Peter M. Waters

Antibody to aquaporin-4 in the long-term course of neuromyelitis optica.

Neuromyelitis optica (NMO) is a severe inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the spinal cord and optic nerves. Recently, a highly specific serum reactivity to CNS microvessels, subpia and Virchow–Robin spaces was described in patients with NMO [called NMO–IgG (NMO–immunoglobulin G)]. Subsequently, aquaporin-4 (AQP4), the most abundant water channel in the CNS, was identified as its target antigen. Strong support for a pathogenic role of the antibody would come from studies demonstrating a correlation between AQP4-Ab (AQP4-antibody) titres and the clinical course of disease. In this study, we determined AQP4-Ab serum levels in 96 samples from eight NMO–IgG positive patients (median follow-up 62 months) in a newly developed fluorescence-based immunoprecipitation assay employing recombinant human AQP4. We found that AQP4-Ab serum levels correlate with clinical disease activity, with relapses being preceded by an up to 3-fold increase in AQP4-Ab titres, which was not paralleled by a rise in other serum autoantibodies in one patient. Moreover, AQP4-Ab titres were found to correlate with CD19 cell counts during therapy with rituximab. Treatment with immunosuppressants such as rituximab, azathioprine and cyclophosphamide resulted in a marked reduction in antibody levels and relapse rates. Our results demonstrate a strong relationship between AQP4-Abs and clinical state, and support the hypothesis that these antibodies are involved in the pathogenesis of NMO.

Glenohumeral Deformity Secondary to Brachial Plexus Birth Palsy

Ninety-four patients who had brachial plexus birth palsy were entered into a prospective study to evaluate the association between persistent palsy, age-related musculoskeletal deformity, and functional limitations. Of these patients, forty-two had either computerized tomography or magnetic resonance imaging to assess the presence and degree of incongruity of the glenohumeral joint, deformity of the humeral head, and hypoplasia of the glenoid as part of the preoperative planning for a reconstructive operation. Functional ability was rated with use of the classification of Mallet, on a scale of 1 to 5. The mean glenoscapular angle (the degree of retroversion of the glenoid) on the affected side was -25.7 degrees compared with -5.5 degrees on the unaffected side. Twenty-six (62 per cent) of the forty-two shoulders had evidence of posterior subluxation of the humeral head, with a mean of only 25 per cent (range, 0 to 50 per cent) of the head being intersected by the scapular line. Progressive deformity was found with increasing age (p < 0.001). The natural history of untreated brachial plexus birth palsy with residual weakness is progressive glenohumeral deformity due to persistent muscle imbalance. The status of the glenohumeral joint must be addressed when the choice between tendon transfer and humeral derotation osteotomy for reconstruction of the shoulder is considered for these patients.

Comparison of the natural history, the outcome of microsurgical repair, and the outcome of operative reconstruction in brachial plexus birth palsy.

BACKGROUND The purposes of this study were to document the natural history of brachial plexus birth palsy, in relation to the recovery of biceps function, in the first six months of life; to assess the outcome after microsurgical repair of the brachial plexus in patients who had no recovery of biceps function at six months; and to compare the results of transfer of the latissimus dorsi and teres major tendons with the results of derotation osteotomy of the humerus and to compare the results of the tendon transfers and the osteotomy with the natural history of the disorder. METHODS Sixty-six patients (sixty-seven lesions) who had brachial plexus birth palsy were seen for an initial evaluation when they were less than three months old. The time of recovery of biceps function was recorded for each month of life for six months from the date of birth. The patients were divided into groups according to the month of life during which recovery of biceps strength was noted. A physical examination and an assessment with use of the functional criteria of Mallet were performed each month. Microsurgical repair of the brachial plexus was performed in six infants who had no evidence of biceps function within the first six months of life. Another group of twenty-seven patients were referred for evaluation of chronic neuropathy after they were six months old. A transfer of the latissimus dorsi and teres major tendons to the rotator cuff was performed in nine of these patients and a derotation osteotomy of the humerus was performed in seven because of an internal rotation contracture or functional weakness of the external rotators of the shoulder. RESULTS Twenty-two infants had recovery of biceps function within the first three months of life and had normal function at the time of the latest evaluation. Infants who had recovery of biceps function during the fourth, fifth, or sixth month of life later had significantly worse function, according to the criteria described by Mallet, than those who had had recovery in the first three months (p<0.005). The clinical results for the six patients who had had microsurgical repair six months after birth were significantly better (p<0.04) than those for the fifteen patients who had had recovery of biceps function in the fifth month of life. However, the results for the patients who had had repair of the brachial plexus were not found to be better than those for the eleven patients who had had recovery of biceps function in the fourth month of life. The improvement in function, as assessed with use of the Mallet criteria, after tendon transfer (p<0.001) and humeral osteotomy (p<0.0001) was significant. CONCLUSIONS The present study confirms the observation of Gilbert and Tassin that it is rare for infants who have recovery of biceps function after the age of three months to have complete neurological recovery. Microsurgical repair was effective in improving function in the small subgroup of patients who had no evidence of recovery of biceps function within the first six months of life.

