Development of the ossified sphenoid bone (SB) ligaments: etiological factors
Ligaments are dense-fibrous structures, attached to skeletal elements and transmitting mechanical forces [
4,
35]. Various ligaments in the human body are ossified to a variable degree (partially or completely) [
35]. Deposits of calcium and heterotopic bone formation were also described within the dura matter folds and spanned between the PCP, dorsum sella, clivus, and petrous bone [
54]. The pathogenesis of bone formation in entheses is a multifactorial process [
36], including the cytokines and several systemic factors, like adipokines and gut hormones, as well as local factors, such as BMP and Wnt signaling; while angiogenesis, mechanical stress, dietary habits, metabolic abnormalities (obesity) [
16], and increased age [
16] may also play a role [
26]. The etiology of heterotopic ligament ossification is a dynamic, and highly complex tissue repair process, that includes trauma/injury, inflammation, mesenchymal stromal cell recruitment, chondrogenic differentiation and ossification formation [
63]. Ligaments’ ossification includes their fibers degenerative alterations, that are associated with a significant increase in mineral content (Ca and P) and decrease in the extracellular matrix (elastin, elastin cross-links, fibrillin, collagen, and glycoprotein) [
38]
. Other authors [
40] reported that aging did not affect the ICRBs morphology, as this phenomenon is not age related and depends on the SB complex embryology. From the other part, Natsis et al. [
33] reported a higher and significant prevalence of the CCLB and ICLB occurrence in older age groups, only in cases of complete ossification. Aging was more strongly correlated with the AICLL complete ossification than the CCLL. Natsis et al. [
35] explained the phenomenon of enthesopathy with the chondrocytes’ occurrence around the ossified area, justifying the high incidence of osseous bridging with aging. Chewing on one side has been considered as a factor responsible for the PTSL and the PTAL ossification in between the pterygoid muscles’ fibers [
9].
In this study, the most ossified ECRL was the PTAL (32.7%) followed by the PTSL (16.03%). Nikolova et al. [
37] found among the ECRBs, the PTSB the most occurred. Natsis et al. [
34] identified a PTAB in 31.7% in a Greek population, results close to the findings of the current study (32.7%). Lower prevalence was reported in a Brazilian (2.73%) [
47] and a Kenyan (8.4%) population [
48]. In the current study, the PTSB presence was recorded in 16.03%, a finding similar to Goyal and Jain [
21] results who identified the PTSB presence in 17.33% in an Indian population. Another study performed in a different Greek population, identified the PTSB in 38% [
2]. The lowest prevalence of the PTSB existence (0.95%) was identified by Krupanidhi et al. [
28] in an Indian population.
Prevalence of the intracranial ligaments’ (ICRLs) ossification
The most ossified ICRL in the order of decreased frequency was the CCLL (24.36%), followed by the PICLL (6.41%) and the AICLL (4.49%). Natsis et al. [
33], investigating the ICRLs’ ossification, in another sample of Greek skulls found the CCLL the most ossified (60.15%), followed by the AICLL (19.5%) and the PICLL (2.4%), contrariwise to this study, in which the PICLL was identified most ossified than the AICLL. Özdoğmuş et al. [
40] in Turks, identified a high incidence of 45% for the CCLBs, and an incidence of 6% for the ICLBs. Keyes [
27] identified a higher prevalence of the CCLBs (27.46%) compared to the ICLBs (8.68%), similar to Inoue et al. [
23] who found the relative prevalence in 36% and 4%, respectively. Skandalakis et al. [
52] in their meta-analysis identified the CCLBs’ pooled prevalence in 32.6%.
A mixed pattern of sphenoid bone (SB) ligaments’ ossification
In this study, isolated and combined ossified ligaments were identified, depending on the location of the ECRLs and ICRLs ossification. The CCLB coexisted with other ossified bars in a higher percentage (8.33%), compared to the PTAB, PTSB, and PICLB that coexisted in 5.77% and the AICLB that coexisted with other ossified bars in 3.85%. Touska et al. [
55] identified the ossification of more than one ligament in 26.7% of the patients. Most of them (76.6%) had a combination of two ossified ligaments, 23.4% had a combination of more than two ligaments and 3.1% a combination of more than three ligaments. Iwanaga et al. [
24] identified the coexistence of PTSB and PTAB in 10%. In this study, one skull was identified with a mixed pattern of ossification for both the AICLL and the PICLL, similar to Archana et al. [
3] type II, who identified the combined ossification of the AICLL and PICLL in 5.6%. In Gibelli et al. [
20] study, the two ossified variants (CCLBs and ICLBs) were often associated, as patients with no ossified sellar ligaments, usually did not present CCLBs (
P < 0.001). Ossified variants among similar populations suggest that excluding racial/ethnic differences, other parameters, such as gender, age, geographical distribution, and genetic and molecular factors could play an important role in ligaments’ ossification [
7].
