Edited by: Alain Hamaoui, Jean-François Champollion University Center for Teaching and Research, France
Reviewed by: Arnaud Saj, Université de Genève, Switzerland; Sébastien Caudron, Université de Lorraine, France
*Correspondence: Leslie M. Decker
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Elhers-Danlos syndrome (EDS) is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS) is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability. Therefore, the purpose of this study was twofold: (i) to assess the impact of somatosensory deficit on subjective visual vertical (SVV) and postural stability; and (ii) to quantify the effect of wearing somatosensory orthoses (i.e., compressive garments and insoles) on postural stability. Six hEDS patients and six age- and gender-matched controls underwent a SVV (sitting, standing, lying on the right side) evaluation and a postural control evaluation on a force platform (Synapsys), with or without visual information (eyes open (EO)/eyes closed (EC)). These two latter conditions performed either without orthoses, or with compression garments (CG), or insoles, or both. Results showed that patients did not exhibit a substantial perceived tilt of the visual vertical in the direction of the body tilt (Aubert effect) as did the control subjects. Interestingly, such differential effects were only apparent when the rod was initially positioned to the left of the vertical axis (opposite the longitudinal body axis). In addition, patients showed greater postural instability (sway area) than the controls. The removal of vision exacerbated this instability, especially in the mediolateral (ML) direction. The wearing of orthoses improved postural stability, especially in the eyes-closed condition, with a particularly marked effect in the anteroposterior (AP) direction. Hence, this study suggests that hEDS is associated with changes in the relative contributions of somatosensory and vestibular inputs to verticality perception. Moreover, postural control impairment was offset, at least partially, by wearing somatosensory orthoses.
The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of hereditary connective tissue diseases, which are present in at least 1/5000 individuals with a majority of women (Sobey,
Indeed, somatosensory information, arising from muscles, skin, and joints, plays a key role in perception, balance and, more broadly in movement. Currently, there is growing evidence that balance and movement are both based on heteromodal integration of three types of sensory modality, visual, vestibular, and somatosensory, which carry redundant, specific and complementary information (Massion,
Mittelstaedt (
Compression garments (CG) have been tested empirically in clinical practice in hEDS, resulting in beneficial effects on pain, fatigue and mobility. Speculatively, the CG, due to their mechanical effect, are thought to enhance joint coaptation and increase the pressure of the subcutaneous connective tissue to a normal range. Hence, CG may enhance somatosensory feedback to the brain and, thus, its contribution to postural control. Similarly, proprioceptive insoles (PI) may enhance plantar cutaneous afferents and postural stability. Therefore, somatosensory orthoses (i.e., CG and PI) offer a therapeutic solution to reduce somatosensory impairments, however weakly evaluated. Along with these observations, previous studies have demonstrated that CG induced an improvement in knee proprioception, and PI decreased the attentional demand for gait (Clark et al.,
The goal of the present study was to assess: (i) the impact of somatosensory deficit on subjective visual vertical (SVV) and postural stability; and (ii) the effects of somatosensory orthoses (i.e., CG and PI) on static postural control. We hypothesized that: (i) somatosensory impairments would modify SVV, strongly impair postural stability and increase the use of visual information; and (ii) enhancing somatosensory feedback with the orthoses would restore the balance in the use of sensory modalities, thus reducing the use of visual information, and consequently enhance postural stability.
Six patients with hEDS (6 females; mean age ± SD: 37 ± 10.41 years) and six healthy, age- and gender-matched control subjects (6 females; mean age ± SD: 36 ± 11.52 years) participated in this study. Patient selection was carried out in the Internal Medicine Department of Caen University Hospital. Inclusion criteria were based on the revised Villefranche criteria, including the presence of generalized joint hypermobility, skin hyperelasticity, chronic musculoskeletal pain, and/or a positive family history (Beighton et al.,
All subjects were treated in strict compliance with the Declaration of Helsinki. The protocol was approved by the CERSTAPS (Ethical Committee of Sport and Physical Activities Research), Notice Number: 2016-26-04-13, approved by the National Academic Commission (CNU) on April 26, 2016. Written informed consent was obtained from all participants.
The CG and PI required in this study were customized based on the needs of each patient by orthotic and prosthetic practitioners (Novatex Medical). CG included pants, vest, and mittens, which covered the entire body of all participants (i.e., trunk, upper and lower limbs; Figure
Postural sway was recorded using a motorized force platform (SYNAPSYS, France). Three strain gauges integrated into the force platform recorded the vertical ground reaction force component. The data were sampled at 100 Hz and transformed by computer-automated stability analysis software (i.e., Synapsys software) to obtain x-y coordinates of the center of pressure (COP).
Perception of the vertical was assessed by the SVV test using the Perspective System® (Framiral®, France).
In the first part of the experiment, participants underwent postural control assessment (duration: 1 h 45 min for patients, and 20 min for controls) followed by SVV assessment (duration: 15 min for all participants).
