Chronic infection and infected non-union of the long bones in paediatric patients: preliminary results of bone versus beta-tricalcium phosphate grafting after induced membrane formation.

PURPOSE: Chronic infection (CO) and infected non-union of the long bones are relatively rare conditions in paediatric patients. Large bone defects secondary to these conditions can be managed with the induced membrane technique. The technique requires grafting of the bone void, although it is not yet established what bone substitute is the best option. The aim of this work was to evaluate the outcome and efficacy of treatment in children with CO and infected non-union of the long bones using the induced membrane technique and bone (BG) versus beta-tricalcium phosphate (BTP) grafting. METHODS: Eight skeletally immature patients with CO and infected non-union of the long bones were treated surgically between 2010 and 2017 by a combination of resection of necrotic infected bone, debridement of surrounding soft tissue, osteosynthesis using a stable internal fixation when needed, and application of antibiotic-laden cement (ALC) spacer inducing new membrane before final bone reconstruction with bone substitutes: BTP in five cases, BG (allograft and/or autologous graft) in three cases. A second surgical step, once inflammatory markers had normalized, consisted of ALC spacer removal, application of BG or BTP graft and concomitant stable osteosynthesis, if needed, if this had not been done during the first surgical stage. All the patients underwent clinical, laboratory and imaging evaluation before and after surgery. Antibiotics were adjusted according to culture and sensitivity. RESULTS: Mean patient age at time of diagnosis was 13 ± four years (range, 4-16) and all had at least a 12-month follow-up (range 12-60). Estimated time for induced membrane formation was significantly shorter in patients treated with BTP compared with BG: 3±1 vs. 10±2 (p = 0.02). This result was confirmed by multivariate analysis (p = 0.044) taking into account adjustment for age of patients and time after initial surgery. Time of final union was about 5.5 ± 4.1 months (range 2-66). At the last follow-up visit, bone had healed and all the patients had resumed daily living and sports activities. CONCLUSION: The induced membrane technique with BG or BTP graft can achieve bone healing in large bone defects secondary to CO and infected non-union in children and adolescents. The choice of bone substitute is important. Our preliminary results show graft integration and bone healing can be expected sooner if BTP is used as bone void filler.

Deep postoperative spine infection treated by negative pressure therapy in patients with progressive spinal deformities.

BACKGROUND: The aim of the study is to review the outcome of using the VAC system in children and adolescents who have developed postoperative spinal infection after posterior instrumented spinal fusion, and to evaluate whether this technique is also feasible in patients treated with posterior instrumented fusion with polyester sublaminar bands. METHODS: A total of 11 out of 118 consecutive children and adolescents (5 males) with deep postoperative spinal infection were identified; infections were categorised as early (acute), delayed (subacute) or late (chronic) according to time of onset. Irrespective of the etiology and the onset, all the deep infections were managed with the reported technique. All the patients had regular clinical and radiological follow-up. RESULTS: Eight out of 11 patients developed an early (72.7%), 2 a delayed (18.2%) and 1 a late deep postoperative infection (9.1%); 7 out of 11 (63.6%) showed severe mental compromise. No statistically significant differences were observed for mean number of VAC dressing changes (p = 0.81) and mean length of hospitalisation comparing patients with early infection versus patients with delayed or late infections (p = 0.32). Mean number of VAC dressing changes (p = 0.02) and mean number of hospitalisation days (p = 0.05) were higher in patients with underlying neurological disorders than in those without, while mean length of hospitalisation was longer in neuromuscular patients. CONCLUSIONS: The application of the VAC system, as an adjunct to surgical debridement and adequate antibiotic therapy, is a reliable method for the treatment of postoperative infection in children and adolescents undergoing spinal instrumentation and fusion. It can reduce the need for further complex soft-tissue procedure, removal of hardware with consequent loss of correction, and pseudoarthrosis. Finally, the use of VAC therapy is not contraindicated in patients treated with hybrid constructs with sublaminar bands. LEVEL OF EVIDENCE: III.

Rod Migration Into the Spinal Canal After Posterior Instrumented Fusion Causing Late-Onset Neurological Symptoms.

