Investigation of dermal collagen nanostructures in Ehlers-Danlos Syndrome (EDS) patients.

Ehlers-Danlos syndromes (EDS) represent a group of rare genetic disorders affecting connective tissues. Globally, approximately 1.5 million individuals suffer from EDS, with 10,000 reported cases in Canada alone. Understanding the histological properties of collagen in EDS has been challenging, but advanced techniques like atomic force microscopy (AFM) have opened up new possibilities for label-free skin imaging. This approach, which explores Type I collagen fibrils at the nanoscale, could potentially enhance EDS diagnosis and our knowledge of collagen type I-related connective tissue disorders. In the current study, we have employed AFM to examine ex-vivo skin biopsies from four individuals: one with classical EDS (cEDS), one with hypermobile EDS (hEDS), one with hEDS and Scleroderma (hEDS-Scleroderma), and one healthy control. Picrosirius red (PS) staining was used to highlight collagen differences in the samples. For each case, 14 images and 1400 force curves were obtained, with seven images and 700 force curves representing healthy collagen (PS-induced red staining) and the rest showcasing disrupted collagen (yellow staining). The results showed that PS staining was uniform throughout the control section, while cEDS and hEDS displayed localized areas of yellow staining. In the case of hEDS-Scleroderma, the yellow staining was widespread throughout the section. AFM images revealed irregular collagen fibrils in the disrupted, yellow-stained areas, contrasting with aligned and well-registered collagen fibrils in healthy, red-stained regions. Additionally, the study assessed the ability of non-AFM specialists to differentiate between healthy and disrupted collagen in AFM images, yielding substantial agreement among raters according to Fleiss's and Cohen's kappa scores (0.96 and 0.79±0.1, respectively). Biomechanical analysis revealed that normal healthy collagen exhibited a predominant population at 2.5 GPa. In contrast, EDS-affected collagen displayed subpopulations with lower compressive elastic modulus, indicating weaker collagen fibrils in EDS patients. Although these findings pertain to a limited number of cases, they offer valuable insights into the nanoscale collagen structure and biomechanics in individuals with EDS. Over time, these insights could be developed into specific biomarkers for the condition, improving diagnosis and treatment for EDS and related connective tissue disorders.

Automated, Vision-Based Goniometry and Range of Motion Calculation in Individuals With Suspected Ehlers-Danlos Syndromes/Generalized Hypermobility Spectrum Disorders: A Comparison of Pose-Estimation Libraries to Goniometric Measurements.

Generalized joint hypermobility (GJH) often leads clinicians to suspect a diagnosis of Ehlers Danlos Syndrome (EDS), but it can be difficult to objectively assess. Video-based goniometry has been proposed to objectively estimate joint range of motion in hyperextended joints. As part of an exam of joint hypermobility at a specialized EDS clinic, a mobile phone was used to record short videos of 97 adults (89 female, 35.0 ± 9.9 years old) undergoing assessment of the elbows, knees, shoulders, ankles, and fifth fingers. Five body keypoint pose-estimation libraries (AlphaPose, Detectron, MediaPipe-Body, MoveNet - Thunder, OpenPose) and two hand keypoint pose-estimation libraries (AlphaPose, MediaPipe-Hands) were used to geometrically calculate the maximum angle of hyperextension or hyperflexion of each joint. A custom domain-specific model with a MobileNet-v2 backbone finetuned on data collected as part of this study was also evaluated for the fifth finger movement. Spearman's correlation was used to analyze the angles calculated from the tracked joint positions, the angles calculated from manually annotated keypoints, and the angles measured using a goniometer. Moderate correlations between the angles estimated using pose-tracked keypoints and the goniometer measurements were identified for the elbow (rho =.722; Detectron), knee (rho =.608; MoveNet - Thunder), shoulder (rho =.632; MoveNet - Thunder), and fifth finger (rho =.786; custom model) movements. The angles estimated from keypoints predicted by open-source libraries at the ankles were not significantly correlated with the goniometer measurements. Manually annotated angles at the elbows, knees, shoulders, and fifth fingers were moderately to strongly correlated to goniometer measurements but were weakly correlated for the ankles. There was not one pose-estimation library which performed best across all joints, so the library of choice must be selected separately for each joint of interest. This work evaluates several pose-estimation models as part of a vision-based system for estimating joint angles in individuals with suspected joint hypermobility. Future applications of the proposed system could facilitate objective assessment and screening of individuals referred to specialized EDS clinics.

