Microsurgical anatomy of safe entry zones on the ventrolateral brainstem: a morphometric study

Surgery of the brainstem is challenging due to the complexity of the area with cranial nerve nuclei, reticular formation, and ascending and descending fibers. Safe entry zones are required to reach the intrinsic lesions of the brainstem. The aim of this study was to provide detailed measurements for anatomical landmark zones of the ventrolateral surface of the human brainstem related to previously described safe entry zones. In this study, 53 complete and 34 midsagittal brainstems were measured using a stainless caliper with an accuracy of 0.01 mm. The distance between the pontomesencephalic and bulbopontine sulci was measured as 26.94 mm. Basilar sulcus-lateral side of pons (origin of the fibers of the trigeminal nerve) distance was 17.23 mm, transverse length of the pyramid 5.42 mm, and vertical length of the pyramid 21.36 mm. Lateral mesencephalic sulcus was 12.73 mm, distance of the lateral mesencephalic sulcus to the oculomotor nerve 13.85 mm, and distance of trigeminal nerve to the upper tip of pyramid 17.58 mm. The transverse length for the inferior olive at midpoint and vertical length were measured as 5.21 mm and 14.77 mm, consequently. The thickness of the superior colliculus was 4.36 mm, and the inferior colliculus 5.06 mm; length of the tectum was 14.5 mm and interpeduncular fossa 11.26 mm. Profound anatomical knowledge and careful analysis of preoperative imaging are mandatory before surgery of the brainstem lesions. The results presented in this study will serve neurosurgeons operating in the brainstem region.


Introduction
The anatomical organization of the human brainstem is a complex amalgam of compact neuronal groups and dispersed cell areas with varying cytoarchitecture. Structures of the brainstem are very diverse with respect to functions they participate in, neuroactive elements they contain, and neural pathways they accommodate. Surgery of the brainstem is challenging due to the complexity of the area with numerous nuclei, the reticular formation, and ascending and descending fibers. Safe entry zones are required to reach the intrinsic lesions of the brainstem. The study gives detailed measurements for anatomical landmark zones of the ventrolateral surface of the human brainstem such as the lateral mesencephalic sulcus, peritrigeminal area, and inferior olive.
Infratentorial lesions such as neoplastic lesions, vascular malformations, and abscesses are important in the brainstem region due to the presence of important structures in this restricted area. The majority of brainstem tumors are glial tumors [1][2][3]. Gliomas within the brainstem comprise 10-20% of pediatric central nervous system tumors [4,5]; in adults, this ratio is about 5% [4]. Gliomas can be classified into four groups: focal, cervicomedullary, exophytic, and diffuse [4,6]. Focal tumors are generally located in the midbrain, especially tectum, pons, and bulbus [7]. If focal tumors are slow growing-lower grade, they can be operable [6,7].
Surgery of the brainstem, despite advances in microsurgical techniques, intraoperative imaging, and intraoperative electrophysiological monitoring, remains to be challenging. In-depth understanding the surface anatomy and inner architecture of the brainstem is critical for planning the appropriate approach, choosing the safe entry points, and avoiding complications during surgery. Safe entry zones have been described for lesions in the ventrolateral surface of the brainstem. Particularly for lesions in the interpeduncular fossa and cerebral peduncles, a tyranssylvian approach with pterional or orbitozygomatic craniotomy is preferred. Here, dissection proceeds by passing through the opticocarotid triangle and the brainstem is entered lateral to the oculomotor nerve between the posterior cerebral and superior cerebellar arteries. In this region, perforating arteries passing through the posterior perforated substance, peduncular vein, oculomotor nerves, and the interpeduncular cisterns are located. Motor fibers of the pyramidal tract in the cerebral peduncles are the intrinsic structures related to this approach [19,20]. For exposing the midbrain and upper one-third of the pons, a subtemporal transtentorial approach can be used to reveal the oculomotor and trochlear nerves that requires the division of the tentorium posteriorly to the entrance of the trochlear nerve and the pontomesencephalic sulcus [20][21][22]. In this approach, surrounding structures, the vein of Labbé, the temporal lobe, and the proximity of the trochlear nerves and the superior cerebellar artery to the tentorium must be protected during the incision of the tentorium [19]. A pretemporal transcavernous approach is also possible. In this approach, the safe entry zone is indicated by a small rectangular area lateral to the oculomotor nerve, between the posterior cerebral artery and the superior cerebellar artery and through the internal segment of the peduncles [20,23]. For lesions in the ventrolateral surface of the medulla, a far lateral approach provides adequate exposure. Here, the lower cranial nerves, the vertebral artery, and posterior inferior cerebellar artery are exposed [19,20,22,23]. A suboccipital approach with laminectomy of the atlas exposes the olive, the lower cranial nerves, and the C1 spinal nerve. This provides the neurosurgeon a surgical space of 13.5 mm [19]. Operating the lesions on the anterolateral surface of the pons at the level of the cerebellopontine angle and middle cerebellar peduncle is possible with a retrosigmoid approach following retromastoid craniotomy [19,23]. Here, the lower cranial nerve complex and the facial and vestibulocochlear nerves are in proximity. The arachnoid between the lower cranial nerve complex and the facial and vestibulocochlear nerves complex is opened and foramen of Luschka is exposed [19]. Presigmoid and transpetrous approaches are used to reach the peritrigeminal region that is surrounded by the pyramidal tract and the pontomedullary sulcus. Lesions located at the lateral midbrain surface can be approached through the lateral mesencephalic sulcus [22][23][24].
