Phillip N. Williams

Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls

Background: An autoimmune-mediated mechanism has been proposed for both pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and Tourette syndrome (TS). Confirmatory evidence has, in part, been based on controversial findings of autoantibodies in the sera of children with these disorders. Objective: To compare antineuronal antibody profiles in subjects with TS and PANDAS to age-matched controls. Methods: Sera were obtained from 48 children with PANDAS, 46 with TS, and 43 age-matched controls. Serum autoantibodies were measured by use of ELISA and Western immunoblotting against a variety of epitopes, including human postmortem caudate, putamen, and prefrontal cortex (Brodmann area 10). Immunoreactivity was also measured against commercially available α- and γ-enolase, aldolase C, and pyruvate kinase M1. Several assays were repeated after preabsorption of sera with M6 strain streptococci. Results: Median ELISA optical density readings were similar among the groups. Western blot analyses showed complex staining patterns with no differences in any tissue region based on the number of bands, reactivity peaks at molecular weights 98, 60, 45, and 40 kDa, or total area under ScanPack (Biometra, Gottingen, Germany)–derived peaks. Immunoreactivity against four putative pathologic antigens did not differentiate the clinical groups. Repeat immunoblotting after serum preabsorption with streptococci showed no loss of reactivity. ELISA values exceeding a specified cutoff did not predict changes in binding to either brain epitopes or commercial antigens. Conclusions: Results do not support the hypothesis that PANDAS and Tourette syndrome are secondary to antineuronal antibodies. Longitudinal studies are required to determine whether autoantibodies correlate with fluctuations in clinical activity.

Dopaminergic polymorphisms in Tourette syndrome: Association with the DAT gene (SLC6A3)

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by involuntary motor and phonic tics. The pattern of inheritance and associated genetic abnormality has yet to be fully characterized. A dopaminergic abnormality in this disorder is supported by response to specific therapies, nuclear imaging, and postmortem studies. In this protocol, dopaminergic polymorphisms were examined for associations with TS and attention‐deficit hyperactivity disorder (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine converting enzyme (dopamine β‐hydroxylase), and the acid phosphatase locus 1 (ACP1) gene. DNA was obtained from 266 TS individuals ± ADHD and 236 controls that were ethnicity‐matched. A significant association, using a genotype‐based association analysis, was identified for the TS‐total and TS‐only versus control groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01, respectively). Population structure, estimated by the genotyping of 27 informative SNP markers, identified 3 subgroups. A statistical re‐evaluation of the DAT1 DdeI polymorphism following population stratification confirmed the association for the TS‐total and TS‐only groups, but the degree of significance was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a significant association between the presence of TS and a DAT polymorphism. Since abnormalities of the dopamine transporter have been hypothesized in the pathophysiology of TS, it is possible that this could be a functional allele associated with clinical expression.