Development of a facile method to compute collagen network pathological anisotropy using AFM imaging.

Type I collagen, a fundamental extracellular matrix (ECM) component, is pivotal in maintaining tissue integrity and strength. It is also the most prevalent fibrous biopolymer within the ECM, ubiquitous in mammalian organisms. This structural protein provides essential mechanical stability and resilience to various tissues, including tendons, ligaments, skin, bone, and dentin. Collagen has been structurally investigated for several decades, and variation to its ultrastructure by histology has been associated with several pathological conditions. The current study addresses a critical challenge in the field of collagen research by providing a novel method for studying collagen fibril morphology at the nanoscale. It offers a computational approach to quantifying collagen properties, enabling a deeper understanding of how collagen type I can be affected by pathological conditions. The application of Fast Fourier Transform (FFT) coupled with Atomic Force Microscope (AFM) imaging distinguishes not only healthy and diseased skin but also holds potential for automated diagnosis of connective tissue disorders (CTDs), contributing to both clinical diagnostics and fundamental research in this area. Here we studied the changes in the structural parameters of collagen fibrils in Ehlers Danlos Syndrome (EDS). We have used skin extracted from genetically mutant mice that exhibit EDS phenotype as our model system (Col1a1Jrt/+ mice). The collagen fibrils were analyzed by AFM based descriptive-structural parameters, coupled with a 2D Fast Fourier Transform(2D-FFT) approach that automated the analysis of AFM images. In addition, each sample was characterized based on its FFT and power spectral density. Our qualitative data showed morphological differences in collagen fibril clarity (clearness of the collagen fibril edge with their neighbouring fibri), D-banding, orientation, and linearity. We have also demonstrated that FFT could be a new tool for distinguishing healthy from tissues with CTDs by measuring the disorganization of fibrils in the matrix. We have also employed FFT to reveal the orientations of the collagen fibrils, providing clinically relevant phenotypic information on their organization and anisotropy. The result of this study can be used to develop a new automated tool for better diagnosis of CTDs.

A Scoping Review of Epidural Spinal Cord Stimulation for Improving Motor and Voiding Function Following Spinal Cord Injury.

Objectives: To identify and synthesize the existing evidence on the effectiveness and safety of epidural spinal cord stimulation (SCS) for improving motor and voiding function and reducing spasticity following spinal cord injury (SCI). Methods: This scoping review was performed according to the framework of Arksey and O'Malley. Comprehensive serial searches in multiple databases (MEDLINE, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, LILACS, PubMed, Web of Science, and Scopus) were performed to identify relevant publications that focused on epidural SCS for improving motor function, including spasticity, and voiding deficits in individuals with SCI. Results: Data from 13 case series including 88 individuals with complete or incomplete SCI (American Spinal Injury Association Impairment Scale [AIS] grade A to D) were included. In 12 studies of individuals with SCI, the majority (83 out of 88) demonstrated a variable degree of improvement in volitional motor function with epidural SCS. Two studies, incorporating 27 participants, demonstrated a significant reduction in spasticity with SCS. Two small studies consisting of five and two participants, respectively, demonstrated improved supraspinal control of volitional micturition with SCS. Conclusion: Epidural SCS can enhance central pattern generator activity and lower motor neuron excitability in individuals with SCI. The observed effects of epidural SCS following SCI suggest that the preservation of supraspinal transmission is sufficient for the recovery of volitional motor and voiding function, even in patients with complete SCI. Further research is warranted to evaluate and optimize the parameters for epidural SCS and their impact on individuals with differing degrees of severity of SCI.

Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Generalized Hypermobility Spectrum Disorder: Protocol for a Pilot and Feasibility Randomized Controlled Trial.

