Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis?

Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Upper arm length model suggests transient bilateral asymmetry is associated with right thoracic adolescent idiopathic scoliosis (RT-AIS) with implications for pathogenesis and estimation of linear skeletal overgrowth.

INTRODUCTION: In girls with adolescent idiopathic scoliosis (AIS) the finding of abnormal extra-spinal bilateral skeletal length asymmetries in upper limbs, periapical ribs, and ilia begs the question whether these bilateral asymmetries are connected in some way with pathogenesis. MATERIAL AND METHODS: We investigated upper arm length (UAL) asymmetries in two groups of right-handed girls aged 11-18 years with right thoracic adolescent idiopathic scoliosis (RT-AIS, n=95) from preoperative and screening referrals (mean Cobb angle 46°) and healthy controls (n=240). Right and left UAL were measured with a Harpenden anthropometer of the Holtain equipment, Asymmetry was calculated as UAL difference, right minus left, in mm. Repeatability of the measurements was assessed as technical error of the measurement and coefficient of reliability. RESULTS: In girls with RT-AIS, UAL asymmetry was greater than in healthy girls, regressed negatively with age and correlated significantly with Cobb angle and apical vertebral rotation. In healthy girls, UAL asymmetry was unrelated to age. Plotted against years after estimated menarcheal age, UAL asymmetry decreased significantly for girls with RT-AIS but not for healthy girls. DISCUSSION AND CONCLUSIONS: The apparent transience of the abnormal UAL asymmetry suggests it is not secondary to spinal deformity but pathogenetically associated with it. We suggest two hypotheses to account for these changes: (1) a transient asymmetry process with growth velocity; and (2) in the light of subsequent research, early skeletal overgrowth with catch-down growth affecting right but not left upper arm. The relation of the upper arm length asymmetry to the increased length of periapical left ribs reported for RT-AIS is unknown. Right upper arm length may provide a more simple model than arm span, for estimating linear skeletal overgrowth of girls with RT-AIS.

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Postural differences in the shoulder girdle during normal locomotion in treadmill vs. over ground walking.

In a clinical setting, most musculoskeletal assessment related to gait is undertaken using a treadmill which is additionally widely used during gait and neurological rehabilitation. Although previous studies have reported the range of motion of gait characteristics during running, there is a paucity of information on normative walking data applicable to clinical assessment. Movements and posture of the shoulder girdle is an important indication of back and upper extremity function. While studies indicate that shoulder girdle kinematics are changed during shoulder dysfunction there is little information on the postural relationship between the shoulder and pelvis. The present investigation aims to create a normative database for kinematics during treadmill walking by examining the differences between the treadmill and over ground walking patterns. Additionally, the research will also assess shoulder girdle posture and to establish its relationship with the pelvic complex which will contribute to further understanding scoliotic posture and movement. 14 normal subjects walked over ground at a self-selected speed followed by walking on the treadmill at a speed matched to each subject's respective average over-ground speed. Three-dimensional kinematic data was captured using a passive marker based motion analysis system (Vicon Peak, UK). Angular and temporal kinematic parameters were estimated. The results indicate differences in angular kinematics between over-ground and treadmill locomotion. These differences should be considered when treadmill kinematics are used for clinical evaluation as opposed to over ground ambulation is scoliosis and other conditions.

Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin.

This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation. Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies.

Examination of relative movement between the back and lower limb.

The importance of trunk movement in human gait has been established by many studies. However, these investigations have examined trunk/pelvis motion or the pelvic/thoracic motion in isolation to lower limb kinematics. Studies quantifying spinal deformities and the range of spinal and trunkal movement have concentrated on spinal/back movement, with the subject performing tasks, such as flexion, while maintaining a static position. There is also a paucity of data detailing the real relative motion between the back and lower limb during gait, an important consideration when testing the Nottingham 'flag-pole' hypothesis for spinal curvature generation. Research into the use of opto-electronic gait analysis systems to measure dynamic back movements has shown the capability of these systems in producing repeatable patterns of back movements. While using a motion analysis system, if a relationship between the spinal movement and lower limb kinematics could be established, such a relationship would provide a new opportunity for range of movement studies in conditions like scoliosis. Furthermore, establishing such a relationship would allow investigation into the influence of one segment over another during locomotion. This present study has examined the movement of markers placed on the back and pelvis, used in three-dimensional opto-electronic systems for gait studies, in relation to the markers placed on the lower limbs. The results of a pilot study have highlighted relative movements between various segments in simple tasks like flexion, lateral bending and negotiating steps, which have implications for spinal deformity generation. The findings also demonstrate the points to be considered in order to define dynamic trunk and spinal movement. Further ongoing studies are being undertaken to validate the findings.

Study of marker placements in the back for opto-electronic motion analysis.

