Introduction
Central neurocytoma (CN) is an intraventricular brain tumor with the properties of both glial and neuronal differentiation. These neoplasms are rare (less than 1% of all tumors of the central nervous system (CNS)). However, they account about 50% of all intraventricular tumors in adults [1]. It is supposed that these tumors originate from persistent neurocytes of the subependymal plate of the lateral ventricles [2]. Only about 500 cases of CN have been described since the first publication of J. Hassoun et al. in 1982 [3]. To date, the most representative series are reported by Qian H. et al (n=92, 2012), Konovalov A.N. et al. (n=84, 2006), Wang M. et al. (n=63, 2018) [4—6]. CN is regarded as biologically benign neoplasm comprising mitotically inactive cells with slow growth rate. General prognosis is favorable [4, 7, 8]. Literature data on surgical treatment of CN indicate a gradual improvement of the postoperative outcomes. Great number of complications and low surgical quality were reported in early publications. For example, J. Hassoun et al. (1982) reported that radical surgery was possible only in 50% of cases [7]. According to S. Nishio et al. [9], complete resection may be also performed in less than 50% of cases. Moreover, postoperative complications are common [11]. According to the reports published in the last decade, complete resection is achieved in 71— 91% of cases [4, 10, 11].
There were 230 patients with CN who underwent surgery at the Burdenko Research Institute of Neurosurgery for the period 1992—2017. Treatment outcomes in 84 patients operated in 1992—2004 were published in 2006 [5]. Management of these patients was gradually improved in our center along with accumulation of experience. Certain changes occurred in the diagnosis and principles of surgical intervention.
Surgical treatment of CN for the period from 2008 to 2017 is analyzed in this report. The publication was divided into two parts considering large amount of data. Localization of CNs, choice of surgical approach and early postoperative results are analyzed in the first part.
Material and methods
The study included 115 patients with verified CN who were operated in 2008—2017. Age of patients ranged from 14 to 66 years (median — 30 years). Patients aged 20—30 years prevailed. There were 51 men and 64 women.
X-ray characteristics of central neurocytomas
CT-pattern of CN is characterized by local heterogeneous tumor comprising single and multiple petrificates and cysts. Tumors were large in most cases. The maximum linear dimension was 8 cm. This value was over 4 cm in 60% of cases.
Magnetic resonance imaging (MRI) is the main method of visualization of CN. MRI was performed in all patients. Intensity of tumor was close to that received from the cerebral cortex on T1WI in 66% of cases (n=76). Neurocytomas are characterized by mixed intensity on T2WI. A feature of these neoplasms is the presence of small cysts in tumor structure, which are better distinguishable on T2WI. In our sample, cystic changes were observed in 69% of cases (Fig. 1).
The degree of contrast enhancement of the tumor (CT/MRI) is variable. However, intensity of accumulation is moderate as a rule (78.5% of cases in our sample). Intensive accumulation of contrast agent was observed in 7.5% of cases. Accumulation was minimal or absent in 14% of cases. In our opinion, MRI is preferable over CT to assess spread of tumor through ventricular system, its relationships with septum pellucidum, corpus callosum and medulla invasion grade (Fig. 2).
These tumors are very diverse regarding localization in the lateral ventricles. CN may be localized in one or several parts of the same ventricle. Moreover, biventricular placement may be observed in case of invasion through interventricular septum. Infiltrative growth to periventricular structures may be observed in some cases. Tumor spread to the 3rd ventricle was found in 25 patients (Fig. 3).
We did not find literature data on classification of CN depending on dimensions and relationship to the ventricles. We classified all tumors into 4 groups considering their dimensions: small (maximum linear dimension <2 cm) — 17 (15%) cases; medium (2—4 cm) — 29 (25%) cases; large (4—6 cm) — 53 (46%); giant (> 6 cm) — 16 (14%) cases.
All tumors were divided into the following groups depending on localization in the lateral ventricles: A) anterior (in anterior horns) — 39 cases, B) median (predominant localization in the body of the ventricles) — 50 cases, C) posterior (predominant localization in the trigone and posterior horns) — 10 cases, D) advanced (occupy all departments of the lateral ventricles) — 16 cases (Fig. 3).
Clinical manifestations of CN
The most common clinical manifestation of CN was intracranial hypertension (ICH). These symptoms were found in 61 (53%) patients. ICH signs in the fundus of the eye were diagnosed in 67 patients. Mnestic and mental disorders were common too (34 (29.5%) and 23 (20%) patients, respectively). Pyramidal symptoms were detected in 12 (10.5%) patients (Table 1).