BACKGROUND: Dyspnea is a prevalent symptom in individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and generalized hypermobility spectrum disorder (G-HSD), yet its contributors have not been identified. One known contributor to dyspnea is respiratory muscle weakness. The feasibility and effectiveness of inspiratory muscle training (IMT) in combination with standard-of-care rehabilitation (aerobic, resistance, neuromuscular stabilization, and balance and proprioception exercises) in improving respiratory muscle strength and patient-reported outcomes in patients with hEDS or G-HSD have not been evaluated. OBJECTIVE: This study aims to evaluate dyspnea, respiratory muscle strength, and patient-reported outcome measures (PROMs) in hEDS or G-HSD compared with healthy controls and to assess the feasibility of a randomized controlled trial of IMT and standard-of-care rehabilitation for improving respiratory muscle strength, exercise capacity, and PROMs compared with standard-of-care rehabilitation in hEDS and G-HSD. METHODS: The study will include 34 participants with hEDS or G-HSD and 17 healthy, age- and sex-matched controls to compare respiratory muscle structure and function and PROMs. After baseline assessments, participants with hEDS or G-HSD will be randomized into the intervention group and provided IMT combined with Ehlers-Danlos Syndrome standard-of-care rehabilitation or into the usual care group, and provided only standard-of-care rehabilitation for 8 weeks. The intervention group will be prescribed IMT in their home environment using the POWERbreathe K5 IMT device (POWERbreathe International Ltd). IMT will comprise 2 daily sessions of 30 breaths for 5 days per week, with IMT progressing from 20% to 60% of the baseline maximal inspiratory pressure (MIP) over an 8-week period. Feasibility will be assessed through rates of recruitment, attrition, adherence, adverse events, and participant satisfaction. The primary pilot outcome is MIP change over an 8-week period in hEDS or G-HSD. Secondary outcomes will include the evaluation of dyspnea using Medical Research Council Scale and 18-point qualitative dyspnea descriptors; diaphragmatic thickening fraction using ultrasound; respiratory muscle endurance; pulmonary function; prefrontal cortical activity using functional near-infrared spectroscopy; aerobic capacity during cardiopulmonary exercise testing; quality of life using Short Form-36; and scores from the Depression, Anxiety, and Stress scale-21. These measures will also be performed once in healthy controls to compare normative values. Multivariable regression will be used to assess the contributors to dyspnea. Paired 2-tailed t tests will be used to assess the changes in MIP and secondary measures after 8 weeks of IMT. RESULTS: Study recruitment began in August 2021 and, with several disruptions owing to COVID-19, is expected to be completed by December 2023. CONCLUSIONS: This study will provide a better understanding of the factors associated with dyspnea and the feasibility and effectiveness of IMT combined with standard-of-care rehabilitation. IMT may be a novel therapeutic strategy for improving respiratory muscle function and patient-reported outcomes in individuals with hEDS or G-HSD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04972565; https://clinicaltrials.gov/ct2/show/NCT04972565. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44832.

Ultrasound-guided injection of the elbow: Cadaveric description for the proximal to distal approach.

BACKGROUND: Ultrasound (US) guided intra-articular elbow injections are commonly performed in clinical practice. OBJECTIVE: To describe a proximal to distal approach for US-guided intra-articular elbow injection. DESIGN: Cadaveric study. SETTINGS: Academic institution. METHODS: Both elbows of a single cadaver were injected with green-colored water-diluted latex dye using the US-guided proximal to distal approach. In the left elbow, the needle was kept in situ; in the right elbow, the needle was removed. Subsequently, a layer-by-layer anatomical dissection was performed in both elbows. MAIN OUTCOME MEASURES: Presence and distribution of the latex dye and location of the needle tip within the elbow joint capsule. RESULTS: Anatomical dissection of both elbows confirmed the correct intra-articular position of the needle tip in the left elbow as well as correct placement of the latex dye bilaterally. During layer-by-layer dissection of the left elbow, the position of the radial nerve was observed anterior to the needle. CONCLUSIONS: This cadaveric observation demonstrated that the US-guided proximal to distal approach is a convenient technique to access the elbow joint. Compared to the previously described techniques, the in-plane, proximal to distal approach may provide excellent needle visibility during the entire procedure, precisely targeting the articular space. The preliminary data need to be validated in additional clinical studies.

Ultrasound-guided injection of the hip: Cadaveric description for the lateral approach.

