Yuji Atsuta

A longitudinal study of congruent sagittal spinal alignment in an adult cohort.

Study Design. A 10+-year longitudinal study of 100 adult volunteers. Objectives. To identify congruent lumbar lordosis in association with other sagittal spinopelvic parameters. Summary of Background Data. The aging spine poses difficult problems in determining appropriate lumbar lordosis. The concept of congruent spinal alignment is preferred over that of normal spinal alignment, yet the definition of sagittal spinal congruity in elderly population has not been well documented. Methods. A population-based recruitment of adult volunteers and follow-up of 10+ years was conducted. A total of 100 healthy volunteers with baseline age of 50+ years were subjected to standing entire spine radiographs. Radiologic parameters included lumbar lordosis, sacral inclination, sagittal spinal balance, and other sagittal alignments. Results. Average age of the subjects was 62.0 years at baseline and 73.9 years at follow-up. Lumbar lordosis with <5° change during observation was defined as stable lumbar lordosis (n = 34). Regression analyses of the baseline parameters revealed that sacral inclination was the sole predictor of stable lumbar lordosis (lumbar lordosis = 0.8 * sacral inclination, r = 0.94, P < 0.0001). Baseline lumbopelvic congruity, determined as 0.7 ≤ lumbar lordosis/sacral inclination ≤ 0.9, was associated with minimum alterations in sagittal spinal alignment, whereas subjects with incongruent lumbopelvic relationships were predisposed to developing kyphosis and spinal imbalance. Conclusions. Our study substantiates previous results showing that the strongest determinant of lumbar lordosis is sacral alignment. Appropriate lumbar lordosis was estimated to be 80% of sacral inclination using standing radiographs, and the proposed lumbopelvic congruity could measure stability in sagittal spinal alignment. This study provides practical data for the assessment of sagittal spinal alignment in the aging spine.

A prospective study of de novo scoliosis in a community based cohort.

Study Design. A 12-year prospective study of de novo scoliosis in a community based cohort. Objective. To investigate factors associated with development of de novo scoliosis. Summary of Background Data. De novo scoliosis is becoming one of the most prevalent findings in the aging spine, and this condition is associated not only with severe back or leg symptoms but also with complicated surgical outcomes. Cross-sectional studies were limited in distinguishing de novo scoliosis from preexisting deformities, and there had been controversies over the etiology of degenerative scoliosis. Methods. Community based volunteers were recruited, then examined by orthopedic physicians. Radiologic measurements using entire spine radiographs included the angle of scoliosis and sagittal spinal curvatures, sagittal spinal balance, grade of bone atrophy, number of degenerated discs, and vertebral fractures. We defined radiologic parameters, the disc index, and lateral osteophyte difference to evaluate the asymmetrical spinal degeneration. Results. A total of 60 subjects aged 50–84 years and without scoliosis at baseline were selected and followed for a mean of 12.0 years. De novo scoliosis ≥10° developed in 22 subjects, and logistic regression analysis revealed that the baseline disc index and lateral osteophyte difference values were independent predictors (P < 0.05). Conclusions. Incidence of de novo scoliosis was predictable by assessing asymmetric disc degeneration in frontal radiograph. More than 20% decrease in unilateral disc height or more than 5 mm longer osteophyte on one side led to increased incidence of de novo scoliosis, which might also influence long-term results of spinal surgery.

