Mobilization of the outer cavernous membrane decreases bleeding and improves resection in spheno-clinoidal meningiomas without cavernous sinus extension: A randomized controlled trial
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.227306
Source of Support: None, Conflict of Interest: None
Keywords: Bleeding, cavernous sinus, spheno-clinoidal meningioma
Bleeding in large spheno-clinoidal meningiomas is a challenge because it prevents the obtaining of a clean surgical field for a comfortable neurovascular dissection. This, in addition to other factors, affects the extent of resection.,, The source of this bleeding is mainly the middle meningeal artery and the meningio-hypophyseal trunk.,, An early surgical interruption of these vessels requires mobilization of the outer cavernous membrane. This approach is standard for spheno-cavernous meningiomas, where the outer cavernous membrane divides the tumor into an intra-dural resectable part, and an intra-cavernous part. However, mobilization of the outer cavernous membrane for cases without cavernous sinus involvement is not a common practice. The aim of this study was to determine whether or not an additional mobilization of the outer cavernous sinus membrane as part of the surgical approach, in large spheno-clinoidal meningiomas without cavernous sinus extension, would decrease bleeding and increase the extent of resection.
The study was approved by the Institutional Review Board of the Faculty of Medicine, Cairo University [Protocol code N-44-2016, registered on Clinicaltrial.gov (NCT02863484)] and conducted as a randomized controlled single blinded trial, with a 1:1 allocation, according to the ethical guidelines of the declaration of Helsinki.
Inclusion and exclusion criteria
Only adult patients (≥18 years) with large (≥ 4 cm in maximum diameter) spheno-clinoidal meningiomas, without cavernous sinus involvement, were included in the study. Malignant or recurrent meningiomas, neurofibromatosis, small tumors (<4 cm in maximum diameter), or tumors with evidence of cavernous sinus involvement, were not included in the study. Also, tuberculum sella and olfactory groove meningiomas were not included in the study. The patients who suffered an intra-operative vascular injury were not included in the study.
Prior to commencement of the trial (pilot study)
13 patients (7 in the treatment group and 6 controls) were operated to explore and standardize the technique and size of the skin incision, craniotomy, and the amount of blood loss before dural opening.
Allocation was based on a computer generated random number protocol. Randomization numbers were concealed in closed opaque envelops.
This study recruited 94 cases. In 35 cases (37.22%), the tumors were located at the medial sphenoid wing (clinoidal meningiomas); in 12 (12.8%) cases, at the lateral sphenoid wing; and, in 38 (40.4%) cases, at the middle sphenoid wing. In 9 cases (9.6%), an en-plaque meningioma was present.
Both groups were operated upon by a single surgeon to reduce the operator dependent variability in terms of surgical skills and techniques. Both groups underwent a fronto-temporal craniotomy. In the study group, mobilization of the outer cavernous sinus membrane was performed before opening of the dura; while, the control group was operated upon by opening the dura without mobilization of the outer cavernous membrane, as has been described previously.,, In the patients in whom mobilization of the outer layer of the lateral wall of the cavernous sinus was performed, the operative technique included resection of the lesser wing of the sphenoid bone. This was followed by performance of an orbitotomy using a high-speed drill. After the orbitotomy, the periorbita was exposed and dissected bluntly from the outer surface of the greater wing of the sphenoid bone [Figure 1] and [Figure 2]. Using a small bone nibbler, the greater wing of the sphenoid bone was removed along with the remaining part of the lesser wing of the sphenoid bone, down to the level of the base of the anterior clinoid process. This opened the superior orbital fissure and exposed the meningeal-orbital fold. Using sharp dissection, the tentorial fold was divided, and, using blunt dissection, the dura of the outer layer of the lateral wall of the cavernous sinus was peeled away, exposing the oculomotor and trochlear nerves, followed by the ophthalmic division of the trigeminal nerve, then the maxillary division, and finally, the mandibular division. At this stage, the foramen spinosum was reached, and the main trunk of the middle meningeal artery was coagulated and divided [Figure 3] and [Figure 4]. Finally, the dura was elevated off the apex of the petrous bone with dissection of the greater petrosal nerve [Figure 5]. In the cases showing extension into the posterior fossa, the apex of the petrous bone was drilled away, the