Functional Outcomes After Total Shoulder Arthroplasty in Obese Patients

BACKGROUND Obesity is increasingly prevalent in the United States. There are several reports of outcomes in obese patients after total knee or hip replacement. The purpose of this study was to compare the functional outcomes and complications of obese patients undergoing shoulder arthroplasty with those of overweight or normal-weight patients. METHODS Seventy-six patients who underwent primary total shoulder arthroplasty were grouped according to body mass index. The groups were classified as: normal, which was denoted by a body mass index of <25 kg/m2 (twenty-six patients); overweight, which was denoted by a body mass index of 25 to 29.9 kg/m2 (twenty-five patients); and obese, which was denoted by a body mass index of ≥30 kg/m2 (twenty-five patients). Preoperative demographics and perioperative and postoperative complications were recorded. The American Shoulder and Elbow Surgeons score, Short Form-36, and visual analog scale pain and fatigue scores were evaluated at baseline and at the two-year follow-up visit. RESULTS In the normal group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 38.4 ± 15.5 points preoperatively to 80.2 ± 19.4 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 38.3 ± 6.5 points preoperatively to 53.7 ± 11.3 points at two years postoperatively (p < 0.001); the visual analog scale pain scores decreased from a mean score of 62 points preoperatively to 12 points at two years postoperatively (p < 0.001). In the overweight group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 37.4 ± 18.1 points preoperatively to 75.2 ± 24.9 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 36.1 ± 8.0 points preoperatively to 39.8 ± 12.2 points at two years postoperatively (p = 0.21); the visual analog scale pain scores decreased from 68 points to 18 points (p < 0.001). In the obese group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 35.8 ± 12.5 points preoperatively to 80.0 ± 20.6 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 36.3 ± 8.4 points preoperatively to 40.7 ± 12.4 points at two years postoperatively (p = 0.15); the visual analog scale pain scores decreased from 66 points preoperatively to 11 points at two years postoperatively (p < 0.001). There was one deep infection in the overweight group that required surgical irrigation and debridement. Two revisions of the components were required in the normal group. CONCLUSIONS Obesity did not have a detrimental effect on the improvement of short-term shoulder function. However, the overall physical function of obese and overweight patients does not significantly improve after total shoulder arthroplasty. In the normal body mass index group, patients did improve overall physical function after total shoulder arthroplasty. LEVEL OF EVIDENCE Prognostic level II. See Instructions for Authors for a complete description of levels of evidence.

Tennis injuries: Epidemiology, pathophysiology, and treatment

Tennis places high loads on the joints of players, with supraphysiologic forces being generated at the shoulder and elbow hundreds of times per match. Acute injuries tend to affect the lower extremity; chronic injuries usually involve the upper extremity. Commonly encountered upper extremity conditions include rotator cuff injury, internal impingement, superior labral tears, and epicondylitis of the elbow. Serving is the most strenuous stroke in tennis, with the highest peak muscle activity in the shoulder and forearm occurring during this stroke. The kinetic chain links upper extremity, lower extremity, and core muscle segments by transmitting coordinated activation and motion; in this regard, any pathologic process that disturbs the groin, hip, and abdominal musculature can further result in an increased risk of injury to the shoulder and upper extremity. Evolution in equipment and in play surfaces has also affected the type and frequency of injuries. Prevention programs that address the muscular imbalances throughout the kinetic chain may help reduce the incidence of both acute and chronic injuries experienced by tennis athletes.

The epidemiology of single season musculoskeletal injuries in professional baseball

The aim of this descriptive epidemiology study was to evaluate the injury incidence, pattern and type as a function of position in one professional baseball organization for one complete season. The study was carried out in a major academic center. Participants were all major/minor league baseball players playing for one professional organization. The disabled/injury list of one single professional baseball organization (major and minor league players) was reviewed for all of the injuries and the number of total days missed secondary to each injury. All injuries were categorized into major anatomic zones that included: shoulder, elbow, wrist/hand, back, abdomen/groin, hip, knee, and ankle/foot. The data was further stratified based on the injury type and the number of days missed due to that particular injury and a statistical analysis was performed. In pitchers, elbow injuries (n=12) resulted in 466 days missed. In catchers, wrist injuries (n=4) resulted in 89 days missed. In position players, abdominal/groin injuries (n=16) resulted in 318 days missed and shoulder injuries (n=9) resulted in 527 days missed. Overall, 134 players were injured and a total of 3209 days were missed. Pitchers had 27 times and 34 times the rate of days missed due to elbow injuries compared to position players and all players, respectively. Abdominal and groin injuries caused the pitchers to have 5.6 times and 6.4 times the rate of days missed than the position and all players, respectively. Both elbow and abdominal/groin injuries are the most disabling injury pattern seen in pitchers. Among the position players, shoulder injuries resulted in the most days missed and knee injuries resulted in the highest rate of days missed in both pitchers and catchers.

