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PubMed2000

Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.

Chromosome Mapping↗
PubMed1988

Cervical myelopathy due to ossification of the posterior longitudinal ligament. A clinical, radiological and evoked potentials study in six Chinese patients.

Six consecutive Chinese patients with cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) who presented in a 4 yr period were studied. There were 5 males and 1 female whose mean age at presentation was 67 yrs. The common clinical features were spastic tetraparesis more marked in the lower limbs, spinothalamic and posterior column sensory deficits of varying degree and sphincter disturbance in advanced cases. OPLL was diagnosed on plain radiographs and cord compression ascertained by conventional and computer-assisted myelography. Somatosensory evoked potentials correlated with posterior column signs and appeared to reflect the clinical course following treatment. While the cord pathology in OPLL is similar to that of cervical spondylotic myelopathy (CSM), the pathogenetic mechanism probably differs in one aspect. Compression by OPLL is the determining factor in most cases whereas the combined presence of a congenitally narrow canal and spondylosis is essential for the development of CSM. Other contributory factors include coexisting spondylosis, a congenitally narrow canal, friction between cord and OPLL during neck movement and acute trauma. Cord damage is probably mediated by ischaemia which is due to disturbances of the microcirculation caused by the mechanical factors.

Aged↗
PubMed1995

Spinal cord morphology and pathology in ossification of the posterior longitudinal ligament.

We analysed nine autopsy cases of ossification of the posterior longitudinal ligament (OPLL) to elucidate the relationship between morphology and pathology of the spinal cord. The cross-sectional shape of the spinal cord at the most severely affected segment was classified into two categories: boomerang (convex lateral surfaces and concave anterior surface) and triangular (angular lateral surfaces and flat anterior surface). In the cases with a boomerang shape, even when the compression was severe, major pathological changes were restricted to the grey matter and the white matter was relatively well preserved. No secondary descending degeneration of the lateral columns was seen, and ascending degeneration of the posterior column was restricted to the fasciculus cuneatus whose fibres were derived from the affected segments. In the cases with a triangular shape, pathological changes were more severe, both white matter and grey matter were involved, and only the anterior columns were free of pathological changes. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciculus gracilis, were observed. The transverse area of the spinal cord was > 60% of normal in most of the cases with a boomerang shape, but it was reduced to < 60% of normal in more than one segment in the cases with a triangular shape. The compression ratio of the spinal cord (sagittal diameter/transverse diameter x 100%) was not related to pathological changes. In conclusion, a triangular-shaped spinal cord with transverse area of < 60% of normal in more than one segment appeared to be associated with severe and irreversible pathological changes in cases of OPLL.

Adult↗
PubMed2005

Clinical significance of heterotopic ossification in cervical disc replacement: a prospective multicenter clinical trial.

OBJECTIVE: Heterotopic ossification (HO) is a well-known complication in joint replacements, but its occurrence and clinical effect on cervical artificial discs has not yet been studied. The purpose of this study was to investigate the incidence of HO in cervical disc replacement, to identify any associated risk factors for HO, and to examine the relationship of HO with clinical outcomes. METHODS: The patient data for this observational study were obtained from the original Bryan Disc Study by the European Consortium. Occurrence of HO was defined by the McAfee classification on the cervical lateral x-rays at 12 months after surgery. Secondary outcome measurements included Odom's criteria and the Medical Outcomes Study Short-Form 36-Item Health Survey. RESULTS: Sixteen (17.8%) of the 90 studied patients experienced HO, and 6 (6.7%) of these patients experienced Grade 3 and 4 HO. Ten patients' (11%) artificial discs were shown to have movement of less than 2 degrees on flexion and extension cervical x-ray at 12 months, with 4 of these patients having HO of Grade 3 or 4. Male sex (chi2 = 4.1; P = 0.0407) and older patients (P = 0.023; odds ratio = 1.10; 95% confidence interval = 1.01-1.19) were associated with development of HO. CONCLUSION: There is a strong association of the occurrence of HO with subsequent loss of movement of the implanted cervical artificial disc. We have found that sex and age are two possible risk factors in the development of HO after cervical disc replacement.

Adult↗
PubMed1999

Polyarticular heterotopic ossification complicating critical illness.

A patient with generalized heterotopic ossification (HO) complicating critical illness due to necrotizing pancreatitis is described; data on two other cases with HO are briefly presented. The clinical features, prevention and therapy of HO are discussed. The effect of surgical therapy of the HO in our three patients was good.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Involvement of bone morphogenic protein-2 (BMP-2) in the pathological ossification process of the spinal ligament.

