of life.</p><p>Results</p><p>Both groups improved at the end of the rehabilitation period and we did not find significant between-group differences in any of the principal posturographic measures with the exception of higher sway area and limit of stability on the instrumental functional reach test during visual deprivation at T1 in the Equistasi group. As for the secondary outcome, we found an overall better outcome in patients enrolled in the Equistasi group: 1) significant improvement at T1 on Berg Balance Scale (+45.0%, p = .026), Activities-specific Balance Confidence (+83.7, p = .004), Falls Efficacy Scale (−33.3%, p = .026) and PDQ-39 (−48.8%, p = .004); 2) sustained improvement at T2 in terms of UPDRS-III, Berg Balance Scales, Time Up and Go and PDQ-39; 3) significant and sustained reduction of the falls rate.</p><p>Conclusions</p><p>This pilot trial shows that a physiotherapy program for training balance in association with focal mechanical vibration exerted by a wearable proprioceptive stabilizer might be superior than rehabilitation alone in improving patients’ balance.</p><p>Trial Registration</p><p>EudraCT <a href="https://eudract.ema.europa.eu/" target="_blank">2013-003020-36</a> and ClinicalTrials.gov (<a href="http://clinicaltrials.gov/" target="_blank">number not assigned</a>)</p></div

The CONSORT flow diagram for this study.

<p>The CONSORT flow diagram for this study.</p

Static stabilometry values of the two groups enrolled in the study at each time point.

<p>Abbreviations: *: significantly different than T0 (p = .008); **: significantly different than Equistasi (p = .011); COP: centre of pressure; EC: eyes closed; EO: eyes open.</p><p>Static stabilometry values of the two groups enrolled in the study at each time point.</p

Clinical variables of the two groups enrolled in the study and their comparisons at each time point.

<p>Bold-typed values represent significant improvement; abbreviations: *: score reduction means improvement; ∧: score increase means improvement; ABC: Activities-specific Balance Confidence; BBS: Berg balance scale; FES: Falls Efficacy Scale; TUG: timed up and go, UPDRS: unified PD rating scale.</p><p>Clinical variables of the two groups enrolled in the study and their comparisons at each time point.</p

The wearable postural stabilizer (Equistasi) employed in the present study.

<p>The wearable postural stabilizer (Equistasi) employed in the present study.</p

The sway area and the displacement along the AP axis (expressed as value normalized to the baseline) at the instrumental FRT during EO (left panels) and EC (right panels) conditions.

<p>Data are presented as mean ± standard deviation. Abbreviations: AP: antero-posterior; EC: eyes closed; EO: eyes open; *: p = .006; **: p = .02; ***: p = .01 (Wilcoxon signed-rank test).</p

Water-based vs. non-water-based physiotherapy for rehabilitation of postural deformities in Parkinson's disease: A randomized controlled pilot study

Objective: Our aim was to evaluate the feasibility of a hydrotherapy treatment in patients with Parkinson\u2019s disease and the effectiveness of this treatment on balance parameters in comparison to a traditional landbased physical therapy. Design: A randomized single-blind controlled trial. Setting: Outpatients. Subjects: Thirty-four patients with Parkinson\u2019s disease in Hoehn-Yahr stage 2.5\u20133. Intervention: Group 1 hydrotherapy treatment, group 2 land-based rehabilitation treatment. The two groups underwent the same rehabilitation period (60 minutes of treatment, five days a week for two months). Main measures: The primary outcome measures were the centre of the pressure sway area recorded with open and closed eyes, using a stabilometric platform. Secondary outcome measures were Unified Parkinson\u2019s Disease Rating Scale II and III, Timed Up and Go Test, Berg Balance Scale, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, Falls diary and Parkinson\u2019s Disease Questionnaire-39. Results: Hydrotherapy treatment proved to be feasible and safe. Patients in both groups had a significant improvement in all outcome variables. There was a better improvement in patients who underwent hydrotherapy than in patients treated with land-based therapy in the centre of pressure sway area closed eyes (mean SD change: 45.4 SD64.9 vs. 6.9 SD45.3, p = 0.05), Berg Balance Scale (51.2 SD3.1 vs. 6.0 SD3.1, p = 0.005), Activities-specific Balance Confidence Scale (16.8 SD10.6 vs. 4.1 SD5.4, p = 0.0001), Falls Efficacy Scale ( 125.9 SD4.8 vs. 121.9 SD1.4, p = 0.003), Parkinson\u2019s Disease Quetionnaire-39 ( 1218.4 SD12.9 vs. 128.0 SD7.0, p = 0.006) and falls diary ( 122.4 SD2.2 vs. 120.4 SD0.5, p = 0.001)

Effects of a sensory-motor orthotic on postural instability rehabilitation in Parkinson's disease: a pilot study

Proprioceptive deficits have been largely documented in PD patients, thus external sensory signals (peripheral sensory feedback) are often used to compensate the abnormalities of proprioceptive integration. This pilot study aims to evaluate the feasibility and the effectiveness of a rehabilitation-training program, combined with the use of a sensory-motor orthotic in improving balance in a small sample of PD patients

Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies

Gene expression is controlled by epigenetic deregulation, a hallmark of cancer. The DNA methylome of canine diffuse large B-cell lymphoma (cDLBCL), the most frequent malignancy of B-lymphocytes in dog, has recently been investigated, suggesting that aberrant hypermethylation of CpG loci is associated with gene silencing. Here, we used a multi-omics approach (DNA methylome, transcriptome and copy number variations) combined with functional in vitro assays, to identify putative tumour suppressor genes subjected to DNA methylation in cDLBCL. Using four cDLBCL primary cell cultures and CLBL-1 cells, we found that CiDEA, MAL and PCDH17, which were significantly suppressed in DLBCL samples, were hypermethylated and also responsive (at the DNA, mRNA and protein level) to pharmacological unmasking with hypomethylating drugs and histone deacetylase inhibitors. The regulatory mechanism underneath the methylation-dependent inhibition of those target genes expression was then investigated through luciferase and in vitro methylation assays. In the most responsive CpG-rich regions, an in silico analysis allowed the prediction of putative transcription factor binding sites influenced by DNA methylation. Interestingly, regulatory elements for AP2, MZF1, NF-kB, PAX5 and SP1 were commonly identified in all three genes. This study provides a foundation for characterisation and experimental validation of novel epigenetically-dysregulated pathways in cDLBCL