BACKGROUND: Rod migration into the spinal canal after posterior instrumented fusion is a rare complication causing late-onset neurological symptoms. The purpose of the present study is to report a case of a 13-year-old boy with spastic cerebral palsy and related neuromuscular kyphoscoliosis who developed late-onset neurological deterioration secondary to progressive implant migration into the spinal canal over a 5-year period. METHODS: A decision was made to remove both rods to achieve decompression. Intraoperative findings were consistent with information gained from preoperative imaging. The rods were found to have an intracanal trajectory at T9-T10 for the right rod and T12-L2 for the left rod. RESULTS: The cause of implant migration, with progressive laminar erosion slow enough to generate a solid mass behind, was progressive kyphosis in a skeletally immature patient with neuromuscular compromise. CONCLUSIONS: Fixation type, early surgery, and spasticity management contributed significantly to the presenting condition. Mechanical factors and timing of surgery played a decisive role in this particular presentation. LEVEL OF EVIDENCE: Level IV--Case report and review of the literature.

Radiological, clinical and functional evaluation using the Quick Disabilities of the Arm, Shoulder and Hand questionnaire of children with medial epicondyle fractures treated surgically.

PURPOSE: The main goal of this study was to retrospectively evaluate the clinical, functional and radiographic outcomes of displaced medial epicondyle fractures with or without associated elbow dislocation in children undergoing surgical treatment and to evaluate upper-extremity function with the Quick Disbilities of the Arm, Shoulder and Hand (Quick DASH) questionnaire. The hypothesis was that patients with associated elbow dislocation would have similar functional outcome to patients with displaced fractures with or without intra-articular entrapment of the medial epicondyle. METHODS: A review of medical charts was performed to identify all children and adolescents who underwent surgical treatment for displaced medial epicondyle humeral fractures managed at a single institution. Patients with a closed fracture on plain radiographs, presence of growth cartilages and managed surgically were included in the study. Fractures were radiologically assessed on anteroposterior and lateral radiographs and rated according to Papavasiliou and Crawford classification. Functional outcome was measured with the Quick DASH questionnaire. Sixty-six patients met inclusion criteria, and 38 children presented with isolated displaced medial epicondyle fracture (Group A: type II and type III) and 28 with medial epicondyle fractures associated with elbow dislocation (Group B: type IV). RESULTS: The Papavasiliou and Crawford system classified 36 fractures as type II (54.6%), two (3%) as type III and 28 as type IV (42.4%). All patients underwent open reduction. Fracture fixation was performed with K-wires in 26 (35%) children and a with single screw in 40 (65%). Mean follow-up was 37.5 months (range, 12-68). Overall complication rate was 18%. In particular, three adverse events (3/38, 8%) were recorded in Group -A and nine (9/28, 32%) in Group B (p = 0.003). Mean Quick DASH score at final follow-up was 4.6 ± 3.8 (range, 0-15.9) and was not significantly different between Groups A (5.4 ± 4.3; range, 0-15.9) and B (4.1 ± 3.5; range, 0-15.9) (p > 0.05). CONCLUSIONS: Children with type II, III and IV medial epicondyle fractures undergoing surgical treatment have good radiological, clinical and functional outcome but warrant special attention to detect intra-articular entrapment of the broken epicondyle. In these cases, both patient and family should be warned of the potential risk of loss of elbow range of motion and possibly poor functional outcome, especially if treatment is delayed.

Successful treatment of chronic osteomyelitis in children with debridement, antibiotic-laden cement spacer and bone graft substitute.

PURPOSE: Chronic osteomyelitis and infected nonunion are relatively rare conditions in pediatric patients and are more frequently seen in developing countries. Although relatively rare, they are medically and surgically challenging. Here we report a novel surgical technique used to manage five patients with chronic osteomyelitis of long bones. METHODS: Five skeletally immature patients with chronic osteomyelitis and infected nonunion of the long bones were treated surgically between 2010 and 2014 by a combination of resection of necrotic infected bone, debridement of surrounding soft tissue, and application of antibiotic-laden cement spacer inducing periosteal membrane before final bone reconstruction. Once inflammatory markers normalized, all the patients were re-operated for cement removal, bone graft substitution, and concomitant osteosynthesis of the affected bone, if needed. All patients underwent MRI, CT scan, and laboratory evaluation prior to surgery. The antibiotic regimen was started empirically and then adjusted according to culture and sensitivity results. RESULTS: Mean patient age at the time of diagnosis was 11 years (range 4-14), and all patients had at least 2-year follow-up (range 2-5). At last follow-up, clinical and laboratory evaluation had normalized, the bone had healed, and all patients had resumed daily living and sports activities. CONCLUSION: Surgical debridement is the standard approach to chronic osteomyelitis. Use of antibiotic-laden cement is recommended to penetrate local infection, with antibiotic therapy playing an adjunctive role. The cement also induces membrane formation that aids bone reconstruction. LEVEL OF EVIDENCE: IV.

