Brain Activity Changes in Somatosensory and Emotion-Related Areas With Medial Patellofemoral Ligament Deficiency.

BACKGROUND: Patellar instability with medial patellofemoral ligament (MPFL) deficiency is a common sports injury among young people. Although nonoperative and surgical treatment can provide stability of the patella, patients often have anxiety related to the knee. We speculate that neural dysfunction may be related to anxiety in these patients; however, the mechanism in the brain that generates this anxiety remains unknown. QUESTIONS/PURPOSES: (1) How does brain activity in patients with MPFL deficiency change in the areas related to somatic sensation against lateral shift of the patella? (2) How does patella instability, which can lead to continuous fear or apprehension for dislocation, influence brain activity in the areas related to emotion? METHODS: Nineteen patients with MPFL deficiency underwent surgical reconstruction in our hospital from April 2012 to March 2014. Excluding seven patients with osteochondral lesions, 12 patients (five males and seven females; mean age, 20 years) with MPFL deficiency were sequentially included in this study. Eleven control subjects (four males and seven females; mean age, 23 years) were recruited from medical students who had no history of knee injury. Diagnosis of the MPFL deficiency was made with MR images, which confirmed the rupture, and by proving the instability with a custom-made biomechanical device. Brain activity during passive lateral stress to the patella was assessed by functional MRI. Functional and anatomic images were analyzed using statistical parametric mapping. Differences in functional MRI outcome measures from the detected activated brain regions between the patients with MPFL deficiency and controls were assessed using t tests. RESULTS: Intergroup analysis showed less activity in several sensorimotor cortical areas, including the contralateral primary somatosensory areas (% signal change for MPFL group 0.49% versus 1.1% for the control group; p < 0.001), thalamus (0.2% versus 0.41% for the MPFL versus control, respectively; p < 0.001), ipsilateral thalamus (0.02% versus 0.27% for the MPFL versus control, respectively; p < 0.001), and ipsilateral cerebellum (0.82% versus 1.25% for the MPFL versus control, respectively; p < 0.001) in the MPFL deficiency group than in the control group. In contrast, the MPFL deficiency group showed more activity in several areas, including the contralateral primary motor area (1.06% versus 0.6% for the MPFL versus control, respectively; p < 0.001), supplementary motor area (0.89% versus 0.52% for the MPFL versus control, respectively; p < 0.001), prefrontal cortex (1.09% versus 1.09% for the MPFL versus control, respectively; p < 0.001), inferior parietal lobule (0.89% versus 0.62% for the MPFL versus control, respectively; p < 0.001), anterior cingulate cortex (0.84% versus 0.08% for the MPFL versus control, respectively; p < 0.001), visual cortex (0.86% versus 0.14% for the MPFL versus control, respectively; p < 0.001), vermis (1.18% versus 0.37% for the MPFL versus control, respectively; p < 0.001), and ipsilateral prefrontal cortex (1.1% versus 0.75% for the MPFL versus control, respectively; p < 0.001) than did the control group. CONCLUSIONS: Less activity in the contralateral somatosensory cortical areas suggested that MPFL deficiency may lead to diminished somatic sensation against lateral shift of the patella. In contrast, increased activity in the anterior cingulate cortex, prefrontal cortex, and inferior parietal lobule may indicate anxiety or fear resulting from patellar instability, which is recognized as an aversion similar to that toward chronic pain. CLINICAL RELEVANCE: This study suggests that specific brain-area activity is increased in patients with MPFL deficiency relative to that in controls. Further longitudinal research to assess brain activity and proprioception between patients pre- and postreconstructive knee surgery may reveal more regarding how patella instability is related to brain function. We hope that based on such research, a neural approach to improve patella-instability-related brain function can be developed.

Delayed gadolinium-enhanced MRI of cartilage and T2 mapping for evaluation of reparative cartilage-like tissue after autologous chondrocyte implantation associated with Atelocollagen-based scaffold in the knee.

OBJECTIVE: To elucidate the quality of tissue-engineered cartilage after an autologous chondrocyte implantation (ACI) technique with Atelocollagen gel as a scaffold in the knee in the short- to midterm postoperatively, we assessed delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping and clarified the relationship between T1 and T2 values and clinical results. MATERIALS AND METHODS: In this cross-sectional study, T1 and T2 mapping were performed on 11 knees of 8 patients (mean age at ACI, 37.2 years) with a 3.0-T MRI scanner. T1implant and T2implant values were compared with those of the control cartilage region (T1control and T2control). Lysholm scores were also assessed for clinical evaluation. The relationships between the T1 and T2 values and the clinical Lysholm score were also assessed. RESULTS: There were no significant differences in the T1 values between the T1implant (386.64 ± 101.78 ms) and T1control (375.82 ± 62.89 ms) at the final follow-up. The implants showed significantly longer T2 values compared to the control cartilage (53.83 ± 13.89 vs. 38.21 ± 4.43 ms). The postoperative Lysholm scores were significantly higher than the preoperative scores. A significant correlation was observed between T1implant and clinical outcomes, but not between T2implant and clinical outcomes. CONCLUSION: Third-generation ACI implants might have obtained an almost equivalent glycosaminoglycan concentration compared to the normal cartilage, but they had lower collagen density at least 3 years after transplantation. The T1implant value, but not the T2 value, might be a predictor of clinical outcome after ACI.

A Single Case Study Comparing High Tibial Osteotomy With Matrix-Associated Autologous Chondrocyte Implantation With Medial Collateral Ligament Release Treating Bilateral Severe Medial Knee Osteoarthritis.

