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Objective: To evaluate recurrence and early postoperative complications (sepsis) following surgical excision combined with radiotherapy for troublesome hip heterotopic ossification in patients with spinal cord injury and traumatic brain injury., Design: Retrospective case-control study., Setting: Data relating to patients with spinal cord injury or traumatic brain injury who underwent surgical excision of hip heterotopic ossification were retrieved from the BANKHO database. Case patients underwent excision + radiotherapy and controls underwent excision only. Control patients were matched to case patients according to sex and age (± 4 years)., Participants: Data from 19 case patients and 76 controls were analysed., Interventions: Not applicable., Main Outcome Measure: The primary end-point was recurrence of heterotopic ossification. Secondary end-points were postoperative complications and, more specifically, sepsis that required surgical revision., Results: There was no difference between the odds ratios (OR) for recurrence for each group (OR case group = 0.63, OR spinal cord injury subgroup = 0.45 and OR head injury subgroup = 1.04). The rate of sepsis requiring surgical revision was significantly higher in the case group (p < 0.05)., Conclusion: Based on the results of this case-control study, we suggest that radiotherapy should not be combined with surgery in patients with troublesome hip heterotopic ossification undergoing excision. Radiotherapy does not appear to prevent recurrence and, moreover, it is associated with an increased risk of postoperative sepsis.

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury-induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad.

Background: Neurogenic heterotopic ossification (NHO) is usually treated by surgical excision. Postoperative infection (POI) is a possible complication, whose epidemiology, causative organisms, and risk factors are poorly known. We therefore conducted a case-control study to (1) identify the risk factors for POI after surgical excision of NHO at the hip, (2) determine the frequency of POI, (3) and identify the causative organisms., Hypothesis: Risk factors for POI after NHO excision at the hip can be identified., Material and Methods: In this retrospective case-control study, the BANKHO database for patients with NHO at our centre was used to identify risk factors by comparing patients with and without POI after NHO excision at the hip. To this end, odds ratios (ORs) with their 95% confidence intervals (95%CIs) were computed for each main criterion. Postoperative follow-up was at least 6 months., Results: Between 1993 and 2013, 411 hip NHO excisions were performed. Among them, 42 (10%) were followed by POI. The American Society of Anesthesiologists (ASA) score was I in 2/42 (5%) patients with vs. 74/369 (20%) patients without POI, II in 30/42 (71%) patients with vs. 258/369 (70%) patients without POI, and III in 10/42 (24%) patients with vs. 37/369 (10%) patients without POI (P<0.01). Mean age was 31±11 years (range, 17-79years) in the group with POI and 39±14 years (range, 15-77years) in the group without POI (P<0.01). The NHO was related to spinal cord injury in 26/42 (62%) patients with POI compared to 92/369 (25%) patients without POI (P<0.01). ORs indicated a significant risk increase in patients with an ASA score of III (2.84; 95%CI, 1.28-6.31), age younger than 30 years (1.85; 95%CI, 1.03-3.32), and spinal cord injury as the cause of NHO (4.89; 95%CI, 2.67-8.98). The predominant organisms were staphylococci (skin flora) in the patients with spinal cord injury and bacteria commonly found in intensive care units in the other patients., Discussion: A higher ASA score, younger age, and spinal cord injury as the cause of NHO at the hip are risk factors for POI. The proportion of patients with POI after hip NHO excision was 10%, in accordance with previous reports. POI was more common among patients with spinal cord injury (22% vs. 5% in the other patients). Neither changes in prophylactic antibiotic therapy regimens nor the institution of a detailed skin preparation protocol affected the frequency of POI. Skin pH alterations may deserve to be investigated with the goal of diminishing the risk of POI, most notably in spinal cord injury patients., Level of Evidence: III, case-control study., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Neurogenic Myositis Ossificans (NMO) is a rare disabling pathology characterized by peri-articular heterotopic ossifications following severe peripheral or central nervous system injuries. It results in ankylosis and vessels or nerves compressions. Our study aimed to describe the pre-operative findings of patients with NMO of the hip using biphasic computerized tomography (CT)., Methods: Between 2006 and 2012, we retrospectively analyzed 101 consecutive patients with hip NMO. We analyzed all CTs and surgical reports following a standardized grid depicting the osteoma and its relations with joint capsule, vessels and nerves and bone mineralization. We studied surgical complications and recurrence during follow-up. Chi2-test and Fischer's test were performed to compare qualitative values with respectively normal and non-normal distribution. Quantitative values were analyzed with a one factor analysis of variance (ANOVA) test. Agreement between pre-surgical CT and surgical observations was evaluated with Cohen's kappa test., Results: Correlation between pre-operative CT and surgical findings was excellent regarding relationships with vessels (0,82) and was good concerning relationships with sciatic nerves (0.62) and with joint capsule (0.68). Close contact or disruption of joint capsule (p = 0.005), joint space narrowing (p = 0.007) and bone demineralization (p < 0.001) were correlated with NMO recurrence., Conclusions: Biphasic enhanced-CT allows pre-operative assessment of NMO with good correlation to surgical observations and helps prevent surgical complications.

