BACKGROUND: Neurogenic Heterotopic ossification (NHO) is a potential sequalae and a detrimental complication following neurological insult. It is characterized by formation of localized gradually progressive, peri-articular lamellar bone formation in extra-skeletal tissues. We would like to report a rare case of heterotopic ossification involving all 4 limbs, in which we tried to restore joint mobility to improve his functional status so that he could perform his daily tasks.
METHODS: We present a case of a 33-year-old bed ridden male, diagnosed with NHO involving all 4 limbs (bilateral hip, right knee, right shoulder, left elbow). The patient had a crippled posture, significant pain and impaired range of motion hampering movement of all four limbs which prevented him from lying down supine, sitting, walking and performing activities of daily living. After three surgeries, the patient achieved wheelchair mobilization and upright posture with the assistance of calipers.
CONCLUSIONS: The management of NHO requires a multidisciplinary approach involving orthopaedic surgeons, neurologists & rehabilitation specialists. Prognosis of NHO depends on factors such as extent of ossification, underlying neurological condition & patients overall health.

OBJECTIVE: Neurogenic heterotopic ossification (NHO) of the hip is a frequent complication of spinal cord injuries, often requiring surgical management. Pre-surgical imaging assessment is essential, usually with computed tomography (CT)-scan. We aimed to compare magnetic resonance imaging (MRI) and CT for pre-surgical imaging assessment of the NHO, particularly for their relationships with vessels and nerves.
METHODS: This prospective study included consecutive patients who underwent surgery for NHO from July 2019 to April 2022. All patients had CT angiography and MRI including Zero Echo Time and TRICKS sequences. Radiologists used standardized reports for CT and MRI to evaluate NHO and their features, bone mineralization, and relation to the arteries, veins and nerves. Agreement between pre-surgical CT and MRI was evaluated.
RESULTS: Twenty-four patients (mean age: 53.5 ± 12.2 years) were included, among which 7 had bilateral NHO (31 hips). NHO were anterior in 15/31 hips (48 %), multifragmented in 25/31 hips (81 %). Mild and significant demineralization was most frequent. Gutter and tunnel were reported in 11.1 % of the arteries. Nerves were more often identified in MRI than in CT-scan. Agreement coefficients between CT and MRI were excellent for NHO location (0.95) and implantation (0.92), good for fragmentation (0.70), contact with joint capsule (0.66), bone mineralization (0.74), and relation to arteries (0.85), veins (0.76), sciatic nerve (0.7) and moderate for femoral nerve (0.47).
CONCLUSIONS: MRI exhibited a good agreement with CT for pre-surgical assessment of NHO of the hip, especially to evaluate their relationships with the arteries, veins and sciatic nerve. Femoral nerves were more often identified in MRI than in CT-scan.

Neurogenic heterotopic ossification (NHO) is widely recognised as an aberrant bone formation in soft tissue following central nervous system injury. It is most frequently associated with pain and limited movement, especially in the hip. However, it may be neglected in patients with paraplegia with a pressure ulcer (PU). We report the case of an 18-year-old male patient who presented with a hard-to-heal ischial tuberosity PU and who had undergone three operations at other hospitals during the previous six months, which had failed to repair the PU. There was a history of paraplegia as a consequence of spinal cord injury two years previously. Computed tomography and three-dimensional reconstruction showed massive heterotopic ossification (HO) in the wound bed and around the right hip. Histological findings were consistent with a diagnosis of HO. The HO around the wound was completely excised, negative pressure wound therapy was used to promote granulation, and a gluteus maximus musculocutaneous flap was used to cover the wound. We conclude that for patients with paraplegia, with a hard-to-heal PU, it should be determined whether it is associated with NHO. Surgical resection of HO surrounding the wound and improving the microcirculation are critical for repair and reconstruction of these PUs.