Cerebrovascular pathology during the progression of experimental Alzheimer's disease.

Clinical and experimental evidence point to a possible role of cerebrovascular dysfunction in Alzheimer's disease (AD). The 5xFAD mouse model of AD expresses human amyloid precursor protein and presenilin genes with mutations found in AD patients. It remains unknown whether amyloid deposition driven by these mutations is associated with cerebrovascular changes. 5xFAD and wild type mice (2 to 12months old; M2 to M12) were used. Thinned skull in vivo 2-photon microscopy was used to determine Aß accumulation on leptomeningeal or superficial cortical vessels over time. Parenchymal microvascular damage was assessed using FITC-microangiography. Collagen-IV and CD31 were used to stain basal lamina and endothelial cells. Methoxy-XO4, Thioflavin-S or 6E10 were used to visualize Aß accumulation in living mice or in fixed brain tissues. Positioning of reactive IBA1 microglia and GFAP astrocytes at the vasculature was rendered using confocal microscopy. Platelet-derived growth factor receptor beta (PDGFRß) staining was used to visualize perivascular pericytes. In vivo 2-photon microscopy revealed Methoxy-XO4(+) amyloid perivascular deposits on leptomeningeal and penetrating cortical vessels in 5xFAD mice, typical of cerebral amyloid angiopathy (CAA). Amyloid deposits were visible in vivo at M3 and aggravated over time. Progressive microvascular damage was concomitant to parenchymal Aß plaque accumulation in 5xFAD mice. Microvascular inflammation in 5xFAD mice presented with sporadic FITC-albumin leakages at M4 becoming more prevalent at M9 and M12. 3D colocalization showed inflammatory IBA1(+) microglia proximal to microvascular FITC-albumin leaks. The number of perivascular PDGFRß(+) pericytes was significantly decreased at M4 in the fronto-parietal cortices, with a trend decrease observed in the other structures. At M9-M12, PDGFRß(+) pericytes displayed hypertrophic perivascular ramifications contiguous to reactive microglia. Cerebral amyloid angiopathy and microvascular inflammation occur in 5xFAD mice concomitantly to parenchymal plaque deposition. The prospect of cerebrovascular pharmacology in AD is discussed.

Serial elongation, derotation and flexion (EDF) casting under general anesthesia and neuromuscular blocking drugs improve outcome in patients with juvenile scoliosis: preliminary results.

PURPOSE: Juvenile scoliosis (JS), among different types of spinal deformity, remains still a challenge for orthopedic surgeons. Elongation, derotation and flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three-dimensional correction concept. The primary objective of the present study was to measure changes on plain radiographs of patients with JS treated with EDF plaster technique. The second aim was to evaluate the effectiveness of the EDF plaster technique realized under general anesthesia (GA) and neuromuscular blocking drugs, i.e. curare, on the radiological curve correction. METHODS: A retrospective comparative case series study was performed in which were included forty-four skeletally immature patients. Three patient groups were selected. Group 1: EDF cast applied with patients awaken and no anesthesia; Group 2: EDF cast applied under GA without neuromuscular blocking drugs; Group 3: EDF cast applied under GA with neuromuscular blocking drugs. All the patients were treated with two serial EDF casts by 2 months and a half each. All measurements were taken from the radiographic exams. Cobb's angle; RVAD and Nash and Moe grade of rotation were assessed before and after applying the cast. Thirty-four (77.3 %) patients were followed up at least 24 months after removal of last EDF cast. RESULTS: Eighteen patients (3 males, 15 females) were included in Group 1, 12 (2 males, 10 females) in Group 2 and 14 (5 males, 9 females) in Group 3. Serial EDF casting was more effective at initial curve reduction and in preventing curve progression when applied under GA with neuromuscular blocking drugs, i.e. curare. RVAD and Nash and Moe score improved significantly in all groups of patients treated according to principles of EDF technique. During follow-up period, six patients required surgery in Group 1 (6/18; 33.3 %), 3 patients required surgery in Group 2 (3/12; 25 %) and 2 patients underwent surgery in Group 3 (2/14; 15 %). CONCLUSIONS: Preliminary results show EDF casting is effective in controlling the curve in both frontal (Cobb's angle) and transverse plane (rib vertebral angle and apical vertebral rotation degree).

