V. James Raso

Melatonin levels in idiopathic scoliosis. Diurnal and nocturnal serum melatonin levels in girls with adolescent idiopathic scoliosis.

Study Design Matched pairs of adolescent girls were used to compare serum melatonin levels in adolescent patients and control subjects with idiopathic scoliosis during the day and in the middle of the night. Objectives To compare serum melatonin levels in patients with adolescent idiopathic scoliosis and matched control subjects during the day and in the middle of the night. Summary of Background Data Recent studies using the chick as the animal model have suggested that the pineal gland and its main product, melatonin, might be involved in the cause of scoliosis. There have been no studies of melatonin levels in patients with adolescent idiopathic scoliosis. Methods Blood was collected from seven adolescent girls with idiopathic scoliosis and a group of seven age‐matched control subjects. Two samples were collected, one in the middle of the day and one in the middle of the night, to examine the diurnal variation of melatonin production. Serum melatonin levels were measured using a radioimmunoassay technique. Results No significant differences were found in serum melatonin levels between experimental and control groups either during the day, when melatonin levels were low, or during the night, when melatonin levels were high. Conclusions Whereas pinealectomy in young chickens leads to reduced melatonin levels and the development of scoliosis, the results of this study suggest that melatonin levels in mature patients who already have severe scoliosis do not differ from healthy subjects. Whether melatonin levels differ in humans between healthy subjects and patients with scoliosis at the time of onset of the disease remains to be seen.

Dynamic upper limb proprioception in multidirectional shoulder instability.

The ability of subjects with multidirectional shoulder instability to use proprioception to complete a series of upper limb repositioning tasks was investigated. Twelve subjects with multidirectional instability and 12 control subjects were blindfolded and instructed to use proprioception to reproduce a self-selected target position as accurately as possible. Subjects completed 10 repetitions for each limb using three distinct upper limb movements: overhead reaching, scapular plane pointing, and humeral external rotation with abduction. A three-dimensional video motion analysis system tracked limb position and determined spatial hand position error. Subjects with multidirectional shoulder instability showed significantly greater hand position error than control subjects. No hand position error differences were found between the symptomatic and the asymptomatic limbs of subjects in the instability group. Inter-repetition error for subjects in both groups improved significantly during the first three movement cycles. These results suggest that after movement initiation, dynamic proprioception was a factor in improving hand position accuracy in both groups, but to a lesser degree in subjects with multidirectional instability. Consequently, subjects with multidirectional instability may have a reduced capacity to use proprioception to refine and control the motor output of the upper limb.

The nature and distribution of the innervation of human supraspinal and interspinal ligaments

Study Design To use fresh, human supraspinal and interspinal ligments and document their innervation. Objectives To characterize the innervation of the human supraspinal and interspinal ligaments. Summary of Background Data The nature and distribution of the innervation of spinal ligaments remains unknown. Methods Sections of spinal ligaments were labeled with a fluorescent antibody against neurofliament proteins and observed with a confocal microscope. Results. The ligaments were found to be well innervated. Innervation was equally distributed along the ligament, symmetrically distributed between left and right sides, and more densely distributed in the periphery. Pacinian corpuscles were scattered randomly, close to blood vessels, whereas Ruffini corpuscies were in the periphery, close to the collagen bundles. Conclusions Human supraspinal and interspinal ligaments are well innervated. This innervation might from the basis of neurologic feedback mechanisms for the protection and stability of the spina. These mechanisms might also be important in the development of diseases such as scoliosis.

The Effects of Melatonin Therapy on the Development of Scoliosis After Pinealectomy in the Chicken

The mechanism underlying the development of scoliosis after pinealectomy in young chickens is unknown. However, since the main product of the pineal gland is melatonin, melatonin remains an obvious focus in studies designed to discover this mechanism. One confounding factor is that serum melatonin levels are close to zero after pinealectomy but scoliosis does not develop in all chickens that have had this procedure. Therefore, the role of melatonin in the development of scoliosis in chickens after pinealectomy remains controversial. In the current investigation, two pilot studies demonstrated that a physiological therapeutic dose of melatonin (2.5 milligrams per kilogram of body weight) restored the circadian rhythm of melatonin, as measured by serum assay. In the main study, this dose was administered daily starting either immediately after the pinealectomy or two weeks after it, when scoliosis had developed. Scoliosis was assessed on weekly radiographs, and the Cobb angle was determined for all chickens in which scoliosis developed. Overall, scoliosis developed in only 56 percent (fifty) of the eighty-nine chickens that had had a pinealectomy; this rate was consistent throughout all experimental groups. Scoliosis did not develop in any of the control chickens, which did not have a pinealectomy. On the basis of the average Cobb angles in the chickens in which scoliosis had developed, it was determined that neither the prevalence nor the pattern of the scoliosis was affected by the therapy in any of the experimental groups. It was thus concluded that melatonin therapy after pinealectomy in young chickens has no effect on the development or progression of scoliosis. These results raise doubts regarding the role of melatonin in the development of scoliosis after pinealectomy in the young chicken.

