Risk factors influencing cerebral venous infarction after meningioma resection

After the approval of the hospital ethics committee and the informed consent of the patients or their families, the clinical and imaging data of 1127 patients with intracranial meningiomas who underwent resection in the Department of Neurosurgery, Tangdu Hospital, Air Force Medical University from March 2011 to July 2020 were retrospectively collected and analyzed. All operations were performed by experienced senior doctors. Age, sex, tumor size, tumor location, peritumoral edema, peritumoral vein, tumor resection degree and pathological grade were included. The size of the tumor was taken as its largest diameter on MRI. The location of the tumors was divided into superficial meningiomas: convexity, parasagittal and falx meningiomas; deep meningiomas: skull base and other meningiomas. Peritumoral edema was divided into two groups: no-mild and moderate-severe. EI (edema index) = edema plus tumor volume/tumor volume (EI = 1, no edema; EI = 1–1.5, mild edema; EI = 1.5–3, moderate edema; EI > 3, severe edema). Peritumoral veins were divided into key veins (Labbe, Trolard, Rolando, etc.) and collateral anastomotic veins. The degree of tumor resection was evaluated by intraoperative and postoperative enhanced MRI. Gross total resection (GTR) was defined as Simpson grades I–III, while subtotal resection (STR) was defined as grades IV–V. Histopathological grading was performed according to the 2016 WHO criteria. The patients were followed up for an average of 6 months. The prognosis of the patient after a venous infarction was evaluated by the GOS score.

CVI (postoperative CT scan) was defined as a new or a larger low-density area around the tumor resection or hemorrhage around the low-density area in the brain parenchyma after the operation. CVI included symptomatic and asymptomatic. Symptomatic CVI was the occurrence of neurological dysfunction, epilepsy and a disturbance of consciousness that matched the venous infarction area. The patient had no clinical manifestations, but the imaging considered that CVI was asymptomatic venous cerebral infarction. In this study, we focused on additional medical or surgical treatment for patients with symptomatic CVI.

The tumor specimens were histopathologically examined and analyzed. Hematoxylin-eosin (HE) staining was performed on the 5μm section of the tumor center. Images are observed and captured using equipments including microscopes (LEICA DM 2500), objective lenses (LEICA 10 × /0.25), camera (LEICA DFC310 FX), detector (LEICA CMS GmbH D-35578 Wetzlar) and software (LEICA Application Suite, version 4.0.0). The resolution was measured at 300 dpi with automatic exposure and white balance.

Categorical variables were expressed as numbers (percentages), and the difference was evaluated by the chi-squared test or Fisher’s exact test, as appropriate. To detect independent risk factors associated with the incidence of CVI, univariate regression analysis was adopted. Risk factors with p < 0.05 in univariate regression analysis were selected for further multivariate regression analysis. Odds ratios (ORs) along with 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted by using R software version 4.0 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria. http://​www.​R-project.​org/​).

Postoperative venous infarction occurred in 53 of 1127 patients (4.7%) who had undergone surgical resection for meningioma. There were 37 of symptomatic infarction and 16 of asymptomatic infarction. 35 superficial meningiomas (12 convexity, 15 parasagittal and 8 falx) and 18 deep meningiomas (14 skull base and 4 lateral ventricle). Venous infarction was most commonly associated with falx meningioma (10.7%, 8 of 75), followed by parasagittal (6.8%, 15 of 220), convexity (3.5%, 12 of 335), skull base and lateral ventricle (3.6%, 18 of 497). Among 37(3.3%) of symptomatic infarction, 28 superficial meningiomas (8 convexity, 12 parasagittal and 8 falx) and 9 deep meningiomas (7 skull base and 2 lateral ventricle). Venous infarction was most commonly associated with falx meningioma (10.7%, 8 of 75), followed by parasagittal (5.4%, 12 of 220), convexity (2.4%, 8 of 335), skull base and lateral ventricle (1.8%, 9 of 497) (Tables 1 and 2).

The main manifestations after infarction were a deterioration of consciousness after hemorrhage (6 cases), headache (10 cases), limb dysfunction (14 cases), epilepsy (7 cases), or aggravation of the original symptoms. The disturbance of consciousness (6 cases) mostly occurred 1–3 days after the operation and showed progressive worsening. 37 cases of symptomatic cerebral venous infarction were divided into mild (20 cases, score of 13–15), moderate (10 cases, score of 9–12) and 7 cases (severe, score of 3–8). 16 cases were asymptomatic (mild, score of 15). The hematoma was removed in emergency situations, and the bone flap was removed when necessary. Other symptoms showed chronic aggravation over 3–7 days and were gradually relieved over 8–14 days. The symptoms were relieved most obviously within 1 month after the operation, but no obvious further improvement was found after 3 months. The overall prognosis was good. After an average follow-up of 6 months, there was 1 case of severe disability (muscle strength grade 0 of one limb, loss of deep and shallow sensation, injury of the Rolando vein), 1 case of vegetative survival (injury of the Labbe vein), and 1 case of death (death due to severe intracranial infection after cerebral venous infarction) (Table 3).