Displaced Tibial Shaft Fractures With Intact Fibula in Children: Nonoperative Management Versus Operative Treatment With Elastic Stable Intramedullary Nailing.

BACKGROUND: The main objective of this study was to retrospectively evaluate the clinical and radiographic outcomes of displaced tibial shaft fractures with intact fibula in children after nonoperative management and operative treatment by elastic stable intramedullary nailing. METHODS: A study was performed on 80 consecutive children, 56 males, 24 females from 2 Institutions, with displaced and closed tibial shaft fracture with intact fibula. All patients underwent regular clinical and radiographic follow-up visits for at least 2 years after injury. RESULTS: In total, 26 patients (group A-Institution I) were treated surgically by elastic stable intramedullary nailing and 54 patients (18 patients from group B-Institution I and 36 patients from group C-Institution II) were treated nonoperatively with closed reduction and casting. groups A, B, and C did not significantly differ on sex (P=0.37), side (P=0.54), and fracture site (P=0.14).Valgus deformity was significantly controlled in group A patients only (P=0.001); during follow-up in group B patients (P=0.017), and showed no significant change between pretreatment images and last follow-up in group C patients (P=0.71). Procurvatum deformity was significantly controlled in group A patients only (P=0.001); it showed no significant improvement after conservative treatment in group B (P=0.73) and C patients (P=0.8). Recurvatum was significantly improved in group A (P<0.001) and C patients (P<0.001) but remained unchanged in group B patients (P=0.15). Varus deformity improved significantly in all patient groups.Immobilization time was significantly shorter in group A compared with group B and C patients (P<0.001).However, numerical differences, although statistically significant, were not clinically relevant for all variables but immobilization time. CONCLUSIONS: This study showed good functional and radiologic outcomes in the pediatric population who had sustained closed, traumatic, displaced fracture of tibial diaphysis without associated fibula fracture.On the basis of the findings reported here, it is not contraindicated to operate skeletally immature patients with displaced fracture of tibial diaphysis without associated fibula fracture. However, results were essentially the same and either method is a satisfactory choice for pediatric tibia shaft fractures with an intact fibula. In particular, we found that conservative treatment was as efficacious as surgical treatment apart from the length of time for immobilization. LEVEL OF EVIDENCE: Level III.

Complications of elastic stable intramedullary nailing of femoral shaft fractures in children weighing fifty kilograms (one hundred and ten pounds) and more.

AIM: The purpose of this study was to assess treatment outcomes in children weighing 50 kg (110 pounds) or more with displaced femur shaft fractures treated by elastic stable intramedullary nailing (ESIN) and to identify potential correlations between nail size/medullary canal diameter ratio and outcome. METHODS: Twenty out of 117 consecutive children surgically treated by ESIN for displaced fractures of the femoral shaft with no associated neurovascular injury weighed 50 kg (110 pounds) or more. All patients underwent regular clinical and radiographic follow-up for at least one year after their index surgery. RESULTS: The average patient age at the time of injury was 13.1 years (25th and 75th interquartile range [IQR] = 11.7-14.5). The mean follow-up was 27.4 months (IQR = 18.4-36.8). Overall, nine (45 %) adverse events were observed. The rate of complications was higher among children weighting 55 kg and over (67 %) than in children weighing less than 55 kg (35 %) and among children aged 13 years old or older (72 %) than among children younger than 13 years old (11 %). DISCUSSION: Femoral shaft fractures in children and adolescents weighing 50 kg (110 pounds) and over and older than ten years of age have an increased rate of complications. CONCLUSION: Heavier patients have a greater chance of complications. In particular, patients younger than 13 years old and weighing less than 55 kg can be safely managed with ESIN, but older and heavier patients should preferably be treated with rigid fixation systems due to a greater complication rate. However, further studies are needed to consolidate the conclusions.

