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Facet tropism is the angular asymmetry between the left and right facet joint orientation. Although debatable, facet tropism was suggested to be associated with disc degeneration, facet degeneration and degenerative spondylolisthesis in the lumbar spine. The purpose of this study was to explore the relationship between facet tropism and facet degeneration in the sub-axial cervical spine.
A total of 200 patients with cervical spondylosis were retrospectively analyzed. Facet degeneration was categorized into 4 grade: grade I, normal; grade II, degenerative changes including joint space narrowing, cyst formation, small osteophytes (3 mm) without fusion of the joint; grade IV, bony fusion of the facet joints. Facet orientations and facet tropisms with respect to the transverse, sagittal and coronal plane were calculated from the reconstructed cervical spine, which was based on the axial CT scan images. The paired facet joints were then categorized into three types: symmetric, moderated tropism and severe tropism. Univariate and multivariate analysis were performed to evaluate the relationship between any demographic and anatomical factor and facet degeneration.
Facet degeneration was assessed according to a recently published criteria [20]. For each patient, the facet degeneration on both the left and right side from C2-C3 to C6-C7 level were categorized into 4 grades according to articular space, cyst formation, and articular process hypertrophy. Briefly: grade I, normal; grade II, degenerative changes including joint space narrowing, cyst formation, small osteophytes (3 mm) without fusion of the joint seen on sagittal images; grade IV, bony fusion of the facet joints. The CT scans were read by one radiologist and one senior spine resident. We first tested the reliability of the grading system in 20 patients. CT scans were assigned to the two readers in a random sequence at the interval of 2 weeks. The intra-observer and inter-observer reliability was assessed by intraclass correlation (ICC) value (excellent for the ICC value from 0.9 to 1, good for 0.7 to 0.89, fair for 0.5 to 0.69, low for 0.25 to 0.49, poor for 0 to 0.24). In the later part of this study, when two different grading results were presented for one facet joint, the lower grade was assigned as the final grading results, as indicated by the previous study [20]. The facet joints were further categorized into normal (grade I) and degenerated (grade II or above) for later analysis.
The facet orientations with respect to the transverse, sagittal and coronal plane were determined on the reconstructed cervical spine (Fig. 1). First, the CT data in DICOM format was imported into the commercially available software Mimics 17.0 (Materialize, Belgium) to reconstruct the cervical spine. Second, five planes were identified on the reconstructed cervical spine: two facet planes, the plane bisects the facet joint space on either side; transverse plane, the plane parallel to the superior endplate of the vertebral body and perpendicular to the sagittal plane; sagittal plane, the plane bisects the vertebral body; and coronal plane, the plane perpendicular to both the transverse plane and the sagittal plane. Third, the normal vectors of the five planes were used to calculate the angles between two planes for the determination of the facet orientations as follows:
Illustration of the determination of the facet orientations in reconstructed cervical spine. The facet plane bisects the facet joint space; the transverse plane parallel to the superior endplate of the vertebral body and perpendicular to the sagittal plane; the sagittal plane bisects the vertebral body; the coronal plane are perpendicular to both the transverse plane and the sagittal plane (a). The normal vectors of one facet plane (n1) and transverse plane (n2), of which the coordinates were used for the calculation of the angle between the facet plane and transverse plane (b)
Results from the multivariate analysis suggested that several demographic and anatomical factors, including gender, age, cervical level and facet tropism, were associated with facet degeneration in the sub-axial cervical spine.
Several studies suggested that gender was associated with facet degeneration in the cervical spine [20, 23]. Park et al. [20] reported that both facet degeneration above grade II and above grade III were more common in males. Morishita et al. [24] found that hypertrophic change of facet joint occurred more frequently in males. Uhrenholt et al. [19] performed histological observation on 40 subjects and demonstrated that facet cartilage flaking and splitting were more common in males, On the contrary, in the present study, the results from the multivariate analysis when taken the sub-axial cervical spine as a whole showed, that facet degeneration were more common in females. However, in the sub-group analysis according to levels, we found that gender was only related to facet degeneration at C2-C3 level. Therefore, we suggested that gender may not be independently associated with facet degeneration. Nevertheless, cross-sectional study of large sample was needed to verify this finding.
