Comparison of Short-Term Surgery Outcomes Between Older and Younger Patients With Middle Third Parasagittal and Falx Meningioma


 Background and Purpose

Middle third parasagittal and falx meningiomas can cause severe neurological deficits. The incidence of meningioma rises with age and comorbidities. Elderly patients may suffer from operative complications and recover more slowly than younger patients. The aim of this study was to assess the clinical characteristics and surgery outcomes between younger and elderly patients with meningiomas.
Methods

The patients of middle third parasagittal and falcine meningiomas operated from January 2011 and December 2019 were reviewed in this retrospective study. All lesions arose from the middle third of the falx or superior sagittal sinus (SSS). The complications, such as peritumoral edema, operative blood loss, and neurological deficit, and postoperative hospital stay, were compared between groups.
Results

Forty-three elderly patients and 63 younger patients were included in the current study. The elderly had larger and more aggressive lesions than younger individuals (P=0.013). Moreover, the aging group had severe peritumoral edema (P=0.019) and longer postoperative hospital stay (P=0.009) than younger patients, while the younger suffered from higher blood loss (P=0.022) and reoperation (3 vs. 1) at perioperative period. Furthermore, no significant difference was detected in the neurological deficit between the two groups (p=0.97).
Conclusions

Although severe peritumoral edema gave rise to larger lesions, elderly patients with the middle third of parasagittal and falcine meningiomas shared similar surgery outcomes as younger individuals. However, after considering all the factors, elderly patients were more likely to develop minor postoperative complications compared to younger ones.


Introduction
The incidence of parasagittal meningioma ranges from 16.8-30% among all intracranial meningioma [1,2]. Parafalcine meningiomas account for about 8.5% of the intracranial meningioma [3], while falcine meningiomas represent approximately 9% of all intracranial meningiomas [4]. Parasagittal meningiomas are distinguished based on the anterior, middle, and posterior locations along the sinus [4]. Compared to the anterior and posterior third meningiomas, the third middle lesions cause motor function deterioration in the early disease stage and have a poor postoperative outcome. Regarding the discrepancy of physiological conditions, younger patients recover faster from operation than older patients [5]. In this study, we compared the clinical characteristics and surgery outcomes between older and younger middle third parasagittal and falx meningioma patients.
Parasagittal and falx meningioma involving the middle third is associated with a high incidence of motor function deterioration either as a symptom or during the postoperative period [4,6]. Thus, preserving the venous system's integrity and cerebral cortex during surgical resection may be challenging [7]. Owing to the incidence of meningioma increasing with age and aging physiology and comorbidities, elderly patients might suffer from more operative-related complications and recover more slowly than younger patients [5].
The number of old people is increasing every year. According to some statistics, the proportion of the world's population >60 years in more developed regions will increase by 38% by 2050 [8]. Mental health and physical well-being are crucial during older age. The Middle third of parasagittal and falx tumors belong to a speci c category of brain diseases. The central cortex may be easily damaged or oppressed by the lesions, leading to a series of neurological de cits [7]. It has been reported that age over 65 years is predictive of greater inpatient death, LOS, total charges, and some of inpatient complications [9]. However, opposite views were also reported by some other studies [5]. The aim of this study was to compare the short-term surgical outcomes of elderly patients (>60 years) affected by the middle third of parasagittal and falx meningioma to those of a contemporary cohort.