Serial elongation derotation flexion (EDF) casting for patients with infantile and juvenile scoliosis.

Infantile and juvenile scoliosis, among different types of spinal deformity, is still a challenge for pediatric orthopedic surgeons. The ideal treatment of infantile and juvenile scoliosis has not yet been identified as both clinicians and surgeons still face multiple challenges, including preservation of the thoracic spine, thoracic cage, lung growth and cardiac function without reducing spinal motion. Elongation, derotation, flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three dimensional correction concept. This cast offers three-dimensional correction and can control the evolution of the deformity in some cases. Spinal growth can be guided by EDF casting as it can influence the initially curved spine to grow straighter. This article aimed to provide a comprehensive review of how infantile and juvenile scoliosis can affect normal spine and thorax and how these deformities can be treated with serial EDF casting technique. A current literature review is mandatory in order to understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in young and very young patients.

Risk factors for re-fracture in children with diaphyseal fracture of the forearm treated with elastic stable intramedullary nailing.

A retrospective study aims to investigate predisposing factors leading to re-fracture in patients with nails still in place and to identify potential correlations between nail size-to-medullary canal diameter ratio and re-fracture, working to the hypothesis that a higher ratio correlates with a higher risk of re-fracture. Rates of re-fracture with nail still in place after forearm elastic stable intramedullary nailing are higher in younger pediatric patients. Re-fractures occurred at a mean age of 6.7 years (range 5-8.7). While the role of body frame and bone medullary diameter remains unclear, there are grounds for adjusting treatment strategy for age, weight and bone medullary diameter to achieve effective outcome. History of previous forearm fracture and open treatment may also be further risk factors.

Displaced humeral shaft fractures in children and adolescents: results and adverse effects in patients treated by elastic stable intramedullary nailing.

PURPOSE: The objectives of this study were to retrospectively investigate the clinical and radiological outcome of humeral shaft fractures treated by ESIN in children <16 years old and to evaluate the functional outcome of these injuries using the short version of the Disabilities of the Arm, Shoulder and Hand Outcome questionnaire (Quick DASH(®)). METHODS: We retrospectively evaluated children with fractures of the humeral shaft, surgically treated by ESIN. All the patients were regularly followed clinically and radiographically for at least 1 year after their index surgery. After hardware removal, the patients were asked to answer the short version of the Disabilities of the Arm, Shoulder and Hand Outcome questionnaire (Quick DASH). RESULTS: Thirty-eight patients met the inclusion criteria. Mean age at the time of trauma was 11.1 years. Mean follow-up was 30 months. All fractures healed, but three patients had a residual valgus of >10°, two a residual varum of >10°, four a residual recurvatum deformity of >10°, and one a residual procurvatum deformity of >10°. Four complications were observed. Functional outcome was nevertheless good in all the patients, with a mean Quick DASH(®) score of 3. CONCLUSION: The study shows good clinical and functional outcomes in children and adolescents with closed isolated fractures of the humeral shaft surgically treated by ESIN, even with ensuing mild residual frontal and sagittal plane deformity. However, conservative treatment has also been advocated in the scientific literature for this type of injuries, and surgical treatment should not be considered as the only option for the management of humeral shaft fractures in older children and adolescents.

Outcome of isolated olecranon fractures in skeletally immature patients: comparison of open reduction and tension band wiring fixation versus closed reduction and percutaneous screw fixation.

PURPOSE: The olecranon fracture is an uncommon injury reported to incur many possible complications in children. The aim of this study was to compare the outcome of two different surgical techniques in isolated olecranon fracture. METHODS: We retrospectively evaluated 22 children with isolated olecranon fracture treated by open reduction and tension band wiring fixation versus closed reduction and percutaneous screw fixation. We compared the dislocation before and after surgery by radiography. The patients were evaluated clinically with Quick DASH(®). RESULTS: Both techniques showed good radiological and clinical outcome (Quick DASH(®) 1.82 vs. 3.42) with no statistically significance difference (p > 0.05). In two cases (16.6 %) of the group treated with cannulated screw, it was necessary to convert into open reduction to obtain optimal reduction of the fracture. All the children returned to previous activity. In four cases, the extension of the elbow was slightly reduced (15°-20°), with no statistically significant difference in the two groups. CONCLUSION: It is not contraindicated to operate skeletally immature patients with displaced olecranon fracture. However, results were essentially the same, and so either method is a satisfactory choice for pediatric displaced olecranon fractures, with equally acceptable radiological results and similar rate of complications and clinical outcome at final follow-up. LEVEL OF EVIDENCE: III.