CASE: A 62-year-old woman with bilateral severe medial unicompartmental knee osteoarthritis underwent right high tibial osteotomy (HTO) at the age of 49 and left matrix-associated autologous chondrocyte implantation covering with periosteum (pMACI) with medial collateral ligament (MCL) release at age 52 years. At the 13-year follow-up, she could walk and trek with good clinical scores, had high patient satisfaction, and had cartilaginous reparative tissue seen at second-look arthroscopy in her left knee. CONCLUSION: This case suggests that pMACI with MCL release might be a possible alternative to HTO in a varus knee undergoing cartilage replacement surgery when HTO is contraindicated.

Evaluation of magnetic resonance imaging and clinical outcome after tissue-engineered cartilage implantation: prospective 6-year follow-up study.

BACKGROUND: Autologous chondrocyte implantation (ACI) is an important procedure when repairing cartilage defects of the knee. We previously reported several basic studies on tissue-engineered cartilage, and conducted a multicenter clinical study in 2009. In this clinical study, we evaluated the patients' clinical scores and MRI findings before and after tissue-engineered cartilage implantation, and compared the data obtained at 1 year and approximately 6 years post-implantation. METHODS: Fourteen patients who underwent implantation of tissue-engineered cartilage to repair cartilage defects of the knee were evaluated. Tissue-engineered cartilage was produced by culturing autologous chondrocytes three dimensionally in atelocollagen gel. The patients were evaluated clinically using the Lysholm score, and the original knee-function score at pre-implantation and at 1 year and approximately 6 years post-implantation. MRI scans were obtained at the same observation periods. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used to quantify clinical efficacy based on the MRI findings. RESULTS: In approximately 6 years of follow-up, none of the 14 patients reported any subjective symptoms of concern. The mean Lysholm score and the original knee-function score (63.0 ± 10.1, 59.9 ± 5.7) significantly improved at 1 year after implantation (86.4 ± 11.8, 94.1 ± 9.2), and were maintained until 6 years after implantation (89.8 ± 6.2, 89.9 ± 11.2), although some patients showed deterioration of Lysholm and original knee scores between 1 year post-implantation and the final follow-up. The mean MOCART score was 13.2 ± 12.0 pre-implantation, and 62.5 ± 24.7 at 1 year and 70.7 ± 22.7 at approximately 6 years post-implantation. The MOCART scores at 1 year and 6 years were significantly higher than the pre-implantation score, but there was no significant difference between the scores at 1 and 6 years, indicating that the MRI results at 1 year after implantation were maintained for the next 5 years. CONCLUSIONS: The clinical scores and MRI findings after implantation of tissue-engineered cartilage were improved at 1 year after implantation and were maintained until 6 years after implantation.

A "sandwich" method of reconstruction of the medial patellofemoral ligament using a titanium interference screw for patellar instability in skeletally immature patients.

BACKGROUND: No standard surgical procedure for medial patellofemoral ligament (MPFL) reconstruction exists in skeletally immature patients with patellar instability. This study aimed to evaluate the clinical effectiveness of a novel reconstruction technique for the MPFL in patients with patellar instability because of non-closure of the epiphyseal line. METHODS: The "sandwich" method was fixation of the patella between a double-stranded semitendinosus tendon through the posterior third of the femoral insertion of the medial collateral ligament (MCL) as a pulley with a titanium interference screw in a single patellar tunnel. Five knees in five patients were studied: four with recurrent and one with habitual patellar dislocations. Subjects underwent MPFL reconstruction with or without lateral release. Patients were evaluated using pre-operative and post-operative physical and radiographic examinations, including apprehension testing, assessment of tilting and congruence angles, medial and lateral shift ratios under stress measured using X-ray imaging, and Kujala and Lysholm scores. RESULTS: No patient experienced recurrent post-operative episodes of dislocation or subluxation. By the final follow-up, patellar apprehension had disappeared in all patients. In addition, all patients showed significant improvement in the following: tilting angle, congruence angle, lateral shift ratio, Kujala score, and Lysholm score. CONCLUSIONS: The MPFL reconstruction methods, using a double-stranded semitendinosus autograft and sparing the femoral physeal line in non-closure of the epiphyseal line, provide acceptable short-term results for the treatment of patellar instability.

Elbow Brace Promotes Postoperative Rehabilitation of Osteochondral Graft in Young Athletes with Osteochondritis Dissecans of the Humeral Capitellum.

OBJECTIVE: Treatment of large advanced osteochondritis dissecans (OCD) of the elbow in young athletes is challenging. METHODS: We retrospectively reviewed the results in 9 baseball players (mean age, 13.7 years; range, 12-15 years) who were followed up for a mean 21.1 months (range, 12-36 months) after osteochondral autograft. In this operation, cylindrical osteochondral plugs were harvested from a lateral femoral condyle and transferred to the lesion in humeral capitellum. After immobilizing the elbow by a splint for 2 weeks, the patients were encouraged to do range of motion exercises using an elbow brace with a hinge for 2 months. The elbow brace was applied to avoid excess stress to the implants on the capitellum and to the lateral collateral ligament. Patients were clinically assessed by the Japanese Orthopaedic Association elbow score (JOA score) and morphologically by radiographs as well as by magnetic resonance imaging (MRI). RESULTS: Patients started playing catch at 3 months and returned to baseball at competitive level at around 6 months postoperatively. The average JOA score was 68.0 points before operation and improved to 98.7 points at follow-up. Bony fusion between the implants and host bone was observed radiographically at 3 months. MRI confirmed a durable load-bearing articular surface of the capitellum at 1 year. CONCLUSIONS: Osteochondral autograft with postoperative rehabilitation using an elbow brace is a reasonable treatment for young athletes with an advanced lesion of OCD of the elbow who desire a relatively quick return to their pre-injury sports activity level.

Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.