Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Gene therapy and cement injection for restabilization of loosened hip prostheses.

Loosening of orthopedic hip prostheses is an increasing health problem. In elderly patients with comorbidity,revision surgery may lead to high mortality rates. A less invasive surgical technique is therefore required to reduce these patient risks. To this end a percutaneous gene therapy approach was designed to destroy the periprosthetic loosening membrane, and enable refixing of the hip prosthesis with percutaneous bone cement injections under radiological guidance. In this phase 1/2 dose-escalating gene therapy clinical trial, 12 patients were treated. Toxicity and hip function variables were monitored up to 6 months posttreatment. All patients completed the study and no dose-limiting toxicity was observed. Improvement in walking distance, independence,and pain was demonstrated particularly in patients receiving 3 x 10(10) and 1 x 10(11) viral particles. Taken together, these data show that this gene therapy approach targeted at the interface membrane around a loosened hip prosthesis is a feasible treatment option for elderly patients for whom surgical intervention is not appropriate.

Autologous transplantation of porcine myogenic precursor cells in skeletal muscle.

Myoblast transplantation is a potential therapy for severe muscle trauma, myopathies and heart infarct. Success with this therapy relies on the ability to obtain cell preparations enriched in myogenic precursor cells and on their survival after transplantation. To define myoblast transplantation strategies applicable to patients, we used a large animal model, the pig. Muscle dissociation procedures adapted to porcine tissue gave high yields of cells containing at least 80% myogenic precursor cells. Autologous transplantation of 3[H]-thymidine labeled porcine myogenic precursor cells indicated 60% survival at day 1 followed by a decay to 10% at day 5 post-injection. Nuclei of myogenic precursor cells transduced with a lentivirus encoding the nls-lacZ reporter gene were present in host myotubes 8 days post-transplantation, indicating that injected myogenic precursor cells contribute to muscle regeneration. This work suggests that pig is an adequate large animal model for exploring myogenic precursor cells transplantation strategies applicable in patients.

Structural changes in muscle and glenohumeral joint deformity in neonatal brachial plexus palsy.

BACKGROUND: Internal rotation contracture of the shoulder is common in children with neonatal brachial plexus palsy. A long-standing contracture may cause osseous deformities in the developing shoulder. The purpose of the study was to evaluate the relationship between osseous deformities of the glenohumeral joint and structural differences due to muscle denervation in the rotator cuff muscles. METHODS: One hundred and two children with residual neonatal brachial plexus palsy underwent magnetic resonance imaging of both shoulders. The glenoid version and posterior, medial, and superior subluxation of the humeral head were measured. The shapes of the glenoid and the humeral head were categorized, and the infraspinatus, supraspinatus, subscapularis, and deltoid muscles were scored as being normal, atrophic, or atrophic with fatty degeneration. RESULTS: Muscle degeneration was most prominent in the subscapularis muscle. Glenoid version correlated with the structural differences in the subscapularis muscle. Posterior subluxation of the humeral head and the shape of the glenoid correlated with all abnormal rotator cuff muscles. Superior humeral subluxation correlated only with changes in the supraspinatus muscle. Medialization and the shape of the humeral head were not associated with atrophic changes of the rotator cuff. Regeneration of the rotator cuff muscles was not significantly different in patients with a C5-C6 (C7) or a complete brachial plexus lesion. However, the changes in glenoid version, the degree of posterior humeral subluxation, and the degree of medial humeral subluxation were significantly more severe in patients with a C5-C6 (C7) lesion compared with those in patients with a complete lesion of the brachial plexus. CONCLUSIONS: Structural differences in the rotator cuff muscles alter the direction of the humeral head forces on the developing glenoid fossa and can lead to osseous deformities. Glenohumeral deformities are significantly greater with a C5-C6 (C7) lesion than with a complete brachial plexus lesion in which the large internal rotators are also affected. Reducing the muscular imbalance that occurs with a C5-C6 (C7) lesion could diminish glenohumeral joint incongruency and may improve the outcome of subsequent soft-tissue release or tendon transfer surgery.

Retention of estradiol negative feedback relationship to LH predicts ovulation in response to caloric restriction and weight loss in obese patients with polycystic ovary syndrome.

The present study tests the hypothesis that specific endocrine, metabolic, and anthropometric features distinguish obese women with polycystic ovary syndrome (PCOS) who resume ovulation in response to calorie restriction and weight loss from those who do not. Fifteen obese (body mass index 39 +/- 7 kg/m(2)) hyperandrogenemic oligoovulatory patients undertook a very low calorie diet (VLCD), wherein each lost > or =10% of body weight over a mean of 6.25 mo. Body fat distribution was quantitated by magnetic resonance imaging. Hormones were measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals before intervention and after 7 days of VLCD. Responders were defined a priori as individuals exhibiting two or more ovulatory cycles in the course of intervention, as corroborated by serum progesterone concentrations > or =18 nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex hormone-binding globulin (SHBG) concentration but were otherwise indistinguishable from nonresponders. Body weight, the size of body fat depots, and plasma insulin levels declined to a similar extent in responders and nonresponders. Also, SHBG increased, and the free testosterone index decreased comparably. However, responders exhibited a significant decline of circulating estradiol concentrations (from 191 +/- 82 to 158 +/- 77 pmol/l, means +/- SD, P = 0.037) and a concurrent increase in LH secretion (from 104 +/- 42 to 140 +/- 5 U.l(-1).day(-1), P = 0.006) in response to 7 days of VLCD, whereas neither parameter changed significantly in nonresponders. We infer that evidence of retention of estradiol-dependent negative feedback on LH secretion may forecast follicle maturation and ovulation in obese patients with PCOS under dietary restriction.