Outcome of Displaced Fractures of the Distal Metaphyseal-Diaphyseal Junction of the Humerus in Children Treated With Elastic Stable Intramedullary Nails.

BACKGROUND: The main objective of this study was to retrospectively evaluate the clinical and radiographic outcomes of displaced distal humeral metaphyseal-diaphyseal junction fractures in children treated by elastic stable intramedullary nailing (ESIN). METHODS: During the study period, 14 consecutive children with fractures of the distal humeral metaphyseal-diaphyseal junction were surgically treated by ESIN. All patients underwent full-length preoperative and postoperative anteroposterior and lateral radiographs of the injured humerus. One year after the index surgery, patients were asked to answer the short version of the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (Quick DASH). RESULTS: During the study period, fractures of the distal metaphyseal-diaphyseal humeral junction represented 1.5% (16/1100) of all humeral fractures. Fourteen patients underwent surgery and met the inclusion criteria. The male to female ratio was 1:1. The average patient age at the time of injury was 9.7 years (range, 3.6 to 13.7 y). The left and right sides were equally affected. The mean follow-up was 28.1 months (range, 20 to 38 mo).Radiologically, no secondary displacement, nail migration, loss of fixation, consolidation delay, nonunion, or refracture was noted. None of the patients showed signs of growth arrest on either radiologic or clinical assessment.All patients returned to their previous daily and sport activities without discomfort or difficulty, and they were free of pain at their last follow-up visits. The injured elbow range of motion was comparable with that of the contralateral side at the last follow-up visit in all patients. The mean Quick DASH score was 0.81 (range, 0 to 6.8). CONCLUSIONS: We recommend surgery for displaced fractures of the distal humeral metaphyseal-diaphyseal junction. ESIN results in stable reduction, good rotational control, and faster mobilization. LEVEL OF EVIDENCE: Level IV.

Redistribution of PDGFRß cells and NG2DsRed pericytes at the cerebrovasculature after status epilepticus.

PURPOSE: The role of cerebrovascular dysfunction in seizure disorders is recognized. Blood-brain barrier (BBB) damage in epilepsy has been linked to endothelial and glial pathophysiological changes. Little is known about the involvement of pericytes, a cell type that contributes to BBB function. METHODS: NG2DsRed mice were used to visualize cerebrovascular pericytes. The pattern of vascular and parenchymal distributions of platelet-derived growth factor receptor beta (PDGFRß) cells was evaluated by immunohistochemistry. Status epilepticus was induced in NG2DsRed or C57BL/6J mice by intraperitoneal kainic acid (KA). Animals were perfused intracardially using FITC-Dextran or FITC-Albumin to visualize the cerebrovasculature. Colocalization was performed between NG2DsRed, PDGFRß and microglia IBA-1. Confocal 3D vessel reconstruction was used to visualize changes in cell morphology and position. PDGFRß expression was also evaluated in vitro using organotypic hippocampal cultures (OHC) treated with kainic acid to induce seizure-like activity. Co-localization of PDGFRß with the vascular marker RECA-1 and NG2 was performed. Finally, we assessed the expression of PDGFRß in brain specimens obtained from a cohort of patients affected by drug resistant epilepsy compared to available autoptic brain. RESULTS: In vivo, severe status epilepticus (SE) altered NG2DsRed vascular coverage. We found dishomogenous NG2DsRed perivascular ramifications after SE and compared to control. Concomitantly, PDGFRß(+) cells re-distributed towards the cerebrovasculature after severe SE. Cerebrovascular NG2DsRed partially colocalized with PDGFRß(+) while parenchymal PDGFRß(+) cells did not colocalize with IBA-1(+) microglia. Using in vitro OHC we found decreased NG2 vascular staining and increased PDGFRß(+) ramifications associated with RECA-1(+) microvessels after seizure-like activity. Cellular PDGFRß and NG2(+) colocalization was observed in the parenchyma. Finally, analysis of human TLE brains revealed perivascular and parenchymal PDGFRß(+) cell distributions resembling the murine in vivo and in vitro results. PDGFRß(+) cells at the cerebrovasculature were more frequent in TLE brain tissues as compared to the autoptic control. CONCLUSIONS: The rearrangement of PDGFRß(+) and vascular NG2DsRed cells after SE suggests a possible involvement of pericytes in the cerebrovascular modifications observed in epilepsy. The functional role of vascular-parenchymal PDGFRß(+) cell redistribution and the relevance of a pericyte response to SE remain to be fully elucidated.

