European Journal of Cardiovascular Medicine

The floor of the middle cranial fossa contains several foramina that are of great anatomical and clinical importance, as they serve as passageways for major cranial nerves and blood vessels. The greater wing of the sphenoid bone typically presents three constant foramina, namely the foramen rotundum, foramen ovale, and foramen spinosum, along with a few smaller and variable openings. Among these accessory foramina, the foramen vesalius and the cavernous foramen may be found in close proximity to the foramen ovale. The foramen vesalius is considered an inconsistent foramen, and its presence and characteristics vary considerably among individuals and populations [1]. Previous studies have shown wide regional and ethnic variations in the incidence, morphology, and dimensions of the foramen vesalius [2]. Although a sound understanding of the three-dimensional topographic anatomy and morphometric parameters of cranial foramina is essential, this alone may not ensure safe surgical practice. Detailed knowledge of anatomical variations is equally critical, particularly for clinicians performing invasive diagnostic or therapeutic procedures involving the skull base, head, and neck region [2]. The foramen Vesalius, also known as the emissary sphenoidal foramen, is a small and variable but often bilaterally symmetrical opening situated anteromedially to the foramen ovale and lateral to the foramen rotundum [1]. It transmits the sphenoidal emissary vein, which establishes a venous connection between the cavernous sinus and the pterygoid venous plexus. Through this communication, extracranial venous blood can enter the intracranial venous system. Consequently, infections from extracranial sources, particularly those involving the orbit, paranasal sinuses, or upper facial region, may spread to the cavernous sinus, potentially resulting in cavernous sinus thrombosis. Clinically, this condition may present with severe pain in the orbital and frontal regions due to involvement of the ophthalmic division of the trigeminal nerve, while trismus may occur if the mandibular nerve is affected [2]. Emissary veins are valveless and play a crucial role in equalising intracranial and extracranial venous pressure. Under normal physiological conditions, blood flow through these veins is minimal; however, in situations of raised intracranial pressure, they may serve as significant alternate pathways for venous drainage [2]. From a surgical perspective, the foramen ovale is frequently accessed during neurosurgical procedures such as percutaneous treatments for trigeminal neuralgia. Due to the close anatomical relationship between the foramen ovale and the foramen vesalius, there is a risk of inadvertent needle misplacement into the foramen vesalius during such procedures. Accidental puncture of the cavernous sinus can lead to serious and potentially life-threatening complications, emphasising the importance of precise anatomical knowledge of this region [2-4]. Despite its clinical relevance, data on the morphology and morphometry of the foramen vesalius remain limited, particularly from eastern India. Bihar represents a densely populated region with diverse genetic and ethnic backgrounds, yet region-specific anatomical data are scarce. Local morphometric studies are essential, as population-based variations may influence surgical outcomes and procedural safety. The present study was therefore undertaken to analyse the morphological patterns and morphometric dimensions of the foramen vesalius in adult human dry skulls. The findings of this study are expected to contribute valuable baseline data for anatomists and provide clinically relevant information for neurosurgeons, anaesthetists, and other clinicians performing procedures involving the middle cranial fossa

This cross-sectional observational study was conducted on adult human dry skulls of unknown age and sex available in the Department of Anatomy, Indira Gandhi Institute of Medical Sciences, Patna, Bihar (India). All procedures were conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.

Sample Size Calculation

The sample size was estimated using G*Power software (Version 3.1.9.7). Based on effect sizes reported in previously published morphologic and morphometric studies on cranial foramina, an effect size of 0.5, a power (1−β) of 0.80, and an α-error probability of 0.05 were considered for the calculation [5]. The minimum required sample size was calculated to be 54 adult human dry skulls. To account for potential exclusion due to damaged specimens and to improve the robustness of observations, the final sample size was rounded up to 60 adult dry skulls, which were included in the present study.

Inclusion Criteria

• Adult human dry skulls with an intact floor of the middle cranial fossa.
• Skulls showing well-preserved sphenoid bone anatomy.
• Specimens suitable for clear identification of cranial foramina.
• Both male and female bones were considered.

Exclusion Criteria

• Skulls with a damaged, broken, or eroded middle cranial fossa floor.
• Skulls with distorted sphenoid bone anatomy affecting foraminal identification.

