General statement
The current work represents the first morphometric study of normal cervical intervertebral foramina in Jordanian population. The age spectrum therein was set to ensure that the body skeletal growth phase has already been established, and the process of physiological adaptation to lifestyle, including nutrition, occupation, physical activity, and skeletal remodeling has already set in. The absence of ensuing spine degenerative changes was affirmed through radiologic evaluation. We can, therefore, assume that all our measurements most likely represent normal morphometric descriptive values for the Jordanian population in pre-adult and adult age.
Relevance and importance of the study
The relevance of conducting this descriptive research is academic and clinical in nature. The 3-dimensional anatomy of cervical intervertebral foramina is by no means luxurious database to achieve successful performance of surgical procedures and minimizing iatrogenic injuries [30].
The necessity of adequate evaluation of the dimensions of the intervertebral foramina and establishing a normative database of the morphometric analysis of this structure cannot be to overemphasized in order to be able to confirm or exclude foraminal stenosis [16].
The methodology
In addition to high spatial resolution and better direct visualization, 3-D reconstructed computer tomography offers adequate means of rotating the images in the desired directions, thus compensating for the normally tilted position of cervical intervertebral foramina and obtaining face on views thereof [27], which adds substantially to the accuracy and reliability of measurements.
Inter-studies and inter-racial differences
For the purpose of comparison of our measurements with corresponding published data, representative studies in the literature [1; 5, 24] were chosen on basis of comparable study samples and methodologies (Table VI). This comparison clearly shows considerable similarity regarding FH and FW values of cervical intervertebral foramina. However, it should be kept in mind, that inter-population variations make inter-study comparisons of only limited value as previously suggested [29]. In the light of our results, it could be assumed, nevertheless, that inter-population differences are negligible, once the choice of study cases and of the measurement techniques and parameters definitions are relatively unified.
Level-dependent measurements
Our data showed that the overall mean values of FH, irrespective of age, gender, or side exhibited an average craniocaudal decrease of 23% between maximal and minimal values at the levels of C2/C3 and C7/T1, with the most obvious drop of values along the sequence of intervertebral levels evident between C2/C3 and C3/4 (20%). Between the levels C3/C4 through C6/C7 the change is inconsistent and the percentage of either increase or decrease between successive levels. On the other hand, the overall mean values of FW exhibited an average craniocaudal difference of 20% between the maximal values at the lowest intervertebral levels (C7/T1) and the minimal level of this parameter at the level of C3/C4. The gradual increase of FW towards C7/T1 became increasingly obvious averaging 12% at the lowest intervertebral levels. In spite of the overall cranio-caudal increase pattern, however, it is interesting to note that an initial decrease of width is seen between C2/C3 and C3/C4 averaging 9%. This reciprocal cranio-caudal pattern of FH and FW of normal cervical intervertebral foramina confirms the findings of Barakat and Hussein [2]. The differential behavior resides probably in the nature of two components. On one hand, the skeletal set up of the foramina in response to mechanical burden put on successive vertebrae along the cervical spine may play a determining role. On the other hand, the relative varying size of the neural and vascular structures the intervertebral foramina house at different vertebral levels may contribute significantly to this pattern. In this regard, the size of the intervertebral foramen has been reported to vary depending on axial loading [14]. In fact, radiculopathy has been reported to mostly affect C7 followed by C6 [4]. The pattern of increasing FW in caudal cervical intervertebral foramina and increased mean cross-sectional area thereof has been already documented, and may, therefore, create more space for the different structures normally residing or passing through the foramina at these levels [1; 11; 20; 26]. In fact, the brachial plexus roots [3], and prominent vascular elements [10], may necessitate increased FW in lower cervical intervertebral foramina. In contrast, upper cervical nerve roots were reported to be smaller than their lower counterparts [27]. The greater dimensions of the cervical intervertebral foramen at the level C2/C3, as clearly evident in our results, could be related to the large size of anterior epidural venous plexus, an anterolateral structure, being prominent at this level, as it has been already demonstrated [13], and could explain the results of Lentell et al. [24], who found that FH, rather than FW, was responsible for C2/C3 being the largest. This differential cranio-caudal pattern of linear parameters could account for some of the contradictory findings reported in the literature regarding level-dependent, varying results of cervical intervertebral foraminal area and volume. The differential impact of each linear parameter could find its relative echo on foraminal area or volume at any particular vertebral level in accordance with the differential degree this linear value plays in determining the value of foraminal area of volume.
