Ebook: Research into Spinal Deformities 5
This publication covers many different fields of research from genetics and molecular biology to surgical treatment. During the last decade the field of research has widened and new research groups have emerged, reflecting the changes in the world’s economical and political scene. In this context, globalization definitely has a positive meaning. Our understanding of the mechanisms leading to spinal deformity is improving, but further research into all fields concerned is mandatory. This book reflects our current knowledge and is intended for readers with a scientific, critical and open mind. It serves as a basis for future research and as a source of discussion. Research into Spinal Deformities 5 contains papers on the following subjects: Genetics; Etiology and Pathogenesis; Biomechanics & Imaging; Conservative Treatment; Surgical Treatment; and Quality of Life.
The 6th Biennial Meeting of the International Research Society of Spinal Deformities was held on 21–24 June 2006 at “Het Pand” in Ghent, Belgium.
More than 140 papers and posters were presented, covering many different fields of research from genetics and molecular biology to surgical treatment. During the last decade the field of research has widened and new research groups have emerged, reflecting the changes in the world's economical and political scene. In this context globalisation definitely has a positive meaning.
Progress has been made, but the goals of our Society have not been reached yet.
Our understanding of the mechanisms leading to spinal deformity is improving, but further research into all fields concerned is mandatory.
This book reflects our current knowledge and is intended for readers with a scientific, critical and open mind. It will serve as a basis for future research and as a source of discussion. The content of the papers is each individual author's responsibility.
It has been an honour to be your host in Ghent and to act as your editor.
This would have been impossible without the enormous help of my co-editor, our secretary for life, Peter Dangerfield. As a native speaker, he had the immense task of putting all the papers into proper English, for which we owe him very much.
Lieve Ectors and Luc Niville from King Conventions did an exemplary job and if we reached all the deadlines, it is thanks to them.
Publishing this book would have been impossible without the assistance of our sponsors.
We are greatly indebted to DePuy Spine, Spine Vision, Stryker and Medtronic.
May your stay in Ghent have been an enjoyable one and an inspiration for future work.
Gent, 15 June 2006
Dirk Uyttendaele, MD, PhD
Many studies have demonstrated the role of melatonin in the etiology of AIS. Previous studies have shown that there is no evidence of mutations in the melatonin receptor 1A gene in AIS patients. In this study, we have examined the role of melatonin receptor 1B in predisposition for AIS. Using haplotype block tagging technique, a set of tagging SNPs were defined for MTNR1B from the Han Chinese data of the International HapMap project. The association between the tagging of single nucleotide polymorphisms (tSNPs) in MTNR1B region and the occurrence of AIS was studied. Method: 473 AIS girls and 311 normal controls were recruited. The age range of the patients was between 10 and 18 years old. The maximum Cobb was recorded at latest follow-up in AIS patients. Three of five tSNPs were studied; they were all located within the coding region of the MTNR1B gene. Results: There was no significant difference in the genotype or allelic frequencies (AF) of the 3 tSNPs between AIS and controls. In a case-only analysis, no difference in curve severity in AIS patients was found among patients with different genotypes (by one-way ANOVA). Discussion: The 3 tSNPs showed no association with either the occurrence of AIS or the maximum Cobb angle within AIS girls. Further analysis of the remaining tSNPs within the regulatory region of the MTNR1B gene and other related genes in the melatonin signaling pathway may provide further information on the role of the melatonin in AIS girls.
We studied the relationship between cytogenetic abnormalities in buccal epithelial cells and metabolic shifts in children with scoliosis and kyphosis. The incidence of nucleus abnormalities and the corresponding metabolic shifts were found to depend on the presence of spinal deformities and ecological factors. The problem of formation of risk groups for spinal deformities in ecologically unfavorable regions is discussed.
A pathogenetic mechanism of the idiopathic scoliosis (IS) has been established on the basis of in-depth morphological and biochemical investigations of structural components of the spine in patients with IS (surgical material). We have shown that IS develops on the basis of disturbance of proteoglycans (PG) synthesis and formation in vertebral growth plates. The found keratan sulphate-related fraction is likely a marker of genetic changes in PGs in IS. Long-term our studies demonstrated a major-gene effect in IS. The study has shown that aggrecan gene expression is significantly decreased in cultivated chondroblasts from patients with IS. The presence of keratan sulphate-related fraction and keratan sulphate increase are associated with luminicene increase.
