Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients.

BACKGROUND: In our previous whole-genome sequencing study of 30 unrelated northern Chinese Han patients, we identified six single nucleotide polymorphisms (SNPs) in the interleukin 17 receptor C (IL17RC) and collagen type VI α1 chain (COL6A1) genes that were potentially associated with thoracic ossification of the posterior longitudinal ligament (T-OPLL). To determine whether these six SNPs are associated with susceptibility to T-OPLL in the northern Chinese Han population, we performed a case-control association study to confirm specific susceptible loci in the expanded samples. METHODS: The six SNPs in the IL17RC and COL6A1 genes were analyzed in 200 northern Chinese individuals (100 patients and 100 control subjects) using the Sequenom system. RESULTS: The genotype distributions and allele frequencies of each SNP in the control and patient groups were compared. rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 showed potential pathogenic loci for T-OPLL in the northern Chinese Han population, whereas rs151158105 did not. At the genotype level, the differences in the genotype frequencies of rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 between T-OPLL cases and controls reached statistical significance. CONCLUSIONS: To the best of our knowledge, this is the first association study of susceptibility genes in Han Chinese patients with T-OPLL. The results revealed five SNPs in the IL17RC and COL6A1 genes that represented potentially pathogenic mutations in patients with T-OPLL.

Prevalence and Distribution of Ossified Lesions in the Whole Spine of Patients with Cervical Ossification of the Posterior Longitudinal Ligament A Multicenter Study (JOSL CT study).

Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity.

Prevalence, distribution, and morphology of thoracic ossification of the posterior longitudinal ligament in Japanese: results of CT-based cross-sectional study.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To gain an insight into the prevalence, morphology, and distribution of thoracic ossification of the posterior longitudinal ligament of the spine (T-OPLL) by computed tomography (CT) and review of the literature. SUMMARY OF BACKGROUND DATA: The epidemiology and cause of T-OPLL remains obscure. To date, to the best of our knowledge, there is no study that has comprehensively evaluated the thoracic spine by CT to assess the prevalence, distribution, and morphology of T-OPLL in a sufficiently large size of sample with wide distribution of age. METHODS: The participants of this study were the patients who have undergone chest CT for the examination of pulmonary diseases in our institute. The patients with previous thoracic spine surgery and younger than 15 years were excluded. Prevalence, distribution, and morphology of T-OPLL were reviewed. RESULTS: A total of 3013 patients (1261 females and 1752 males) with the mean age of 65 years were recruited. The CT-based evidence of T-OPLL was noted in 56 (38 females and 18 males) individuals (1.9%). Most frequently encountered type was liner type, followed by continuous cylindrical type and mixed type. Continuous waveform and beaked type were less frequently encountered. Statistical analyses revealed that T-OPLL was noted at a significantly higher rate among the females. The mean age of T-OPLL-positive males was significantly higher than that of T-OPLL-negative males. Furthermore, there was significant difference of body mass index between T-OPLL-positive and T-OPLL-negative individuals. Most of T-OPLLs were confirmed in higher or middle thoracic regions and the highest peak was found at T3-T4. T-OPLL was noted after the age of 40 years with the peak distribution found at the age of 60 years. CONCLUSION: The prevalence of T-OPLL in Japanese was 1.9%. Further studies that characterize definitive subtypes of T-OPLL on CT are warranted so as to establish possible association between clinical manifestations and size and/or subtypes of T-OPLL. LEVEL OF EVIDENCE: N/A.

Analysis of demographics, risk factors, clinical presentation, and surgical treatment modalities for the ossified posterior longitudinal ligament.

