Subacromial space outlet in female patients with multidirectional instability based on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder measured by ultrasound.

OBJECTIVE: The objective of the study was to compare the acromiohumeral distance (AHD) between patients diagnosed with hypermobility type of the Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD) and healthy controls by evaluating the relative amount the tendon occupies in the subacromial area. Furthermore, the aim was to evaluate if there was a change in AHD with arm elevation within and between groups. METHODS: Twenty-nine female patients with hEDS/HSD (aged 34 ± 12.9 years) and 20 healthy controls (aged 33 ± 10.8 years) participated in the study. The supraspinatus tendon (SST) thickness and AHD were measured using ultrasound. The interplay between the SST and the AHD was expressed as the occupation ratio (OcAHD), calculated as the SST thickness as a percentage of AHD. The measures were performed in the resting position and in subsequently 45° and 60° of active arm elevation in the scapular plane. RESULTS: The main finding is that patients with hEDS/HSD have a larger subacromial space outlet compared with the controls when measured by ultrasound. Furthermore, in both groups, we found an increased OcAHD during active arm elevation compared with the resting position, which indicates that similar mechanisms occur for patients with hEDS/HSD and healthy controls. CONCLUSION: Patients with hEDS/HSD have a larger available subacromial space outlet compared with healthy individuals. OcAHD increased during active arm elevation compared with the resting position in both groups. This knowledge is important when designing rehabilitation exercise programs for shoulder instability patients with abnormal glenohumeral biomechanics.

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects.

PURPOSE: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls. METHODS: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale. FINDINGS: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001). IMPLICATIONS: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome.

OBJECTIVE: To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. METHODS: We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. RESULTS: We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. CONCLUSION: There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.

Arterial tortuosity syndrome: 40 new families and literature review.

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People.

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. OBJECTIVES: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity. STUDY DESIGN: A controlled experimental study. SETTING: The study was conducted at the Human Physiology lab of a University. METHODS: Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis. RESULTS: Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability. LIMITATIONS: Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations. CONCLUSIONS: Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.Key words: Aerobic exercise, aerobic power index, autonomic nervous system, exercise-induced analgesia, exercise-induced hypoalgesia, fibromyalgia, heart rate variability, stress-induced analgesia, pain.

Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls.

AIM: This study provides insight into the profile and importance of autonomic symptoms in the hypermobility type (HT) of Ehlers-Danlos syndrome (EDS). The impact of these symptoms is put into perspective by comparing with fibromyalgia (FM) and two other EDS types. METHODS: Overall, 80 patients with EDS-HT participated, as well as 11 with classical EDS (cEDS), seven with vascular EDS (vEDS), 38 with FM, and 43 healthy controls. All participants filled out the autonomic symptom profile (ASP). Furthermore, they were inquired about quality of life (QOL, SF-36) and factors contributing to the EDS disease burden, e.g., hypermobility (5-point questionnaire, GHQ), fatigue (checklist individual strength, CIS), pain (pain detect questionnaire, PDQ), affective distress (hospital anxiety and depression scale, HADS), and physical activity (Baecke). RESULTS: The total autonomic symptom burden was higher in EDS-HT (57.9 ± 21.57) than in controls (11.3 ± 19.22), cEDS (32.3 ± 19.47), and vEDS (29.1 ± 19.18), but comparable to FM (53.8 ± 19.85). Especially orthostatic and gastrointestinal complaints were prevalent. The importance of autonomic symptoms in EDS-HT was emphasized by the correlation with lowered QOL (r = -0.402), fatigue (r = 0.304), and pain severity (r = 0.370). Although affective distress and decreased physical activity are often suggested as possible causes for dysautonomia, the ASP did not correlate with the HADS and Baecke score. By contrast, the correlation of the GHQ (r = 0.298) and PDQ (r = 0.413) with the ASP supports the hypothesis that joint hypermobility and neuropathy may play a role in the development of autonomic symptoms. CONCLUSION: Autonomic symptoms, especially orthostatic and gastrointestinal complaints, are frequent extraarticular manifestations of EDS-HT and contribute to the disease burden.

Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review.

OBJECTIVE: The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects. METHODS: To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined. RESULTS: Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep. CONCLUSION: FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.

Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers-Danlos syndrome.

OBJECTIVES: To describe medication use, surgery, and physiotherapy, and to examine the effect of these treatment modalities on functional impairment and amount of complaints among patients with the hypermobility type of Ehlers-Danlos syndrome (EDS-HT). DESIGN: Cross-sectional study. SETTING: Physical and rehabilitation medicine department and center for medical genetics. PARTICIPANTS: Patients with EDS-HT (N=79; 8 men, 71 women) were recruited for this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients filled out questionnaires regarding type of complaints, medication use, surgery, physiotherapy, and outcome of treatment. Functional impairment in daily life was measured by the Sickness Impact Profile. Pain severity was assessed with visual analog scales. RESULTS: Patients reported a large number of complaints, a considerable presence of severe pain, and a clinically significant impact of disease on daily functioning. Most patients (92.4%) used medications, among which analgesics were the most prevalent. Fifty-six patients (70.9%) underwent surgery, including mainly interventions of the extremities and abdomen. Forty-one patients (51.9%) are currently enrolled in a physical therapy program, mainly comprising neuromuscular exercises, massage, and electrotherapy. Patients with a high consumption of analgesics, who visited the physiotherapist, or who underwent surgery had a higher dysfunction in daily life. Only 33.9% of the patients who underwent surgery and 63.4% of patients in physical therapy reported a positive outcome. CONCLUSIONS: Patients with EDS-HT have numerous complaints and an impaired functional status that strongly determine their high rate of treatment consumption. The outcome of surgical and physiotherapy treatment is disappointing in a large percentage, which illustrates a strong need for evidence-based therapy.

Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: a comparative study with fibromyalgia and rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to investigate functional impairment and the impact of pain in patients with Ehlers-Danlos syndrome, hypermobility type (EDS-HT), and to compare the burden of disease with that in women with fibromyalgia (FM) and rheumatoid arthritis (RA). METHODS: A total of 206 female patients were compared (72 with EDS-HT, 69 with FM, and 65 with RA). Functional impairment was assessed with the Sickness Impact Profile (SIP), and the psychosocial impact of chronic pain was quantified with the Multidimensional Pain Inventory (MPI). Data on symptoms were collected. RESULTS: SIP results showed clinically relevant health-related dysfunction in all groups. Significantly poorer physical, psychosocial, and overall function was found in the EDS-HT group compared with the RA group. In comparison with the FM group, the EDS-HT group reported similar physical and overall function, but better psychosocial function. T scores from the MPI revealed significantly higher levels of pain severity and life interference due to pain, and a lower level of perceived life control, in the EDS-HT group compared to the RA group. In contrast, the EDS-HT group showed significantly lower levels of pain severity, life interference, and affective distress in comparison with the FM group. Social support for help in coping with pain was similar between the 3 groups. CONCLUSION: EDS-HT is associated with a consistent burden of disease, similar to that of FM and worse than that of RA, as well as a broad impact of chronic pain on daily life, which needs to be addressed in the health care system.