Takuya Numasawa

Genetic mapping of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.

Axial symptoms after cervical laminoplasty with C3 laminectomy compared with conventional C3-C7 laminoplasty: a modified laminoplasty preserving the semispinalis cervicis inserted into axis.

Study Design. Results of C4–C7 laminoplasty with C3 laminectomy and C3–C7 laminoplasty were compared. Objectives. To clarify prospectively whether the modified laminoplasty preserving the semispinalis cervicis inserted into C2 could reduce the axial symptoms compared with conventional laminoplasty reattaching the muscle to C2. Summary of Background Data. Intraoperative damage of the semispinalis cervicis is relevant to the development of axial symptoms after laminoplasty. In C3–C7 laminoplasty, however, it is difficult to preserve the muscle insertion into C2 while opening the C3 lamina. Methods. The axial symptoms of 40 patients (Group A) with C4–C7 laminoplasty with C3 laminectomy were compared with those of 16 patients (Group B) with C3–C7 laminoplasty. The cross-sectional areas of the cervical posterior muscles were measured on magnetic resonance images. Results. The number of patients with no postoperative axial symptoms increased (P = 0.035) from 19% to 52.5%, and the number of patients whose symptoms worsened after surgery decreased (P = 0.020) from 50% to 17.5%. The average atrophy rate of cross-sectional area was smaller (P < 0.001) in Group A (2.4%) than in Group B (10.8%). Conclusions. This method was less invasive to the cervical posterior muscles than C3–C7 laminoplasty. This is an effective procedure for preventing postoperative axial symptoms.

Human retinoic X receptor β : Complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the ligament. OPLL is a very common disorder, in fact it constitutes the leading cause of myelopathy among Japanese. In the previous report, we provided the genetic linkage evidence that the genetic susceptibility of OPLL mapped to HLA complex of chromosome 6. As a candidate gene approach, retinoic X receptor β (RXRβ), assigned to chromosome 6p21.3 adjacent to HLA class II, was analyzed for a possible causality. To start screening for the molecular variants of RXRβ in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXRβ and elucidated the genomic organization of the gene. The human RXRβ is composed of 10 exons spanning over 6.2 kb of genomic DNA. Sequence analysis of the promoter region revealed a GC‐rich sequence without TATA motif. We have identified three distinct molecular variants, one was in exon 10 and two were in the intergenic region between RXRβ and collagen 11A2 (COL11A2). Two variants in the intergenic region, 3′ end + 140 and 3′ end + 561, exhibit statistically significant associations with OPLL in case‐control study (p = 0.0028 for 3′ end + 140 and p = 0.034 for 3′ end + 561). These results indicate that the genetic causality of OPLL lies within or close to the RXRβ/COL11A2 locus.

Spinal cord shift on magnetic resonance imaging at 24 hours after cervical laminoplasty.

Study Design. A prospective study in 19 patients after cervical laminoplasty, using magnetic resonance imaging. Objective. To evaluate the value of spinal cord shift at 24 hours after cervical laminoplasty. Summary of Background Data. Postoperative C5 palsy is a noticeable complication within 1 week after cervical laminoplasty. The root tethering due to the posterior shift of the spinal cord after laminoplasty was reported as one of the causes of C5 palsy. However, the spinal cord shift after surgery within 1 week is unknown. Methods. The posterior shift of the spinal cord was measured in 19 consecutive patients on magnetic resonance images at 24 hours and 2 weeks after cervical laminoplasty. Results. The mean posterior shift of the spinal cord at 24 hours was 2.8 mm, with the maximum at the C5 level, decreasing to 1.9 mm at 2 weeks. The posterior shift of the spinal cord at C5 was correlated with the amount of the dura mater at C4, C5, and C6 levels. In a patient with right C5 palsy, posterior shift at C5 level was 5.5 mm, decreasing to 3.0 mm at 2 weeks after surgery. The posterior shift of the spinal cord was not correlated with the sagittal alignment. Conclusion. The posterior shift of the spinal cord at 24 hours had a tendency to shift more posteriorly than that observed at 2 weeks after cervical laminoplasty. C5 palsy may be prevented if the expansion of dura mater, which is strongly correlated with the posterior shift, can be controlled.

Gender-specific haplotype association of collagen α2 (XI) gene in ossification of the posterior longitudinal ligament of the spine

AbstractAmong Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen α2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11A2 haplotype with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males, with a prevalence ratio of 2 : 1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males.