Objective: A systematic review of the literature to determine whether in patients with neurological heterotopic ossification (NHO) after traumatic brain injury, the extent of the neurological sequelae, the timing of surgery and the extent of the initial NHO affect the risk of NHO recurrence., Data Sources: We searched MEDLINE via PubMed and Cochrane library for articles published up to June 2015. Results were compared with epidemiological studies using data from the BANKHO database of 357 patients with central nervous system (CNS) lesions who underwent 539 interventions for troublesome HO., Results: A large number of studies were published in the 1980s and 1990s, most showing poor quality despite being performed by experienced surgical teams. Accordingly, results were contradictory and practices heterogeneous. Results with the BANKHO data showed troublesome NHO recurrence not associated with aetiology, sex, age at time of CNS lesion, multisite HO, or "early" surgery (before 6months). Equally, recurrence was not associated with neurological sequelae or disease extent around the joint., Conclusions: The recurrence of NHO is not affected by delayed surgery, neurological sequelae or disease extent around the joint. Surgical excision of NHO should be performed as soon as comorbid factors are under control and the NHO is sufficiently constituted for excision., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Study Design: Review of the literature., Objectives: It is widely believed that the timing of surgery and the size of the initial Neurological Heterotopic Ossification (NHO) affect the recurrence risk of NHO after SCI. A large number of studies were published in the 80s and the 90s, mostly of poor quality despite the fact that they were carried out by experienced surgical teams. The aim of this study was to suggest recommendations relating to the timing of excision of heterotopic ossification after SCI following the analysis of a recent review of the literature., Setting: France., Methods: A systematic literature search was performed in the PubMed Embase from January 2002 until June 2014 using the MESH headings 'spinal cord injury', 'paraplegia', 'heterotopic ossification' and 'surgery'. Results were compared with results from epidemiological studies based on the BANKHO database (patients who underwent surgery for troublesome HO after central neurological system (CNS) lesions in our center (357 patients, 539 surgeries))., Results: Few studies were found in the literature, results were sometimes contradictory and practices heterogeneous. Results from the BANKHO database showed that troublesome recurrence of NHO was not associated with 'early' surgery (before 6 months), and no association was found between recurrence and the size of the NHO around the joint (Brooker status)., Conclusion: We suggest that surgical excision of the NHO should be carried out when it begins to be troublesome, as soon as comorbid factors are under control and the HO is sufficiently constituted for excision.