Anterior Cruciate Ligament Reconstruction With Autologous Hamstring Can Preoperative Magnetic Resonance Imaging Accurately Predict Graft Diameter

Background: Recent clinical investigations have identified inadequate autograft hamstring graft diameter (<8 mm) to be predictive of failure after reconstruction of the anterior cruciate ligament (ACL). Purpose/Hypothesis: The objective of this study was to determine the utility of preoperative magnetic resonance imaging (MRI) variables of the hamstring tendons for the prediction of graft diameter at the time of surgery. The hypothesis was that cross-sectional area (CSA) of the hamstring tendon measured on MRI could accurately predict graft diameter, and threshold measurements could be established to predict graft diameter at the time of surgery. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 84 consecutive skeletally mature patients prospectively enrolled in our ACL reconstruction patient registry were identified for study purposes. Patients were included if they underwent an MRI of the affected knee at our institution prior to ACL reconstruction with hamstring (HT) autograft. Graft preparation was performed via a standard quadrupled hamstring technique after harvesting both the gracilis and semitendinosus (4-GST). The smallest diameter end of the HT autograft was then utilized for measurement analysis. Total CSA was calculated for both hamstring tendons using the “region of interest tool” on the corresponding proton density–weighted axial image of the knee at the widest condylar dimension. Three independent reviewers measured the MRI scans so that intra- and interrater reliability of the measurements could be determined. A trend analysis was then undertaken to establish correlations between the MRI CSA and graft diameter. Predictive analysis was then performed to establish threshold MRI measurement values for specific graft diameters and determine whether any patient-specific factors would affect graft diameter (age, sex, and body mass index). Results: Mean patient age at the time of surgery was 36 years (range, 11-57 years). Intra- and interrater reliability measurements achieved near-perfect agreement for CSA measurements, with intraclass correlation coefficients (ICCs) of 0.994 and 0.932, respectively. Trend analysis demonstrated that increasing CSA correlated well with increasing overall diameter of the graft (P < .001). Receiver operating characteristic (ROC) curves were generated to evaluate threshold CSA measurements for various graft diameters. Maximum sensitivity values of 21.64, 25.25, and 28.256 mm2 were established for the respective graft diameters of 8, 9, and 10 mm in the 4-GST group. Independent patient factors of younger age, shorter stature, and female sex were significantly associated with graft diameter (P = .019, .034, and .028, respectively). Conclusion: Preoperative MRI can be used to accurately predict quadrupled hamstring autograft diameter at the time of surgery. A total cross-sectional area of >22 mm2 can reliably provide a graft diameter of >8 mm at the time of surgery.

Trabecular bone microarchitecture and characteristics in different regions of the glenoid.

Success of shoulder surgery depends on implant fixation to the glenoid trabecular bone. The purpose of this study was to evaluate the anatomic characteristics of the normal glenoid trabecular bone microarchitecture to help assist in implant design and provide data for finite element analyses. Eight cadavers without evidence of osteoarthritis were used. Glenoids were scanned with micro-computed tomography and then divided into lateral and medial, then superior, inferior, anterior, and posterior quadrants (8 total segments). Each segment was analyzed for total mineral density, bone volume fraction, structure model index, and trabecular thickness (Tb.Th), number (Tb.N), and separation. Bone volume fraction was significantly higher (P<.05) in the posterolateral (20.8%±4.5%) and posteromedial (18.6%±2.5%) regions. Both Tb.N and Tb.Th were also highest in the posterolateral (Tb.N, 1.74±0.374 mm; Tb.Th, 0.148±0.017 mm) and posteromedial (Tb.N, 1.49±0.401 mm; Tb.Th, 0.165±0.016 mm) regions. Trabecular separation was greatest in the superomedial segment (1.00±0.181 mm) and lowest in the posterolateral region (0.663±0.121 mm). For structural model index, both the posterolateral (0.314) and posteromedial (0.312) regions had lower values than the other regions. The posterior segment of the normal glenoid in both the lateral and medial regions has the highest density, which is attributed to the increased trabecular number and thickness with decreased separation. This increased density may be attributed to the posterior directed loading of the glenohumeral joint. The trabecular microarchitecture in the glenoid is plate-like, as indicated by the low structural model index.

Athletic Performance at the National Basketball Association Combine After Anterior Cruciate Ligament Reconstruction.