To assess the SVV, each participant, in a completely darkened room, was shown, in front of them, the projection of a luminous rod (laser line 2 m in length placed 3 m in front of them). Participants could rotate the rod around its center in the clockwise or counterclockwise directions using a transmitter, and were instructed to place the rod vertically with respect to the true gravitational vertical. All subjects performed the SVV test in three conditions: standing, sitting and lying on their right side. In this latter condition, participants lay in a standard position on a stretcher with an adjustable head-rest, which was positioned identically initially for each participant (body and head were tilted, respectively, at 90° and 72°). Subjects were asked to minimize their movements during the tests. Each condition comprised four trials: two with the rod initially oriented to the right side (i.e., 30° to the right—clockwise) and two to the left side (i.e., −30° to the left—counterclockwise). The tests and conditions were randomly distributed within each participant.
Postural sway was measured for 52 s while participants stood on a force platform. Participants were asked to stand still, barefoot, arms hanging freely, feet positioned at an angle of 30°, and to focus on a visual reference mark fixed 1.5 m in front of them in their individual line of vision. The assessment comprised four conditions with two tests each lasting 52 s, with a 20 s rest between each test, and 5 min between each condition. The start and stop signals were given 3 s before and 3 s after each acquisition. The four conditions were: (1) control condition (CC; without orthoses); (2) CG; (3) PI; and (4) the combination of CG and PI (CG-PI). Each condition was performed with either eyes open (EO) or eyes closed (EC). Participants also underwent dual-task (combining postural control with a cognitive task) and dynamic (sinusoidal translation of support) trials under the four above-mentioned conditions (results are not included in the present article). To minimize any order effects during testing, such as fatigue effects, all conditions and trials (EO/EC) were randomized among subjects. A training test was performed before testing (Figure
Design of the postural control assessment.
SVV evaluation error was scored in degrees of deviation from the vertical. Mean errors were calculated across conditions, according to the initial orientation of the rod. Errors were scored negatively when the subjective vertical was oriented to the left, and positively when it was oriented to the right.
Postural sway parameters calculated from the COP recordings were as follows: the anteroposterior and mediolateral sway standard deviation (SD-AP/SD-ML; mm) and the sway area (AREA-CE; mm2) corresponding to the 95% confidence elliptic area included within the COP path.
The SVV (angle of deviation from the vertical) and postural (AREA-CE, SD-AP and SD-ML) dependent variables failed to display an acceptable normal distribution (Shapiro-Wilk test). Consequently, non-parametric tests were used for statistical analysis.
The Mann-Whitney U-test was used to compare healthy controls to hEDS patients on verticality perception and postural stability. A Friedman test was used to determine differences between the performances carried out in each postural condition (CC, CG, PI and CG/PI) and each SVV condition (standing, seated, lying: right and left initial orientation). When the result of the Friedman test was significant, we subsequently used a Wilcoxon test for matched samples to determine the effects of vision (EO and EC) and somatosensory orthoses on postural stability. We used the Bonferroni method to correct for multiple comparisons. Statistical significance was set at 0.05. Statistica (version 10, Statsoft, Inc., Tulsa, OK, USA) was used to perform all analyses.
We first analyzed perception of the visual vertical in each position (standing, seated, lying on the right side) using the Mann-Whitney U-test. In standing condition, hEDS patients oriented the vertical more in left side than controls, when the initial orientation of the rod was also on the left (
Comparison of subjective visual vertical (SVV) performance between hEDS patients and controls in different body positions:
The Friedman test revealed significant differences in verticality perception according to the initial orientation of the rod (right and left) and body position (sitting, standing and lying on the right) in hEDS patients (
Regardless of the position, the initial orientation of the rod seems to influence the verticality perception of hEDS patients (sitting:
Compared with controls, hEDS patients showed impaired postural stability, as reflected by their increased sway area (EO,
Comparison of AREA-CE (area of 95% confidence circumference, mm2) obtained by hEDS patients and controls, with and without somatosensory orthoses (CG, compression garments; PI, proprioceptive insoles; CG-PI, both somatosensory orthoses): in
The Friedman test was conducted to assess the effects of somatosensory orthoses on postural stability in hEDS patients in four conditions (control, PI, CG, and PI-CG), with (EO) and without (EC) vision. Then, as six side-by-side comparisons were carried out within each
The Friedman test revealed that somatosensory orthoses tended to have a significant effect on sway area (
Comparison of SD-AP (standard deviation of anteroposterior center-of-pressure (COP) displacement: mm) obtained by hEDS patients and controls, with and without somatosensory orthoses (CG, compression garments; PI, proprioceptive insoles; CG-PI, both somatosensory orthoses): in
Comparison of SD-ML (standard deviation of mediolateral COP displacement: mm) obtained by hEDS patients and controls, with eyes open (EO) and eyes closed (EC) depending on the somatosensory orthoses worn (CG, compression garments; PI, proprioceptive insoles; CG-PI, both somatosensory orthoses). Box plots represent median and quartiles, and dots represent performance of each participant as follows: controls: black; patient 1: red; patient 2: green; patient 3: purple; patient 4: light blue; patient 5: orange; patient 6: dark blue.