IGF-I has a pivotal role in bone growth and could be one of the putative disease-modifier genes in AIS. Two SNPs in IGF-I gene promoter region were studied for any association with occurrence of AIS and for their effect on the curve severity among AIS. Methods: 506 AIS girls (Cobb>20°) and 227 age-matched Chinese girls were recruited. The spine (L2-L4) and hip BMD of the subjects were measured by DXA. A subgroup of AIS patients (N=340) who were followed-up to skeletal maturity and the maximum Cobb's angle was recorded. Two SNPs were genotyped by PCR-RFLP (rs5742612 and rs2288377). The chi-square test and one-way ANOVA were used to test the association between genotypes and quantitative parameters, respectively. Results: No association was between the genotypes and the occurrence of AIS and the BMD of the spine and hip. The allelic frequency of T allele was 0.69 in AIS and control. However, the Cobb's angle was higher in patients with the homozygous T allele (Mean Cobb's angle: 38.1° in TT vs 35.9° in TC vs 33.2° in CC group; p=0.04). Discussion: Interestingly, IGF-I polymorphism affects the curve severity of AIS though it was not associated with onset of AIS per se. It indicates that IGF-I may be a disease modifying gene. The importance of IGF-I in skeletal growth makes it a good candidate gene which would play a role in the documented association of rapid growth with curve progression in AIS.
With the use of multiplanar reformat Magnetic Resonance imaging, AIS patients were found to have significantly reduced pedicle widths on concavity. Pattern of vertebral asymmetry was also exaggerated with smaller pedicle width, length and area on concavity. The cord appeared more roundish and was deviated to the concavity at apical vertebra in AIS. A tethering force might therefore be present on the cord along the transverse axis in AIS, accounted by the relatively fixed position of the exit nerve roots and deviation of the cord from the exit foraminae of the corresponding vertebra.
The article provides basic explanation of “syndrome of contractures” (Mau) at newborns and babies and it's conjunction with biomechanical etiology of the so-called idiopathic scoliosis (Karski 1995-2006). The authors analyzed children with “syndrome of contractures” and noted its relevance to some clinical symptoms at children with scoliosis. Newborns and babies with clinical signs of “syndrome of contractures” require further spine examination already at age of 3-4 in order to detect “danger of oncoming scoliosis” and to introduce neo-prophylaxis. The research based on “syndrome of contractures” can explain predominance of female gender of patients with scoliosis, sides of curves, side of rib hump, progression and sensibility to new rehabilitation exercises.
This study investigated how an adolescent idiopathic scoliosis progresses with time. 154 consecutive measurements from 26 consecutive AIS patients were analyzed. Each subject had at least four successive scans at six-month intervals.
Progression patterns of Cobb angle and apex lateral deviation were extracted from 34 serial data sets of the most common AIS type RT-LL, in the format of four serial data sets, by using the fuzzy c-means clustering technique. Progression of spinal deformity was predicted with previous serial data of Cobb angle and apex lateral deviation by using a GCV extrapolating technique alone and in conjunction with progression patterns.
Our results showed that scoliotic progression appears to follow progression patterns. Progression of spinal deformity has potential to be accurately predicted with previous serial spinal deformities by using GCV extrapolating technique with assistance of progression patterns.