Outcome of displaced distal tibial metaphyseal fractures in children between 6 and 15 years of age treated by elastic stable intramedullary nails.

UNLABELLED: From June 1995 to August 2012, 18 children were treated surgically using elastic stable intramedullary nails for displaced closed fractures of the distal metaphysis of the tibia. The patients were followed radiographically and clinically on a regular basis until union was clinically and radiographically achieved. Thirteen boys and five girls with a mean age at trauma of 11 ± 2.9 years (range 6-15) were included in the study. Radiographically, all fractures healed without evidence of delayed union, re-fracture, hardware migration. All patients were pain free at last follow-up and all regained full, normal activities including sports. LEVEL OF EVIDENCE: IV.

Pyogenic tenosynovitis of the flexor hallucis longus in a healthy 11-year-old boy: a case report and review of the literature.

Pyogenic tenosynovitis of the flexor hallucis longus (FHL) is a rare condition in young healthy patients. We report the case of a healthy 11-year-old boy who presented with a history of fever and painful swelling below the medial malleolus of the left ankle. Imaging and laboratory findings suggested infectious tenosynovitis of the FHL. Methicillin-sensitive Staphylococcus aureus was isolated on culture following surgery. Antibiotherapy was initiated and continued until inflammatory markers returned to normal. Six months post-surgery, he resumed sport activities and inflammatory markers remained within normal limits. We review also the literature and discuss the clinical characteristics of this condition.

Epileptiform activity induces vascular remodeling and zonula occludens 1 downregulation in organotypic hippocampal cultures: role of VEGF signaling pathways.

Recent studies suggest that blood-brain barrier (BBB) permeability contributes to epileptogenesis in symptomatic epilepsies. We have previously described angiogenesis, aberrant vascularization, and BBB alteration in drug-refractory temporal lobe epilepsy. Here, we investigated the role of vascular endothelial growth factor (VEGF) in an in vitro integrative model of vascular remodeling induced by epileptiform activity in rat organotypic hippocampal cultures. After kainate-induced seizure-like events (SLEs), we observed an overexpression of VEGF and VEGF receptor-2 (VEGFR-2) as well as receptor activation. Vascular density and branching were significantly increased, whereas zonula occludens 1 (ZO-1), a key protein of tight junctions (TJs), was downregulated. These effects were fully prevented by VEGF neutralization. Using selective inhibitors of VEGFR-2 signaling pathways, we found that phosphatidylinositol 3-kinase is involved in cell survival, protein kinase C (PKC) in vascularization, and Src in ZO-1 regulation. Recombinant VEGF reproduced the kainate-induced vascular changes. As in the kainate model, VEGFR-2 and Src were involved in ZO-1 downregulation. These results showed that VEGF/VEGFR-2 initiates the vascular remodeling induced by SLEs and pointed out the roles of PKC in vascularization and Src in TJ dysfunction, respectively. This suggests that Src pathway could be a therapeutic target for BBB protection in epilepsies.

Extracellular interactions between GluR2 and N-cadherin in spine regulation.

Via its extracellular N-terminal domain (NTD), the AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons. Here we show that the first N-terminal 92 amino acids of the extracellular domain are necessary and sufficient for GluR2's spine-promoting activity. Moreover, overexpression of this extracellular domain increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Biochemically, the NTD of GluR2 can interact directly with the cell adhesion molecule N-cadherin, in cis or in trans. N-cadherin-coated beads recruit GluR2 on the surface of hippocampal neurons, and N-cadherin immobilization decreases GluR2 lateral diffusion on the neuronal surface. RNAi knockdown of N-cadherin prevents the enhancing effect of GluR2 on spine morphogenesis and mEPSC frequency. Our data indicate that in hippocampal neurons N-cadherin and GluR2 form a synaptic complex that stimulates presynaptic development and function as well as promoting dendritic spine formation.