BACKGROUND: Ultrasound (US)-guided intraarticular hip joint injections are commonly performed using an in-plane anterior approach, which has several limitations. OBJECTIVE: To describe and report a "lateral" (lateral to medial) approach for US-guided intraarticular hip injection. DESIGN: Cadaveric investigation. SETTING: Academic institution, department of anatomy. PARTICIPANTS: One cadaveric specimen. METHODS: Both hips of a single cadaver were injected using the US-guided lateral approach. In the left hip, the needle was inserted and kept in situ. The right hip was injected with white-colored water-diluted latex dye. Subsequently, a layer-by-layer anatomical dissection was performed. MAIN OUTCOME MEASURES: Presence and distribution of latex dye and location of needle tip within the joint capsule of the hip. RESULTS: Anatomical dissection of the left and right hips confirmed the correct intraarticular position of the needle tip and the placement of the latex dye, respectively. During layer-by-layer dissection of the left hip, positions of the lateral cutaneous nerve and the lateral circumflex femoral artery were observed anterior to the needle, 30 mm for the nerve and 8 mm for the artery. CONCLUSIONS: This preliminary study demonstrated that the US-guided lateral approach is a convenient technique to access the hip joint in a cadaveric specimen. Compared with the "classical" anterior technique, the lateral approach may provide several advantages, including improved needle visibility, theoretically decreased risk of vascular injury, and less risk of needle contamination. Because injury to the lateral epiphyseal arteries is possible when lateral approach is used, caution is required, especially in children. These preliminary conclusions will need to be validated in future/larger clinical studies.

Post-Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current Knowledge and Future Directions.

Background: Post-viral pain syndrome, also known as post-viral syndrome, is a complex condition characterized by persistent pain, fatigue, musculoskeletal pain, neuropathic pain, neurocognitive difficulties, and sleep disturbances that can occur after an individual has recovered from a viral infection. Aims: This narrative review provides a summary of the sequelae of post-viral syndromes, viral agents that cause it, and the pathophysiology, treatment, and future considerations for research and targeted therapies. Methods: Medline, PubMed, and Embase databases were used to search for studies on viruses associated with post-viral syndrome. Conclusion: Much remains unknown regarding the pathophysiology of post-viral syndromes, and few studies have provided a comprehensive summary of the condition, agents that cause it, and successful treatment modalities. With the COVID-19 pandemic continuing to affect millions of people worldwide, the need for an understanding of the etiology of post-viral illness and how to help individuals cope with the sequalae is paramount.

Contexte: Le syndrome de la douleur post-virale, également connu sous le nom de syndrome post-viral, est une affection complexe caractérisée par des douleurs persistantes, de la fatigue, des douleurs musculosquelettiques, des douleurs neuropathiques, des difficultés neurocognitives et des troubles du sommeil qui peuvent survenir après la guérison d'une infection virale.Objectifs: Cette revue narrative présente un résumé des séquelles des syndromes post-viraux, des agents viraux qui les causent, ainsi que de la pathophysiologie, des traitements et des considérations futures pour la recherche et les traitements ciblés.Méthodes utilisées: Les bases de données Medline, PubMed et Embase ont été utilisées pour rechercher des études sur les virus associés au syndrome post-viral.Conclusion: La physiopathologie des syndromes post-viraux reste largement méconnue et peu d'études ont présenté un résumé complet de l'affection, des agents qui la provoquent et des modalités de traitement efficaces. Alors que la pandémie de COVID-19 continue d'affecter des millions de personnes dans le monde, il est primordial de comprendre l'étiologie de la maladie post-virale et de savoir comment aider les individus à faire face aux séquelles.

Cryoneurolysis for non-cancer knee pain: A scoping review.

Background and objective: Cryoneurolysis involves percutaneous insertion of a cryoprobe induced to extremely cold temperatures to disrupt peripheral nerve conduction. The primary objective of this scoping review is to summarize and critically appraise the current evidence for the benefits and safety of cryoneurolysis for non-cancer knee pain. The secondary objective is to describe the variations in cryoneurolysis techniques used. Methods: MEDLINE, EMBASE, PubMed, Cochrane Library, and Web of Science were searched from their inception to February 2023 for any primary literature investigating the use of cryoneurolysis for non-cancer-related knee pain. Data was extracted for study characteristics, intervention characteristics, and clinical outcomes. Results: Fourteen studies were identified, including three randomized controlled trials, four retrospective cohort studies, and seven case studies/series. Two studies included knee osteoarthritis patients, three studies included non-specific chronic knee pain patients; and nine studies included pre- or post-total knee arthroplasty patients. Ten studies targeted the infrapatellar branch of the saphenous nerve while the remaining four studies did not report the nerve targeted. Studies consistently demonstrated improvements in pain, function, quality of life, and opioid consumption. Most adverse events were mild and self-limiting. Considerable variations in technique parameters were observed. Conclusions: Cryoneurolysis is a promising intervention to improve outcomes in non-cancer knee pain populations, particularly in mild-to-moderate knee osteoarthritis and pre-total knee arthroplasty populations. However, cryoneurolysis for knee pain remains largely investigational as more high-quality randomized controlled trials are required to further elucidate efficacy as well as optimal nerve selection and technique.