The clinical impact of the ossified bars’ existence
SB (partial or complete) ECRLS or ICRLs ossification may entrap and compress the passing neurovascular structures causing mechanical irritation, vessels’ occlusion, and obstruction of surgical pathways [
37]. The osseous bars may obstruct cranial foramina (e.g., FO) and form barriers (e.g., ICLBs or CCLBs) than hinder trans-sphenoidal surgery. In cases of combination of such accessory osseous formations with atypical adjacent foramina (of a variant morphology, i.e., of an extensive size or an atypical shape or both), the skull base imaging is essential to reveal typical or variable anatomy of the area. The gold standard imaging tool remains the 3DCT scan [
30,
56,
60], offering a detailed depiction, and permitting the meticulous registration of the complicated (typical and variant) anatomy of the sella, essential for the identification of the ICA pathology [
14]. Moreover, the ITF tissues’ depiction by this tool, and the use of neuro-navigation helps the FO approach, with accuracy and safety [
19,
56]. Liu et al. [
31] confirmed better clinical outcomes, lower recurrence rates, and shorter operation time when assisting from the guidance technique during FO radiofrequency thermocoagulation. The identification of the SB partial or complete ECRLs ossification may force radical modifications in selecting optional trajectory to access safely the FO, as their topography across the FO can significantly hinder the surgical procedure [
60]. Otherwise, a wrong trajectory can lead to injury of the vital anatomical structures, like the ICA, the internal jugular vein, the eustachian tube, the ocular motor nerves (III, IV, and VI), and other neurovascular structures running to the orbit [
15,
44,
60].
The extracranial complete PTAB is of greater clinical importance compared to the complete PTSB [
46], due to its lateral location in relation to the FO and greater thickness (4 mm according to Chouke and Hodes [
10]) comparing to the PTSB which is thinner and located medially to the FO, and thus do not create a barrier for the needle to be inserted through its lumen. The PTAB may compress on the trigeminal nerve’s mandibular division [
2,
53] causing chewing disorders, pain, and numbness of the buccal area and tongue and parotid gland salivatory changes [
43]. The PTAB may also hinder the transoval approaches for the treatment of trigeminal neuralgia [
29]. In such difficult cases, the surgeon cannot reach FO during percutaneous procedures after repeated attempts in different angles [
62]. Matys et al. [
32] suggested that when the anterior access of the FO was blocked by a PTAB, the FO could be alternatively approached from an inframandibular direction. Additionally, the neurovascular structures perforating FO (the mandibular and the superficial lesser petrosal nerves, the accessory meningeal artery, and an emissary vein connecting with the pterygoid venous plexus) may be injured, resulting in neuropathy and postoperative hemorrhage, in the ITF [
44].
The PTSB presence is of importance during retropharyngeal and parapharyngeal surgery and in anesthetic blockade, as may act as a barrier to the needle’s passage through FO [
45]. In cases of a PTAB and a PTSB coexistence, a different treatment approach is selected, using the microvascular decompression or the stereotactic radiosurgery.
The PTAB coexistence with a FO variant in shape and size, in cases of obstruction, poses a risk of inadvertent cannulation of the foramen lacerum [
15]. Coincidence of a small and narrow FO, with an ossified PTAL, a FO atypical orientation and an abnormal basicranial angulation can be troubleshooting for performing FO standard canulation, or effective percutaneous rhizotomy of the trigeminal nerve [
15]. In addition, the presence of a variant pterygoid process ridge may obscure the FO, rendering the FO cannulation procedure competitive [
59]. Iwanaga et al. [
25] pointed out the relationship in between the base of the lateral pterygoid plate posterior border with the FO and highlighted that in cases of a distance between them (distant or removed type) the failure of percutaneous procedures for treating trigeminal neuralgia is certain.
The existence of the ICLBs and CCLBs may impede surgical approaches to the paraclinoid, sellar, and parasellar regions. Their clinical impact also depends on the size, location, and type of formation (complete or incomplete). In such cases, stepwise disconnection of the bony structures of the sella is recommended to avoid destruction of the anatomical structures involved in the lesions [
18,
64]
. Thus, standard endoscopic endonasal operations perform at the sella region may require modification to minimize risk of neurosurgical complications (e.g., rupture of the paraclinoid aneurysm, ICA damage, while removal of the clinoidal meningiomas). Specifically, the CCLBs existence may cause ICA compression, tightening or stretching, resulting in an insufficient blood supply to the brain [
40]. The existence of a complete CCLB may complicate the anterior clinoidectomy (necessary to expose cavernous sinus and access the ICA clinoid segment for management of aneurysms, neoplasms, and traumatic parasellar lesions) [
3,
55,
65], and increase the risk of carotid laceration [
23,
50], especially in cases of the ICA aneurysmal branches [
39]
. In addition, the MCP is a reliable landmark for localization of the cavernous sinus’ anteromedial roof and the transition between the ICA intracavernous and paraclinoidal segments during endoscopic endonasal approach to the sellar, parasellar, and suprasellar region [
11,
18]. Divya et al. [
13] pointed out the positive correlation in between the sella bridging and the existence of impacted canines and hyperdontia, thus highlighted this ossification as a diagnostic marker of the underlying dental anomalies. In complex cases of ECRLs and ICRLs ossification with an altered FO morphology and morphometry, and coexisted variants, the preoperative 3DCT scan may reveal the possible obstruction of the needle by the PTAB, as well as the asymmetry of the FO location bilaterally [
15]. In addition, skull base surgeons should also consider preoperatively possible racial, gender, and age differences, especially when applying novel techniques or modifying the surgical approach in tumor resection or aneurysm repair cases in the sella [
7].