Study design
This study was approved by the Ethics Committee of Guangdong 999 Brain Hospital, Medical College of JiNan University and was conducted in accordance with the latest revision of the Declaration of Helsinki. Data from patients with the middle third of parasagittal and falx meningioma, who underwent surgery in Guangdong 999 Brain Hospital from January 2011 to December 2019, were extracted from the hospital's electronic records. According to World Health Organization (WHO), those aged>65 years are de ned as the elderly population in developed countries, while the de nition in developing countries is >60 years. In the current study, all the subjects were Chinese; >60-year-old patients were classi ed into the elderly group, while those <60 years old into the younger group. Complications, such as symptoms, peritumoral edema, comorbidities, operative blood loss, and neurological de cit, postoperative hospitalization duration, and subgroup analyses were compared to investigate the differences between the two categories. According to the longest diameter of lesions, we classi ed tumor size into 3 categories: tiny (less than 2cm), median (2-5 cm), and giant (lager than 5cm) group. Operation blood loss was classi ed into 3 grades: general group (<400ml), medium group (400-1000ml), and massive group (>1000ml). Referring to previous literature [10], peritumoral edema was classi ed into 3 grades: negligible, mild, and severe. The extent of tumor resection was categorized according to the Simpson meningioma resection grade [11]. Since the majority of the patients underwent selective surgery and the duration between the admitting day and operating day varied in these patients, the length of postoperative hospital stay was selected as one of the events to evaluate surgical outcomes. The postoperative hospital stay deadline was de ned as the day of discharging or transferring to other departments, such as oncology and rehabilitation.

Clinical management
All the patients underwent magnetic resonance imaging (MRI) and/or computed tomography (CT) scan within 2 weeks prior to surgery. MR venography (MRV), CT angiography (CTA), and digital subtraction angiography (DSA) were performed if necessary. Dexamethasone and/or mannitol were preoperatively administered to the patients with severe peritumoral edema on T2-weighted MRI. The indications for emergency operation included cerebral hernia, cerebral or tumor hemorrhage, and rapid tumor progression. All the surgeries were performed by experienced surgeons. The surgical trajectory and position depended on whether the tumor was located in the anterior half or posterior half of the central falx. The surgical bone window depended on whether the lesion was unilateral or bilateral. An interhemispheric approach was taken on the non-dominant side in the patients with bilateral lesions.
Neuronavigation system (Brainlab, Germany), Cavitron ultrasonic surgical aspirator (Integra, USA), and electrophysiological monitoring (Cadwell, USA) were used as adjuncts to microsurgical tumor resection. The lesions were diagnosed according to "The 2016 World Health Organization Classi cation of Tumors of the Central Nervous System" [12]. All residual tumors and WHO II-III meningioma patients were recommended to receive adjuvant therapy treatment, including chemotherapy and radiotherapy.    A volume of 503±619 mL (range: 100-3300 mL) mean blood loss operation was signi cantly higher in the younger group than in the elderly patients (mean: 374±322 mL, range: 100-1400 mL) (P=0.022). Furthermore, 7 (11.1%) cases of young patients underwent massive blood loss compared to 3 (7%) cases in the elderly group.
Elderly patients spent an average of 17.25±5.8 days at the Neurosurgery Department after the operation, which was signi cantly longer than that by the younger group (13.50±3.8 days) (P=0.009).
The younger group presented more operative complications, such as subdural effusion, incision infection, operative eld bleeding, and subdural hematoma, than the elderly ( Table 2). The operative eld bleeding and subdural hematoma have the highest frequency of operative complications in both elderly (n=3) and younger groups (n=3). One 56-year-old woman died on day 2 after the operation; her primary chief complaint was repeated seizures for 3 years. An aneurysm clip was used to prevent bleeding of ruptured SSS in a 65-year-old male who suffered an 1800-mL blood loss during the surgery for resection of a huge meningioma involving SSS.
Pathologically, WHO grade I, II, and III meningiomas affected both groups, albeit no pathological difference was observed (P=0.154, Table 4). Simpson grade I and II resection achieved 88.3% (n=38) and 90.47% (n=57) success in the elderly and younger groups, respectively (P=0.787). A residual tumor (Simpson grade III and IV) was found in 5 (11.63%) and 6 (9.52%) patients in the two groups, respectively (p=0.787). Moreover, 5 patients rejected further treatment. Two patients in each group experienced tumor recurrence. Tumor recurrence 2 2 * Nimodipine was used on a young who was diagnosed as anaplastic subtype

