Keith M. Bagnall

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.

Paraspinal muscle imbalance in adolescent idiopathic scoliosis.

Twelve muscle biopsy samples were taken at operation for spinal instrumentation from each of seven patients suffering from idiopathic scoliosis (one male and six female patients; mean age 14.3 years). The samples were collected from two specific sites (superficial and deep) on both sides on the vertebral column at the level of the apex of the primary curve and two vertebral levels above and below the apex. The results of this study support and extend the findings of other workers. Not only was a significantly larger percentage of Type I fibers found in multifidus muscle at the apex of the curve on the convex side as other workers have found but also in the superficial muscles above and below the apex of the curve on the convex side. These results present a complex picture of muscle fiber characteristics associated with idiopathic scoliosis.

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.

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.

Muscle spindles in the paraspinal musculature of patients with adolescent idiopathic scoliosis.

Electromyographic studies have determined that muscle Imbalance and asymmetry of stretch receptors in the paraspinal muscle of patients with idiopathic scoliosis may have a large role to play in the development and production of the deformity. This project consisted of a detailed histologic and histochemical analysis of the distribution of muscle spindles in paraspinal musculature of patients suffering from Idiopathic scoliosis, using the reduced form of nicotinamide-adenine dinucleotide (NADH), adenosine triphosphatase (ATPase), and Tri-chrome stain techniques. Muscle biopsy samples were taken at operation for spinal Instrumentation from each of 13 patients (mean age: 16.2 years; 3 males, 10 females) with all but one female exhibiting right thoracic curves. The samples were collected from two specific sites (superficial and deep) on both sides of the vertebral column at the level of the apex of the primary curve and two vertebral levels above and below the apex. From the results there appear to be few muscle spindles in the scoliotic muscle of this region. All of the patients from whom muscle samples were taken possessed at least one sample with a muscle spindle. However, each patient had very few samples which contained a minimum of one muscle spindle (mean: 20.3%; SD: 12.6). It is clear that further examination is necessary, particularly In the area of comparison with ‘normal’ standards when these standards become available.

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 histochemical composition of human vertebral muscle.

This paper describes the ranges of variation of characteristics present in human vertebral muscle. The samples used are from subjects who had a relatively brief history of spinal dysfunction. The samples have been taken in a precise manner and from a specific vertebral level with both sides of the vertebral column being studied including both superficial and deep muscles. These values for typical muscle for the ages investigated now can be used in studies involving abnormal vertebral muscle.

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