Objective: To describe the characteristics of neurogenic heterotopic ossification (NHO) based on clinical tests, electroneuromyography (ENMG) and CT in a database of patients with lesions of the central nervous system who required sciatic nerve neurolysis along with posterior hip NHO resection, and to determine the respective roles of ENMG and CT in the management of posterior hip NHOs in patients who are unable to communicate or express pain., Methods: The consistency of the ENMG results with clinical findings, CT results and macroscopic signs of lesions was retrospectively assessed after sciatic nerve neurolysis and ablation of 55 posterior hip NHOs., Results: Sciatic nerve neurolysis was necessary in 55 cases (47.4%; 55 out of 116). CT showed contact of the NHO with the nerve in all cases: 5 in contact with no deflection, 3 in contact with deflection, 21 moulded into a gutter and 26 entrapped in the NHO. There were clinical signs of sciatic nerve lesion in 21.8% of cases (12 out of 55). ENMG showed signs of sciatic nerve lesions in only 55.6% (10 out of 18), only 4 of whom presented with clinical signs of a nerve lesion. No significant relationship was found between clinical symptoms and ENMG findings of sciatic nerve compression (n = 13, p = 0.77)., Conclusion: Nerve compression by NHO is likely an underdiagnosed condition, particularly in patients who are unable to communicate. Diagnosis of sciatic compression by NHO should be based on regular clinical examinations and CT. ENMG is not sufficiently sensitive to be used alone for surgical decision-making.

Primary Objective: To determine the features of stroke-related HO in a large sample of patients and to assess if HO risk is increased by haemorrhagic stroke., Research Design: A case control study (risk factor of a rare event using retrospective analysis)., Methods and Procedures: Sixty-one patients with stroke-81 troublesome HOs-were included, each was matched with four controls, i.e. 244 patients with no HO after stroke. Matching criteria were age (±3.5 years) and sex. Data recorded were time from stroke to surgery, ischaemic or haemorrhagic stroke and presence of HO risk factors., Main Outcomes and Results: Mean age at time of stroke = 46.02 ± 11.4 years (15.9-76.3) for the case sub-group. Time from stroke to surgery = 23.4 ± 27.8 months (3.6-150.0). There was a significant relationship between haemorrhagic stroke and HO development (OR = 3.01; 95% CI = 1.14-7.98; p < 0.05), but not for ischaemic stroke. This became non-significant when all matching and risk factors were included in the model (adjusted OR = 1.98; 95% CI = 0.60-6.54; p = 0.26)., Conclusion: Haemorrhagic stroke appears to increase the risk of HO development. Further studies are required to determine if this risk factor is independent from other comorbid factors.

The timing of surgery with regard to recurrence risk after neurologic heterotopic ossification (HO) excision is still debated. This study investigated the association between recurrence risk after HO excision in traumatic brain injury (TBI) patients and (1) the operative delay and (2) the degree of neurologic sequelae (Garland status). A case-control study was performed. Patients who developed troublesome HO requiring surgery after TBI with (case, n = 16) or without recurrence (control, n = 64) were retrospectively included. Other matching criteria were sex and age at the time of surgery (± 4 years). The median delay for first HO surgery was 13.7 months (interquartile range: 9.0-37.1) for the case group and 13.2 months (interquartile range: 7.8-30.0) for the control group. No significant link was found between recurrence and operative delay (P = .54), even after inclusion of all matching factors (P = .53), or Garland status (P = .81). The inclusion of Garland status into the model did not change this result (P = .64). After TBI, no link was found between HO operative delay and recurrence. In spite of a common notion of a relationship between initial severity of TBI and HO development, no link was found between HO recurrence risk and the severity of sequelae.