Thus, we can conclude that moderate clinical symptoms are observed in most cases despite large dimensions of tumors.
Indications for surgery
Surgery is indicated in patients with intraventricular tumor associated with neurological symptoms and MR-signs of neurocytoma. Severe concomitant diseases is first contraindication for surgery. In our opinion, resection is reasonable even in patients with giant tumors and no significant comorbidities because this is the only chance to help a patient. An exception may be tumors with advanced infiltrative growth and invasion of functionally important structures.
Anesthetic management of resection of neurocytoma
Anesthetic management is of great importance considering difficulties of resection of neurocytoma. All patients of our sample were operated under general anesthesia. The main scheme of anesthetic management was total intravenous anesthesia (TIVA) based on propofol and fentanyl. Napropine solution 0.75% was used for local anesthesia of soft tissues. We applied normal ventilation mode (PaCO2=36—38 mm Hg). Intraoperative monitoring corresponded to the standard adopted in our clinic: non-invasive and invasive blood pressure, BIS (bispectral index) and TOF (neuromuscular monitoring).
Vascular approach. Induction of anesthesia and tracheal intubation were followed by obligatory catheterization of several peripheral veins and one major vein (mainly internal jugular vein) with multiple-lumen catheter.
Infusion therapy. Infusion therapy was predominantly based on crystalloid solutions. Synthetic colloids (gelofusin or voluven) were used for blood volume substitution in case of moderate blood loss (within 30% of total blood volume). More severe blood loss (over 30% of total blood volume) was managed using derivatives of autologous blood (fresh-frozen plasma prepared in accordance with autologous donation program, washed autologous red blood cells obtained by using of Cell Saver system (Fresenius)). Reinfusion of autologous red blood cells was used in all patients. Donor components (FFP, packed red blood cells, cryoprecipitate) were used in case of severe blood loss and insufficient volume of autologous blood derivatives. Activated factor VII (Coagil, Generium) was administered in patients with severe secondary hemostatic disorders confirmed by TEG data.
As soon as surgery was completed, all patients were transferred to the intensive care unit for subsequent monitoring under ongoing sedation. Delayed awakening was preferred.
Surgical approaches to central neurocytoma
Anterior transcortical and transcallosal approaches were mainly used. Transcortical approach through incision of parietal cortex was used in some patients with predominant posterior localization of the tumor in lateral ventricle. The choice of access was based on a thorough analysis of MRI data. The volume and localization of the tumor, severity of hydrocephalus were considered. The primary objective was analysis of the possibility to resect all parts of the tumor under visual control with minimal brain injury.
Anterior transcortical approach was made through an incision of the cortex in projection of superior or middle frontal gyrus or through superior frontal groove from the side of predominant localization of the tumor. Supine position of patient with a slight (10—15°) head turn in opposite direction was optimal. Craniotomy did not exceed 3.0—3.5 cm in the projection of Kocher point. Transcortical approach was carried out through white the matter towards ventricular system. This approach was used for anterior and median tumors, median neoplasms with lateral spread, large tumors with lateral and contralateral spread associated with hydrocephalus (Evans’ index>0.5) (Fig. 4).
Craniotomy for transcortical approach was displaced anteriorly in patients with advanced tumors occupying all parts of the lateral ventricle. Therefore, the angle of attack would maximize visualization and resection of tumor along its axis.
Transcallosal approach. Transcallosal approach was preferred for median or unilateral tumors without significant lateral growth. This access was used in patients with small and medium tumors and in cases of absent or mild hydrocephalus. The advantage of this approach is exposure of both lateral ventricles and the absence of cortical incision. The shortcoming is the risk of injury of the veins flowing into superior sagittal sinus. Linear skin incision was followed by dissection of the bone flap 3.5x3 cm. Two-thirds of this flap were placed anterior and 1/3 posterior to the coronal suture. Dura mater was opened with a base turned to superior sagittal sinus. There are usually no large veins flowing into superior sagittal sinus in the area anterior to coronal that facilitates an approach. Corpus callosum was exposed along the cerebral falx. Corpus callosum was dissected over the tumor between the pericallosal arteries. Dissection of corpus callosum may be performed lateral to pericallosal arteries in case of asymmetric arrangement of the tumor. Dimension of incision of corpus callosum is determined by tumor size and usually does not exceed 2 cm. This approach may be used in patients with severe hydrocephalus for resection of the tumors spreading posteriorly (to the body and lateral parts of lateral ventricles) (Fig. 5).
