Hypermobility Type Research Articles

Treatment of Pediatric Chronic Pain with Tramadol Hydrochloride: Siblings with Ehlers‐Danlos Syndrome ‐ Hypermobility Type

To evaluate the effectiveness of tramadol hydrochloride for the treatment of chronic pain refractory to previous treatment in two pediatric patients. Tramadol hydrochloride was administered (50 mg/day to 150 mg/day) to two siblings with Ehlers-Danlos syndrome - Hypermobility type refractory to previous pharmacological treatments, and changes in pain intensity and physical activity were assessed. Pain intensity decreased and physical activity improved within days of starting therapy. Positive results have been maintained for 30 months. Tramadol hydrochloride was a safe and effective treatment for relieving chronic pain in two pediatric patients suffering from the hypermobility type of Ehlers-Danlos syndrome. No morbidity or side effects were noted during the 30-month follow-up.

Reduced skin thickness: a new minor diagnostic criterion for the classical and hypermobility types of Ehlers-Danlos syndrome

The diagnosis of Ehlers-Danlos syndrome (EDS) is mainly based on clinical criteria, although in some instances a sound molecular diagnosis is available. Clinical signs can be divided into two categories: one with high diagnostic specificity and the other with low specificity. Despite the fact that reduced skin thickness is one of the dermatological features in patients with EDS, this issue has not been analysed in greater detail. To determine skin thickness in patients with the classical and the hypermobility types of EDS. In 21 patients with classical type of EDS and in nine patients with hypermobility type of EDS, skin thickness was analysed at different body sites by cross-sectional b-mode scans obtained with a 20-MHz ultrasound system. We found a significant decrease in skin thickness in both types of EDS, which was highest at the chest and at the distal part of the lower leg. We propose that the reduced thickness of the dermis as determined by high-resolution 20-MHz ultrasound can be used as a new minor criterion in the diagnosis of the classical and the hypermobility types of EDS.

British consultant rheumatologists' perceptions about the hypermobility syndrome: a national survey.

Three hundred and nineteen UK-based consultant rheumatologists, members of the British Society for Rheumatology (a response rate of 76%), responded to a questionnaire concerning their perceptions of the (benign joint) hypermobility syndrome (HMS). The questions were wide-ranging and covered the nature of the condition, its clinic prevalence, criteria for diagnosis, the efficacy of chosen treatments, the impact of the syndrome on affected individuals and the contribution that it makes to the overall burden of rheumatic disease morbidity. Ninety-two per cent of the respondents believed in the HMS as a distinct clinical entity but only 39% accepted it as a distinct pathological entity. Only 42% were prepared to comment on whether the HMS and Ehlers-Danlos syndrome, hypermobility type (formerly EDS type III) were one and the same entity. There was striking variability in estimated clinic prevalence and no consensus about the diagnostic criteria being used. There was little enthusiasm for treatments currently available. Nearly one-half of the respondents were sceptical about a significant impact of the HMS on people's lives and three-quarters about a significant contribution to the overall burden of rheumatic disease. There was little sign of awareness of findings in recent published studies. It seems unlikely, therefore, that evidence-based medicine is being practised in this area of rheumatology. An unexpected finding was a refreshing enthusiasm for joining regional interest groups on hypermobility (25% of all UK consultants expressed interest).

The Pro-α3(V) Collagen Chain: COMPLETE PRIMARY STRUCTURE, EXPRESSION DOMAINS IN ADULT AND DEVELOPING TISSUES, AND COMPARISON TO THE STRUCTURES AND EXPRESSION DOMAINS OF THE OTHER TYPES V AND XI PROCOLLAGEN CHAINS