OBJECT: Ossification of the posterior longitudinal ligament (OPLL) is a rare disease that results in progressive myeloradiculopathy related to pathological ossification of the ligament from unknown causes. Although it has long been considered a disease of Asian origin, this disorder is increasingly being recognized in European and North American populations. Herein the authors present demographic, radiographic, and comorbidity data from white patients with diagnosed OPLL as well as the outcomes of surgically treated patients. METHODS: Between 1999 and 2010, OPLL was diagnosed in 36 white patients at Barrow Neurological Institute. Patients were divided into 2 groups: a group of 33 patients with cervical OPLL and a group of 3 patients with thoracic or lumbar OPLL. Fifteen of these patients who had received operative treatment were analyzed separately. Imaging analysis focused on signal changes in the spinal cord, mass occupying ratio, signs of dural penetration, spinal levels involved, and subtype of OPLL. Surgical techniques included anterior cervical decompression and fusion with corpectomy, posterior laminectomy with fusion, posterior open-door laminoplasty, and anterior corpectomy combined with posterior laminectomy and fusion. Comorbidities, cigarette smoking, and previous spine surgeries were considered. Neurological function was assessed using a modified Japanese Orthopaedic Association Scale (mJOAS). RESULTS: A high-intensity signal on T2-weighted MR imaging and a history of cervical spine surgery correlated with worse mJOAS scores. Furthermore, mJOAS scores decreased as the occupying rate of the OPLL mass in the spinal canal increased. On radiographic analysis, the proportion of signs of dural penetration correlated with the OPLL subtype. A high mass occupying ratio of the OPLL was directly associated with the presence of dural penetration and high-intensity signal. In the surgical group, the rate of neurological improvement associated with an anterior approach was 58% compared with 31% for a posterior laminectomy. No complications were associated with any of the 4 types of surgical procedures. In 3 cases, symptoms had worsened at the last follow-up, with only a single case of disease progression. Laminoplasty was the only technique associated with a worse clinical outcome. There were no statistical differences (p > 0.05) between the type of surgical procedure or radiographic presentation and postoperative outcome. There was also no difference between the choice of surgical procedure performed and the number of spinal levels involved with OPLL. CONCLUSIONS: Ossification of the posterior longitudinal ligament can no longer be viewed as a disease of the Asian population exclusively. Since OPLL among white populations is being diagnosed more frequently, surgeons must be aware of the most appropriate surgical option. The outcomes of the various surgical treatments among the different populations with OPLL appear similar. Compared with other procedures, however, anterior decompression led to the best neurological outcomes.

Ossification of the posterior longitudinal ligament in non-Asians: demographic, clinical, and radiographic findings in 43 patients.

OBJECT: Ossification of the posterior longitudinal ligament (OPLL) is a disorder afflicting as many as 2% of East Asians. However, reports of OPLL in non-Asians have been sporadic in the medical literature. This study describes clinical and radiographic findings with OPLL in non-Asians at a tertiary care center treating a diverse multiethnic population. METHODS: Over a 6-year period, 43 patients not of East Asian descent presented to an urban tertiary medical center with OPLL. Patient data, including ethnicity, spinal cord function, Nurick grade, radiographic findings, OPLL subtype, and degree of cervical stenosis, were recorded. RESULTS: The average patient age was 59 years (range 32-92 years) with 18 women and 25 men. There were 22 Caucasian patients, 17 Hispanic patients, and 4 Black patients. With respect to the radiographic findings, OPLL morphology was continuous in 19, segmental in 17, mixed in 6, and other in 1. Average canal diameter was 7.6 mm (range 4.2-9.0 mm) at the most stenotic points. The mean Nurick grade was 2.95 at presentation, but 7 of the patients had OPLL identified incidentally and with early or minimal symptoms and signs of myelopathy. CONCLUSIONS: Ossification of the posterior longitudinal ligament in non-Asians demonstrates similar demographic and radiographic characteristics as in East Asians. The representation of different ethnic groups mirrors the demographics of the medical center population in general, showing no specific predilection for particular ethnic groups. Surgical decompression in appropriately selected patients results in similar rates of improvement when compared with the Japanese literature.

Ossification of the posterior longitudinal ligament in the cervical spine: an 11-year comprehensive national epidemiology study.