Feasibility of video-based joint hypermobility assessment in individuals with suspected Ehlers-Danlos syndromes/generalised hypermobility spectrum disorders: a single-site observational study protocol.

INTRODUCTION: Ehlers-Danlos syndromes (EDS)/generalised hypermobility spectrum disorders (G-HSD) affect the connective tissue of the body and present with a heterogeneous set of symptoms that pose a challenge for diagnosis. One of the main diagnostic criteria of EDS/G-HSD is generalised joint hypermobility, which is currently assessed by clinicians during a physical exam. However, the practice for measuring joint hypermobility is inconsistent between clinicians, leading to high inter-rater variability. Often patients are misdiagnosed with EDS/G-HSD based on an incorrect hypermobility assessment, leading to increased referral rates and resource utilisation at specialised EDS clinics that results in unnecessary emotional distress for patients. An objective, validated and scalable method for assessing hypermobility might mitigate these issues and result in improved EDS/G-HSD patient care. METHODS AND ANALYSIS: This study will examine the use of videos obtained using a smartphone camera to assess the range of motion (ROM) and hypermobility of the joints assessed in Beighton score and more (spine, shoulders, elbows, knees, ankles, thumbs and fifth fingers) in individuals with suspected EDS/G-HSD. Short videos of participants will be captured as they undergo a formal assessment of joint hypermobility at the GoodHope EDS Clinic at Toronto General Hospital. Clinicians will measure the ROM at each joint using a clinical-grade goniometer to establish ground truth measurements. Open-source human pose-estimation libraries will be used to extract the locations of key joints from the videos. Deterministic and machine learning systems will be developed and evaluated for estimating the ROM at each joint. Results will be analysed separately for each joint and human pose-estimation library. ETHICS AND DISSEMINATION: This study was approved by the Research Ethics Board of the University Health Network in Toronto on 26 April 2022. Participants will provide written informed consent. Findings from this study will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05366114.

Exercise and Rehabilitation in People With Ehlers-Danlos Syndrome: A Systematic Review.

Objective: To conduct a systematic review examining the effect of exercise and rehabilitation in people with Ehlers-Danlos syndrome (EDS). Data Sources: The following databases were systematically searched: MEDLINE, MEDLINE In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health. The final time point captured by the search is November 27, 2020. Study Selection: Eligible study designs included case-control, case-series, prospective cohort, retrospective cohort, and intervention studies of structured exercise or rehabilitation interventions. Eligible populations included adults (18 years or older) with EDS (all subtypes) and hypermobility spectrum disorders. The search was restricted to articles published in English. Data Extraction: Data were extracted by 2 independent reviewers. Risk of bias was assessed using the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials (RCTs) and Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) for non-RCTs. Reporting quality of RCTs was assessed using the Consolidated Standards for Reporting of Trials statement with the harms extension. Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data Synthesis: The search yielded 10 eligible studies including 330 participants. The study designs included 5 RCTs, 1 cohort, 2 single-arm interventions, 1 retrospective, and 1 feasibility study. All studies showed some improvement in a physical and/or psychological outcome after the intervention period. One adverse event (nonserious) potentially related to the intervention was reported. Of the 5 RCTs, 2 were rated as high quality with low risk of bias using PEDro, and the majority of non-RCTs were rated as critical risk of bias by ROBINS-I. Conclusions: The results suggest that exercise and rehabilitation may be beneficial for various physical and psychological outcomes. Adequately powered and rigorous RCTs of exercise and rehabilitation interventions for people with EDS are needed.

Comparison of the spread pattern of medial-to-lateral and lateral-to-medial rotator interval injections: A cadaveric study.

Objective: Rotator interval (RI) corticosteroid injections are used to alleviate pain associated with adhesive capsulitis, though the pattern of injectate spread remains unclear. The purpose of this anatomical study was to assess the staining patterns of intra-articular, intracapsular/extrasynovial, and pericapsular structures of the glenohumeral joint following medial-to-lateral and lateral-to-medial RI injections. Design: Ten cadaveric specimens were injected with a methylene blue dye injectate: five using a medial-to-lateral RI injection technique and five using a lateral-to-medial RI injection technique. Serial dissection was performed to assess the staining of intra-articular, intracapsular/extrasynovial, and pericapsular structures. The frequency of capture and degree of staining were compared between injection groups. Results: The lateral-to-medial injection resulted in the capture of all intra-articular; intracapsular/extrasynovial; and pericapsular structures, whereas the medial-to-lateral injection did not consistently stain all structures. Intracapsular/extrasynovial structures (superior glenohumeral ligament and the long head of biceps tendon) were more darkly stained in the lateral-to-medial group, and pericapsular structures (supraspinatus tendon and coracohumeral ligament) were more darkly stained in the medial-to-lateral group. Conclusion: The frequency of capture and degree of staining of intra-articular, intracapsular/extrasynovial, and pericapsular structures of the glenohumeral joint differed between medial-to-lateral and lateral-to-medial RI injection techniques, which may influence outcomes in pain management for adhesive capsulitis.