Changes in serum melatonin levels in response to pinealectomy in the chicken and its correlation with development of scoliosis

Study Design. Normal, sham, and groups of chickens subjected to pinealectomy from which serum melatonin levels were measured and correlated with scoliosis development in a period of 5 weeks. Objectives. To measure serum melatonin levels in chickens subjected to pinealectomy and control chickens and correlate findings with development of scoliosis. Summary of Background Data. In a previous study by others, scoliosis developed in 100% of chickens subjected to pinealectomy, and serum melatonin levels were found to be reduced. Previous results in a study by the authors showed scoliosis developing in only approximately 55% of chickens that underwent pinealectomy. Methods. Young chickens were subjected to pinealectomy. Control groups consisted of sham operation and normal groups. Radiographs and blood samples were taken at weekly intervals to monitor scoliosis development and measure serum melatonin levels using radioimmunoassay techniques. Results. Scoliosis developed in only 52% of chickens that underwent pinealectomy, but all had low levels of serum melatonin and no circadian rhythm. The chickens in the two control groups maintained normal serum melatonin levels and rhythms. Conclusions. Pinealectomy in young chickens reduces serum melatonin levels and eliminates the melatonin circadian rhythm. It can also produce scoliosis, but low levels of serum melatonin are a poor predictor of development of scoliosis

Pineal transplantation after pinealectomy in young chickens has no effect on the development of scoliosis.

Study Design. Three experimental groups and one control group of chickens underwent different surgical procedures to determine the effects of pineal gland transplantation on the development of scoliosis. Objective. To determine whether transplantation of the pineal gland to the body wall musculature maintains serum melatonin levels at normal values and prevents the development of scoliosis. Summary of Background Data. Scoliosis occurs consistently after pinealectomy in young chickens. Many characteristics of this scoliosis are similar to those seen in patients with adolescent idiopathic scoliosis. It is not clear whether the underlying mechanism is dependent on reduced levels of serum melatonin or some other aspect of the extensive surgery. Methods. Four groups of chickens were selected: normal chickens, pinealectomized chickens, chickens that underwent simple cutting of the pineal stalk, and chickens that underwent transplantation of the pineal gland into the body wall. Development of scoliosis was determined from measurement of the Cobb angle from weekly radiographs. Results. All of the experimental groups showed the same levels of incidence and the same patterns of scoliosis development. Serum melatonin levels were reduced to nearly zero in all the experimental groups for the duration of the experiment. Scoliosis developed in none of the normal chickens. Conclusions. Neither transplantation of the pineal gland into the body wall musculature nor simple cutting of the pineal stalk was able to maintain normal levels of serum melatonin because both procedures reduced levels to nearly zero. The incidence and pattern of scoliosis development in these groups were the same as those for the pinealectomized group. Reduction of serum melatonin levels remains a prerequisite for scoliosis development in young chickens.

The critical stage of pinealectomy surgery after which scoliosis is produced in young chickens.

Study Design. Stages of the surgical procedure for pinealectomy in chickens were identified. Groups of chickens were selected for each stage. Scoliosis development was identified from radiographs. Objectives. To determine the critical stage of surgery for pinealectomy after which scoliosis develops in young chickens. Summary of Background Data. Pinealectomy in young chickens consistently produces scoliosis in young chickens that has many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. The mechanism behind this phenomenon remains unknown. Methods. Five distinct stages in the pinealectomy surgery were identified. Groups of chickens were selected to undergo surgery to represent these five stages. Scoliosis was determined from weekly radiographs. Results. Cutting the pineal stalk was identified as the critical stage in the surgery after which scoliosis developed. The incidence of scoliosis did not increase after more extensive surgery in which the pineal bulb was removed from the skull. This stage was also correlated with a significant reduction of serum melatonin levels. Conclusions. Cutting the pineal stalk was identified as the critical stage of pinealectomy surgery after which scoliosis may develop. This stage was also correlated with the significant reduction of average serum melatonin levels. These results allow the focus of attention into the mechanism behind this phenomenon to center on the consequences of cutting the pineal stalk rather than total removal of the pineal gland.