Cervical range of motion and alignment after laminoplasty preserving or reattaching the semispinalis cervicis inserted into axis.

Study Design A radiographic study in 111 patients using radiographs was conducted. Objective To clarify whether the modified laminoplasty with C3 laminectomy preserving the semispinalis cervicis (SSC) inserted into C2 could maintain the postopertive range of motion (ROM) and sagittal alignment compared with conventional C3-C7 laminoplasty reattaching the muscle to C2. Summary of Background Data Intraoperative injury of the SSC is relevant to the significant loss of ROM and the malalignment after laminoplasty. To expose the C3 lamina, however, the SSC inserted into C2 could not be preserved in conventional C3-C7 laminoplasty. Methods The ROM and sagittal alignment of 70 patients (group A) (52 men, 18 women, mean age 59 y, mean follow-up period 1 y and 7 mo) with C4-C7 laminoplasty with C3 laminectomy were compared with those of 41 patients (group B) (28 men, 13 women, mean age 59 y, mean follow-up period 2 y and 6 mo) with C3-C7 laminoplasty using radiographs of the cervical spine. Results Regarding C2-C7 ROM, the postoperative ROM was larger (P=0.003) and the decrease rate of ROM was smaller (P=0.0006), and decreased ROM in extension was smaller (P<0.0001) in group A. Regarding O-C2 ROM, the increased ROM was smaller (P=0.043) and increased ROM in extension was smaller (P=0.001) in group A. Regarding O-C7 ROM, the postoperative ROM was larger (P=0.029) in group A. Regarding the cervical alignment, the increased lordotic angle at O-C2 was smaller (P=0.046) in group A. Conclusions This modified laminoplasty preserving the SSC inserted into C2 is an effective procedure for maintaining postoperative ROM, especially in extension, and sagittal alignment of the upper cervical spine well.

Simple foot tapping test as a quantitative objective assessment of cervical myelopathy.

Study Design. A clinical and cohort study. Objective. The first purpose of this study was to investigate the standard value of a simple foot tapping test (FTT) in a large healthy population. The second purpose was to elucidate the validity of FTT as a quantitative assessment of lower extremity motor function for cervical compressive myelopathy. Summary of Background Data. Several clinical performance tests have been reported as objective assessments for the severity of cervical myelopathy. The FTT is the simplest and easiest method for a quantitative analysis of lower limb motor dysfunction in the upper motor neuron diseases. However, there were few studies about the FTT in cervical myelopathy. Methods. We recruited 252 patients who were diagnosed with cervical myelopathy and 792 healthy volunteers who participated in a health promotion project. Among the patients, 126 who underwent surgery were evaluated both before and 1 year after surgery. We performed the FTT and grip and release test and evaluated the modified Japanese Orthopaedic Association (JOA) score for cervical myelopathy. Results. The mean value of FTT was 23.8 ± 7.2 in myelopathic patients, which was significantly lower than 31.7 ± 6.4 in healthy controls and decreased with age. The value of FTT significantly correlated with the lower extremity motor function of modified JOA score and the value of grip and release test. Among the patients who underwent surgery, the average value of FTT was 22.4 ± 7.0 preoperatively and improved to 28.4 ± 8.1 at 1 year postoperatively. Postoperative gain of FTT significantly correlated with the gain of JOA score. Conclusion. The FTT results correlated with those of other tests for cervical myelopathy, and the FTT scores were improved by surgery. The FTT is an easy and useful quantitative assessment method for lower extremity motor function in patients with cervical myelopathy, especially those who cannot walk.

Mesenchymal stem cell isolation and characterization from human spinal ligaments.

Mesenchymal stem cells (MSCs) have a fibroblast-like morphology, multilineage potential, long-term viability and capacity for self-renewal. While several articles describe isolating MSCs from various human tissues, there are no reports of isolating MSCs from human spinal ligaments, and their localization in situ. If MSCs are found in human spinal ligaments, they could be used to investigate hypertrophy or ossification of spinal ligaments. To isolate and characterize MSCs from human spinal ligaments, spinal ligaments were harvested aseptically from eight patients during surgery for lumbar spinal canal stenosis and ossification of the posterior longitudinal ligament. After collagenase digestion, nucleated cells were seeded at an appropriate density to avoid colony-to-colony contact. Cells were cultured in osteogenic, adipogenic or chondrogenic media to evaluate their multilineage differentiation potential. Immunophenotypic analysis of cell surface markers was performed by flow cytometry. Spinal ligaments were processed for immunostaining using MSC-related antibodies. Cells from human spinal ligaments could be extensively expanded with limited senescence. They were able to differentiate into osteogenic, adipogenic or chondrogenic cells. Flow cytometry revealed that their phenotypic characteristics met the minimum criteria of MSCs. Immunohistochemistry revealed the localization of CD90-positive cells in the collagenous matrix of the ligament, and in adjacent small blood vessels. We isolated and expanded MSCs from human spinal ligaments and demonstrated localization of MSCs in spinal ligaments. These cells may play an indispensable role in elucidating the pathogenesis of numerous spinal diseases.