Upper extremity injuries in the paediatric athlete.

Injuries to the upper extremity in paediatric and adolescent athletes are increasingly being seen with expanded participation and higher competitive levels of youth sports. Injury patterns are unique to the growing musculoskeletal system and specific to the demands of the involved sport. Shoulder injuries include sternoclavicular joint injury, clavicle fracture, acromioclavicular joint injury, osteolysis of the distal clavicle, little league shoulder, proximal humerus fracture, glenohumeral instability and rotator cuff injury. Elbow injuries include supracondylar fracture, lateral condyle fracture, radial head/neck fracture, medial epicondyle avulsion, elbow dislocation and little league elbow. Wrist and hand injuries include distal radius fracture, distal radial physeal injury, triangular fibrocartilage tear, scaphoid fracture, wrist ligamentous injury thumb metacarpalphalangeal ulnar collateral ligament injury, proximal and distal interphalangeal joint injuries and finger fractures. Recognition of injury patterns with early activity modification and the initiation of efficacious treatment can prevent deformity/disability and return the youth athlete to sport.

Effect of Tendon Transfers and Extra-articular Soft-tissue Balancing on Glenohumeral Development in Brachial Plexus Birth Palsy

BACKGROUND Persistent muscle imbalance and soft-tissue contractures can lead to progressive glenohumeral joint deformity in patients with brachial plexus birth palsy. The objective of this investigation was to determine the effects of correction of external rotation weakness and internal rotation contractures with tendon transfers and extra-articular soft-tissue releases on glenohumeral development in patients with brachial plexus birth palsy. METHODS Twenty-five patients with brachial plexus birth palsy who underwent latissimus dorsi and teres major tendon transfers to the rotator cuff-with or without concomitant musculotendinous lengthenings-were evaluated clinically and radiographically before the operation and at a minimum of two years (average, forty-three months) postoperatively. Shoulder function was prospectively assessed with use of the modified Mallet classification system, in which aggregate shoulder function is assigned a score of 5 to 25 points. Glenoid version and humeral head subluxation were quantified with magnetic resonance imaging or computed tomography, and glenohumeral deformity was graded. RESULTS Clinically, all patients demonstrated improved global shoulder function, with the mean aggregate Mallet score improving from 13 points preoperatively to 18 points postoperatively (p < 0.01). As seen radiographically, the mean glenoid retroversion improved from 22 degrees preoperatively to 16.5 degrees postoperatively (p = 0.012). The mean posterior humeral head subluxation improved from 30% to 37% (p = 0.03). No patient had progressive worsening of the glenohumeral deformity. CONCLUSIONS Latissimus dorsi and teres major tendon transfers to the rotator cuff, combined with appropriate extraarticular musculotendinous lengthenings, significantly improved global shoulder function but led to only modest improvements in glenoid retroversion and humeral head subluxation. No profound glenohumeral remodeling occurs after these extra-articular rebalancing procedures, even when they are performed in patients of a young age. While the long-term clinical and radiographically apparent effects at skeletal maturity are uncertain, soft-tissue rebalancing procedures alone were found to have halted the progression of, but not to have markedly decreased, glenohumeral dysplasia at the time of a two to five-year follow-up.

Neurovascular injury and displacement in type III supracondylar humerus fractures.

Summary From July 1987 to January 1991, 59 consecutive type III supracondylar humerus fractures in children were identified at Childrens Hospital, Boston. Twenty-nine patients (49%) had evidence of neurovascular compromise. The median nerve was involved in 15 (52%) of these patients and was associated with posterolateral displacement in 87% of cases. The radial nerve was involved in eight (28%) of these patients and was associated with posteromedial displacement in every case. Injuries to the brachial artery occurred in 11 (38%) of these patients and was associated with posterolateral displacement in 64% and posteromedial displacement in 36% of cases. We conclude that posterolateral displacement in type III supracondylar humerus fractures is strongly associated with median nerve injuries. Posteromedial displacement is responsible for injuries to the radial nerve in virtually every instance. Brachial artery injuries may occur with either type of displacement. Neurovascular injury is higher than previously reported in these fractures.

Lateral entry compared with medial and lateral entry pin fixation for completely displaced supracondylar humeral fractures in children. A randomized clinical trial.