Epidemiology of Degenerative Lumbar Scoliosis: A Community-based Cohort Study

Study Design. A 12-year prospective study of pre-existing and de novo degenerative lumbar scoliosis (DLS) among community-based female volunteers. Objective. To investigate serial entire spine radiographs of healthy female volunteers and to clarify radiographical characteristics and predictors of pre-existing and de novo DLS. Summary of Background Data. DLS is among the most frequent spinal defomities in the aging spine; however, the onset or the natural course of this condition has not been elucidated. Methods. A total of 144 female volunteers were recruited from population register. Radiographical measurements using entire spine radiographs included thoracic kyphosis (T4–12), lumbar lordosis (LL) (L1–5), sacral inclination angle, pelvic incidence, sagittal balance (C7 plumb), coronal L4 endplate angle (L4 tilt), and scoliotic angle by Cobb method. More than 10° of scoliosis was diagnosed as DLS. L4 vertebral size was measured (divided by body height) as well as lateral osteophyte formation and lateral disc wedge angle. Results. Mean baseline age and follow-up period were 54.4 years and 12.1 years, respectively. Pre-existing DLS (pre-DLS) was found in 42 subjects (29.2%) at baseline. Among pre-DLS, 11 subjects (26%) showed more than 5° progression in scoliosis. De novo DLS has developed in 30 subjects (29.4%) among those without baseline scoliosis. Cox proportional hazards models revealed younger age, smaller L4 size, lower LL, greater DLS angle, and L4 tilt at baseline to be the risk factors of progression of pre-DLS and smaller L4 size, unilateral osteophyte formation, and lateral disc wedging to the risk of development of de novo DLS. Conclusion. This study indicated that younger age, smaller L4 size, lower LL, greater DLS angle, and L4 tilt at baseline should be evaluated as predictors of progression of pre-DLS. Early signs of asymmetric disc degeneration and smaller L4 size should also be evaluated as predictors of development of de novo DLS.

Changes in the sagittal spinal alignment of the elderly without vertebral fractures: a minimum 10-year longitudinal study

BackgroundThoracic hyperkyphosis, or loss of lumbar lordosis, is often equated with osteoporosis because vertebral fractures are assumed to be a major causative factor. However, recent evidence suggests that up to one-half of the patients with hyperkyphosis have no evidence of underlying vertebral fracture. The shape characteristics of the intervertebral discs and their role in determining kyphotic curvature have been investigated. The spinal sagittal parameters and segmental disc angles of elderly subjects were examined during a longitudinal follow-up.MethodsA total of 53 subjects (20 men, 33 women) without vertebral fractures during a more than 10-year follow-up were included in this study, undergoing standing lateral radiographs of the spine using 36-inch film at baseline and final follow-up. The mean age of the subjects was 63 years (range 50–77 years) at baseline and 75 years (range 62–88 years) at follow-up; and the mean follow-up period was 11 years 11 months.ResultsThe lumbar lordosis and the sacral inclination angle decreased and the C7-plumbline distance increased with age. Among a total of 664 discs, 70 discs (10.5%) showed anterior wedging over 5° at follow-up. In contrast, 39 discs (5.9%) showed posterior wedging over 5°. The subjects had only discs with anterior wedging, decreased total lumbar lordosis, and the C7 plumbline displaced anteriorly. However, when the subjects had discs with posterior wedging, the C7 plumbline and sagittal spinal balance tended to be maintained. This compensatory mechanism was seen in younger subjects.ConclusionsA decrease in the total lumbar lordosis and the sacral inclination angle occurred with age. Increasing age correlated with a more forward sagittal vertical axis, depending on a decrease in the total lumbar lordosis. The cause of loss of lumbar lordosis in the subjects without vertebral fracture was anterior wedging of the segmental discs. Posterior wedging of the thoracic and lumbar segmental discs then could occur, compensating for the loss of lumbar lordosis.

Radiographic analysis of newly developed degenerative spondylolisthesis in a mean twelve-year prospective study.