Knee Ablation Approaches.

Genicular nerve radiofrequency ablation has quickly become one of the most promising interventions for chronic knee pain secondary to osteoarthritis, with consistent improvements in pain and function. Although there are multiple techniques using slightly variable lesion locations, cannulas, lesion types, and imaging modalities, the clinical effectiveness targeting the anterior branches of the superior medial, superolateral, and inferior medial has reproducibly demonstrated clinically and statistically significant improvements up to 24 months after the procedure with minimal adverse events. This article summarizes the current knowledge of the sensory innervation of the knee joint, the principles of radiofrequency ablation, and the current literature on clinical outcomes.

The GoodHope Ehlers Danlos Syndrome Clinic: development and implementation of the first interdisciplinary program for multi-system issues in connective tissue disorders at the Toronto General Hospital.

Ehlers-Danlos Syndrome (EDS) are a heterogeneous group of genetic connective tissue disorders, and typically manifests as weak joints that subluxate/dislocate, stretchy and/or fragile skin, organ/systems dysfunction, and significant widespread pain. Historically, this syndrome has been poorly understood and often overlooked. As a result, people living with EDS had difficulty obtaining an accurate diagnosis and appropriate treatment, leading to untold personal suffering as well as ineffective health care utilization. The GoodHope EDS clinic addresses systemic gaps in the diagnosis and treatment of EDS. This paper describes a leap forward-from lack of awareness, diagnosis, and treatment-to expert care that is tailored to meet the specific needs of patients with EDS. The GoodHope EDS clinic consists of experts from various medical specialties who work together to provide comprehensive care that addresses the multi-systemic nature of the syndrome. In addition, EDS-specific self-management programs have been developed that draw on exercise science, rehabilitation, and health psychology to improve physical and psychosocial wellbeing and overall quality of life. Embedded into the program are research initiatives to shed light on the clinical presentation, underlying mechanisms of pathophysiology, and syndrome management. We also lead regular educational activities for community health care providers to increase awareness and competence in the interprofessional management of EDS beyond our doors and throughout the province and country.

A review of respiratory manifestations and their management in Ehlers-Danlos syndromes and hypermobility spectrum disorders.

BACKGROUND: Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD) are a heterogeneous group of heritable genetic connective tissue disorders with multiple characteristics including joint hypermobility, tissue fragility, and multiple organ dysfunction. Respiratory manifestations have been described in EDS patients, but have not been systematically characterized. A narrative review was undertaken to describe the respiratory presentations and management strategies of individuals with EDS and HSD. METHODS: A broad literature search of Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL was undertaken from inception to November 2020 of all study types, evaluating EDS/ HSD and pulmonary conditions. This narrative review was limited to adult patients and publications in English. RESULTS: Respiratory manifestations have generally been described in hypermobile EDS (hEDS), classical and vascular EDS subtypes. Depending on EDS subtype, they may include but are not limited to dyspnea, dysphonia, asthma, sleep apnea, and reduced respiratory muscle function, with hemothorax and pneumothorax often observed with vascular EDS. Respiratory manifestations in HSD have been less frequently characterized in the literature, but exertional dyspnea is the more common symptom described. Respiratory symptoms in EDS can have an adverse impact on quality of life. The respiratory management of EDS patients has followed standard approaches with thoracotomy tubes and pleurodesis for pleural manifestations, vocal cord strengthening exercises, continuous positive pressure support for sleep apnea, and exercise training. Reduced respiratory muscle function in hEDS patients responds to inspiratory muscle training. CONCLUSION: Respiratory symptoms and manifestations are described in EDS and HSD, and have generally been managed using conservative non-surgical strategies. Research into the prevalence, incidence and specific respiratory management strategies in EDS and HSD is needed to mitigate some of the associated morbidity.