The aim of this study was to monitor BMD changes occurring during periods of rapid growth and to investigate whether osteopenia was a persistent phenomenon in skeletally matured AIS girls. 196 AIS Chinese girls and 122 healthy controls, aged 11-16, were follow-up for 3.5 years. Bilateral femoral neck bone mineral density (BMD) and volumetric BMD (vBMD) of the distal tibia were obtained by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Osteopenia was defined if the age-adjusted BMD was below or equal to –1 standard deviation (SD). The average age at the final follow-up was 16.8 years old. The median initial Cobb angle for this group of patients was 26°. The prevalence of osteopenia at the baseline measurement was 35.9%. Longitudinal BMD results demonstrated that 86.0% of osteopenic AIS girls had persistently low BMD at the time of skeletal maturity (age of 16). vBMD of distal tibia of AIS was significantly lower than that of the controls throughout the age of 13 to 17 during the period of rapid growth. In addition, there were also significant differences in vBMD among AIS (moderate and severe group) and the controls by one-way ANOVA (p<0.05). The present study for the first time revealed that over 86% of osteopenic AIS patients had persistently low BMD, at both distal tibia and femoral neck regions, at the time of skeletal maturity. Early detection and treatment of AIS-related osteopenia might help in maximizing peak bone mass during peripubertal growth that thereby minimizing risks of developing osteoporotic fractures later in life.
Whether visual impairment influences the prevalence of scoliosis in humans or not remains controversial. The purpose of this study was to assess the prevalence of scoliosis in blind women in a Mediterranean region.
Material and Method: A total of 26 blind women aged 40 years (median, range 20 – 67) were screened for scoliosis. The existence of a possible trunk hump was measured by the forward bending test using the Pruijis Scoliometer. Reading of an Angle of Trunk Inclination (ATI) greater or equal to 7 degrees was used as a cut-off criterion for radiological examination. Standing postero-anterior and lateral spinal radiographs were obtained. Menarche and circadian rhythm was recorded.
Results: 11 out of 26 women had a scoliosis with an average Cobb angle of 19 degrees (range 12 – 28). The average ATI was 8 degrees. Thoracolumbar was the most common type of curve identified (9 out of 11, 6 were to the right and 3 to the left). The median age of menarche was 13 years (range, 11 – 15). None of the blind women reported any difficulty sleeping and had a circadian rhythm related to a 24-hour day.
Discussion: The prevalence of scoliosis was 42.3%, while the prevalence in the general population in the same regime is 2.9%. Blind women had a later age of menarche (13 versus 12.58 yrs) compared with normal girls. The postural etiology of scoliosis in blind people has been reported. The possible role of light in association to melatonin production, age at menarche and high prevalence of scoliosis in blind women is presented and discussed.
Extra-spinal skeletal length asymmetry have been reported for the upper limbs and periapical ribs of patients with thoracic adolescent idiopathic scoliosis. This paper reports (1) a third pattern with relative lengthening of the ilium on the concavity of lower spine scolioses, and (2) a fourth pattern of relative lengthening of the right total leg and right tibia unrelated statistically to the severity or side of lower spinal scolioses. The findings pose the question: are these anomalous extra-spinal left-right skeletal length asymmetries unconnected with the pathogenesis of AIS. Or, are they indicative of what may also be happening to some vertebral physes as an initiating pathogenic mechanism for the scoliosis?
Left-right skeletal length asymmetries in upper limbs related to curve side and severity have been detected with adolescent idiopathic scoliosis (AIS). This paper reports upper arm length asymmetry in thoracic scoliosis related significantly to apical vertebral rotation in school screening referrals. The reason(s) for the association of upper arm length asymmetry with apical vertebral rotation is unknown and three factors are considered: (1) neuromuscular mechanisms from primary or secondary causes, (2) relative concave neurocentral synchondrosis overgrowth, and (3) relative concave periapical rib length overgrowth, A putative anomaly of growth plates (physes) of ribs, neurocentral synchondroses and upper arms, would account for the findings. A solution to this dilemma may emerge from the results of surgery should concave periapical rib resections become evaluated further for right thoracic AIS in girls.