The study focused on evaluating the morphological characteristics and morphometric parameters of the foramen vesalius on the floor of the middle cranial fossa. Each skull was carefully examined under adequate illumination to identify the presence or absence of the foramen Vesalius. The incidence of occurrence was recorded and classified as bilateral or unilateral. To confirm the patency of the foramen and to exclude false or blind openings, a thin copper wire was gently passed through the foramen wherever present.

Morphometric assessment was carried out by measuring the maximum diameter of the foramen vesalius using a digital vernier calliper with an accuracy of 0.01 mm. In cases of very small foramina, calibrated probes with diameters of 0.25 mm, 0.50 mm, and 0.75 mm were used to ensure accurate assessment. The shape of the foramen was documented as round, oval, or irregular, and observations were recorded separately for the right and left sides. The presence of duplication of the foramen Vesalius, if any, was also noted bilaterally.

Statistical Analysis

All observations were systematically recorded and tabulated. The collected data were entered into Microsoft Excel and analysed using Statistical Package for the Social Sciences (SPSS) software, version 14.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were applied to summarise the data. The incidence of the foramen vesalius was expressed as frequency and percentage, including unilateral and bilateral occurrences. The morphometric measurements were presented as mean ± standard deviation (SD). The normality of data distribution was assessed using the Shapiro–Wilk test. A side-wise comparison of the maximum diameter of the foramen vesalius between the right and left sides of the middle cranial fossa was performed using the Student’s t-test. A p-value ≤ 0.05 was considered statistically significant. Morphological variations, including the shape (round, oval, irregular) and duplication of the foramen Vesalius, were analysed descriptively and expressed as percentages.

Out of a total of 120 sides examined from 60 adult dry skulls, the foramen vesalius was found to be present in 45 sides (37.5%), while it was absent in 75 sides (62.5%) (Table 1). Unilateral presence was more common than bilateral occurrence. The foramen was observed unilaterally on the right side in 27 sides (22.5%) and on the left side in 14 sides (11.67%) (Figures 1 and 2). Bilateral presence was noted in 2 skulls, contributing to 4 sides (3.33%). On side-wise comparison, the foramen vesalius was observed more frequently on the right side (29 sides, 24.17%) compared to the left side (16 sides, 13.33%). This difference in distribution between the right and left sides was found to be statistically significant (Chi-square test, p = 0.024).

Table 1: Side-wise distribution and laterality of foramen vesalius (n = 120 sides)

Percentages are calculated per side (n = 120 sides obtained from 60 adult dry skulls).

*Bilateral presence refers to two skulls contributing four sides.

The mean maximum diameter of the foramen vesalius on the right side was 0.95 ± 0.60 mm, while on the left side it was 1.05 ± 0.65 mm. Although the mean diameter was slightly greater on the left side compared to the right, the difference between the two sides was not statistically significant (Student’s t-test, p = 0.53) (Table 2).

Table 2: Comparison of the maximum diameter of the foramen vesalius

Among the 45 foramina Vesalius identified, the round shape was the most common morphology, observed in 30 cases (66.67%), followed by the oval shape in 11 cases (24.44%) and the irregular shape in 4 cases (8.89%). On the right side, round-shaped foramina were seen in 17 cases (37.78%), oval in 9 cases (20%), and irregular in 3 cases (6.67%). On the left side, round shape was noted in 13 cases (28.89%), oval in 2 cases (4.44%), and irregular in 1 case (2.22%). Statistical analysis using the Chi-square test showed no significant difference in the distribution of shapes between the right and left sides (χ² = 2.44, df = 2, p = 0.296) (Table 3).

Table 3: Side-wise distribution of shapes of the foramen vesalius

Percentages calculated based on the total number of foramina observed (n = 45).

Figure 1: Middle cranial fossa showing foramen vesalius on the right side.

Figure 2: Middle cranial fossa showing foramen vesalius on the left side.

The cranial base, particularly the middle cranial fossa, develops mainly from cartilaginous precursors and is therefore considered a part of the chondrocranium. The cartilaginous and bony elements of the skull base are derived from neural crest cells and paraxial mesoderm during the fourth week of intrauterine life [6]. A distinctive feature of skull base development is that the major neurovascular structures are established before mesenchymal condensation and ossification. Consequently, the cranial foramina are determined early in development, even before the surrounding bones are completely formed. Ossification of the cranial base occurs through endochondral ossification, similar to that seen in long bones, with multiple ossification centres acting functionally as primary centres. Growth takes place in the intervening cartilage between adjacent centres, and the first ossification centres of the sphenoid bone appear in the lesser and greater wings during the eighth and ninth weeks of gestation, respectively [1]. Variations in the timing or pattern of this developmental process may explain the inconstant nature of certain foramina, including the foramen Vesalius.

