Morphometry of the synovial folds of the lateral atlanto-axial joints: the anatomical basis for understanding their potential role in neck pain.

PURPOSE: Intra-articular synovial folds of the cervical spine are considered to be a potential source of neck pain and disability. The purpose of the present study was to devise and validate a method to determine the normal morphometry of the synovial folds as a basis for understanding their functional and clinical significance. METHODS: Nine cadaver cervical spines were sectioned in the sagittal plane. The presence of the synovial folds at the lateral atlanto-axial joints was determined and their morphology described. Depth of projection, cross-sectional area and volume of the ventral and dorsal synovial folds of the right and left lateral atlanto-axial joints were measured from sagittal sections and compared. The relationship between synovial fold dimensions and subject age and cartilage degeneration were determined. Repeat measurements were made for the calculation of method reliability, and the water displacement method was used to determine method validity. RESULTS: There was a trend for ventral synovial folds to be larger than dorsal synovial folds. There was no correlation between synovial fold dimensions and age and extent of cartilage degeneration. Measurement reliability ranged from intraclass correlation coefficient 0.95-1.00 (intra-observer), 0.95-1.00 (test-retest) and 0.61-1.00 (inter-observer). Limits of agreement for the sectional and water displacement methods for the measurement of synovial fold volume were -1.04 ± 3.35 mm(3). CONCLUSIONS: A reliable method for quantifying synovial fold dimensions was devised. The results of this study provide a basis for the determination and diagnosis of pathologies affecting the synovial folds.

Synovial folds - a pain in the neck?

The synovial folds of the cervical spine are regarded as a potential source of neck pain and headache, especially following whiplash injury. Damage to the synovial folds following motor vehicle trauma has been well documented in post-mortem studies. However, methods of identifying injury to the synovial folds in the survivors of motor vehicle trauma have proven elusive to date. Recently, it has been made possible to image the synovial folds in vivo using magnetic resonance imaging. This now makes it feasible to investigate the potential involvement of synovial folds in the generation of neck pain and headache and its relief using spinal manipulation. This paper reviews critically the morphology of the synovial folds of the cervical spine that underpins the hypotheses proposed to explain their functional and clinical significance and a new system of naming and classifying the synovial folds is presented. Although there is some evidence to support the contribution of the synovial folds to neck pain, several theories have little or no support and require investigation and further evaluation. These findings have implications for understanding the anatomical basis of neck pain and headache and the rationale for the use of spinal manipulation in their management.

The influence of age, anthropometrics and range of motion on the morphometry of the synovial folds of the lateral atlanto-axial joints: a pilot study.

The purpose of this study was to investigate the effect of age, anthropometrics and cervical range of motion upon synovial fold volume. Ten healthy female subjects aged 20-40 years were included in the study. Age, height, body mass, dimensions of the head and neck and cervical range of motion of each subject were measured. Magnetic resonance (MR) images of the cervical spine were acquired; the volume of the ventral and dorsal synovial folds of the right and the left lateral atlanto-axial joints was measured using seed growing and thresholding methods. Using Spearman's correlation coefficient, it was determined that there was no correlation between synovial fold volume and age. Synovial fold volume was positively correlated with subject height and neck length but negatively correlated with body mass, body mass index and the circumference of the head and neck. The relationship between synovial fold volume and range of cervical motion varied with the plane of movement. The ability to image the synovial folds of the lateral atlanto-axial joints using MR imaging to determine their normal morphology provides the basis for investigating synovial fold pathology in patients with neck pain and headache.

MeltMADGE for mutation scanning of specific genes in population studies.

MeltMADGE reconfigures the mutation scanning process of denaturing gradient gel electrophoresis so that the independent variable is time rather than space and the dependent (denaturing) variable is temperature rather than concentration of chemical denaturant. Use of a thermal ramp enables the use of a homogeneous gel and therefore of high-density arrays of wells such as those of microplate array diagonal gel electrophoresis (MADGE). In this configuration, electrophoresis of products on 10-12 96-well meltMADGE gels can be conducted in a 1- to 2-liter tank in a 1- to 2-h run, enabling the scanning of a target amplicon in over 1,000 subjects simultaneously. Gels are read by imaging the fluorescence of UV-excited ethidium bromide, giving a simple, economical system for identifying rarer sequence variants in target genes; it is suitable for large-scale case-control or population studies and other comparable applications. Different amplicons with similar melting characteristics can also be combined in the same run.

Synovial folds of the lateral atlantoaxial joints: in vivo quantitative assessment using magnetic resonance imaging in healthy volunteers.

STUDY DESIGN: Analysis of magnetic resonance (MR) images of healthy volunteers. OBJECTIVE: To develop and validate an imaging protocol and measurement technique to describe the morphology and quantify the dimensions of the synovial folds of the lateral atlantoaxial joints in vivo. SUMMARY OF BACKGROUND DATA: The synovial folds of the lateral atlantoaxial joints are considered to be a potential source of neck pain and headache, especially following whiplash injury. Until recently, it has not been possible to image the synovial folds in vivo and consequently their normal morphology is not fully understood. METHODS: MR images of the cervical spine of 17 volunteers (4 male and 13 female) were acquired using a 1.5-tesla scanner. The morphology of the synovial folds at the lateral atlantoaxial joints was described and their presence determined. The volume and cross-sectional area of the ventral and dorsal synovial folds of the right and left lateral atlantoaxial joints were measured and compared. The relationship between the dimensions of the synovial folds and subject age was examined. Twenty synovial folds were measured twice by one observer and once by a second observer for the determination of measurement reliability. RESULTS: There was a significant difference in volume (chi [3] = 17.54, P = 0.000) and cross-sectional area (chi [3] = 18.95, P = 0.000) between the ventral and dorsal synovial folds of the left and right lateral atlantoaxial joints. There was no correlation between synovial fold dimensions and age. The reliability of the measurements ranged from intraclass correlation coefficient 0.95 to 0.99 (intraobserver reliability) and intraclass correlation coefficients 0.75 to 0.82 (interobserver reliability). CONCLUSION: MR imaging was successfully implemented as a noninvasive method for visualizing the synovial folds of the lateral atlantoaxial joints and quantifying their dimensions in healthy volunteers. The results of this study provide a basis for future studies investigating synovial fold pathology in patients with neck pain and headache.

Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population.

We have developed a mutation-scanning approach suitable for whole population screening for unknown mutations. The method, meltMADGE, combines thermal ramp electrophoresis with MADGE to achieve suitable cost efficiency and throughput. The sensitivity was tested in blind trials using 54 amplicons representing the BRCA1 coding region and a panel of 94 unrelated family breast cancer risk consultands previously screened in a clinical diagnostic laboratory. All 10 common polymorphisms, 15/15 previously identified disease-causing mutations, and three previously untested single base changes were identified. Assays of LDLR exons 3 and 8 were validated in 460 familial hypercholesteremics and detected 8/9 known variants. We then applied the exon 3 assay in several DNA banks representing approximately 8000 subjects with known cholesterol values and applied both assays in one DNA bank (n = 3600). In exon 3 we identified one previously reported moderate mutation, P84S (n = 1), also associated with moderate hypercholesteremia in this subject; an unreported silent variant, N76N (n = 1); and known severe hypercholesteremia splice mutation 313+1G-->A (n = 2). Around exon 8 we identified a paucimorphism (n = 35) at the splice site 1061-8T-->C (known to be in complete linkage disequilibrium with T705I) and unreported sequence variants 1186+11G-->A (n = 1) and D335N G-->A (n = 1). The cholesterol value for D335N was on the 96.2 percentile and for T705I, 2/35 carriers were above the 99th percentile. Thus, variants with predicted severe, moderate, and no effect were identified at the population level. In contrast with case collections, CpG mutations predominated. MeltMADGE will enable definition of the full population spectrum of rare, paucimorphic, severe, moderate (forme fruste), and silent mutations and effects.

Effects of neck extensor muscles fatigue on balance.

OBJECTIVE: Measure the effects of cervical extensor muscle isometric contraction on cervical surface electromyographic spectral shift and balance in healthy subjects. DESIGN: Experimental within-subject design. BACKGROUND: Postural instability can be induced by mechanically stimulating cervical muscle spindles. Postural changes are also observed in individuals who suffer from chronic neck pain or whiplash injury. Furthermore these subjects appear to experience neck musculature fatigue more quickly, which in turn not only affects the neck function but also seems to affect the balance in a standing posture. METHODS: Using a force platform, balance was measured, in 10 blindfolded college students before and after isometric voluntary contraction in neck extension at 5% and 25% maximum voluntary isometric contraction for a period of 5, 10 and 15 min. Paired posturographic data were analysed for differences. Control measurements were performed on the same subjects by measuring balance before and after subjects sitting quietly for 5, 10 and 15 min without performing isometric contraction. RESULTS: The results indicate that a 25% maximal isometric contraction of the neck extensors for 10 and 15 min duration produced significant changes in some posturographic parameters in young healthy males. Furthermore, this contraction also produced a significant cervical muscle electromyography median frequency spectrum shift of the lower frequencies. CONCLUSIONS: Balance was affected by 15 min of 25% maximal isometric contraction of the extensor cervical muscles. Posturographic parameters affected are similar to parameters observed in subjects that have suffered a whiplash injury. RELEVANCE: This study contributes to our understanding of functional aspects of cervical muscle fatigue. The similarity of results with other studies performed on subjects suffering from chronic neck pain and from whiplash injuries may suggest a similar cause for loss of postural control. Ultimately, this may help us in developing objective evaluation procedures for subjects suffering from neck complaints.

Manual 768 or 384 well microplate gel 'dry' electrophoresis for PCR checking and SNP genotyping.

Electrophoresis continues to be a mainstay in molecular genetic laboratories for checking, sizing and separating both PCR products, nucleic acids derived from in vivo or in vitro sources and nucleic acid-protein complexes. Many genomic and genetic applications demand high throughput, such as the checking of amplification products from many loci, from many clones, from many cell lines or from many individuals at once. These applications include microarray resource development and expression analysis, genome mapping, library and DNA bank screening, mutagenesis experiments and single nucleotide polymorphism (SNP) genotyping. PCR hardware compatible with industry standard 96 and 384 well microplates is commonplace. We have previously described a simple system for submerged horizontal 96 and 192 well polyacrylamide or agarose microplate array diagonal gel electrophoresis (MADGE) which is microplate compatible and suitable for PCR checking, SNP typing (restriction fragment length polymorphism or amplification refractory mutation system), microsatellite sizing and identification of unknown mutations. By substantial redesign of format and operations, we have derived an efficient 'dry' gel system that enables direct 96 pin manual transfer from PCR or other reactions in microplates, into 768 or 384 well gels. Combined with direct electrode contact in clamshell electrophoresis boxes which plug directly to contacts in a powered stacking frame and using 5-10 min electrophoresis times, it would be possible (given a sufficient supply of PCRs for examination) for 1 million gel tracks to be run per day for a minimal hardware investment and at minimal reagent costs. Applications of this system for PCR checking and SNP genotyping are illustrated.