Several workers consider that the etiology of adolescent idiopathic scoliosis (AIS) involves undetected neuromuscular dysfunction. During normal development the central nervous system (CNS) has to adapt to the rapidly growing skeleton of adolescence, and in AIS to developing spinal asymmetry from whatever cause. Examination of evidence from (1) anomalous extra-spinal left-right skeletal length asymmetries, (2) growth velocity and curve progression, and (3) the CNS body schema, parietal lobe and temporoparietal junction, led us to propose a new etiologic concept namely of delay in maturation of the CNS body schema during adolescence. In particular, the development of an early AIS deformity at a time of rapid spinal growth the association of CNS maturational delay results in the CNS attempting to balance a lateral spinal deformity in a moving upright trunk that is larger than the information on personal space (self) already established in the brain by that time of development. It is postulated that the CNS maturational delay allows scoliosis curve progression to occur - unless the delay is temporary when curve progression would cease. The putative maturational delay in the CNS body schema may arise (1) from impaired sensory input: (2) primarily in the brain; and/or (3) from impaired motor output. Oxidative stress with lipid peroxidation in the nervous system may be involved in some patients. The concept brings together many findings relating AIS to the nervous and musculo-skeletal systems and suggests brain morphometric studies in subjects with progressive AIS.
The aim of the present study is to investigate whether the deformation of the intervertebral disc contributes to the progression of idiopathic scoliotic curves. In the standing posteroanterior x-rays of 92 scoliotic curves the following readings were obtained: Cobb angle (CA), apical vertebral rotation (AVR), apical vertebral wedging (AVW) and the adjacent to the apical vertebra Upper (UIVDW) and Lower (LIVDW) InterVertebral Discs Wedging. The statistical analyses included inter - intraobserver reliability test, descriptives, monofactorial linear regression and Pearson correlation coefficient, with p<0.05 considered statistical significant (SS).
The mean thoracic CA was 13.4°, lumbar CA 13.8°, thoracic AVR 5.3°, lumbar AVR 4.7°, thoracic AVW 1.4°, lumbar AVW 1.5°, thoracic UIVDW 1.6°, thoracic LIVDW 1°, lumbar UIVDW 1.3° and lumbar LIVDW 2°. Both thoracic and lumbar CA regressed SS with lumbar LIVDW, lumbar UIVDW, thoracic LIVDW and thoracic AVW. Lumbar LIVDW correlates SS with thoracic CA, lumbar CA and thoracic LIVDW. An inter and intra-observer error was below 1°.
The eccentric intervertebral disc in the scoliotic spine, through variation in its water concentration produces asymmetrically cyclical load during the 24-hour period and an asymmetrical growth of the vertebral body (Hueter-Volkman's law). The statistical analysis revealed that AVW appears later when already CA increases, the IVDW is more important than AVW and the LIVDW, which is greater than UIVDW, is the most frequent correlated radiographic parameter.
The deformation of the apical intervertebral disc seems to be an important contributory factor in the progression of a scoliotic curve.
Adolescent Idiopathic Scoliosis (AIS) prevalence has been reported to be different in various geographic latitudes and demonstrates higher values in northern countries. A study on epidemiological reports from the literature was conducted to record the prevalence of AIS among the general population of boys and girls, aged 10-16 years old, in different geographic latitudes, in order to test the hypothesis that the prevalence of AIS among boys and girls is different in various geographic latitudes and to examine if there is a possible association between them. Seventeen peer-reviewed published papers reporting AIS prevalence in the general population of boys and girls from most geographic areas of the northern hemisphere were retrieved from the literature. The geographic latitude of each centre where a particular study was originated was documented. The statistical analysis included a linear regression forward modeling procedure of the AIS prevalence by latitude, weighted by sample size.
According to the modelling of the data, a significant positive association between prevalence of AIS and latitude was found for girls (p<0.001), following a rather curvilinear trend, but not a significant positive association was found for boys (p<0.111).
A positive association between prevalence of AIS and geographic latitude is reported only for girls in the present study. Prevalence of AIS in boys is not associated significantly with geographic latitude. This differing significant association implicates the possible role of environmental factors in the pathogenesis of AIS that may act in a different way between boys and girls.