superior petrosal sinus was ligated and the tentorium was divided all the way to the tentorial incisura taking care not injure the trochlear nerve. After completion of the extra-dural phase of the procedure, the tumor was detached from the basal temporal dura forming the outer layer of the lateral wall of the cavernous sinus and excised with it. The avascular tumor in the middle cranial fossa was then removed all the way to the free border of the tentorium. The Sylvian fissure was then split, utilizing a lateral to medial trajectory, and then from inside to outside, a process that was facilitated by the relaxation that had been achieved at the base of the brain by the removal of the middle-fossa part of the tumor. At this stage, the avascular field facilitated the sharp dissection in the subarachnoid plane between the tumor and the middle cerebral artery. The plane was then maintained proximally to the carotid bifurcation, and finally to the internal carotid artery [Figure 6] and [Figure 7]. After securing the major vessels, the medial part of the tumor was dissected to expose the optic nerve, and the optico-carotid triangle was cleared of the tumor. In the cases who showed no evidence of a good plane of dissection, a piece of tumor was left attached to the vessel in question. In cases who showed evidence of extension of the tumor into the optic canal, the anterior clinoid process was drilled away extradurally, and the falciform ligament was divided, followed by opening of the dura propria with mobilization of the optic nerve and exposure of the ophthalmic artery with removal of the tumor from the optic canal. Reconstruction of the basal temporal dura was done using pericranium, and, after securing hemostasis, the wound was closed in layers.
The primary outcome of this study was the difference in the amount of blood lost during surgery between both groups of patients. Blood loss was calculated as the sum of the numerical value of the net weight of the sponges used during surgery, and the numerical value of the difference in the amount of fluid estimated to be present in the aspiration compartment and the total amount of irrigation fluids administered. The numbers of blood units given were also determined.
The secondary outcome variables were the estimated blood loss (EBL) calculated according to Mercurelli's formula, the extent of tumor resection and the amount of blood transfusion.
Radiological follow up was performed 6 weeks after surgery.
49 patients underwent mobilization of the outer cavernous sinus membrane (constituting the group termed as 'with mobilization' [WM]) prior to proceeding with the tumor removal; and. 45 patients underwent direct removal of the tumor, without mobilization of the outer cavernous sinus membrane (constituting the group termed as 'no mobilization' [NM]). The number of patients, the location of tumors, and the surgical approaches adopted, are shown in [Table 1].
All statistical analyses were done using the Statistical Package for the Social Sciences (SPSS 23, IBM Inc.). For testing of hypothesis, the unpaired t-test was used and a P< 0.05 was considered significant.
121 patients were assessed for eligibility. 15 patients were not included (9 not meeting the inclusion criteria, 3 refused to participate in the randomization, and 3 were not included for other reasons). 106 patients were randomized, with 52 patients being allocated to the mobilization arm, and 54 being allocated to the non-mobilization arm. 3 patients were lost to follow up in the WM group, and 9 patients were lost to follow up in the NM group. Thus, the study finally included 49 patients in the WM group, and 45 patients in the NM group.
72 (76.6%) cases were female, and 22 (23.4%) were male patients. 13 (13.8%) patients were less than 35 years of age, 56 (59.6%) patients were between 35 and 55 years of age, and 25 (26.6%) patients were above the age of 55 years [Table 1].
In the beginning, the estimated blood volume (EBV), hemoglobin% (HGB), red blood cell count (RBC), tumor size and hematocrit (HCT) were compared in both the groups using the T-test for two independent groups. This was done to determine that both groups were comparable. There was no statistically significant difference between both the groups regarding: EBV, HGB and RBC, tumor size and hematocrit (with a P value of 0.657, 0.1, 0.089, 0.085 and 0.373, respectively). [Figure 8] shows the mean values for each of the variables compared in both the groups.
Secondly, for each tumor location, both groups were assessed to determine that a comparable percentage-distribution of cases were included in each group. For each location, there was a relatively good similarity, as shown by the Kolmogorov-Smirnov (KS) test (P = 0.917). [Figure 9] shows the percentage distribution of tumors at different locations compared between both the groups.