The Friedman test revealed that somatosensory orthoses significantly impacted AP sway SD (
The increased sway area found in hEDS patients without vision and somatosensory orthoses (
In the standing condition, the results obtained by hEDS patients suggest a greater deviation from true gravitational vertical than controls. This effect seems to be less apparent in the sitting condition. These findings suggest that hEDS is associated with changes in the neural processing of somatosensory inputs, which could in turn alter judgment of the SVV (Trousselard et al.,
In line with previous studies, hEDS patients showed significant difficulties in controlling COP displacements (i.e., increased sway area—confidence ellipse area), especially when visual information was absent (Galli et al.,
In hEDS patients (notably the most unstable cases), the wearing of somatosensory orthoses seems to reduce their postural instability (i.e., sway area) to such an extent that their performances became comparable to those of controls in eyes-open condition. However, further investigations will be required to confirm these preliminary observations with a larger sample. Interestingly, this effect turned out to be even more pronounced in the absence of visual information. Wearing the two orthoses in combination seems to help patients stabilize their balance and minimize their AP sway SD. Thus, the combined wearing of orthoses could induce a synergetic effect. Indeed, it seems to improve postural stability more than the wearing of the CG or PI separately in the eyes-closed condition for both sway area and AP sway SD. Therefore, one can reasonably hypothesize that the increased cutaneous plantar sensation applied by pressure on sole receptors from PI could be concurrent with the increased cutaneous sensation and joint position sense promoted by CG. Hence, the combination of CG and PI could possibly enhance the available somatosensory information and, consequently, balance, even without vision. In addition, it is noteworthy that removal of visual information increases the impact of somatosensory orthoses on postural stability, especially in the AP direction. We thus suggest that, in the EO condition, visual information compensates for the lack of somatosensory information. Consequently, the removal of vision obliges patients to rebalance their use of sensory modalities in favor of somatosensory information, thus reinforcing the somatosensory input provided by orthoses. In contrast, ML stability appears to be scarcely affected by the somatosensory orthoses and remained sensitive to visual input. This result supports our previous hypothesis, which assumed that visual information was, at least in part, responsible for ML stability. Besides, our results showed no effect of somatosensory orthoses on overreliance on visual input in hEDS patients. Also, their postural strategy, which consists in compensating their lack of somatosensory information by ample use of visual information, appears to have persisted although the somatosensory input was enhanced. It is thus legitimate to assume that, in order to modify the strategy adopted by these patients, prolonged wearing of somatosensory orthoses would be necessary. The long-term use of somatosensory orthoses would both stimulate and preserve somatosensory receptors and thus develop and consolidate the neural network, supporting a more balanced sensory-motor strategy. Lastly, unlike previous studies which found no effect for PI and CG, our study suggested their efficacy on postural stability in hEDS patients (Hijmans et al.,
This pilot study presents a number of limitations. First, the study was conducted on a small sample. Second, the methodology used to investigate SVV could be improved in several respects: (i) the number of trials performed (Piscicelli et al.,
Collectively, the functional explorations performed on hEDS patients, using posturography and SVV, suggest an imbalance in the integration of sensory inputs. The results tended to show that somatosensory impairment modifies both verticality perception (Aubert effect) and postural instability. More specifically, results from postural assessment suggest a re-weighting of multisensory integration in favor of visual input. This compensatory strategy, adopted by the patients in order to maintain their balance, may diminish their adaptability, which could, at least in part, account for their postural instability. In contrast, our findings suggest an enhancement of somatosensory feedback induced by the orthoses, thus facilitating postural control, which in turn tends to become more stable. Lastly, this is the first investigation assessing the effect of somatosensory orthoses in hEDS patients, providing new perspectives for improving medical care. However, the observations in this pilot study need to be confirmed by further investigations with a larger number of subjects. Yet, they strongly suggest that postural and SVV assessments are potentially useful tools for the diagnosis and monitoring of this pathology.
LMD and EGD designed the study. LMD, EGD and PL carried out the experiment. EGD, LMD and CC analyzed the data. EGD and LMD conceived the figures. EGD, LMD, SB, BB and PD interpreted the results and drafted the manuscript. BB, AS and EV screened potential participants to determine their eligibility for the study. All authors revised the manuscript and approved its final version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This research was funded by the Normandy Integrative Biology, Health, Environment Doctoral School (EGD), the Regional Council of Basse-Normandie (equipment funding), and the “Association des Patients Normands Ehlers Danlos” (APNED, President: Dr. Claire El Moudden). We sincerely thank the company NOVATEX Medical® for providing customized compression garments and proprioceptive insoles for the patients, and all the participants in our study.