Thoracic hypokyphosis with increasing axial rotational instability is claimed to be a primary factor for the initiation of Idiopathic Scoliosis (IS) according to some authors. The objective of this study was to compare the sagittal configuration of the spine in two groups of girls with and without scoliosis in order to determine whether thoracic hypokyphosis and/or lumbar hypolordosis are initiating factors for AIS or not. A group of 207 consecutive non-treated girls diagnosed with IS (12.7 y ± 1.8) measured with the Formetric® system were compared to a control group of 45 non-scoliotic girls of the same age (12.4 y ± 2). The Cobb angle for the whole scoliosis sample was 26°± 13.6 and the angle of axial rotation 12.4°± 7.7 (Perdriolle). The patient group was divided into subgroups by their Cobb angle ie G1 (5°-19°, n=79), G2 (20°-34°, n=81), G3 (≤35°, n=47). The values of the kyphotic angle and lordotic angle were compared. The kyphotic angle was not significantly different in the patients group (48.7° ± 9.4) compared to the control group (51.5° ± 10) while the lordotic angle was slightly but significantly lower in the patient group (39.3° ± 9.4) than in control (42.3° ± 8.8); however, the lordotic angle in G1 (40.5° ± 8.3) was not lower than that of the controls. Non-scoliotic girls and those with a mild scoliotic curve had the same angle of thoracic kyphosis and lumbar lordosis. Both angles tended to decrease in progressive curves. Neither thoracic hypokyphosis or lumbar hypolordosis are considered to be initiating factors for scoliosis but are factors in its progression.
For future research of predictors of AIS, it would be advantageous to identify a general population in which the development of AIS is greatly increased when compared to the normal population. The probability of predicting future development of AIS among younger relatives of current patients based on the probability of AIS incidence was assessed from the research literature. Although there is considerable literature relating to familial relationships of the probability of developing AIS or having AIS, the probability is relatively low in most cases. Even with the best of predicted probabilities, the identification of patients with a high probability of developing AIS remained low. The identification of people among the general population who have a high probability of developing AIS based on the probabilities expressed in the literature is not possible.
Anomalous extra-spinal left-right skeletal length asymmetries have been detected in girls with adolescent idiopathic (AIS) in four sites (1) upper limbs, (2) periapical ribs, (3) ilium, and (4) right leg and right tibia. This paper on adolescent girls with lower spine scoliosis reports (1) a fifth pattern of left-right ilio-femoral length asymmetry associated with sacral alar height asymmetry, and (2) bilateral anomalous lengthening of the tibia relative to the foot. The findings are consistent with the hypothesis that at the time of diagnosis of AIS in girls there are anomalies of skeletal proportions associated with a predisposition to curve progression; these proportions are in three dimensions - left-right, cephalo-caudal in the trunk (proximo-distal in the lower limbs), and front-back in the trunk. The origin of these anomalies is unknown but possible causes, and of the associated AIS, are genetic and environmental factors acting in embryonic life not expressed phenotypically until years after birth.
In order to explore the concept that scoliosis is fundamentally a loss of left-right symmetry. surface topography was used to measure asymmetry in three dimensions at three levels on the back surface. Statistical analysis of prospectively collected topographic, radiographic and clinical data, in girls with adolescent idiopathic scoliosis, was carried out and comparisons were made with theoretically perfect symmetry (test value of zero). All scoliosis showed statistically significant differences in coronal dimensions, index points on the convex side of the scoliosis being further from the mid-line than those on the concave side. Primary thoracic scoliosis differed from thoracolumbar and lumbar in that they showed directional asymmetry at all levels and in all directions, the side of the scoliosis convexity being broader, taller and thicker. This asymmetry is not due to posture, spinal balance or trunk rotation, as left and right sides are being compared independently of their orientation in space. The asymmetry is of size in three dimensions and size is determined by growth. Growth is a three dimensional process, but does not necessarily occur equally in all three. Differential growth is both directional and regional, particularly during the pubertal growth spurt, when proportions change substantially, and is controlled by many genes, as well as by hormones and signalling molecules. The implication is that scoliotic deformity is the result of asymmetric growth, not confined to the vertebrae, but affecting the entire trunk. This is a developmental, rather than pathological, phenomenon. It makes questions of aetiology redundant and natural history logical.
