Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility

Objective: Anxiety is associated with increased physiological reactivity and also increased “interoceptive” sensitivity to such changes in internal bodily arousal. Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders. This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation. Methods: Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging. Results: We confirmed a significant relationship between state anxiety score and joint hypermobility. Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility. Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex. Conclusions: Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen

The association between muscle strength and activity limitations in patients with the hypermobility type of Ehlers–Danlos syndrome : the impact of proprioception

Purpose: The patients diagnosed with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) are characterized by pain, proprioceptive inacuity, muscle weakness, potentially leading to activity limitations. In EDS-HT, a direct relationship between muscle strength, proprioception and activity limitations has never been studied. The objective of the study was to establish the association between muscle strength and activity limitations and the impact of proprioception on this association in EDS-HT patients. Methods: Twenty-four EDS-HT patients were compared with 24 controls. Activity limitations were quantified by Health Assessment Questionnaire (HAQ), Six-Minute Walk test (6MWT) and 30-s chair-rise test (30CRT). Muscle strength was quantified by handheld dynamometry. Proprioception was quantified by movement detection paradigm. In analyses, the association between muscle strength and activity limitations was controlled for proprioception and confounders. Results: Muscle strength was associated with 30CRT (r = 0.67, p = <0.001), 6MWT (r = 0.58, p = <0.001) and HAQ (r = 0.63, p = <0.001). Proprioception was associated with 30CRT (r = 0.55, p <0.001), 6MWT (r = 0.40, p = <0.05) and HAQ (r = 0.46, p < 0.05). Muscle strength was found to be associated with activity limitations, however, proprioceptive inacuity confounded this association. Conclusions: Muscle strength is associated with activity limitations in EDS-HT patients. Joint proprioception is of influence on this association and should be considered in the development of new treatment strategies for patients with EDS-HT. Implications for rehabilitation : Reducing activity limitations by enhancing muscle strength is frequently applied in the treatment of EDS-HT patients. Although evidence regarding treatment efficacy is scarce, the current paper confirms the rationality that muscle strength is an important factor in the occurrence of activity limitations in EDS-HT patients. Although muscle strength is the most dominant factor that is associated with activity limitations, this association is confounded by proprioception. In contrast to common belief proprioception was not directly associated with activity limitations but confounded this association. Controlling muscle strength on the bases of proprioceptive input may be more important for reducing activity limitations than just enhancing sheer muscle strength

Higher fracture prevalence and smaller bone size in patients with hEDS/HSD-a prospective cohort study

Increased fracture risk in patients with Ehlers-Danlos syndromes has been reported, but the reasons for it are incompletely understood. We aimed to investigate possible determinants of this increased risk and found that hEDS/HSD patients present with a cortical bone size deficit compared with control subjects, possibly related to lower mechanical loading. Introduction The Ehlers-Danlos syndromes (EDS) comprise a group of heritable connective tissue disorders caused by defects in the biosynthesis, secretion, and/or organization of fibrillar collagens which might impair bone strength. Our aim was to compare fracture prevalence, volumetric and areal bone mineral density (BMD), bone geometry, muscle size and the muscle-bone interaction, body composition and longitudinal changes therein between patients with hypermobile EDS (hEDS) or hypermobility spectrum disorder (HSD), and healthy control subjects. Methods Cross-sectional data comprised 39 female hEDS/HSD patients (age 41 +/- 11 years) and 43 age-matched controls. After 8 years, 27 hEDS/HSD and 17 control subjects were re-evaluated. Tibial trabecular and cortical volumetric BMD, bone mineral content (BMC), cortical bone geometry, and lower leg muscle cross-sectional area (CSA) were measured using pQCT. Body composition, areal BMD, and BMC were determined by DXA. Results At baseline, patients with hEDS/HSD presented with a smaller cortical bone area, smaller cortical thickness and muscle CSA, and a higher fracture prevalence than control subjects (all p < 0.05). No differences in areal or volumetric BMD were found. Longitudinally, muscle CSA decreased in both groups and muscle density decreased in the hEDS/HSD group (p < 0.001) whereas all bone parameters remained unchanged. Conclusion hEDS/HSD patients have a cortical bone size deficit compared with controls, possibly contributing to their increased fracture risk. They presented with decreased muscle CSA but normal bone/muscle area ratio, suggesting that this bone size deficit is likely secondary to decreased mechanical loading. Further, there were no arguments for accelerated bone loss in hEDS/HSD subjects