The low abundance fibrillar collagen type V is widely distributed in tissues as an alpha1(V)(2)alpha2(V) heterotrimer that helps regulate the diameters of fibrils of the abundant collagen type I. Mutations in the alpha1(V) and alpha2(V) chain genes have been identified in some cases of classical Ehlers-Danlos syndrome (EDS), in which aberrant collagen fibrils are associated with connective tissue fragility, particularly in skin and joints. Type V collagen also exists as an alpha1(V)alpha2(V)alpha3(V) heterotrimer that has remained poorly characterized chiefly due to inability to obtain the complete primary structure or nucleic acid probes for the alpha3(V) chain or its biosynthetic precursor, pro-alpha3(V). Here we provide human and mouse full-length pro-alpha3(V) sequences. Pro-alpha3(V) is shown to be closely related to the alpha1(V) precursor, pro-alpha1(V), but with marked differences in N-propeptide sequences, and collagenous domain features that provide insights into the low melting temperature of alpha1(V)alpha2(V)alpha3(V) heterotrimers, lack of heparin binding by alpha3(V) chains and the possibility that alpha1(V)alpha2(V)alpha3(V) heterotrimers are incorporated into heterotypic fibrils. In situ hybridization of mouse embryos detects alpha3(V) expression primarily in the epimysial sheaths of developing muscles and within nascent ligaments adjacent to forming bones and in joints. This distribution, and the association of alpha1(V), alpha2(V), and alpha3(V) chains in heterotrimers, suggests the human alpha3(V) gene COL5A3 as a candidate locus for at least some cases of classical EDS in which the alpha1(V) and alpha2(V) genes have been excluded, and for at least some cases of the hypermobility type of EDS, a condition marked by gross joint laxity and chronic musculoskeletal pain. COL5A3 is mapped to 19p13.2 near a polymorphic marker that should be useful in analyzing linkage with EDS and other disease phenotypes.

Expanded Indications for the Pubovaginal Sling

PURPOSE: The usefulness of the pubovaginal sling procedure as primary treatment of stress incontinence associated with urethral hypermobility (type 2) or intrinsic sphincter deficiency (type 3) was determined. MATERIALS AND METHODS: A total of 60 consecutive cases of type 2 or 3 stress urinary incontinence was treated with a pubovaginal sling by 1 surgeon using a previously reported technique. Fluoroscopic urodynamic studies with leak point pressures were used to classify the type of incontinence. Of the 60 women 38 (63%) were diagnosed with type 2 and 22 (37%) with type 3 stress urinary incontience. Of these patients 24 had previously undergone 1 or more anti-incontinence procedures. RESULTS: At a mean followup of 25 months 57 of the 60 patients (95%) were completely continent. In addition, 69% of patients with urgency had resolution of the urgency symptoms following the sling procedure. Transient postoperative urinary retention (median duration 6.5 days) was present in 60% of the patients. However, all women subsequently voided spontaneously without requiring further intermittent or Foley catheterization. Other complications occurred infrequently, and included urinary tract infection (13% of cases), de novo urgency (12%) and persistent incisional pain (5%). CONCLUSIONS: These early results suggest that the pubovaginal sling is a safe and effective treatment for primary or recurrent type 2 or 3 stress incontinence. The most worrisome complication, urinary retention, occurred temporarily in more than half of the patients but eventually resolved in all cases, usually within 10 days.

Expanded Indications for the Pubovaginal Sling: Treatment of Type 2 or 3 Stress Incontinence