To test the denervation of paraspinal muscles and further investigate the pathogenesis of scoliosis associated with syringomyelia via detecting the spread of acetylcholine receptor (AChR) beyond the confines of the functional neuromuscular junction. Patients were divided into three groups: Group A consisted of 25 patients with scoliosis associated with syringomyelia, Group B included 16 adolescents with idiopathic scoliosis, and Group C comprised 10 cases without scoliosis. Bilateral biopsy of paraspinal muscles was performed during scheduled spinal surgery. Histological evaluation used a double-stain immunofluorescence technique for AchR and acetylcholinesterase. Histological analysis showed that 14 of 25 patients in Group A scored positive for the presence of AchR outside of the neuromuscular junction. There was no significant difference of the positive rate between patients with different degrees of cerebellar tonsillar descent, between patients with distended and non-distended syrinx, with syringx length ≤10 vertebral bodies and >10 vertebral bodies, and with Cobb angle ≤45° and >45° (p>0.05). The denervation of paraspinal muscles is present in some patients with scoliosis associated with syringomyelia, suggesting that scoliosis may be caused by a strength imbalance of paraspinal muscles in these patients.
Objective: To find the possible roles of collagen in the pathogenesis of AIS through studies of the distribution of the collagen I and II in the disc annulus fibrous in adolescent idiopathic scoliosis (AIS). Methods: The disc annulus fibrous of apex curve were harvested during anterior surgery and divided into concave and convex samples. 25 AIS cases were covered in this study including 6 males and 19 females, with an average age of 14.6 years (range 12–18years). 11 specimens were intervertebral disc from the thoracic region (from T8 to T11) and 14 sample were from lumbar discs (from L1 to L2). RT-PCR was employed to investigate the distribution and content of collagen I (220bp) and collagen II (359bp) in the intervertebral disc specimens. 1% agarose gel electrophoresis and the Gelwork image analysis system was used in the semi-quantitative analysis of the product. Results: For the AIS group, type I collagen and type II collagen significantly increased on convex side compared with that of the concave side (p<0.01). The same trend was observed in both thoracic and lumber disc annulus fibrosis, but there was no statistical difference expect for the expression of type II collagen in convex side of disc annulus fibrous (p<0.05). Conclusion: The asymmetric expression of collagen I and II collagen showing that there was degeneration in the intervertebral disc of AIS. The abnormal collagen metabolism may be one of reasons in the development of AIS and probably an important factor in the progression of AIS.
To investigate the change of melatonin receptor mRNA expression in bilateral paravertebral muscles in AIS, congenital scoliosis (CS) and controls in order to analyze its relationship to the pathogenesis of AIS. 20 cases with average age of 15.1 ± 2.2 years and average Cobb angle of 56.2° ± 16.1° were included in AIS group. 12 cases with average age of 11.6 ± 3.2 years and average Cobb angle of 59.2° ± 33.3° were included in congenital scoliosis (CS) group. 10 cases without scoliosis comprised a control group. The mRNA expression of melatonin receptor subtype MT1 and MT2 were detected by RT-PCR method. The MT2 mRNA expression on the concave side of paravertebral muscle was higher than that on the convex side in AIS and CS groups (p<0.05), but the MT1 mRNA expression showed no significant difference. In the AIS group, the ratio of MT2 mRNA expression on the concave side compared with the convex side in cases with a Cobb angle less than 50° and cases with a Cobb angle greater than 50° showed no significant difference. The melatonin receptor expression in bilateral paravertebral muscles in AIS is asymmetric, which may be a secondary change.
To investigate the pathogenesis, clinical manifestation and treatment of the adolescent scar contracture scoliosis caused by back scalding during infancy. From August 1997 to May 2005, about 1300 patients with scoliosis received surgery in our department. Only four of them were diagnosed with adolescent scar contracture scoliosis. One patient was first treated with skin expansion, back scar excision, and skin flap transfer, followed with anterior correction with TSRH instrumentation. Two patients were first treated with back scar excision and anterior spinal release, then treated with posterior correction with TSRH instrumentation; thoracoplasty was performed after 50 days in halo-wheelchair traction. The other patient was treated with posterior correction with TSRH instrumentation. No management of scalding was performed on the fourth patient. Anterior release and posterior correction were performed at intervals of 3 weeks. The deformities of four patients were well corrected. The trunk balance was restored and the pelvis leveled. The skin incision wounds healed well. Minor loss of correction was recorded during the last follow-up.