Neurovisceral phenotypes in the expression of psychiatric symptoms

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

Fit to Perform: A Profile of Higher Education Music Students’ Physical Fitness

Musicians are often called athletes of the upper body, but knowledge of their physical and fitness profiles is nonetheless limited, especially those of advanced music students who are training to enter music’s competitive professional landscape. To gain insight into how physical fitness is associated with music making, this study investigated music students’ fitness levels on several standardized indicators. 483 students took part in a fitness screening protocol that included measurements of lung function, flexibility (hypermobility, shoulder range of motion, sit and reach), strength and endurance (hand grip, plank, press-up), and sub-maximal cardiovascular fitness (3-min step test), as well as self-reported physical activity (IPAQ-SF). Participants scored within ranges appropriate for their age on lung function, shoulder range of motion, grip strength, and cardiovascular fitness. Their results for the plank, press up, and sit and reach were poor by comparison. Reported difficulty (22%) and pain (17%) in internal rotation of the right shoulder were also found. Differences between instrument groups and levels of study were observed on some measures. In particular, brass players showed greater lung function and grip strength compared with other groups, and postgraduate students on the whole were able to maintain the plank for longer but also demonstrated higher hypermobility and lower lung function (FEV1) and cardiovascular fitness than undergraduates. 79% of participants exceeded the minimum recommended weekly amount of physical activity, with singers the most physically active group and keyboard players, composers, and conductors the least active. IPAQ-SF scores correlated positively with lung function, sit and reach, press-up and cardiovascular fitness suggesting that, in the absence of time and resources to carry out comprehensive physical assessments with musicians, this one measure alone can provide useful insights. The findings indicate that music students have adequate levels of general health-related fitness, and we discuss whether adequate fitness is enough for people undertaking physically and mentally demanding activities such as making music. We argue that musicians could benefit from strengthening their supportive musculature and enhancing their awareness of strength imbalances

Superior Semicircular Canal Dehiscence in a Patient with Ehlers-Danlos Syndrome: A Case Report.

Superior semicircular canal dehiscence (SSCD) is a bony defect in the middle cranial fossa floor that results in an abnormal connection between the inner ear and cranial vault. Although the etiology of SSCD remains unclear, an inappropriately thin or fragile temporal bone likely predisposes an individual towards developing SSCD. Ehlers-Danlos syndrome (EDS) constitutes a group of genetic connective tissue disorders caused by a defect in the production, processing, or structure of collagen, or its associated proteins. The possible association between SSCD and EDS has not been previously described in the literature. We herein report a case of a 50-year-old female with EDS-hypermobility type who presented with a 15-year history of migraines, vertigo, and tinnitus. The patient was subsequently diagnosed with bilateral SSCD and underwent a right middle fossa (pre-auricular infratemporal) craniotomy for SSCD repair. She reported significant improvement in her auditory and vestibular symptoms, with the exception of continued mild dizziness and disequilibrium at the 3-month follow-up. Due to the rare reports of auditory symptoms in EDS, this case study highlights the importance of considering an otological consultation for auditory manifestations in a patient with EDS and illustrates a potential association between EDS and SSCD

Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome

Background: Whereas mutations affecting the helical domain of type I procollagen classically cause Osteogenesis Imperfecta (OI), helical mutations near the amino (N)-proteinase cleavage site have been suggested to result in a mixed OI/Ehlers-Danlos syndrome (EDS)-phenotype. Methods: We performed biochemical and molecular analysis of type I (pro-) collagen in a cohort of seven patients referred with a clinical diagnosis of EDS and showing only subtle signs of OI. Transmission electron microscopy of the dermis was available for one patient. Results: All of these patients harboured a COL1A1 / COL1A2 mutation residing within the most N-terminal part of the type I collagen helix. These mutations affect the rate of type I collagen N-propeptide cleavage and disturb normal collagen fibrillogenesis. Importantly, patients with this type of mutation do not show a typical OI phenotype but mainly present as EDS patients displaying severe joint hyperlaxity, soft and hyperextensible skin, abnormal wound healing, easy bruising, and sometimes signs of arterial fragility. In addition, they show subtle signs of OI including blue sclerae, relatively short stature and osteopenia or fractures. Conclusion: Recognition of this distinct phenotype is important for accurate genetic counselling, clinical management and surveillance, particularly in relation to the potential risk for vascular rupture associated with these mutations. Because these patients present clinical overlap with other EDS subtypes, biochemical collagen analysis is necessary to establish the correct diagnosis

A systematic review and meta-analysis of Macroplastique for treating female stress urinary incontinence.