Generally, both groups were comparable, as shown by the results of the homogeneity tests performed.
Thirdly, the amount of blood loss and estimated blood loss (EBL) were compared in both the groups using the T-test for two independent samples, as mentioned in [Table 2]. This showed the amount of blood loss and estimated blood loss to be significantly less in the WM group (with the P values being 0.00 and 0.013, respectively).
Fourthly, the amount of residual tumor remaining following the surgical excision was compared between both the groups to determine the group in which a higher rate of radical resection was possible, as showed in [Table 3]. The comparison was done using the T-test for two independent samples. It showed that the group of patients who have received mobilization of the outer cavernous sinus membrane had a higher rate of radical resection, as expressed by a lower volume of residual tumor (P = 0.005).
Assessment of complications
The complications that occurred in our study are illustrated in [Table 4]. Postoperative cranial nerve paralysis was the sole statistically significant variable between both the groups, with an incidence of 26.5% versus 8.8 in the WM and the NM groups, respectively. In the majority of cases, third cranial nerve palsy was the most common deficit found. Almost all cranial nerve deficits resolved spontaneously within the first 3-6 months after surgery with conservative treatment. Facial nerve paralysis was reported in one case (associated with traction on the geniculate ganglion) and resolved after 6 weeks postoperatively. Facial paresthesia was also predominant in the mobilization group; however, this was not a permanent problem in any of the cases.
A 45-year old male patient presented with gradually progressive headache and diminution of vision on the right side. He also had epileptic attacks, which were not controlled by medical treatment. He was kept on phenytoin 100 mg TDS. On examination, his vision was 20/100 on the right side and 20/28 on the left side. Fundus examination revealed a pale optic disc on the right side. Visual field examination showed a homonymous hemianopia on the affected side. The patient was operated upon with mobilization of the outer layer of the lateral wall of the cavernous sinus. The operative blood loss was 400 cc of blood. In spite of the tumor completely encircling the internal carotid artery, the arachnoidal plane could be established with a sharp dissection permitting a complete tumor resection. Post-operative recovery was uneventful. During the follow up period, the patient showed an improvement in his visual condition on the right side. However, the attacks of epilepsy continued in the form of complex partial seizures, inspite of complete tumor removal. The histopathological diagnosis was a meningiothelial meningioma World Health Organization grade I. [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14] demonstrate the pre- and postoperative images of the patient.
A 49-year old female patient presented with headache and blurring of vision. Additionally, this patient had cognitive dysfunction and epileptic attacks. Her neurological examination revealed no abnormality apart from bilateral papilledema grade 4. Neuroimaging showed a clinoidal meningioma.
A standard pterional approach was undertaken. The dura was opened in a C-shaped fashion based on the sphenoid wing. De-bulking of the tumor was then carried out. Although the dissection started at the dural base after coagulation of the tumor tail, yet the tumor was still vascular and bled excessively during its removal. The blood loss during the operation was significant and the patient needed a blood transfusion of 6 units. The post-operative period was stormy as the patient developed cerebral salt wasting syndrome, internal jugular vein thrombosis and communicating hydrocephalus. However, following the successful management of these conditions, the patient was discharged with an improvement in her neurological condition. Her cognitive deficits had improved but never returned to the normal levels. The histopathological diagnosis was a meningiothelial meningioma, World Health Oganisation grade I [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20].
The results of this study indicate that in the two comparable (with respect to tumor size, location and pre-operative hematological features) groups of patients, patients who received mobilization of the outer cavernous membrane showed a significantly lower blood loss, estimated blood loss (EBL), and a better rate of resection.
The better resection obtained in the group of patients who received mobilization of the outer cavernous membrane, reflects an improved ability to perform neurovascular dissection, created by an avascular surgical field. This facilitates a direct excision of the tumor, circumventing the need for a continuous bipolar coagulation at the base of the tumor. Another advantage of mobilization of the outer cavernous membrane was that the procedure helped in advancing the steps of neurovascular dissection during surgery to an earlier phase, in which the neurosurgeon, who was not tired and was in a better state of mind, was better equipped to deal with this critical part of surgery.