The Association Between Scoliosis Research Society-22 Scores and Scoliosis Severity Changes at a Clinically Relevant Threshold

Study Design. Cross-sectional correlation study. Objective. To determine the threshold in spinal deformity severity measurements beyond which there is a progressive decline in health-related quality-of-life (HRQOL). Summary of Background Data. The associations between HRQOL and scoliosis deformity measures are at best moderate when assessed using linear regressions. This may be because HRQOL is not affected until a severity threshold is reached. Identifying the thresholds in deformity beyond which HRQOL deteriorates could assist in treatment recommendations. Methods. The Scoliosis Research Society-22 (SRS-22) questionnaire was completed by 101 females with adolescent idiopathic scoliosis (age, 15.0 ± 1.8; largest Cobb angle, 36.9° ± 14.6°). Radiographs and surface topography were used to quantify the severity of the internal (largest Cobb angle) and external deformity (cosmetic score, decompensation, trunk twist), respectively. Segmented linear regression models were estimated to determine the association between SRS-22 domains and spinal deformity measures. This analysis also identifies deformity thresholds beyond which HRQOL is more affected. The percentage of variance explained (R2) by linear and segmented models were compared (α = 0.05) to identify the best models. Results. Cobb angle predicted significantly more variance in all SRS-22 domains except mental health using segmented models (R2: 0.09–0.30) than linear models (R2: 0.02–0.21). Segmented models with a single threshold estimated at a Cobb angle between 43° and 48° predicted between 3% and 11% more variance compared to corresponding linear model using the same variables. Surface topography parameters were not strongly associated with SRS-22 variables with linear and segmented models explaining less than 10% of the variance. Conclusion. Deterioration in SRS-22 scores is mildly associated with increases in the severity of the internal deformity. HRQOL is stable until the curve reaches a maximal Cobb angle threshold at ≈45° where HRQOL declines linearly with increasing internal deformity. The association between HRQOL and scoliosis severity is low, but is better explained by segmented rather than linear models.

Classifying torso deformity in scoliosis using orthogonal maps of the torso

Analysis of three-dimensional (3D) images of human torsos for torso deformities such as scoliosis requires classifying torso distortion. Assessing torso distortion from 3D images is not trivial as actual torsos are non-symmetric and show an outstanding range of variations leading to high classification errors. As the degree of spinal deformity (and classification of torso shape) influences scoliosis treatment options, the development of more accurate classification procedures is desirable. This paper presents a technique for assessing torso shape and classifying scoliosis into mild, moderate and severe categories using two indices, ‘twist’ and ‘bend’, obtained from orthogonally transformed images of the complete torso surface called orthogonal maps. Four transforms (axial line, unfolded cylinder, enclosing cylinder and subtracting cylinder) were used. Blind tests on 361 computer models with known deformation parameter values show 100% classification accuracy. Tests on eight volunteers without scoliosis validated the system and tests on 22 torso images of volunteers with scoliosis showed up to 95.5% classification accuracy. In addition to classifying scoliosis, orthogonal maps present the entire torso in one view and are viable for use in scoliosis clinics for monitoring the progression of scoliosis.

A NURBS-based technique for subject-specific construction of knee bone geometry

Subject-specific finite element (FE) models of bones that form the knee joint require rapid and accurate geometry construction. The present study introduces a semi-automatic non-uniform rational B-spline (NURBS) technique to construct knee bone geometries from computed tomography (CT) images using a combination of edge extraction and CAD surface generation. In particular, this technique accurately constructs endosteal surfaces and can accommodate thin cortical bone by estimating the cortical thickness from well-defined surrounding bone. A procedure is also introduced to overcome the bifurcation at the femoral condyles during surface generation by combining transverse and sagittal plane CT data. Available voxel- and NURBS-based subject-specific construction techniques accurately capture periosteal surfaces but are limited in their ability to capture endosteal geometry. In this study, the proposed NURBS-based technique and a typical voxel mesh technique captured periosteal surfaces within an order of magnitude of image resolution. The endosteum of diaphyseal bone was also captured with similar accuracy by both techniques. However, the voxel mesh model failed to accurately capture the metaphyseal and epiphyseal endosteum due to the poor CT contrast of thin cortical bone, resulting in gross overestimation of cortical thickness. The proposed technique considered both the local and global nature of CT images to arrive at a description of cortical bone thickness accurate to within 2 pixel lengths.