Introduction and hypothesisMacroplastique® (polydimethylsiloxane injection) is a minimally invasive urethral bulking agent with global clinical literature describing its use over 20 years. This study critically assessed the safety and effectiveness outcomes for adult women treated with Macroplastique for stress urinary incontinence (SUI) through a systematic review and meta-analysis.MethodsA systematic review of the scientific literature from 1990 to 2010 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to quantitatively summarize the safety and effectiveness of Macroplastique for female SUI. A total of 958 patients from 23 cohorts were eligible for inclusion and were analyzed. Random-effects models were used to estimate the improvement and cure rates following treatment at three time periods: short-term (&lt;6 months), mid-term (6-18 months), and long-term (&gt;18 months). Expanded models assessed the effect of reinjection rate on successful treatment outcomes. Adverse event rates were aggregated and reported.ResultsImprovement rates were 75 % [95 % confidence interval (CI), 69-81] in the short-term, 73 % (95 % CI, 62-83) in the mid-term, and 64 % (95 % CI, 57-71) long-term. Cure/dry rates were 43 % (95 % CI, 33-54), 37 % (95 % CI, 28-46), and 36 % (95 % CI, 27-46) over the same respective follow-up periods. Higher study reinjection rates were associated with improved long-term SUI outcomes. No serious adverse events were reported.ConclusionsThis quantitative review supports Macroplastique as an effective, durable, and safe treatment option for female SUI. Meta-analytic evidence suggests that long-term therapeutic benefit is frequently maintained, with some patients requiring reinjection

Association Between Joint Hypermobility Syndrome and Developmental Coordination Disorder – A Review.

Introduction: The term joint hypermobility syndrome (JHS) was adopted after clinicians became aware of the myriad of symptoms associated with this multisystemic condition. JHS is an inherited disorder of connective tissues affecting the musculoskeletal and visceral systems which may contribute to a reduction in health related physical fitness. Pain associated with JHS may be influenced by hypermobility and biomechanical dysfunction. Biomechanical dysfunction observed in patients with JHS may be as a result of impaired motor control and in particular developmental coordination disorder (DCD). DCD (described in the literature utilising the terms clumsy child syndrome; perceptual motor dysfunction; dyspraxia) is a neurodevelopmental condition characterised by coordination difficulties affecting function. The objective of this review is to examine the association between hypermobility, JHS, motor control impairment and DCD. Methods and data sources: EMBASE, MEDLINE, CINAHL, ASSIA, PsychARTICLES, SPORTDiscus and PsycINFO from 1989 - 2009. Research articles written in English and peer reviewed were included. Results: Five research papers were identified. The studies employed a variety of methodologies and assessment tools for reporting joint hypermobility, JHS, motor delay, motor impairments and DCD. All five studies reported on children between the ages of six months and 12 years. Three out of four studies reported on association between impaired motor development, motor delay and joint hypermobility. There was no consensus as to whether motor delay, impaired motor development and joint hypermobility continued as the child matured. One study ascertained that children with JHS reported similar functional difficulties as children with DCD. Conclusion: There was a paucity of literature relating to an association between joint hypermobility, JHS, impaired motor control, motor delay and DCD in children, there was no literature pertaining to adults. This association requires further exploration if professionals are to understand, nurture and manage those reporting these associated conditions

Operative complications and results of the "SPARC" procedure for stress urinary incontinence [Operativne komplikacije i ishod metode SPARC u liječenju statičke inkontinencije mokraće]

The aim of this study was to determine the efficacy and operative complications of the suprapubic arc (SPARC) procedure in stress incontinent women with and without previous anti-incontinence surgery. One-hundred and twenty-one patients with stress urinary incontinence (SUI) were treated with SPARC for correction of urethral hypermobility (N = 65) and intrinsic sphincter deficiency (N = 56) between August 2002 and February 2007. The long-term surgical results, operative complications (bladder injury, retropubic hematoma, de novo urgency and urinary infection) and patients' satisfaction were assessed. The overall complication rate was 9.9% (12/121). The perioperative complication rate was 1.7% including 2 urinary bladder injuries. Significant difference in the overall complications rate was detected between women with and without previous surgery (23/45, 51.1% vs. 6/108, 5.5%, chi2 = 49.89, P < 0.001). The overall postoperative complication rate was 8.3% (10/121) including 4 de novo urgencies, 4 urinary infections and 2 retropubic hematomas. There were 3 patients with postoperative urinary retention managed conservatively, without voiding difficulties on control visits. The objective cure rate after the follow-up was 86.8% (105/121). In patients with SUI and without preceding vaginal operations SPARC is a good method with low incidence of perioperative complications, promising long-term results and high patient satisfaction