The foramen Vesalius, also known as the emissary sphenoidal foramen, is a small and variable opening located in the greater wing of the sphenoid bone. Lanzieri et al. [7] described it as a relatively uncommon structure that is often bilaterally symmetrical. However, classical anatomical descriptions do not always correspond with observations from population-based studies. Andreas Vesalius, in De Humani Corporis Fabrica (1543), reported no significant difference in the frequency of occurrence of the foramen vesalius between the right and left sides. In contrast, the present study demonstrated a significantly higher incidence on the right side (24.17%) compared to the left side (13.33%), indicating a clear lateral asymmetry. This difference may reflect population-specific anatomical variation or differences in sample size and methodology. The overall incidence, as well as unilateral and bilateral distribution observed in the present study, has been compared with earlier studies in Table 4, which shows considerable variability among different authors. Morphometric analysis revealed that the mean maximum diameter of the foramen vesalius in the present study showed slight variation when compared with previously published data (Table 5). Despite these differences, most studies, including the present one, did not demonstrate a statistically significant difference in the maximum diameter between the right and left sides. Lanzieri et al. [7] reported asymmetry of the foramen vesalius in four out of fifty patients and suggested that such asymmetry was more likely related to pathological involvement of surrounding structures rather than normal anatomical variation. In their study, asymmetry was associated with tumour invasion of the emissary vein and foramen Vesalius, including cases of nasopharyngeal melanoma and juvenile angiofibroma. Additional associations were noted with carotid–cavernous fistula and neurofibromatosis. These observations support the view that marked asymmetry of the foramen Vesalius is more often a result of pathological processes rather than developmental variation alone.

In the present study, duplication of the foramen vesalius was not observed. This finding differs from earlier reports, such as those by Kale et al. [8], who reported a 1% incidence, and Singh et al. [9], who observed duplication in 2% of skulls. The absence of duplication in the present series highlights the variability in the occurrence of this anatomical feature among different populations. Previous authors have suggested that duplication of skull base foramina may result from early division of the middle meningeal artery into anterior and posterior branches before entering the cranial cavity, leading to the formation of separate foramina. Although duplication was not encountered in this study, awareness of such variations remains important.

From a clinical perspective, the foramen vesalius is significant because it transmits an emissary vein connecting the cavernous sinus with the pterygoid venous plexus. These valveless veins can serve as potential pathways for the spread of infection from extracranial regions to intracranial venous sinuses. During percutaneous procedures for the management of trigeminal neuralgia, the foramen ovale is commonly targeted. Due to the close anatomical relationship between the foramen ovale and the foramen vesalius, there is a risk of inadvertent needle misplacement into the foramen Vesalius, which may result in cavernous sinus injury and potentially life-threatening intracranial haemorrhage [2,10].

Variations or absence of skull base foramina also have important clinical implications. Although the foramen vesalius itself is inconstant, variations in neighbouring foramina, particularly the foramen spinosum, are clinically relevant. When the foramen spinosum is absent, the middle meningeal artery may originate from alternative sources such as the ophthalmic artery, lacrimal artery, or directly from the petrous or cavernous segments of the internal carotid artery [11,12]. Such vascular variations explain the absence of the foramen spinosum when the middle meningeal artery does not follow its usual extracranial-to-intracranial course [13].

Table 4: Comparison among the incidences of foramen vesalius reported by various authors

Table 5: Comparison among the mean maximum dimensions of the foramen vesalius reported by various authors

Limitations of the study: Although this study provides valuable morphological and morphometric data on the foramen Vesalius, the age and sex of the skulls could not be determined due to the nature of the specimens. Nevertheless, the findings offer important baseline anatomical information that can support future studies incorporating demographic details and advanced imaging techniques.

The present study demonstrates that the foramen vesalius is an inconstant anatomical structure with considerable variation in its presence, laterality, shape, and size. It was more commonly observed on the right side, while round morphology was the predominant shape. Although minor differences in morphometric dimensions were noted between sides, these were not statistically significant. The findings provide region-specific anatomical data that are valuable for anatomists and have important clinical implications for neurosurgeons and clinicians performing procedures involving the middle cranial fossa. A thorough understanding of these variations may help reduce the risk of iatrogenic complications during diagnostic and therapeutic interventions.

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