In all these approaches for resection of intrinsic brainstem lesions, it is valuable to know the morphometry of the anatomical landmarks and their relationships to minimize morbidity. Therefore, the main objective of this study was to provide morphometric measurements of the surface structures of the ventrolateral brainstem to define anatomical safe entry zones for microsurgical resection of the midbrain, pons, and medulla lesions.

Materials and methods
The present study was conducted on 53 complete and 34 midsagittal 10% formalin-fixed human brainstem specimens from the cadaver collection of Ege University, School of Medicine, Department of Anatomy, Izmir, Turkey, in accordance with the provisions of the Declaration of Helsinki 1995 (as revised in Edinburgh 2000). Thirteen parameters were measured for the right and left sides, using a stainless caliper with an accuracy of 0.01 mm using anatomic landmarks in the ventrolateral brainstem area.
-Pontomesencephalic sulcus-bulbopontine sulcus distance (M1): The distance between the superior midpoint to the inferior midpoint of the right part of pons was measured (Fig. 1a) -Basilar sulcus and the lateral side of pons distance (Origin of the fibers of CN V) (M2): The distance between the origin of the fibers of the right trigeminal nerve and the midline of the basilar sulcus was measured (Fig. 1b).
-Transverse length of the pyramid (M3): the measurement was made from the midpoint of the lateral margin to the midpoint of the medial margin of the pyramid (Fig. 2a). The measurement was from the origin of the fibers of the trigeminal nerve to the superior midpoint of the pyramid (Fig. 3b). -Transverse length of the inferior olive (M8): The distance between the midpoint of the lateral margin and the midpoint at the medial margin of inferior olive was measured (Fig. 3c).  (Fig. 4a). -Length of the tectum (M12): The distance from the superior margin of the superior colliculus to the inferior margin of the inferior colliculus was measured (Fig. 4a). -Length of the interpeduncular fossa (M13): The distance between the rostral recess of the interpeduncular fossa and the triangular groove, bounded by left and right cerebral peduncles and the upper midpoint of the pons, was measured (Fig. 4b).

Discussion
The main objective in this study was to measure the distances between the anatomical landmarks of the human brainstem for defining the safe entry zones on the ventrolateral surface of the human brainstem. As discussed here, there are a number of studies on the morphometry of the ventrolateral surface of the human brainstem. In these different measurement parameters, different techniques and study populations are used. This study used a higher number of specimens and more measurement parameters on the same sample set, thus providing a more precise and definitive evaluation of the human brainstem morphometry.
The pontomesencephalic and bulbopontine sulci distance was measured by Kazda and Putz [2] as 28.6 mm (min. 22-max. 33 mm). In this study, we measured the average pontomesencephalic sulcus-bulbopontine sulcus diameter 26.92 mm (min. 21.77-max. 34.19 on the right side; min. 21.94-max. 32.63 mm on the left side). For the basilar sulcus-lateral side of pons distance, Kazda and Putz [2] measured the average length as 18.6 mm on the right side and 19.7 mm on the left side. In the present study, we measured the basilar sulcus-lateral side of pons distance 17.14 mm (min. 14.36-max. 22.12 mm) on the right side, 17.32 mm (min. 14.15-max. 20.07 mm) on the left side, and 17.23 mm for both sides.
Akar et al. [25] measured the transverse length of the pyramid as 6.1 mm (min. 5-max. 7 mm on the right side; min. 4-max. 8 mm on the left side). For the same parameter, Kazda and Putz [2] measured the length as 5.5 mm (min. 4-max. 7 mm). In the present study, we measured the transverse length of the pyramid as 5.38 mm (min. 3.82-max. 86 mm) on the right side and 5.45 mm (min. 4.44-max. 6.78 mm) on the left side. When both the right and lefts sides were considered, the mean pyramid transverse length was 5.42 mm.