Surgical anatomy of the nuchal muscles in the posterior cervicothoracic junction: significance of the preservation of the C7 spinous process in cervical laminoplasty.

Study Design. An anatomic study investigated the attachment of the nuchal muscles to the spinous process. Objective. To investigate the anatomic details of the attachment of the nuchal muscles to the spinous process, and which muscles are spared, and to what extent, when the C7 spinous process is preserved in the cervical laminoplasty. Summary of Background Data. In previous studies, it was reported that the incidence of postoperative axial pain was lower in C3–C6 laminoplasty than in C3–C7 laminoplasty, emphasizing the effectiveness of the former procedure where discission of the nuchal muscles that are attached to the C7 spinous process is avoided. However, there have been no detailed anatomic studies of the attachment of the nuchal muscles to the spinous process at the cervicothoracic junction. Methods. The anatomy of the speculum rhomboideum of the trapezius, rhomboideus minor, rhomboideus major, serratus posterior superior, splenius capitis, and splenius cervicis to the spinous processes of the cervicothoracic junction were studied using 50 cadavers. Results. The possibility of total discission of the speculum rhomboideum of the trapezius was 0% with C3–C6 laminoplasty and 18% with C3–C7 laminoplasty. More than 50% preservation of the speculum rhomboideum of the trapezius is possible in 72% in C3–C6 laminoplasty and 16% in C3–C7 laminoplasty. In C3–C7 laminoplasty, the possibility of partial preservation of the rhomboideus minor, serratus posterior superior, and splenius capitis at the spinous process was 0%, 66%, and 29%, respectively. The rhomboideus major in 16% and the splenius cervicis in 56% could be completely preserved without partial discission of the muscle attachment. On the other hand, in C3–C6 laminoplasty, the muscles that were spared without complete discission of the muscular attachment at the spinous process were the rhomboideus minor in 35%, the serratus posterior superior in 100% and the splenius capitis in 67%. The rhomboideus major in 76% and the splenius cervicis in 80% were completely spared without partial discission of the muscular attachment. Conclusion. The current study confirmed that C3–C6 laminoplasty in which the C7 spinous process is preserved reduces invasion of the nuchal muscles.

Clinical significance of the redundant nerve roots of the cauda equina documented on magnetic resonance imaging

OBJECT Previous reports of redundant nerve roots (RNRs) of the cauda equina have been limited to evaluations based on myelography. Neither the imaging nor the clinical features of RNRs in relation to magnetic resonance (MR) imaging have been elaborated. The MR imaging characteristics of RNRs were evaluated using the Japanese Orthopaedic Association score before and after the surgery. METHODS There were 44 patients with L4-5 spondylolisthesis in which a complete blockage was demonstrated on myelography. All patients underwent posterior L4-5 interbody fusion. Based the myelographic and MR imaging findings, the patients were stratified into the following three groups: RNRs recognized on both myelographic and MR imaging (Group A); RNRs recognized on myelography but not very evident on MR imaging (Group B); and RNRs not recognized on either myelographic or MR imaging (Group C). Among these three groups, pre- and postoperative clinical symptoms were compared. RESULTS There were 16 patients in Group A, 14 in Group B, and 14 in Group C. In terms of preoperative clinical symptoms, there was a significant difference between Groups A and C in the incidence of leg pain and tingling sensation. Significant differences were also noted between Groups A and C and between Groups B and C in ambulatory ability. Evaluation of postoperative clinical symptoms showed a significant difference between Groups A and C in ambulatory ability. CONCLUSIONS Patients with MR imaging evidence of RNRs presented with more severe clinical symptoms. It is believed that the RNR features derived from MR images represent important findings.