Various investigations into anatomical landmarks that could be employed in spine and back surface measurement have highlighted the usefulness of the spinous processes of the vertebra and the posterior superior iliac spines of the pelvis. Earlier studies used an opto-electronic gait analysis system to examine the motion of skin markers and compared results with similar inter-vertebral movement recorded through radiographs. Consistent patterns of movement suggested a relationship between spinal and back surface motion. Further investigations into the use of opto-electronic gait analysis systems to measure dynamic back movements showed the capability of producing repeatable patterns of back movements. However, these studies, mainly measuring the range of movement (ROM) of spine, have not examined the effects of marker placements. While most ROM studies concentrate on stationary repetitive flexion/extension and bending movements, spinal ROM during walking and in scoliosis has not been widely reported. Spinal range of motion is an important indicator of spinal function and is used in the determination of disability and compensation. The present study has evaluated the placement of markers on the back and pelvis, used in three-dimensional opto-electronic systems for gait and movement studies. Various marker configurations have been compared and reported. The findings highlight the drawbacks of previously reported techniques, and particularly indicate that skin movement can adversely affect findings. However, the results confirm the feasibility of application of this technique to investigate dynamic trunk and spinal movement in both normal and deformed spines.

Rotation of the atlantico-axial joint, investigated using CT and MRI.

The vertebral column is composed of a series of joints, each capable of a specific range of movement. To investigate these movements, a study into the physiological range of rotation at the atlanto-axial joint has been undertaken. The movements and their interpretation under imaging conditions are crucial if any underlying spinal deformity or the consequences of trauma are present in an individual. 28 healthy volunteers were examined using dynamic Magnetic Resonance Imaging with maximum head rotation to the right and left sides in turn. An anatomical specimen of the atlanto-occipital joint was imaged using Computed Tomography with the specimen fixed in varying degrees of rotation. The results indicate that there is a significant but incomplete loss of contact between the articular surfaces of C1 (atlas) and C2 (axis). The range of motion to the right was between 20 and 48.5 degrees (mean 32.4 degrees) and to the left was between 13 and 52.75 degrees (mean 3.2 degrees). Statistical significance between left and right movement was not demonstrated. The instantaneous axis of rotation was examined for the joint and was found to be located within the odontoid peg (dens). These findings indicated that a wide range of movement occurs within the atlanto-axial joint in normal subjects. Furthermore, the appearances under imaging could be misinterpreted as a pathological subluxation. This has implications if the subject with a spinal deformity also has a dysplasia associated with a potential subluxation. The siting of the instantaneous axis of rotation within the odontoid is also important in furthering the understanding of the movement of this joint.

Body mass index in relation to truncal asymmetry of healthy adolescents, a physiopathogenetic concept in common with idiopathic scoliosis: summary of an electronic focus group debate of the IBSE.

There is no generally accepted scientific theory for the cause of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE).introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr TB Grivas. It is based on published research from Athens, Greece evaluating schoolchildren age 11-17 years for the relation of body mass index (BMI) to each of truncal asymmetry (TA) and menarcheal status. Girls with relatively lower BMI were found to have a significant excess of severe TAs and significantly later menarche confirming the well-known relation of BMI to menarche. Together with other evidence linking nutritional status to skeletal growth, the observations suggest energy balance via the hypothalamus is related to trunk asymmetry. As with a recent speculative hypothesis for the pathogenesis of AIS in girls, Grivas et al. suggest that the severe TAs involve a genetically-determined selectively increased sensitivity (up-regulation) of the hypothalamus to circulating leptin with asymmetry as an adverse response to stress (hormesis). The TA is expressed bilaterally via the sympathetic nervous system to produce left-right asymmetry in ribs and/or vertebrae leading to severe TAs when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion in the trunk. This EFG discusses the findings and interpretations of the paper by Grivas and colleagues as research at the borderland between the genesis of TA (physiogenesis) and AIS (pathogenesis). It is suggested that TAs, here regarded in common with AIS, result from the combination of secondary sexual development affecting body composition, adolescent skeletal growth velocity, and an asymmetry process. The possible involvement of epigenetic factors is not considered.

Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis? Incorporating presentations on scoliogeny at the 2012 IRSSD and SRS meetings.

This paper aims to integrate into current understanding of AIS causation, etiopathogenetic information presented at two Meetings during 2012 namely, the International Research Society of Spinal Deformities (IRSSD) and the Scoliosis Research Society (SRS). The ultimate hope is to prevent the occurrence or progression of the spinal deformity of AIS with non-invasive treatment, possibly medical. This might be attained by personalised polymechanistic preventive therapy targeting the appropriate etiology and/or etiopathogenetic pathways, to avoid fusion and maintain spinal mobility. Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy.

Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis.

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy.

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.

The International Research Society of Spinal Deformities (IRSSD) and its contribution to science.