The vertical length of pyramid was measured as 19.7 mm (min. 16-max. 22 mm) on the right side, and 18.5 mm (min. 13-max. 21 mm) on the left side in study of Akar et al. [25]. In the present study, we measured the vertical length as 21.43 mm (min. 17.48-max. 23.55 mm) on the right side, and 21.29 mm (min. 17.31-max. 24.18 mm) on the left side; the mean diameter was 21.36 mm.
The safe entry zone for the lateral mesencephalic sulcus is between the substantia nigra anterolaterally and the medial lemniscus posteriorly [23]. Recalde et al. [26] measured lateral mesencephalic sulcus length as 9.6 mm (min. 7.4-max. 13.3 mm). In the present study, we measured this length as 12.8 mm (min. 10.4-max. 14.35 mm) on the right side, and 12.67 mm (min. 9.91-max. 15.75 mm) on the left side. Yang et al. [27] reported the average length of the safe entry zone, extending from the medial geniculate body to the pontomesencephalic sulcus, as 9.6 mm (min. 7.4-max. 13.3 mm), with an average depth of 8 mm (min. 4.9-max. 11.7 mm).
The anterolateral surface of the pons is considered a safe zone for entering the brainstem. Recalde et al. [26] also cut the descending fibers at the level of the trigeminal nerve, resected rostrally, and observed the substantia nigra as well as the intraneural projection of the oculomotor nerve. They measured the distance between the oculomotor nerve where it penetrated the substantia nigra and the lateral mesencephalic sulcus as 8.02 mm (min. 4.9-max. 11.7 mm). In this study, we measured the distance between the oculomotor nerve where it emerged from the anterior surface of the brainstem and the lateral mesencephalic sulcus. This length was 13.99 mm (min. 11.54-max. 15.95 mm) on the right side, 13.71 mm (min. 11.72-max. 15.35 mm) on the left side, and 13.85 mm for both sides.
Recalde et al. [26] also measured the distance between the trigeminal nerve and pyramidal fibers as 4.64 mm (min. 3.1-max. 5.6 mm). In the present study, we measured the distance between the trigeminal nerve where it emerged from ventrolateral surface of brainstem and the upper tip of pyramid as 17.58 mm, 17.36 mm (min. 13.6-max. 22.18 mm) on the right side, and 17.81 mm (min. 14.54-max. 21.68 mm) on the left side.
For the transverse length of the inferior olive, Akar et al. [25] measured the superior and the inferior portions of the inferior olive. However, their measurements for the inferior olive were not at the midpoint line, but more lateral. We measured the transverse length of the inferior olive at the midpoint line as 5.21 mm, 5.24 mm (min. 3.96-max. 6.77 mm) on the right side, and 5.18 mm (min. 4.19-max. 6.59 mm) on the left side. Akar et al. [25] measured the vertical length of inferior olive as 11.7 mm (min. 9-max. 15 mm) on the right side, and 10.8 mm (min. 10 6.48 mm) on the left side, for the superior and inferior colliculi, respectively. The length of tectum was also measured by Sabanciogullari et al. [14] as 13.57 mm (min. 10.3-max. 16 mm). Our results were 14.96 mm (min. 12.9-max. 20.79 mm) on the right side, and 14.04 mm (min. 11.47-max. 15.84 mm) on the left side. When both left and right sides were considered, our mean tectum length was 14.5 mm.
The interpeduncular fossa length was measured 11.72 mm (min. 7-max. 20 mm) on unfixed human brain specimens by Pedroza et al. [28]. In the present study, the interpeduncular fossa length was measured as 11.4 mm (min. 9.67-max. 13.13 mm) of the right side, and 11.13 mm (min. 9.94-max. 11.79 mm) on the left side. When both left and right sides were considered, the mean interpeduncular fossa length was 11.26 mm.
The findings of this study have to be seen in light of some limitations. Quester and Schröder (1997) showed that formalin-fixation lead to changes in size of the brainstem; transverse measurements did not change with fixation; however, there were decreases in longitudinal distances resulted in shrinkage of 1-8% [29]. Also, the response of formalin-fixed brainstem tissue in terms of retraction will not be the same with in vivo.
In conclusion, this study provides the morphometry of the ventrolateral brainstem structures as a reference for surgical approaches to intrinsic brainstem lesions. Thorough anatomical knowledge and careful analysis of preoperative imaging are essential before surgery of brainstem lesions such as gliomas, cavernomas, or abscesses. Presenting many measurement parameters related to safe entry zones to the brainstem, we suggest that the findings of this study may be of significant assistance to neurosurgeons operating on this challenging region.