The bone and hematopoietic tissues coemerge during development and are functionally intertwined throughout mammalian life. Oncostatin M (OSM) is an inflammatory cytokine of the interleukin-6 family produced by osteoblasts, bone marrow macrophages, and neutrophils. OSM acts via two heterodimeric receptors comprising GP130 with either an OSM receptor (OSMR) or a leukemia inhibitory factor receptor (LIFR). OSMR is expressed on osteoblasts, mesenchymal, and endothelial cells and mice deficient for the Osm or Osmr genes have both bone and blood phenotypes illustrating the importance of OSM and OSMR in regulating these two intertwined tissues.
OSM regulates bone mass through signaling via OSMR, adaptor protein SHC1, and transducer STAT3 to both stimulate osteoclast formation and promote osteoblast commitment; the effect on bone formation is also supported by action through LIFR. OSM produced by macrophages is an important inducer of neurogenic heterotopic ossifications in peri-articular muscles following spinal cord injury. OSM produced by neutrophils in the bone marrow induces hematopoietic stem and progenitor cell proliferation in an indirect manner via OSMR expressed by bone marrow stromal and endothelial cells that form hematopoietic stem cell niches. OSM acts as a brake to therapeutic hematopoietic stem cell mobilization in response to G-CSF and CXCR4 antagonist plerixafor. Excessive OSM production by macrophages in the bone marrow is a key contributor to poor hematopoietic stem cell mobilization (mobilopathy) in people with diabetes. OSM and OSMR may also play important roles in the progression of several cancers. It is increasingly clear that OSM plays unique roles in regulating the maintenance and regeneration of bone, hematopoietic stem and progenitor cells, inflammation, and skeletal muscles. Dysregulated OSM production can lead to bone pathologies, defective muscle repair and formation of heterotopic ossifications in injured muscles, suboptimal mobilization of hematopoietic stem cells, exacerbated inflammatory responses, and anti-tumoral immunity. Ongoing research will establish whether neutralizing antibodies or cytokine traps may be useful to correct pathologies associated with excessive OSM production.

We present the case of a 56-year-old male unable to sit because of an ankylosed right hip. This ankylosis originated from combined neurogenic heterotopic ossifications (NHO) and traumatic heterotopic ossifications (THO) as a result of a road traffic accident. Because of multiple ossifications, the proximity of neurovascular structures, and chronic pressure ulcers, a resection was deemed unsafe. We opted for a new articulation distal to the ossifications in unstained tissue. A partial femoral diaphysectomy was performed just distal of the lesser trochanter. and the vastus lateralis was rotated in the new articulation. Postoperatively, the patient was able to sit as his hip could flex again. A partial femoral diaphysectomy with vastus lateralis interposition flap appears to be a valid option in paraplegic patients with extensive heterotopic ossifications (HO) in close proximity to neurovascular structures with a low risk of complications and high gain in hip mobility.

暂无摘要。

Neurogenic heterotopic ossification (NHO) is the formation of mature lamellar bone in peri-articular tissues following a neurological insult, most commonly traumatic brain injury (TBI) or spinal cord injury (SCI). NHO is a debilitating condition associated with significant morbidity and reduced quality of life. However, its pathophysiology remains poorly understood. While surgery is the mainstay of treatment once NHO has been diagnosed, prophylactic options are limited and not well studied. This review aimed to determine the efficacy of various interventions used in the primary prevention of NHO. We conducted an electronic literature search using five databases (PubMed, Embase, ScienceDirect, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) for records published until April 10, 2022. We identified 2,610 potentially eligible records across all databases. Nine reports met our eligibility criteria and were included in this review. Four were clinical trials (three randomized control trials, one nonrandomized trial), four were observational studies, and one was a systematic review/meta-analysis. The medications/interventions used included: warfarin, pulse low-intensity electromagnetic field therapy (PLIMF), bisphosphonates, and nonsteroidal anti-inflammatory drugs (NSAIDs). We did not find conclusive evidence to recommend the use of bisphosphonates and warfarin in the prevention of NHO. On the contrary, we found NSAIDs and PLIMF as effective prophylactic options based on the results of high-quality randomized control trials. Further prospective randomized studies with prolonged follow-ups are needed to confirm the long-term efficacy of these preventive interventions.