In all cases, the choice of the most optimal approach was based on comprehensive analysis of MRI data and 3D-modeling for spatial visualization of the tumor in relation to certain approach.
In 70 (61%) patients, tumors were excised via transcortical approach through superior frontal gyrus. Transcortical access was preferable for unilateral and advanced tumors with significant lateral growth and spread of the tumor to posterior parts of lateral ventricles. These were medium and large tumors (2—6 cm), as well as giant ones (>6 cm).
Posterior transcortical approach through cortical incision of superior parietal lobe was used in 5 patients with tumor predominantly located within the triangle of the lateral ventricle (Fig. 6).
Anterior transcallosal approach was applied in 37 (32%) patients.
Combined approaches were used in 3 cases for resection of giant tumors. These neoplasms almost completely occupied both lateral ventricles and spread to the 3rd ventricle (combination of transcortical and transcallosal approaches — 2, bilateral transcortical approach — 1 case).
Microsurgical resection of central neurocytoma
Quality of resection is the main prognostic factor in the treatment of patients with neurocytomas. Type of resection depends on localization, spread and features of blood supply of the tumor. Since intraventricular surgery requires manipulation on deep cerebral structures, patient’s position, adequate exposure of tumor and adequate brain relaxation are the main requirements for successful surgery. Stroma of neurocytoma is relatively mellow as a rule. Therefore, aspiration by conventional or ultrasonic sucker may be effective. Debridement is associated with parallel cautery and intersection of multiple vessels penetrating the tumor. It is advisable to do these manipulations within the tumor rather in close proximity to the wall of the lateral ventricle infiltrated by the tumor. Hemostasis in case of bleeding from ependymal vessels may be very difficult. Cautery does not result reliable occlusion of thin-walled abnormal vessels and bleeding is ongoing within intact brain tissues. Local hemostatic agents (tachocomb or hemostatic gauze) are preferred in these cases. Exposure of foramina of Monro is essential during resection of CN in anterior parts of lateral ventricles because the neoplasm should be obligatory extracted from the 3rd ventricle (aspiration is usually effective). It is very important to observed and preserved striothalamic veins which may be incorporated in the tumor. Septal veins are usually destructed due to invasion of interventricular septum. Moreover, it is advisable to preserved major veins if certain vascular plexuses are included in the tumor because injury of these veins may be followed by severe bleeding and the need to excise the plexuses. In this regard, resection of tumor from the body and posterior parts of the lateral ventricles is the most difficult stage. Radical resection is essential since hemorrhage into residual tumor can cause life-threatening complications associated with intraventricular bleeding and tamponade of the ventricles. Ventricular drainage is mandatory after resection of tumor. External ventricular drainage was installed in 78 (68%) patients for sanation of hemorrhagic cerebrospinal fluid. Early postoperative CT was made in all cases to evaluate early intraoperative changes. CT was repeated if postoperative bleeding was suspected.
Results
Quality of resection
Quality of resection was evaluated considering the protocol of surgery and data of contrast-enhanced MRI in 3—6 months after intervention.
MRI data were preferred to assess quality of resection. We distinguish the following types of resection: 1. complete resection (CR) — no evidence of residual tumor; 2. Subtotal resection (SR) — small tumor fragments (Fig. 7)
It was found that radical resection (CR and SR) of unilateral tumors (type I, group A) was performed in 67% of cases (30 out of 45 patients). CR and SR were performed in 65% (35 out of 54) of patients with median tumors (type II, groups B and C). Advanced tumors (type III, group D) were accompanied by CR and SR in 44% of cases (7 out of 16 patients) (Table 2).
Analysis of 115 patients revealed that complete resection was performed in 41 (36%) cases, subtotal resection – in 37 (32%) cases, partial resection – in 37 (32%) patients.
Quality of resection depended on dimensions of neurocytoma. CR and SR were more common in patients with small and medium neoplasms (types a and b) (Table 3).
Complications after resection of central neurocytoma
Hemorrhage. Hemorrhage inside residual tumor is one of the most dangerous complications that usually requires immediate surgical revision of surgical wound (Fig. 8).