Discussion
In this study, we compared the differences in short-term surgery outcomes between younger (<65 years old) and older patients (>65 of age) patients with middle third parasagittal and falx meningioma. The incidence of meningioma increases with age, with the peak incidence between the 6 th and 7 th decade of life [13]. Our data suggested that the elderly have more comorbidities, including hypertension, diabetes mellitus, liver disease, renal disease, pulmonary disease, and cardiovascular disease, compared to the younger patients; however, the operative complication rate was similar in the two groups (P=0.97). Simultaneous tumors occurred in 5 younger patients, all females. One of them had uterine broid and osteoma on the left tibia, while the other four had uterine broid, renal clear cell carcinoma, thyroid carcinoma, and glioblastoma, respectively. Multiple primary brain tumors with different histological types occurring in the same patient are extremely rare, and only a few such cases have been reported thus far [14,15]. Tunthanathip reported 6 cases of simultaneous multiple, primary brain tumors, predominantly in aging patients. In this study, one patient (a 55-year-old woman) presented with meningioma and glioblastoma.
Large meningiomas (>5 cm) were likely to occur in elderly patients, accounting for nearly 32.56% (14/43) as compared to 20.63% (13/63) in the younger group (P=0.013). Large meningiomas usually arise in an area of maximal brain compliance [16]. Cerebral atrophy facilitates maximal brain compliance in aging patients, and the symptoms do not appear until the lesion oppresses the central cortex. Furthermore, aged Chinese individuals tend to refuse to see the doctor before their health worsens due to the fear of discovering additional health problems. Some studies showed that the size of this neoplasm is indicative of the factors of fear and denial that occur in many patients, thereby delaying detection and therapy [17,18].
A previous study that investigated 42 patients with primary intracranial meningioma of all locations found preoperative peritumoral edema in 47.6% of patients >65 years old [10]. Our subgroup analyses demonstrated that giant intracranial meningioma invades the vital neurovascular structures and causes severe peritumoral edema. Furthermore, giant meningioma patients revealed severe peritumoral edema incidence rate than patients with medium and tiny meningioma. Severe edema was not detected in patients with tiny meningioma. In a study of 80 giant intracranial meningiomas, only 12.5% (n=10) cases revealed severe peritumoral edema [19]. The 80 lesions were localized at the skull base (n=57), convexity (n=17), and falx/parasagittal (n=6). Thus, we deduced that giant intracranial meningioma located at the middle third parasagittal and falx meningioma in elderly patients would have the highest frequency of severe peritumoral edema than any other subgroup.
Histological subtypes are related to peritumoral edema. Herein, we compared the postoperative peritumoral edema based on histological subtypes. We discovered that peritumoral edema was signi cantly larger in patients with grade II and III meningiomas than grade I meningiomas. In order to minimize any potential surgery-induced damage, the study chose the side of the non-dominant hemisphere to create a surgical window. Furthermore, the tumors were excised through an oblique anterior or a posterior trajectory instead of directly working over the major draining veins and eloquent brain. In a previous study, we utilized this approach to resect deep and tiny falx meningioma. Neuronavigation has been widely applied in neurosurgery [27,28]. Bir et al [29] analyzed 517 cases of meningiomas and concluded that interactive surgical navigation is a useful tool in the operative management of intracranial meningiomas; it can decrease the recurrence rate, blood loss, and length of stay and improve the RFS and performance status. In addition, neuronavigation should be used for small (<2 cm) and deep tumor falx meningioma, or else it would be rather time-consuming to seek out the tumor, thereby causing substantial damage to the brain. All tiny meningiomas were completely resected. In the current study, neuronavigation was applied in most patients as adjuncts to microsurgical tumor resection, and all the tiny meningioma were resected. There was no difference between the two groups according to the neuronavigation application (P=0.775). We proposed that giant parasagittal can be easily identi ed by the neurosurgeons through anatomical markers rather than the assistance of neuronavigation. Giant meningiomas often have a wide basement on the falcine, increasing the di culty of radical resection. Despite the large size, the tumors could be successfully removed from the unilateral side [6].
