James Mahood

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.

The Production of Scoliosis After Pinealectomy in Young Chickens, Rats, and Hamsters

STUDY DESIGN This study involved weekly radiographic examination of pinealectomized rats, hamsters, and chickens to observe the development of scoliosis. OBJECTIVES To determine whether pinealectomy produces scoliosis in animals more closely related phylogenetically to humans than to chickens, namely rats and hamsters, which are representative of mammals. SUMMARY OF BACKGROUND DATA Pinealectomy in 3-day-old chickens has consistently resulted in the development of scoliosis with many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. It has not been determined whether this phenomenon is restricted solely to chickens or is applicable to other animals, especially those more closely related to humans. METHODS The pineal gland was removed from young rats, hamsters, and chickens. All animals underwent radiography weekly to detect the development of any scoliosis. Weight and length measurements were also taken weekly, and serum melatonin levels were determined at the time the animals were killed. RESULTS Scoliosis was not observed in either the rats or the hamsters. In contrast, scoliosis developed in 10 of 21 chickens. Serum melatonin levels in all pinealectomized animals were zero. CONCLUSIONS In contrast to the chickens, pinealectomy does not seem to cause scoliosis in either young rats or hamsters. The reasons for this discrepancy may include differences in the physiology and spinal morphology of the rat and hamster in comparison with the chicken. In the pinealectomized chickens, the results also suggest that future scoliosis development might be indicated by a significant increase in size when they are compared with pinealectomized chickens that do not develop scoliosis. Such differences in growth rates also distinguish patients with adolescent idiopathic scoliosis.

Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans

Study Design. The characteristics of the scoliosis that develops after pinealectomy in young chickens were determined from weekly posteroanterior radiographs. These data were compared with similar data collected from human patients with adolescent idiopathic scoliosis. Objectives. To characterize the scoliosis produced in young chickens after pinealectomy and to compare these characteristics with those seen in human patients with adolescent idiopathic scoliosis. Summary of Background Data. Although it has been recognized that pinealectomy produces scoliosis in chickens, the characteristics of these curves have never been well described other than by simple visual descriptions. Methods. The characteristics of the scoliosis produced in chickens after pinealectomy done 3 days after hatching were measured from radiographs taken at weekly intervals. These characteristics were compared with similar data collected from human patients with adolescent idiopathic scoliosis. Results. Similarities included development of single and double curves, degree of curvature, stability of the curve, numbers of vertebrae involved, direction of rotation, and progression characteristics. Differences included wedged vertebrae in the chickens, in conjunction with curve development and increased variability in vertebrae involved. Conclusions. There are many similarities in the development of scoliosis in young chickens after pinealectomy and in children with adolescent idiopathic scoliosis. The few differences might be related to the different biomechanical properties associated with the spine in the two species.

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

Intra-observer Reproducibility and Interobserver Reliability of the Radiographic Parameters in the Spinal Deformity Study Group's AIS Radiographic Measurement Manual

Study Design. Retrospective cross-sectional assessment of the reproducibility and reliability of radiographic parameters. Objective. To measure the intra-examiner and interexaminer reproducibility and reliability of salient radiographic features. Summary of Background Data. The management and treatment of adolescent idiopathic scoliosis (AIS) depends on accurate and reproducible radiographic measurements of the deformity. Methods. Ten sets of radiographs were randomly selected from a sample of patients with AIS, with initial curves between 20° and 45°. Fourteen measures of the deformity were measured from posteroanterior and lateral radiographs by 2 examiners, and were repeated 5 times at intervals of 3–5 days. Intra-examiner and interexaminer differences were examined. The parameters include measures of curve size, spinal imbalance, sagittal kyphosis and alignment, maximum apical vertebral rotation, T1 tilt, spondylolysis/spondylolisthesis, and skeletal age. Results. Intra-examiner reproducibility was generally excellent for parameters measured from the posteroanterior radiographs but only fair to good for parameters from the lateral radiographs, in which some landmarks were not clearly visible. Of the 13 parameters observed, 7 had excellent interobserver reliability. Conclusions. The measurements from the lateral radiograph were less reproducible and reliable and, thus, may not add value to the assessment of AIS. Taking additional measures encourages a systematic and comprehensive assessment of spinal radiographs.

MRI characteristics of the neurocentral synchondrosis.

Abstract Background and objectives. The neurocentral synchondrosis (NCS) is a cartilaginous growth plate that since the early 1900s has been implicated as a potential cause of adolescent idiopathic scoliosis (AIS). Previous studies have focused only on the closure age without characterizing normal NCS development. Using MRI, the normal development of the NCS image can be characterized, and the stages preceding the disappearance of this image can be specified. Methods. A total of 405 NCSs were visualized in 11 normal pediatric patients using T1 and T2 transverse and sagittal MRI views. The images were correlated and the variety of images recorded to categorize the NCS into developmental stages. Results. The development of the NCS was categorized into five developmental stages. The image of the NCS became absent in a specific pattern along the vertebral column, first in the cervical region (age 6), then in the lumbar region (age 12), and finally in the thoracic region (age 14). Conclusion. The normal development of the NCS at the level of individual vertebrae and also along the vertebral column as a whole was determined using MRI. These patterns of development are valuable and necessary to evaluate the role of the NCS in pathological conditions.

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.

A Pilot Study of Magnetic Resonance Imaging-Guided Closed Reduction of Cervical Spine Fractures

Study Design. We report on a prospective selective case series of 17 patients with cervical fracture-dislocations treated with closed reduction under MRI guidance. Objective. To demonstrate the safe and effective use of in-line axial traction in the reduction of cervical fracture-dislocations using MRI guidance. Summary of Background Data. Closed reduction of the cervical spine for acute fracture-dislocations has been a traditional technique used for restoring vertebral alignment and providing neural element decompression. The safety of this technique has been questioned, with concerns of disc migration and overdistraction causing neurologic worsening cited as reasons to choose operative reduction and decompression as a safer option in some circumstances. Methods. Seventeen patients with fracture-dislocations of the subaxial cervical spine were given a trial of traction under MRI guidance between 1999 and 2003. The incidence of posteriorly herniated disc material was noted, and the diameter of the spinal canal at the injured level was recorded before and after traction. Results. All patients tolerated traction without neurologic worsening. Pretraction disc disruption was found in 15 of 17 (88.2%) of patients, with posterior herniation in 4 of 17 (23.5\%). Traction caused a return of herniated disc material toward the disc space in all cases. Canal dimensions improved in 11 of 17 patients, with canal diameter increasing by a factor of 1.1 to 3.0, with a mean improvement of 1.73. The process of reduction was observed to be a gradual one, with progressive, significant improvement in canal dimensions occurring before anatomic realignment. As distracting force was increased, sequential MRIs showed that canal dimensions did not diminish at any time in any patient. Conclusions. MRI monitoring in closed cervical reduction is a useful research tool for this technique. Closed reduction appears to be safe as used in this preliminary study and is effective in achieving immediate spinal cord decompression.