BACKGROUND Closed reduction and percutaneous pin fixation is the treatment of choice for completely displaced (type-III) extension supracondylar fractures of the humerus in children, although controversy persists regarding the optimal pin-fixation technique. The purpose of this study was to compare the efficacy of lateral entry pin fixation with that of medial and lateral entry pin fixation for the operative treatment of completely displaced extension supracondylar fractures of the humerus in children. METHODS This prospective, randomized clinical trial had sufficient power to detect a 10% difference in the rate of loss of reduction between the two groups. The techniques of lateral entry and medial and lateral entry pin fixation were standardized in terms of the pin location, the pin size, the incision and position of the elbow used for medial pin placement, and the postoperative course. The primary study end points were a major loss of reduction and iatrogenic ulnar nerve injury. Secondary study end points included radiographic measurements, clinical alignment, Flynn grade, elbow range of motion, function, and complications. RESULTS The lateral entry group (twenty-eight patients) and the medial and lateral entry group (twenty-four patients) were similar in terms of mean age, sex distribution, and preoperative displacement, comminution, and associated neurovascular status. No patient in either group had a major loss of reduction. There was no significant difference between the rates of mild loss of reduction, which occurred in six of the twenty-eight patients treated with lateral entry and one of the twenty-four treated with medial and lateral entry (p = 0.107). There were no cases of iatrogenic ulnar nerve injury in either group. There were also no significant differences (p > 0.05) between groups with respect to the Baumann angle, change in the Baumann angle, humerocapitellar angle, change in the humerocapitellar angle, Flynn grade, carrying angle, elbow flexion, elbow extension, total elbow range of motion, return to function, or complications. CONCLUSIONS With use of the specific techniques employed in this study, both lateral entry pin fixation and medial and lateral entry pin fixation are effective in the treatment of completely displaced (type-III) extension supracondylar fractures of the humerus in children. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Reliability of Three Classification Systems Measuring Active Motion in Brachial Plexus Birth Palsy

BACKGROUND Several classification systems for the categorization of function in patients with brachial plexus birth palsy have been proposed. The purpose of this investigation was to determine the intraobserver and interobserver reliability of the modified Mallet Classification, Toronto Test Score, and Hospital for Sick Children Active Movement Scale in the evaluation of these patients. METHODS Eighty children with brachial plexus birth palsy were evaluated by two trained examiners on two different occasions. Intraobserver and interobserver reliability was determined with use of the kappa statistic. RESULTS On the basis of the kappa statistic, intraobserver reliability was good to excellent for individual elements of the modified Mallet Classification, Toronto Test Score, and Active Movement Scale in all age-groups. Interobserver reliability for individual elements of these three systems ranged from fair to excellent. When aggregate Toronto Test and modified Mallet scores were assessed, positive intraobserver and interobserver correlations were noted (Pearson r = 0.70 to 0.98, p < 0.001). Internal consistency (test-retest reliability) as determined by the Cronbach alpha for the aggregate Toronto Test and modified Mallet scores was excellent for each age-group (alpha > 0.90, p < 0.001). CONCLUSIONS The modified Mallet Classification, Toronto Test Score, and Active Movement Scale are reliable instruments for assessing upper-extremity function in patients with brachial plexus birth palsy. The natural history and surgical outcomes of these patients can now be conducted with use of these reliable outcomes instruments.

A systematic review of medial and lateral entry pinning versus lateral entry pinning for supracondylar fractures of the humerus.

The supracondylar fracture of the distal humerus is the most common pediatric fracture in the elbow. This systematic review summarizes the existing data about the effect of medial and lateral (medial/lateral) entry pins versus only lateral entry pin fixation on the risk of iatrogenic nerve injury and deformity or loss of reduction. A literature search identified clinical trials and observational studies presenting the probability of nerve injury and/or deformity or loss of reduction associated with closed reduction and either medial/lateral entry or lateral entry pinning of supracondylar fractures in pediatric patients. Data from 2054 children were identified from 35 studies; 2 randomized trials, 6 cohort studies, and 25 case series. For operative fixation with medial/lateral entry pins, the probability of ulnar nerve injury is 5.04 times higher than with lateral entry pins. When all documented operative nerve injuries are included, the probability of iatrogenic nerve injury is 1.84 times higher with medial/lateral entry pins than with isolated lateral pins. Medial/lateral pin entry provides a more stable configuration, and the probability of deformity or loss of reduction is 0.58 times lower than with isolated lateral pin entry. When the prospective studies alone were analyzed, there were no significant difference in the probability of iatrogenic nerve injury or deformity and displacement, although the confidence intervals were wide. This systematic review indicates that medial/lateral entry pinning, of pediatric supracondylar fractures, remains the most stable configuration and that care needs to be taken regardless of technique to avoid iatrogenic nerve injury and loss of reduction.

Current Concepts in the Management of Brachial Plexus Birth Palsy

Brachial plexus birth palsy, although rare, may result in substantial and chronic impairment. Physiotherapy, microsurgical nerve reconstruction, secondary joint corrections, and muscle transpositions are employed to help the child maximize function in the affected upper extremity. Many present controversies regarding natural history, microsurgical treatment, and secondary shoulder reconstructive surgery remain unresolved in infants with brachial plexus birth palsies. Recent literature has enhanced our understanding of the pathoanatomy and natural history of the injury as well as the surgical indications, expected outcomes, and complications; this literature has led to improved care of these patients. Based on the present evidence, recommendations for both microsurgery and shoulder reconstruction with tendon transfer and arthroscopic and open reductions are presented.