Operative blood loss is a critical parameter for evaluating the surgical effect. Surprisingly, in the current study, the blood loss was substantial in the younger group, which could be attributed to the wide surgical eld and fewer vessels destroyed in the elderly as a result of cerebral atrophy. Furthermore, less blood loss in the elderly may be the bene t from stricter indication and consummated preoperative preparation. SSS involvement was the most common reason for massive blood loss. A total of 9 young patients lost more than 800 mL of blood, of whom 7 (77.8%) had SSS involvement, while among the elderly, 2 (40%) patients showed SSS involvement in 5 massive blood loss patients. The closure of the middle and posterior thirds of the superior sagittal sinus carries a signi cant risk of cortical venous infarction. Surgeons must choose between two operating strategies: to attempt a total meningioma removal, restoring the venous out ow; or to leave residual meningioma and await sinus occlusion by the tumour and the development of collateral ow [30]. In some studies [31,32], patches, bypasses were recommended to reconstruct the damaged veins but not aneurysm clips as they are known to be susceptible to secondary thromboses [31,32]. In the current study, if SSS was damaged during the operation, venous reconstruction was performed using patches or bypasses. An aneurysm clip was used on the sinus wall to reconstruct the ruptured SSS in a 65-year-old man who underwent an 1800-mL blood loss during surgery to resect a huge meningioma involving the third middle SSS. Subtotal resection is one of several alternatives when the operation facing great risks [33].
A signi cant difference in the postoperative hospitalization duration was found between the two groups. Despite substantial blood loss in the younger group, they recovered faster than the aging patients. Supposedly, the aging physiology and comorbidities increase the duration of recovery in aging patients than younger patients [5]. controls and showed that the surgical morbidity in skull-based meningioma surgery was not related to the age of the patient. However, several studies obtained different results [5,36,37]. This discrepancy may construe stringent criteria for selecting appropriate candidates [38] for surgery in some studies, while other studies might apply loose criteria. Furthermore, in the current study, the heavy blood loss might increase the complication rate in the younger group. In the current study, a 56 year-old-woman died; her primary complaint was repeated seizures for 3 years. Thus, we deduced that this patient died of severe epilepsy, which caused secondary cerebral ischemia and hypoxia. Taken together, it can be inferred that elderly patients are more likely to develop minor postoperative complications than younger ones, but none of those complications are life-threatening events, which is consistent with Poon et al [5].
The pathological subtypes of 2 recurrent patients in the elderly group were transitional and atypical, respectively, while the 2 cases in the younger group were transitional and anaplastic, respectively. Magill reported 67 recurrent non-skull base meningiomas with 35 (52.2%) lesions locating at middle 3rd sagittal plane [13]. Middle third parasagittal and falx meningioma operation should apply by experienced surgeons with more patience and surgical technique.

Limitations
Firstly, this study's retrospective nature limits the ability to determine the degree of resident involvement in surgery. Furthermore, this is a single-center study, and the number of patients was not su cient to deduce a convincing conclusion.

Conclusion
In the current study, we found that elderly middle third parasagittal and falx meningioma patients tend to be affected by larger and more aggressive lesions than younger individuals. The older group was associated with severe peritumoral edema and longer postoperative hospital stay than young patients, while the younger group experienced more bleed loss and reoperation at the perioperative period; albeit no signi cant differences were detected in the neurological de cits, complications, and recurrence rate between the two groups. After considering all factors, elderly patients were more likely to develop minor postoperative complications than the younger ones but were not more prone to life-threatening events. The elderly patients need timely imaging checks to receive appropriate treatment.

Declarations Ethics Statement
The study was conducted with the approval of the Ethics Committee of The, Guangdong 999 Brain Hospital, Medical College of JiNan University.And the patient has signed informed consent.