UNASSIGNED: Up to 30% of patients with spinal cord injury and to 20% of patients with traumatic brain injury develop neurogenic heterotopic ossification (NHO). Patients develop restriction in joint range of motion (ROM) and impairment in activities of daily life. When neurological recovery occurs, joints dysfunction represents the cause for patients\' autonomy loss.
UNASSIGNED: We present the case of a 39-year-old Caucasian male involved in a car accident and experienced 14 days of post-traumatic coma. After rehabilitation, no residual motor or sensory neurological deficit was present, but bilateral NHOs surrounding hip joints developed. Seventeen months after trauma, the patient was admitted to our institute. He was confined to bed, absolutely unable to walk, stand or sit. Radiological evaluation consisted in Antero-Posterior X-ray view only, due to the inability to open up his hips for lateral views, and 3D computed tomography scan. \"Functional resection\" of the ossifications was performed and rehabilitation started from day 1 after surgery. At the final follow-up 24 months from the second operation high grade of clinical satisfaction was reported. The patients were able to walk independently, to put on his socks, and to drive a car and bike. Painless right and left hip ROM was, respectively, 100° and 90° for flexion, 10° for extension, 35° and 30° for abduction, and near normal internal and external rotation. The patient referred that further improvement in mobility and fluency was still present day by day.
UNASSIGNED: The rarity of the condition frequently bring to a delay in treatment and the absence of specific guidelines made treatment still dependent on surgeon experiences. A multidisciplinary approach is essential for success. Surgeons should be aware that it is important to refer patients to specialized center, because early resection could provide excellent results, preserving hip, and restoring function and patient independency.

Neurogenic heterotopic ossifications (NHOs) are incapacitating complications of traumatic brain and spinal cord injuries (SCI) that manifest as abnormal bone formation in periarticular muscles. Using a unique model of NHO after SCI in genetically unmodified mice, we have previously established that the innate immune system plays a key driving role in NHO pathogenesis. The role of adaptive immune cells in NHO pathogenesis, however, remains unexplored in this model. Here we established that B lymphocytes were reduced in the spleen and blood after SCI and increased in muscles of mice in which NHO develops, whereas minimal changes in T cell frequencies were noted. Interestingly, Rag1 -/- mice lacking mature T and B lymphocytes, developed NHO, similar to wild-type mice. Finally, mice that underwent splenectomy before SCI and muscle damage also developed NHO to the same extent as non-splenectomized SCI controls. Overall, our findings show that functional T and B lymphocytes have minimal influence or dispensable contributions to NHO development after experimental SCI in mice.

BACKGROUND: Neurogenic heterotopic ossification (NHO) is a frequent complication, often involving the hip. The functional impact may require surgical management and pre-surgical imaging assessment is necessary, usually by computed tomography (CT). We aimed to compare the performances of magnetic resonance imaging (MRI) and CT for bone assessment on pre-surgical imaging of the heterotopic ossifications and their features in NHO of the hip.
METHODS: This single-center prospective preliminary study included all patients who underwent surgery for NHO with joint limitation from July 2019 to March 2020. All patients had a CT after biphasic iodinated solution injection and an MRI including T1-weighted, STIR and ZTE sequences. Standardized reports were completed for both exams for each patient, evaluating location, implantation and fragmentation of NHO, relation to the joint capsule and bone mineralization, then were compared.
RESULTS: Seven patients from 32 to 70 years old (mean = 50.2 ± 17.2 years) were evaluated. NHO were bilateral in 2 patients, for a total of nine hips: six right hips and three left hips. Observed concordance rates between MRI and CT were, respectively, 94.4% for location, 100% for circumferential extension, 87.3% for implantation 88.9% for fragmentation, 77.8% for relation to the joint capsule and 66.7% for bone mineralization. It was 100% for femoral neck fracture and osteonecrosis of the femoral head.
CONCLUSIONS: This preliminary study suggests that pre-surgical MRI imaging should be considered as effective as CT for bone assessment of NHO and their features.
BACKGROUND: ClinicalTrials.gov, NCT03832556. Registered February 6, 2019, https://clinicaltrials.gov/ct2/show/NCT03832556 .