OBJECT: This study aimed to calculate the incidence and prevalence of ossification of the posterior longitudinal ligament (OPLL) in the cervical spine with its comorbid disability. METHODS: Using an 11-year nationwide database in Taiwan (National Health Insurance Research Database), this retrospective study cohort analyzed the incidences of cervical OPLL causing hospitalization. All patients admitted for the diagnosis of OPLL, regardless of surgery, were identified. Age- and sex-specific incidences, Poisson regression, and multivariate logistic regression analysis were conducted. RESULTS: Between 1997 and 2007 covering 241,800,725.8 person-years, 1651 patients were admitted for OPLL. The overall incidence of OPLL-related admission was 6.1 per 1 million person-years. Specifically, male sex and older age were associated with higher OPLL incidences (both p < 0.001). Among the 1651 OPLL patients, 542 (32.8%) received conservative management, 612 (37.1%) had anterior only surgery, 353 (21.4%) had posterior only surgery, and 144 (8.7%) had anterior and posterior surgery. Eighty-five patients were moderately to severely disabled (5.2% cumulative incidence rate). The incidences of disability varied by age, in a decreasing trend, except for the 60- to 69-year-old age group (p = 0.05). Patients who received posterior-only surgery were more likely to have disability. CONCLUSIONS: In a large cohort of the Chinese population, the incidence of cervical OPLL-related admission is 6.1 per 1 million person-years, and the prevalence rate is 7.7 per 100,000 person-years. Higher incidences are observed in elderly and male patients, which implies the disease's degenerative nature. After adjustments for demographics, the incidences and trends of OPLL-related comorbid disability are associated with age and surgical approaches.

RUNX2 polymorphisms associated with OPLL and OLF in the Han population.

BACKGROUND: Runt-related transcription factor 2 (RUNX2), BMP-2, COL6A1, and VDR are four genes that may be related to ossification of the spinal ligament. However, their pathogenetic relevance remains unclear. Most cases of ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) have been reported in Asian populations, but the polymorphic loci in these genes may vary among people of different races. PURPOSES: We identified (1) polymorphic loci in four genes (RUNX2, BMP-2, COL6A1, and VDR) in OPLL and OLF in Chinese Han patients and (2) identified loci related to these diseases. METHODS: We analyzed 19 single nucleotide polymorphisms (SNPs) in four candidate genes in 200 Han individuals (82 patients and 118 control subjects) by the Sequenom system. The genotype distribution and allele frequency of each SNP in the control and patient groups were compared. We then determined the relationships between the loci and the occurrence of OPLL and OLF. RESULTS: Genotyping showed RS1321075 and RS12333172 in RUNX2 differed between the patients and the control subjects. Both loci were located on chromosome 6 and exhibited linkage disequilibrium. One of the two blocks was a haplotype, thus suggesting a link between this block and increased incidence of OPLL and OLF. CONCLUSION: Although the detailed mechanism of the SNP is unclear, our data suggest RUNX2 could be responsible for ectopic bone formation in the spinal ligament in the Chinese Han population. However, we found no obvious connection between polymorphic loci of COLA1, BMP-2, and VDR and the diseases. CLINICAL RELEVANCE: Molecular genetic studies have identified several candidate genes that may be responsible for increased susceptibility to the diseases. Information regarding SNPs among the certain candidate genes may improve understanding of the disease and assist in developing new diagnostic gene tools during early episodes of the disease.

Ossification of the ligamentum flavum in a Caucasian man.

Abnormal ossification of spinal ligaments is a well-known cause of myelopathy in East Asian populations, with ossification of the ligamentum flavum (OLF) and the posterior longitudinal ligament being the most prevalent. In Caucasian populations, OLF is rare, and there has been only 1 documented case of the disease affecting more than 5 spinal levels. In this report, the authors describe the clinical presentation, imaging characteristics, and management of the second published case of a Caucasian man with OLF affecting almost the entire thoracic spine. The literature is then reviewed with regard to OLF epidemiology, pathogenesis, presentation, and treatment.

Paraparesis in a black man brought on by ossification of the ligamentum flavum: case report and review of the literature.

We present the second case of paraparesis secondary to ossification of the ligamentum flavum at the midthoracic region in a black man. Ossification of the ligamentum flavum is frequently described in the Japanese population where the presentation is often in the lower thoracic region. The patient is a 37-year-old black man who, over the 6 months before admission, noticed progressive paraparesis. CT myelogram revealed severe thoracic stenosis by an ossified ligamentum flavum from T4 to T7 with most severe involvement at the T5, T6, and T7 levels. The patient underwent multilevel laminectomies and medial facetectomies from T4 to T7. Over the past decade, ossification of the ligamentum flavum has been reported with increasing frequency in non-Asian patients. This is the third case report in a black man. In addition, ossification of the ligamentum flavum in this particular location is rarely reported. The increased use of advanced neuroimaging techniques in the evaluation of "back pain" may reveal that the prevalence of this condition is higher than expected in non-Asian populations. Improvement in neurologic symptoms secondary to decompressive laminectomies will depend on the degree and duration of spinal cord compression.