Study Design. Prospective study of community-based female volunteers. Objective. To investigate the incidence of newly developed degenerative spondylolisthesis (DS) among those without baseline deformity, and to clarify radiographic characteristics and predictors of DS. Summary of Background Data. There has been limited number of prospective studies of DS. Our on-going cohort study of healthy volunteers enabled long-term observation of highly susceptible perimenopause female subjects. Methods. A final total of 142 female subjects without spondylolisthesis at baseline radiographs were included and followed up for more than 8 years. Standardized serial entire spine radiographs were used to measure spinopelvic alignment, including pelvic incidence (PI), vertebral inclination angle, disc height, vertebral size, and facet orientation. Results. The incidence of newly developed DS was 12.7%. Comparison between DS and non-DS subjects demonstrated that DS subjects had significantly greater baseline lumbar lordosis, PI, vertebral inclination angle, and smaller vertebral size. Exaggerated lumbopelvic alignment was more prominent in L3-DS than in L4-DS, and L4-DS was associated with the decrease in L4/5 disc height. Multivariate analysis revealed that PI, L4 vertebral inclination, adjusted vertebral size, and facet sagittalization were independent predictors of the development of DS. Conclusion. This was the first study to confirm the relationship of PI and the development of DS in a long-term prospective observation. Proposed pathogenetic differences might explain the fact that L4-DS is far more prevalent than L3-DS. The development of DS could be predicted by baseline lumbopelvic morphology among the highly susceptible perimenopause women.

Effects of dry needling at tender points for neck pain (Japanese: katakori): near-infrared spectroscopy for monitoring muscular oxygenation of the trapezius

BackgroundNeck pain (katakori) is a common symptom in adult Japanese people. However, the pathophysiological aspect of this condition has not been well documented to date. The purpose of this study was to investigate the effects of tender point dry needling to the trapezius muscles and the resultant changes in muscular hemodynamics.Methods“Neck pain” patients were defined as those complaining of dull pain or discomfort mainly along the trapezius muscles without serious spinal or shoulder disorders. We used near-infrared spectroscopy to monitor the changes of oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) of the trapezius muscles and a Visual Analogue Scale (VAS) to assess subjective neck pain intensity. Experiment I: Nine subjects with “neck pain” and four control subjects were recruited. Total hemoglobin (Hb) and SdO2 [= oxyHb/(oxyHb + deoxyHb)] were measured before and immediately after needling for 15 min. We compared these parameters and VAS before and immediately after needling. Experiment II: Thirteen subjects with “neck pain” were instructed to perform isometric contraction of their trapezius muscles for 1 min; the half-recovery time of SdO2 (defined as TR) was measured. After that, all subjects underwent needling. On the next day, we repeated the measurements of TR after the same voluntary contraction of the trapezius muscle in the same patients. We compared TR and VAS before and on the day after needling.ResultsExperiment I: All subjects with “neck pain” reported significant pain relief (P = 0.0147) measured by VAS immediately after needling, but total Hb and SdO2 exhibited no significant change after needling. Experiment II: TR was shortened on the day after needling in 10 of 13 patients (P = 0.0043), and neck pain was decreased in 12 patients (P = 0.0158).ConclusionsAfter dry needling, total Hb and SdO2 did not change in real time, but TR was shortened on the next day. These results showed that the shortening of TR would provide a measure by which to assess the effectiveness of treatment for neck pain.

Nitric oxide induced ectopic firing in a lumbar nerve root with cauda equina compression.

Nitric oxide is thought to be involved in the pathophysiology of radiculopathy attributable to herniated intervertebral disc, but its effect on ectopic firing, which is the main source of sciatica, has not been investigated. The authors investigated whether ectopic firing is elicited when the lumbar nerve root is exposed to nitric oxide using rats with and without cauda equina compression. A group of animals had partial L3 laminectomy, and a silicone tube was inserted in the epidural space to compress the cauda equina. A sham operation group and nontreated control group also were prepared. Seven days later, ectopic firing of the nerve root was recorded from the sural nerve. The animals with cauda equina compression showed significantly higher spontaneous firing rates than other groups. After a lumbar epidural administration of sodium nitroprusside, only the animals with cauda equina compression showed a marked increase in the firing rate. These results showed that the nerve roots became hyperexcitable under compression as indicated by increased spontaneous firing and marked sensitivity to nitric oxide. This mechanism may play an important role in the development of sciatica.

FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis.

When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static (‘rear’) cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth. Highlighted article: Body axis elongation is regulated by posterior FGF8 signals . In chicken, nephric duct extension also requires this FGF8 signal, while low FGF8 anteriorly triggers duct lumen formation.