Background: Anterior cruciate ligament (ACL) injuries are significant injuries in elite-level basketball players. In-game statistical performance after ACL reconstruction has been demonstrated; however, few studies have reviewed functional performance in National Basketball Association (NBA)–caliber athletes after ACL reconstruction. Purpose: To compare NBA Combine performance of athletes after ACL reconstruction with an age-, size-, and position-matched control group of players with no previous reported knee injury requiring surgery. We hypothesized that there is no difference between the 2 groups in functional performance. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 1092 NBA-caliber players who participated in the NBA Combine between 2000 and 2015 were reviewed. Twenty-one athletes were identified as having primary ACL reconstruction prior to participation in the combine. This study group was compared with an age-, size-, and position-matched control group in objective functional performance testing, including the shuttle run test, lane agility test, three-quarter court sprint, vertical jump (no step), and maximum vertical jump (running start). Results: With regard to quickness and agility, both ACL-reconstructed athletes and controls scored an average of 11.5 seconds in the lane agility test and 3.1 seconds in the shuttle run test (P = .745 and .346, respectively). Speed and acceleration was measured by the three-quarter court sprint, in which both the study group and the control group averaged 3.3 seconds (P = .516). In the maximum vertical jump, which demonstrates an athlete’s jumping ability with a running start, the ACL reconstruction group had an average height of 33.6 inches while the controls averaged 33.9 inches (P = .548). In the standing vertical jump, the ACL reconstruction group averaged 28.2 inches while the control group averaged 29.2 inches (P = .067). Conclusion: In athletes who are able to return to sport and compete at a high level such as the NBA Combine, there is no significant difference in any combine performance test between players who have had primary ACL reconstruction compared with an age-, size-, and position-matched control group. Clinical Relevance: Athletes with previous ACL reconstruction who are able to return to high-level professional basketball have equivalent performance measures with regard to speed, quickness, and jumping ability as those athletes who have not undergone knee surgery.

Platelet-rich plasma and other cellular strategies in orthopedic surgery

The use of biologics in the treatment of musculoskeletal disease has become increasingly more common as research studies continue to provide further elucidation of their mechanisms in healing. Platelet-rich plasma, patches, growth factors, and stem cells are among the many biologics under active investigation and have varying levels of success in augmenting surgical or nonoperative interventions. However, the limitations of these treatments exist, and clear guidelines for their indications and application have yet to be established. Well-designed clinical trials will help determine the appropriate future use of biologics to ensure consistent outcomes.

The biomechanical evaluation of a novel 3-strand docking technique for ulnar collateral ligament reconstruction in the elbow

BACKGROUND AND HYPOTHESIS The original 2-strand docking technique for elbow ulnar collateral ligament reconstruction has recently been modified to use a 3-strand graft. To date, no biomechanical study has compared the 2 techniques. We hypothesized that the 3-strand docking technique would restore valgus laxity to its native state, with comparable load-to-failure characteristics to the 2-strand docking technique. MATERIALS AND METHODS Sixteen fresh cadaveric elbows were matched to the corresponding contralateral side from the same individual to create 8 matched pairs and were then randomized to undergo ulnar collateral ligament reconstruction using either the 2- or 3-strand technique. Valgus laxity and rotation measurements were quantified using a MicroScribe 3DLX digitizer at various flexion angles for the native state, transected state, and 1 of the 2 tested reconstructed ligaments. Each reconstruction was then tested to failure. RESULTS Valgus laxity for the intact state at elbow flexion angles of 30°, 60°, 90°, and 120° was 7° ± 2°, 7° ± 2°, 6° ± 1°, and 5° ± 2°, respectively. These values were similar to those of both reconstruction techniques. On load-to-failure testing, there was no significant difference in any parameter recorded. Yield torques for the 3- and 2-strand reconstructions were 13.4 ± 4.80 N/m and 11.8 ± 4.76 N/m, respectively (P = .486). The ultimate torques were 15.7 ± 6.10 N/m and 14.4 ± 5.58 N/m for the 3- and 2-strand techniques, respectively (P = .582). CONCLUSION The 3-strand docking technique was able to restore valgus laxity to the native state, with similar load-to-failure characteristics to the 2-strand docking technique.