Purpose The usefulness of the pubovaginal sling procedure as primary treatment of stress incontinence associated with urethral hypermobility (type 2) or intrinsic sphincter deficiency (type 3) was determined. Materials and Methods A total of 60 consecutive cases of type 2 or 3 stress urinary incontinence was treated with a pubovaginal sling by 1 surgeon using a previously reported technique. Fluoroscopic urodynamic studies with leak point pressures were used to classify the type of incontinence. Of the 60 women 38 (63 percent) were diagnosed with type 2 and 22 (37 percent) with type 3 stress urinary incontinence. Of these patients 24 had previously undergone 1 or more anti-incontinence procedures. Results At a mean followup of 25 months 57 of the 60 patients (95 percent) were completely continent. In addition, 69 percent of patients with urgency had resolution of the urgency symptoms following the sling procedure. Transient postoperative urinary retention (median duration 6.5 days) was present in 60 percent of the patients. However, all women subsequently voided spontaneously without requiring further intermittent or Foley catheterization. Other complications occurred infrequently, and included urinary tract infection (13 percent of cases), de novo urgency (12 percent) and persistent incisional pain (5 percent). Conclusions These early results suggest that the pubovaginal sling is a safe and effective treatment for primary or recurrent type 2 or 3 stress incontinence. The most worrisome complication, urinary retention, occurred temporarily in more than half of the patients but eventually resolved in all cases, usually within 10 days.

Application of transrectal sonography in the diagnosis and treatment of female stress urinary incontinence.

One hundred and two women with genuine stress urinary incontinence (SUI) were examined by transrectal sonography and urodynamics. The patients were classified into five types according to their intrinsic and extrinsic continence mechanism defects. Twenty-five patients had a hypermobile bladder neck and urethra (type 1); 31 patients had an incompetent bladder neck and a hypermobile urethra (type 2); 31 patients showed an incompetent urethral sphincter in addition to urethral hypermobility (type 3); 12 patients had a cystocele accompanying incompetent urethral sphincter and hypermobile urethra (type 4); the remaining 3 showed an incompetent urethral sphincter without hypermobility of the urethra (type 5). Whereas the distance from the lower margin of symphysis pubis to the bladder neck (pubovesical ligament; PVL) showed a significant increase in straining state of types 3 and 4, this was not the case in types 1, 2 and 5. There is a significant increase in the posteroinferior rotational of PVL angle on straining compared with resting in types 1, 2, 3, and 4, but not in type 5. The angle on straining also showed an increased tendency from type 1 to 4. The functional degree of SUI showed a significant increase from type 1 to 5. With this classification, the functional class of SUI is thus well correlated with the anatomical defects. The PVL length and the angle of external rotation of this axis are significantly implicated in the severity of SUI.

The Response to Local Anaesthetics (EMLAR-cream) as a Clinical Test to Diagnose between Hypermobility and Ehlers Danlos Type III Syndrome

To make a differential diagnosis of Ehlers Danlos (EDS) Type III syndrome and Hypermobile patients has been difficult. In genetic advising and prognosis of the EDS patients there are need for new tools to separate them from hypermobile patients. Topical analgesics (EMLA cream) was applied to seven EDS patients, ten hypermobile patients, and to fifteen controls. The analgesic efficacy of cutaneous analgesia was evaluated by sensory and pain thresholds to brief argon laser stimuli, and the depth of the cutaneous analgesia was measured by sensory and pain threshold depth to controlled needle insertions. Controls and hypermobiles did not differ in their response to cutaneous analgesia. The thresholds to cutaneous laser stimulation and the depth of analgesia increased significantly less in the Ehlers Danlos patients compared to the other two groups. In clinical practice a needle insertion test can easily be applied to investigate if patients are responders or non-responders to local analgesics.

Dermal changes in Ehlers-Danlos syndrome.

Skin biopsies from thirteen patients suffering from Ehlers-Danlos syndrome, including 6 of the mitis type, 4 of the benign hypermobile type, one of the X-linked type, one of the ocular type and one of the periodontitis type, were studied by electron microscopy after routine preparation. Collagen fibrils showed a distorted arrangement of bent, curled or twisted fibrils and thread-like material. Similar changes may be seen in the skin of other hereditary disorders of connective tissue. However, abnormal collagen fibrils in normal skin suggests one of eight types of Ehlers-Danlos syndrome. Clinical variants cannot be differentiated on the basis of ultrastructural findings. Elastic fibres were normal without degenerative changes. Perineurium was lacking in dermal nerves of most patients. Fibroblast-like cells showed no cystic cisterna of endoplasmic reticula.