Interepithelial signaling with nephric duct is required for the formation of overlying coelomic epithelial cell sheet.

Significance We demonstrate that one type of epithelial tissue acts on another type and also that such interepithelial signaling is important for the coordination between different types of epithelia. When one epithelium is ablated, its adjacent epithelium becomes sensitized to external stress such as that produced by epithelial-to-mesenchymal transition (EMT) inducers. For such interactions, fibronectin serves as a prominent mediator, being translocated from one epithelium (fibronectin-producing) to the other (fibronectin-receiving). This type of interepithelial signaling and the role of fibronectin in these events are conceptually novel and thus open a new way to understand not only how epithelial tissues form in harmony but also how therapeutically to prevent EMT, a critical event in cancer initiation. In most organs of the body, epithelial tissues are supported by their own basement membrane and underlying stroma, the latter being regarded as a complex of amorphous cells, extracellular matrices, and soluble factors. We demonstrate here that an epithelial tube can serve as a component of stroma that supports the formation of epithelial cell sheet derived from a different origin. During development of the mesonephros in chicken embryos, the intermediate mesoderm (IMM), which contains the Wolffian duct (WD) and its associated tubules, is overlain by a sheet of epithelial cells derived from lateral plate (coelomic) mesoderm. We describe that in normal embryos, epitheliogenesis of IMM tubes and the adjacent coelomic cell sheet proceed in a coordinated manner. When the WD was surgically ablated, the overlying coelomic epithelium exhibited aberrant morphology accompanied by a punctated basement membrane. Furthermore, the WD-ablated coelomic epithelium became susceptible to latent external stress; electroporation of Rac1 resulted in epithelial-to-mesenchymal transitions (EMTs) within the coelomic epithelium. The distorted coelomic epithelium was rescued by implanting fibronectin-producing cells in place of the WD, suggesting that fibronectin provided by WD has an important role acting interepithelially. This notion was corroborated further by directly visualizing a translocation of EGFP-tagged fibronectin from fibronectin-producing to -receiving epithelia in vivo. Our findings provide a novel insight into interepithelial signaling that also might occur in adult tissues to protect against EMT and suggest a possible new target for anticancer therapeutic strategy.

Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model: a possible pathogenesis of neurogenic intermittent claudication.

Study Design. An electrophysiologic analysis was performed on a chronic lumbar spinal stenosis model of rats. The effects of venous stasis on ectopic firing originating in the nerve root were investigated. Objectives. To elucidate the mechanisms of neurogenic intermittent claudication in lumbar spinal canal stenosis. Summary of Background Data. Neurogenic intermittent claudication has been known as a characteristic symptom of lumbar spinal canal stenosis (LSCS), but the pathogenesis is poorly understood. Venous stasis of cauda equina has been speculated as a possible factor in the development of symptoms of the lower extremities while walking. On the other hand, ectopic firing originating in the dorsal root ganglia is thought to play an important role in the development of radicular pain or abnormal sensation. However, a direct association between venous stasis and ectopic firing has been never demonstrated. Methods. Using 10 Wistar rats, the LSCS group was prepared by inserting two silicone strips into the L3 and L5 dorsal epidural spaces. Another 10 animals were treated without silicone insertion as a sham group. Fourteen days later, the ectopic firing originating in the L5 nerve root was antidromically recorded from the distal stump of the severed sural nerve. After recording initial spontaneous firing, the posterior vena cava was clamped for 60 seconds to simulate a transient venous stasis and the changes in firing were analyzed. Results. None of the animals in the sham group showed a significant change in firing due to venous stasis. In contrast, most animals in the LSCS group showed a marked increase in firing during the venous stasis with some latency and then returned to the initial firing state after the release of the clamp. This phenomenon was repeated as long as the animals were maintained. Conclusions. We demonstrated that ectopic firing was elicited by venous stasis only in the LSCS animals. Therefore, the venous stasis may be a major factor of neurogenic intermittent claudication.