The impact of age
The adolescence, youth, and adult age groups in our study are expected to lie within an expected non-degenerative phase of development, as verified by clinical and radiological inclusion criteria adopted. The analysis of our results revealed that, irrespective of gender or side, the adolescent age group consistently showed the highest FH values at all intervertebral levels when compared with the other two age groups. This difference averaged 8% and 11% when adolescence age group is compared with youth and adult age groups at all levels. Similarly, the youth age group consistently showed greater FH values averaging 4% as compared with adult age group at all intervertebral levels. The FW values displayed identical age-related pattern of change to FH values, irrespective of gender or side. The highest FW values were seen in the adolescent age group as compared with the youth and adult age groups (7% and 14%) at all intervertebral levels, with an obvious cranio-caudal pattern of increase. Similarly, the youth age group exhibited higher FW values than the adult age group at all intervertebral levels (7%) at all the levels with a similar cranio-caudal pattern of increase of difference. In the light of our data, it becomes reasonable to speculate, that osseous growth with respect to linear dimensions of the cervical intervertebral foramina reaches its summit already at the end of the adolescence phase. Thereafter, and in the absence of degenerative changes, the foramina go through a process of remodeling, as evident by insignificant narrowing of linear diameters. Lower cervical segments seem to be especially involved. Moreover, it should be taken into consideration, that significant non-pathologic, age-dependent changes of cervical intervertebral foraminal dimensions, which are associated with ongoing bone remodeling can be expected, which probably run subtly towards eventual pathologic change at some point of advancing age Interestingly, aging has been reported to be associated with decreased number of myelinated fibers in spinal nerve roots [6; 11], although a correlation between age and nerve size was shown to be lacking [19].
Lentell et al. [24], Rühli et al. [29], and Cramer et al. [8] worked on age-stratified cases including the age spectrum present in our study. The authors reached the conclusion that their obtained data from normal vertebrae showed almost always lack of correlation between individual age and intervertebral foraminal size. In contrast, Humphreys et al. [21] reported that cervical intervertebral FW, but not FH, decreased with age. The differential mode of change i.e., the decrease of FH without concurrent increase of superior FW with age has been reported, and has been proposed to reflect subtle disc narrowing or mild collapse of the vertebral bodies with age [7].
Gender-related differences
The analysis of our data revealed interesting, inter-gender differences in terms of age, side, and intervertebral level. The overall mean values of the FH in males were consistently higher at all intervertebral levels. These differences reached the level of significance at upper intervertebral levels (C2/C3) and at lower intervertebral levels (C7/T1) with mean percentage of difference of 8.5%, irrespective of the side. On the other hand, the overall mean values of the FW revealed only unremarkable and inconsistent inter-gender differences, with significance reached, only at the level of C7/T1 in favor of males. However, and elsewhere across the vertebral levels, male versus female FW differences were in favor of females, although these differences remained statistically insignificant. Accordingly, it becomes plausible to suggest, that a differential FH versus FW sex dimorphism apparently exists. This differential pattern appears to be vertebral level-dependent. Superior and inferior ends of cervical spine seem to show higher values in favor of males, where differences reach statistical significance. Middle cervical levels show the opposite pattern. This differential pattern may account for frequent inconsistencies reported in the existing literature in this regard. In general terms, Jankauskas [22] put forward the notion of stronger impact of the gender, rather than the age, on vertebral dimensions in favor of males. However, such a difference has been shown to be lacking [18]. In specific terms, females were shown to have slightly, statistically insignificantly smaller normal cervical intervertebral FH, FW, and area [1; 20; 24; 29]. In contrast, reversed sexual dimorphism of the FW values of cervical intervertebral foramina in favor of females was claimed [12]. Indeed, the size of spinal structures that enclose neural structures has been long found to favor females [17]. Porter et al. [28] speculated that the amount of epidural fat may be greater in females with subsequent larger neural foramina.
Right versus left side differences
Allometry issues resonated their echo in the field of morphometry of cervical intervertebral foramina. The analysis of our data showed that differential side-related differences of FH, but not FW values, were evident. However, these differences, in favor of the right side at caudal cervical intervertebral levels, and in favor of left side at cranial segments, remained statistically insignificant. Data retrieved from the literature showed that no significant differences between the right and left sides exist regarding cervical intervertebral FH, FW, or area [1, 24]. In specific, left cervical foramina were shown to exhibit higher values of foraminal measurements, especially of FH, which, however, did not cross the statistical significance threshold [5]. On the other hand, it has been advocated that significant right versus left differences of the dimensions of normal cervical intervertebral foramina, irrespective of gender, could to be related to the size of passing structures i.e. brachial plexus roots, which could be correlated with handedness, occupation, constitution, and social differences [3]. It is obvious that simple allometry rules are not a major factor regarding the dimensions of cervical intervertebral foramina. It is interesting to note, in this regard, that statistically significant differences exist between the nerve roots of cervical intervertebral foramina on the right and left sides [23]. Nevertheless, the use of the dimensions of an intervertebral foramen on a particular side, at one particular level, as normal reference to judge the patency of its counterpart at the same level on the opposite side remains justified [8].