OBJECTIVE: To investigate the function of bone morphogenic protein-2 (BMP-2) in the ossification of the spinal ligament (OSL). METHODS: Total RNA was prepared from the cultured spinal ligament cells from patients with OSL and analysed by reverse transcription-polymerase chain reaction using specific primers for BMP-2. BMP-2 mRNA expression in ligament tissues was examined by in situ hybridization. Spinal ligament cells from patients without OSL were treated with BMP-2 and examined for alkaline phosphatase activity. RESULTS: Expression of the BMP-2 gene was detected in cultured spinal ligament cells. In ligament tissues, BMP-2 mRNA was present in the chondrocyte-like cells in the fibrocartilage zone. Exogenous BMP-2 increased alkaline phosphatase activity in spinal ligament cells from patients without OSL. CONCLUSION: The BMP-2 gene is expressed in the spinal ligaments of OSL patients, and exogenous BMP-2 stimulates osteogenic differentiation of spinal ligament cells. The expression of BMP-2 in the spinal ligaments could be a clue in elucidating how heterotrophic osteogenesis develops in ligament tissue.

Aged↗
PubMed1989

Multiple lesions of molluscum contagiosum with metaplastic ossification.

A 30-year-old woman, suffering from systemic lupus erythematosus and treated with azathioprine and methyl-prednisolone, developed seven molluscum contagiosum lesions of the upper part of her left calf. Histological examination revealed metaplastic ossification in the upper dermis, in close relation to each molluscum contagiosum lesion. Such an association has not been reported before; its occurrence in this case is discussed.

Adult↗
PubMed1987

Infantile (desmoid type) fibromatosis with extensive ossification.

Solitary congenital or infantile (desmoid-type) fibromatosis is a benign, but potentially locally aggressive lesion that is best treated by wide local excision. It has been confused with congenital fibrosarcoma and other soft-tissue malignant tumors. To our knowledge, ossification has not been reported previously in this lesion. A case of ossifying solitary congenital fibromatosis is presented with a discussion of its differential diagnosis and histologic distinction from other soft-tissue lesions, including soft-tissue and parosteal osteosarcoma.

Diagnosis, Differential↗
PubMed2002

Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells.

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification. In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-alpha, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present. These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-alpha and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance. Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years. Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.

Adipose Tissue↗
PubMed1992

Heterotopic ossification as a complication of the staged total thigh muscles flap in spinal cord injury patients.

Between 1980 and 1990, 24 total thigh flap procedures were performed at Rancho Los Amigos Medical Center (Downey, CA) by the Pressure Ulcer Management Service. An unexpected occurrence was identified, that is, the rapid development of heterotopic ossification (HO) occurring in the exposed muscle flap between the first and second stages. There were 15 two-stage total thigh flap procedures on 14 patients performed between 1980 and 1990. Of these 15 flap procedures, 11 in 10 patients were found to have HO evident at the second-stage debridement/closure. In comparing our findings with those in other studies (earliest evidence of HO at 19 days), the initial presentation of HO in affected tissues might be even earlier than previously detected. The risks and technical difficulties due to development of HO associated with the two-stage total thigh flap procedure point toward future modifications in preoperative planning that may prove beneficial. Therefore, if the two-stage total thigh flap procedure is necessary, the interval between initial debridement/disarticulation (stage 1) and definitive flap closure (stage 2) should be kept to an absolute minimum. Additionally, HO medicinal prophylaxis (that is, indomethacin or diphosphonates) or radiation after the first stage of the total thigh flap procedure should be considered. Our final conclusion is that the total thigh flap procedure should be done as a one-stage procedure if possible.

Adult↗
PubMed1999

Impact of clinically significant heterotopic ossification on functional outcome after traumatic brain injury.

OBJECTIVE: To assess heterotopic ossification's (HO) impact on functional outcome after TBI. DESIGN: Retrospective with matched control group, single center. SETTING: TBI Model System of Care at the Medical College of Virginia of Virginia Commonwealth University, Richmond, VA. PARTICIPANTS: Twenty-six patients with TBI and triple-phase bone scan confirmed HO were matched with 26 patients without clinical evidence of HO. MAIN OUTCOME MEASURES: Acute and rehabilitation lengths of stay (LOS), Admission and Discharge Functional Independence Measure (FIM) scores, FIM change, FIM efficiency (FIM gains per week), and discharge disposition. RESULTS: The two groups had similar acute care LOS. Patients with HO had significantly longer inpatient rehabilitation LOS and significantly lower FIM mobility and activities of daily living subscale scores on admission and discharge. FIM efficiency was significantly lower for the group with HO. Significantly fewer patients with HO were able to be discharged to home. CONCLUSIONS: HO is associated with a poorer functional outcome; however, it is not clear whether HO causes the decreased function or whether it may serve more generally as an indicator of those patients who will not progress as far or as rapidly during inpatient rehabilitation.