Two cases of meningioma with risk factors (critical vein and superficial) caused hemorrhage after venous infarction by damaging critical vein (Fig. 1).

A case of left frontal parasagittal meningioma with risk factors (peritumoral edema, peritumoral vein, high-grade meningioma, key vein) secondary to venous infarction after injury of cortical pial vein system (Fig. 2). 

Superficial meningioma refers to the convexity, parasagittal and falx, often accompanied by peritumoral veins. The growth pattern spreads along the cistern and embeds into the brain parenchyma, indicating that superficial meningioma has a wider contact surface between the tumor and brain parenchyma than deep meningioma and it lacks a cerebrospinal fluid barrier [8]. Therefore, the probability of injuring the peritumoral vein and cortical pial system during resection is higher than that for deep or other meningiomas.

The previous literature has reported that the bifrontal or near midline approach is a risk factor for cerebral venous infarction. The essence of the approach is to remove the tumor through the bridging vein and sinus, which hinders the exposure or manipulation of the tumor during the resection process so that the operator has to block or accidentally damage the vein around the tumor. At the same time, the previous view was that the frontal cortical vein and the anterior 1/3 superior sagittal sinus could be sacrificed, but clinical cases confirmed that this is definitely not desirable and the risk of infarction after injury will be significantly increased, which may have catastrophic consequences. Previous research [9] has shown predictors of positive motor function in rolandic meningomas, including venous involvement. To prevent CVI, the peritumoral veins and collateral veins of convexity, parasagittal and falx meningiomas can be classified [10‐12]. It was suggested that the key veins should be avoided as much as possible, and the collateral veins should be selectively severed according to the degree of compensation to avoid the occurrence of cerebral venous infarction to the greatest extent.

Peritumoral edema is a common imaging manifestation in patients with meningioma and is a compensatory reaction of damaged brain tissue. The pathogenesis of peritumoral edema includes brain parenchymal compression, secretion of fluids, venous compression and hydrodynamics theory. The presence of brain parenchyma tumor interface-associated edema indicates a poor prognosis of the nervous system [13]. The destruction of the tumor brain arachnoid layer interface leads to the formation of peritumoral edema. Dysplasia of the peritumoral drainage veins can also cause peritumoral edema. Meningiomas with peritumoral edema have a higher probability of destroying the cortical pial venous system. WHO grade II–III (atypical, anaplastic) meningiomas invade the arachnoid, pia mater, brain tissue and adjacent dura mater [14], increase the permeability of the meninges and blood vessels, aggravate the edema, and more easily damage the cortical venous system during the operation, resulting in increased postoperative edema and possibly venous infarction. Therefore, high-grade meningioma and peritumoral edema are risk factors for cerebral venous infarction. During the operation, we should try to separate along the tumor arachnoid boundary and retain part of the cortical venous system in order to reduce the incidence and severity of venous infarction.

Previously, it was reported that tumor growth could destroy the arachnoid interface between tumors and meninges, and tumors ≥ 4 cm are a risk factor for cerebral venous infarction [15], but our data showed that there was no significant difference. Considering that tumors increase in volume, the brain tissue is compressed, the blood–brain barrier is destroyed, and peritumoral edema is formed, but there are still some tumors without peritumoral edema. In addition, its formation may be related to the operation. Usually, for large tumors, we should reduce the tension of the tumor on the vein first, and the possibility of injury is small, which is not different from that of tumors < 4 cm. The data from this group confirmed that there was no difference in the degree of tumor resection. Usually, the residual tumor is closely related to the sinus. For sindou [16] I–III tumors, total resection can be achieved, while for sindou VI–V tumors, surgical resection is limited to reduce the risk. At the same time, the stenosis or occlusion of the sinus will be compensated for by collateral anastomosis. Therefore, the degree of resection is not a risk factor for CVI.

The following strategies can be selected during the perioperative period. MRV or CTV were performed routinely before operation, and a three-dimensional image fusion model (3D) [17] could be established if possible. Intraoperative neurophysiological monitoring and indocyanine green angiography (ICGVA) [18] were used to evaluate the spatial relationship between peritumoral veins and meningiomas, as well as the degree of tumor invasion and venous patency, so as to provide strong evidence for the protection and choice of peritumoral veins during operation. Venous anastomosis was performed after injury [19] when necessary.

Injury to a key vein or the cortical pial vein system can cause CVI, but the severity of CVI after injury differs, and the symptoms of patients are also different, from no obvious symptoms to serious neurological impairment and even disturbances of consciousness. Robertson [20] divided cerebral venous infarction into the acute phase and chronic phase. Severe complications occurred in a short time after the operation in the acute stage and were life-threatening, while the chronic stage lasted for several days to months with mild symptoms. Generally, injury to the critical vein can cause serious complications in the acute stage, including postinfarction hemorrhage, limb and speech dysfunction, epilepsy, coma, etc. Timely review of CT and surgical intervention are needed. After cortical pial venous system injury, the symptoms of the patients gradually worsened, but the symptoms could be relieved after conservative treatment. The prognosis of patients with venous infarction is better if they are treated in time, but damage to a key vein will cause irreversible neurological damage.