Large spheno-clinoidal meningiomas that are associated was a large scale intraoperative bleeding, can be removed by a variety of approaches, but the fronto-temporal approach or its modification is the approach most widely used. Mobilization of the outer cavernous membrane is performed as a standard part of the procedure in spheno-cavernous meningiomas, where this step divides the tumor into an extra-cavernous part and an intra-cavernous part. For the cases, where the tumor exists without a cavernous sinus extension, mobilization of the outer cavernous membrane is not a common practice, and its effect on bleeding and resection has not been proven by a controlled clinical trial.,
Bleeding from the cavernous sinus may be encountered during mobilization of the outer cavernous membrane if an anatomically deficient part of the lateral wall of the cavernous sinus is encountered; however, the cavernous sinus bleeding is easily controllable and usually has not reflected on the overall blood loss. The effectiveness of the technique proposed in this article emanates from the interruption of the end-artery feeders to the tumor only, and not the main-branch vessels (as occlusion of the latter vessels may compromise important collateral vessels). This technique is particularly helpful in controlling tumor feeders emerging from the lateral wall of the cavernous sinus, which originate in the meningio-hypophyseal trunk and represent the main blood supply to spheno-clinoidal meningiomas. Additionally, the division of the middle meningeal artery interrupts an important source of blood supply to the tumor.
Embolization is the method most commonly used to reduce bleeding in meningiomas. To be effective, a complete embolization of all the feeding vessels to the tumor should be undertaken, and this is rarely possible. Additionally, 9-21% of cases develop permanent neurological deficits with a 1% mortality., Most of the complications occur during the process of interrupting the feeders from the internal carotid artery, particularly from the meningio-hypophyseal trunk. Accordingly, the value of embolization in meningiomas present in the spheno-clinoidal region is questionable.,
Injecting hydrogen peroxide into the meningioma is another method of reducing bleeding. It is simple, feasible, cost-effective and safe but not always effective. Ultrasonic-aspiration, laser, or microwave thermo-coagulation are other methods that can be used to reduce bleeding in meningioma surgery; however, they are not regularly effective in reducing bleeding and may be associated with a risk of physical or chemical injury., Unlike these methods mentioned, mobilization of the outer cavernous sinus membrane is not associated with the risk of physical or chemical injury.
The complications reported in this series included aggravation of pre-existing visual deficits; the development of weakness or dysphasia, post-craniotomy syndrome, epilepsy, wound infection, cranial nerve palsy; as well as cerebrospinal fluid (CSF) accumulation leading communicating hydrocephalus requiring a CSF diversion procedure. There were no significant differences in the incidence of complications between both the groups, except for the higher incidence of post-operative cranial nerve deficits. This was significantly higher in the group that received mobilization of the outer cavernous membrane. The commonest postoperative cranial nerve deficit was in the form of third cranial nerve paralysis. However, in all the patients, this deficit resolved spontaneously during the follow-up period, usually within the first 3-6 months after surgery. One patient developed a temporary seventh nerve paralysis due to traction on the geniculate ganglion, but this resolved spontaneously within the first 6 weeks after surgery. No patients suffered from any vascular injury due to the mobilization of the outer cavernous membrane. Other studies describing the same approach have also alluded to similar complications.,,
The actual estimation of the intra-operative blood loss is always associated with an element of inaccuracy; however, the most important factor that determines the usefulness of a particular operative maneuver is the ability to obtain a better resection. The main limitation encountered during the mobilization of the outer cavernous membrane is the need for a specialized training to perform the procedure. This is because the operative technique requires the skill to mobilize the outer cavernous membrane without entering the cavernous sinus or the intra-dural compartment and can be only be perfected after repeated practice in the microsurgical cadaveric lab. This makes the performance of the approach by the neurosurgeon in training (who is usually the one doing the craniotomy) difficult. However, the significance of the approach and the benefits obtained from its execution, should urge future skull base surgeons to practice the technique and acquire the necessary training to perform this complex approach.
In spheno-clinoidal meningiomas without cavernous sinus involvement, routine mobilization of the outer cavernous sinus membrane reduces bleeding. It also helps in cranial nerve dissection (as it advances the stage of the neurovascular dissection during surgery) and permits a more radical resection.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20]
[Table 1], [Table 2], [Table 3], [Table 4]