Activities of Daily Living↗
PubMed1990

Pseudoarthrosis in heterotopic ossification in spinal cord-injured patients.

Heterotopic ossification (HO) of proximal joints is a common complication of spinal cord injury, traumatic brain injury, and burns, and is also seen among an array of other clinical conditions. Of the patients with HO, 3-8% develop ankylosis of the joint involved. Although the etiology of HO is not known, the main goal in its management is to retain the maximum possible functional range of movement in the joint involved. Toward this end, surgical resection of HO with etidronate disodium treatment to mobilize ankylosed joints has been reported, as has forceful joint manipulation in head-injured adults with HO. This paper presents two cases of extensive HO formation around hip and knee joints in patients who developed pseudoarthrosis. Cinradiographic assessment of the joints involved revealed pseudoarthrosis formation at the same axis as the normal anatomical plane of the joint, thus permitting functional range of movement.

Aged↗
PubMed1995

Anterior decompression and fusion for ossification of posterior longitudinal ligament in the thoracic spine.

Twelve cases are reviewed of ossification of posterior longitudinal ligament (OPLL) in the thoracic spine for which anterior decompression and fusion were performed. A transthoracic approach was used in 10 patients, and median sternotomy and a transsternal approach were used in one each. The clinical symptoms and the Japanese Orthopaedic Association (JOA) score improved in 10 patients, whereas they were unchanged in two patients who underwent a revision operation for a previous laminectomy. An anterior procedure that results in adequate decompression of the spinal cord and good spinal stability is recommended for anterior lesions, such as OPLL, which compress the anterior spinal cord at each level of the thoracic spine.

Adult↗
PubMed1986

Technetium-99m MDP demonstration of heterotopic ossification in fibrodysplasia ossificans progressiva.

The extensive heterotopic bone formation in patients with fibrodysplasia ossificans progressiva (FOP) has been documented previously with radiographs. A case in which a Tc-99m MDP bone scan showed increased uptake at sites well before ossification could be documented radiographically is described. This finding suggests that bone scans would likely be useful to monitor the extent of involvement with FOP and to detect areas of new activity.

Child↗
PubMed1988

Subcutaneous ossification of the legs examined by SPECT.

The typical appearance of subcutaneous ossification on a single photon emission computed tomography (SPECT) bone image is reminiscent of the patterns discovered by radiographs and computerized tomography. A case demonstrates the advantage of SPECT imaging to clarify the actual location of soft tissue Tc-99m methylene diphosphonate in this condition.

Female↗
PubMed1999

Expansive laminoplasty for myelopathy in ossification of the longitudinal ligament.

Laminectomy, which had long been used for treatment of cervical spondylotic myelopathy, including ossification of the longitudinal ligament in the cervical spine, had numerous complications such as postoperative malalignment of the cervical spine and vulnerability of the spinal cord caused by total removal of the posterior structures. In 1977 Hirabayashi devised an open door expansive laminoplasty, which is a relatively easier and safer procedure than laminectomy, that eliminated such problems by preserving the posterior elements. The decompression effect of the expansive laminoplasty against a compressed spinal cord is comparable with that of laminectomy and anterior decompression followed by fusion, whereas the expansive laminoplasty has no structural problems and adverse effects on adjacent disc levels that often are associated with anterior decompression followed by fusion. Average recovery rate of expansive laminoplasty for cervical spondylotic myelopathy has been reported to be approximately 60% (Japanese Orthopaedic Association score) and with long term stability. At present, authors consider all patients with cervical spondylotic myelopathy candidates for expansive laminoplasty except for those having preoperative kyphosis and single level lesion without canal stenosis. Two remaining problems of expansive laminoplasty to be solved are prevention of C5,C6 radicular pain and/or paresis, the most frequent complication that occurs in approximately 5% to 10% of the patients, although most complications resolve spontaneously within 2 years, and correction of nonlordotic alignment to lordosis which are essential for posterior decompression effect of expansive laminoplasty by allowing the spinal cord to shift dorsally.

Cervical Vertebrae↗