Background: Heterotopic ossification (HO) is a frequent complication after central nervous system (CNS) damage but has seldom been studied. We aimed to investigate features of HO for the first time in a large sample and the rate of early recurrence of HO in terms of the time of surgery., Methodology/principal Findings: We retrospectively analyzed data from an anonymous prospective survey of patients undergoing surgery between May 1993 and November 2009 in our institution for troublesome HO related to acquired neurological disease. Demographic and HO characteristics and neurological etiologies were recorded. For 357 consecutive patients, we collected data on 539 first surgeries for HO (129 surgeries for multiple sites). During the follow-up, recurrences requiring another surgery appeared in 31 cases (5.8% [31/539]; 95% confidence interval [CI]: 3.8%-7.8%; 27 patients). Most HO requiring surgery occurred after traumatic brain injury (199 patients [55.7%]), then spinal cord injury (86 [24.0%]), stroke (42 [11.8%]) and cerebral anoxia (30 [8.6%]). The hip was the primary site of HO (328 [60.9%]), then the elbow (115 [21.3%]), knee (77 [14.3%]) and shoulder (19 [3.5%]). For all patients, 181 of the surgeries were performed within the first year after the CNS damage, without recurrence of HO. Recurrence was not associated with etiology (p = 0.46), sex (p = 1.00), age at CNS damage (p = 0.2), multisite localization (p = 0.34), or delay to surgery (p = 0.7)., Conclusions/significance: In patients with CNS damage, troublesome HO and recurrence occurs most frequently after traumatic brain injury and appears frequently in the hip and elbow. Early surgery for HO is not a factor of recurrence.

Background: The preoperative Heterotopic Ossification (HO) extent is usually one of the main used criteria to predict the recurrence before excision. Brooker et al built a radiologic scale to assess this pre operative extent around the hip. The aim of this study is to investigate the relationship between the recurrence risk after hip HO excision in Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI) patients and the preoperative extent of HO., Methodology/principal Findings: A case control study including TBI or SCI patients following surgery for troublesome hip HO with (case, n = 19) or without (control, n = 76) recurrence. Matching criteria were: sex, pathology (SCI or TBI) and age at the time of surgery (+/-4.5 years). For each etiology (TBI and SCI), the residual cognitive and functional status (Garland classification), the preoperative extent (Brooker status), the modified radiological and functional status (GCG-BD classification), HO localization, side, mean age at the CNS damage, mean delay for the first HO surgery, and for the case series, the mean operative delay for recurrence after the first surgical intervention were noted., Conclusions/significance: The median delay for first HO surgery was 38.6 months (range 4.5 to 414.5;) for the case subgroup and 17.6 months (range 5.7 to 339.6) for the control group. No significant link was found between recurrence and operative delay (p = 0.51); the location around the joint (0.07); the Brooker (p = 0.52) or GCG-BD status (p = 0.79). Including all the matching factors, no significant relationship was found between the recurrence HO risk and the preoperative extent of troublesome hip HO using Brooker status (OR = 1.56(95% CI: 0.47-5.19)) or GCG-BD status (OR class 3 versus 2 = 0.67(95% CI: 0.11-4.24) and OR class 4 versus 2 = 0.79(95%CI: 0.09-6.91)). Until the pathophysiology of HO development is understood, it will be difficult to create tools which can predict HO recurrence.

Heterotopic ossification (HO) of the hip after injury to the central nervous system can lead to joint ankylosis. Surgery is usually delayed to avoid recurrence, even if the functional status is affected. We report a consecutive series of patients with HO of the hip after injury to the central nervous system who required surgery in a single, specialised tertiary referral unit. As was usual practice, they all underwent CT to determine the location of the HO and to evaluate the density of the femoral head and articular surface. The outcome of surgery was correlated with the pre-, peri- and post-operative findings. In all, 183 hips (143 patients) were included of which 70 were ankylosed. A total of 25 peri-operative fractures of the femoral neck occurred, all of which arose in patients with ankylosed hips and were associated with intra-articular lesions in 18 and severe osteopenia of the femoral head in seven. All the intra-articular lesions were predicted by CT and strongly associated with post-operative complications. The loss of the range of movement before ankylosis is a more important factor than the maturity of the HO in deciding the timing of surgery. Early surgical intervention minimises the development of intra-articular pathology, osteoporosis and the resultant complications without increasing the risk of recurrence of HO.