Our results demonstrated that facet degeneration were more likely to happen at C2-C3 level. At the other end of the cervical spine, C6-C7 had the lowest incidence of facet degeneration. Park et al. [20] found that C2-C3 to C4-C5 levels had higher incidence of facet degeneration. Morishita et al. [24] reported higher incidence of facet joints hypertrophy at mid-level (C4-C5) of the cervical spine. These results suggested that the facet degenerative changes were more likely to happen in the upper sub-axial cervical levels. It was quite different from the lumbar spine, in which facet degeneration tended to occur at the lower lumbar level [25]. Future studies are needed to elaborate the mechanism behind this phenomenon.
There was one theory that facet tropism could create asymmetrical stress distribution in the facet joints. Biomechanical study by Cyron and Hutton [2] demonstrated that facet tropism caused higher compressive load on the facet joints in axial rotation. Kim et al. [26, 27] concluded in their finite element study that facet tropism could increase the local facet contact force. Such an imbalanced loading could result in the development of facet degeneration, such as osteophytes formation and joint space narrowing. Some clinical studies in the lumbar spine confirmed this theory that facet tropism could be associated with facet degeneration [7]. Shin et al. [7] conducted a retrospective study on 42 patients with 51 lumbar levels replaced with artificial discs. At the 36 months follow-up, the progressive facet arthrosis (PFA) levels had significantly larger facet tropism than the non-PFA levels. However, little is known about the relationship between facet tropism and facet degeneration in the cervical spine. Results from our multivariate analysis suggested that the facet tropism with respect to the sagittal plane seemed to be associated with facet degeneration. Clinical observations and finite element studies are warranted to assess the impact of facet tropism on the cervical facet joints.
Facet tropism was common in the sub-axial cervical spine. Incidence of facet degeneration was highest at C2-C3 level, whereas lowest at C6-C7 level. Facet degeneration was associated with older age and more severe facet tropism with respect to the sagittal plane.
The majority of the excitatory synapses in central nervous systems are formed onto dendritic spines. Morphologically, dendritic spines appear to be micrometer-sized membrane protrusion from the neuronal dendrites; functionally they serve as compartments for post-synaptic molecules. They come in a variety of shapes [1], most commonly as one of the following: filopodia-like, stubby, mushroom-shaped and cup-shaped. The shape and the size of a spine is determined by the underlying actin cytoskeleton [2], as spines contain a high concentration of filamentous (F-) actin molecules and are mostly devoid of microtubules. In recent years, advanced live cell imaging techniques have revealed that the spines are remarkably dynamic, changing size and shape in a matter of minutes [3]-[5]. These morphological changes are widely believed to affect functional properties of the individual synapses and by extension the neuronal network, and therefore are directly linked to brain's cognitive functions, such as memory and learning. A large body of evidence now exists to support this proposition. For example, many studies have demonstrated changes in spine morphology following electrophysiologically induced long-term potentiation (LTP) or long-term depression (LTD) [6]. Furthermore, a dynamic F-actin cytoskeleton is required for establishing LTP and LTD [7]-[9]. Finally, recent studies in culture showed that the direct application of stimuli to individual spines resulted in an enlargement of the spine and this enlargement required actin [10], [11]. Therefore understanding the actin cytoskeleton is of central importance to the studies of synaptic and neuronal function.
We expressed EosFP-actin in hippocampal neurons. As shown in Figure 2, the green fluorescence of EosFP-actin colocalized with endogenous actin molecules, which is highlighted by phalloidin staining (Figure 2A), as well as the post-synaptic marker PSD95 (Figure 2B). These data indicated that the localization of expressed tdEosFP-actin fusion protein corresponds to that of endogenous actin in dendrites and dendritic spines.
Unlike in lamellipodia, single-molecule data obtained in dendritic spines exhibited a high level of heterogeneity (Movie S3). We observed at least four different types of F-actin molecules based on their kinematic behaviors. 1. Actin molecules with no detectable motion. Close to half of all molecules belong to this category, making it the dominant category. 2. Actin molecules with vectorial retrograde motion. Although previous results had demonstrated redistribution of actin in the retrograde direction (i.e., towards the dendritic shaft), it has not been directly shown before that that a vectorial flow of the filaments contributes to such redistribution. 3. Actin molecules with vectorial anterograde motion. These molecules move into the spine away from the dendritic shaft. Although the number of molecules in this category is small, this type of kinematic dynamics is completely unexpected. Both the retrograde moving molecules and the anterograde moving molecules seem to coexist in the same spine (see for example, Movie S4), which indicates that the direction of actin flow is not dependent either on the specific spine or on the existing physiological state of the spine 4. Finally, molecules with random-walk type of motion. Examples of each type of molecule are shown in Figure 3A and 3B. 2b1af7f3a8