From the time of its initial, informal meetings starting in 1980 to its formal creation in 1990, the IRSSD has met on a bi-annual basis to discuss all aspects of the spine and associated deformities. It has encouraged open discussion on all topics and, in particular, has tried to be the seed-bed for new ideas. The members are spread around the world and include people from all areas of academia as well as the most important people, the patients themselves. Most notably, application of the ideas and results of the research has always been at the forefront of the discussions. This paper was conceived with the idea of evaluating the impact made by the IRSSD over the last 30 years in the various areas and is intended to create discussion for the upcoming meeting in Montreal regarding future focus: "We are lost over the Atlantic Ocean but we are making good time."

Assessment of the centre of pressure pattern and moments about S2 in scoliotic subjects during normal walking.

BACKGROUND CONTEXT: Research employing gait measurements indicate asymmetries in ground reaction forces and suggest relationships between these asymmetries, neurological dysfunction and spinal deformity. Although, studies have documented the use of centre of pressure (CoP) and net joint moments in gait assessment and have assessed centre of mass (CoM)-CoP distance relationships in clinical conditions, there is a paucity of information relating to the moments about CoM. It is commonly considered that CoM is situated around S2 vertebra in normal upright posture and hence this study uses S2 vertebral prominence as reference point relative to CoM. PURPOSE: To assess and establish asymmetry in the CoP pattern and moments about S2 vertebral prominence during level walking and its relationship to spinal deformity in adolescents with scoliosis. PATIENT SAMPLE: Nine Adolescent Idiopathic Scoliosis subjects (8 females and 1 male with varying curve magnitudes and laterality) scheduled for surgery within 2-3 days after data collection, took part in this study. OUTCOME MEASURES: Kinetic and Kinematic Gait assessment was performed with an aim to estimate the CoP displacement and the moments generated by the ground reaction force about the S2 vertebral prominence during left and right stance during normal walking. METHODS: The study employed a strain gauge force platform to estimate the medio-lateral and anterior-posterior displacement of COP and a six camera motion analysis system to track the reflective markers to assess the kinematics. The data were recorded simultaneously. RESULTS: Results indicate wide variations in the medio lateral direction CoP, which could be related to the laterality of both the main and compensation curves. This variation is not evident in the anterior-posterior direction. Similar results were recorded for moments about S2 vertebral prominence. Subjects with higher left compensation curve had greater displacement to the left. CONCLUSION: Although further longitudinal studies are needed, results indicate that the variables identified in this study are applicable to initial screening and surgical evaluation of scoliosis.

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

Biomechanical spinal growth modulation and progressive adolescent scoliosis--a test of the 'vicious cycle' pathogenetic hypothesis: summary of an electronic focus group debate of the IBSE.

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention.

The classification of spinal deformities.

Any methods of classification of scoliosis deformity devised should recognise different aetiological and pathological causes of the conditions and their likely impact on the natural history of the spinal curvature. Such classification should aim to aid clinicians in their approach to treatment. Furthermore, any such system must have a high reliability and validity. Several approaches have been reported. Pathological classifications have been devised which relate to the system or tissue affected by the underlying pathology, such as congenital anomalies which affect the skeletal elements of the spine, general neurological problems or muscular disorders. Classification by age of onset has also been adopted, using criteria such as infancy or adolescence. However, most attention has been focussed on structural features of the spine in developing anatomical classifications. Features such as the apex or magnitude of a curvature or its rotation are important clinical signs and are widely used in surgical practice. This paper reviews the different classification reported but make no attempt to justify one as being ideal. However, since the biological processes contributing to the deformity and its subsequent natural history are still unclear, it remains difficult to develop a fully reliable and all embracing system of classification.

The atlanto-axial joint: physiological range of rotation on MRI and CT.

AIMS: To measure the range of rotation and determine the instantaneous axis of rotation of the atlanto-axial joint in healthy volunteers using magnetic resonance imaging (MRI) and to highlight the appearances of the rotated atlanto-axial joint on computed tomography (CT) and MRI. MATERIALS AND METHODS: Twenty-eight healthy volunteers were examined using MRI during maximal head rotation. In addition, an anatomical specimen of the atlanto-axial joint, fixed in varying degrees of rotation, was imaged using CT. RESULTS: At the extremes of physiological rotation in healthy subjects there is striking but incomplete loss of contact between the articular surfaces of the atlas (C1) and the axis (C2). The range of rotation to the right was 20-48.5 degrees (mean 32.4 degrees ) and to the left was 13-52.75 degrees (mean 34.2 degrees ). There was no significant difference between rotation to the right and left (P = 0.455). Total rotation was 45-88.5 degrees (mean 69.25 degrees ). The instantaneous axis of rotation was located within the odontoid peg. CONCLUSION: There is a wide range of atlanto-axial rotation in normal subjects. The instantaneous axis of rotation lies within the odontoid peg. The appearances of the rotated atlanto-axial joint are striking and may be misinterpreted as subluxation.