The main cause of hemorrhage is residual tumor fragments. Hemorrhage into residual tumor followed by hematomas in the bed of excised neoplasm was observed in 25 (22%) patients (the volume of postoperative hematoma exceeded or was comparable to volume of excised tumor). Hemorrhage within the first postoperative day occurred in 21 cases. Medication was preferred only in 3 of these patients. In 18 cases, extraction of hematoma and residual tumor was made in early postoperative period (within 24—48 hours after initial surgery). Subsequent redo debridement of hematoma was required in 4 out of 18 patients. Recurrent hemorrhage occurred within 3—5 days after revision. Redo surgery was carried out within 4—6 days after initial operation. In 4 out of 25 patients in satisfactory condition, debridement of small hematomas was performed on the 5—6th postoperative day. Partial resorption of blood clots by that time facilitated evacuation of hematoma. The main cause of hemorrhage inside the residual tumor is associated with incomplete hemostasis. There are no smooth muscle elements in the vessels supplying tumor. As a result, cautery does not result complete occlusion of the vascular lumen and bleeding is ongoing. Moreover, adequate hemostasis is prevented by the presence of cavernous veins inside the tumor. These cavities are filled with venous blood. Another cause of hemorrhage may be impairment of venous outflow from vascular plexuses of the tumor. This is possible in case of intraoperative cautery of large plexus veins on the background of intact afferent arteries. Therefore, one should strive to preserve the largest veins if vascular plexuses are included in the tumor. Analysis of the incidence of postoperative hematomas depending on surgical approach showed that there were no significant differences between various accesses. Hematomas in the bed of excised tumors were more common (85% of cases) in patients with large and giant neoplasms characterized by infiltrative growth. The worst postoperative results were observed after emergency procedures performed for progressive symptoms of brain dislocation. In this group (n=18), 2 patients died and 2 patients were discharged in a vegetative status. Thus, unfavorable outcomes were noted in 22% of cases.
Occlusive hydrocephalus was detected in 23 (20%) patients. In 80% of cases, aggravation of hydrocephalus was noted in 2—3 days after surgery. Five out of 23 patients required additional operation for restoration of cerebrospinal fluid circulation. External ventricular drainage was installed in 18 patients including 8 cases of intraoperative deployment of the drain for sanation of cerebrospinal fluid. Subsequently, ventriculo-peritoneal bypass was deployed in 14 of them to resolve hydrocephalus in early postoperative period after sanation of cerebrospinal fluid. The terms of VPB installation were 10—35 days after resection of tumor. Aggravation of postoperative hydrocephalus did not depend on the quality of resection of tumor. Complete resection was followed by occlusion of cerebrospinal pathways due to hematoma in lateral ventricle occluding foramina of Monro. In case of partial resection, progression of hydrocephalus was caused by residual tumor and blood clots blocking cerebrospinal fluid circulation through the interventricular orifices and cerebral aqueduct. Our previous experience and analysis of delayed complications (that will be discussed in the next article) revealed a peculiar complication after resection tumors spreading to the body and triangle of lateral ventricle – detachment of inferior or posterior horns. In this regard, we prophylactically performed stenting of the foramina of Monro and cerebral aqueduct using a catheter in case of the risk of impaired circulation of cerebrospinal fluid through the interventricular orifices and cerebral aqueduct. The catheter was passed from the lateral ventricle through the foramina of Monro and further into cerebral aqueduct (interventricular septum was absent after surgery). The catheter connecting the body of the lateral ventricle and inferior horn was left in case of the risk of detachment of inferior horn. None of those patients who underwent stenting for prevention of ventricular system separation subsequently needed implantation of bypass system or microsurgical dissection of adhesions to restore CSF circulation in the lateral ventricle.
Subdural and epidural hematomas in early postoperative period were revealed in 3 cases. Subdural hygroma was diagnosed in 1 patient in 8 days after resection of tumor.
Postoperative period in patients with neurocytomas
Assessment of treatment outcomes and neurological status was carried out in early postoperative period until discharge. Resection of tumor was followed by clinical aggravation with transient deterioration of general cerebral and focal symptoms in almost all patients. Degree and duration of this aggravation were various. In 50% of cases, postoperative state was characterized by reduced voluntary activity, drowsiness or anxiety, motor or speech agitation. These patients were characterized by rapid regression of clinical symptoms within 7—8 days after surgery. Complete recovery was observed at discharge (n=57, 50%). Other patients had complicated course with more severe and persistent aggravation of clinical symptoms including mnestic disorders (mild-to-moderate disorientation, fixation amnesia), stem disorders (impaired photoreaction, Magendie’s symptom, restriction of reflex gaze upward). Cognitive impairment in early postoperative period was diagnosed in 30 (27%) out of 115 patients including 23 (20%) patients with preoperative cognitive impairment and its deterioration after surgery. In 55 (50%) patients, mnestic disturbances de novo or aggravation of preoperative disorders (34 (29.5%) patients) were observed after surgery. Postoperative speech disorders (sensory-motor aphasia) were noted in 10 patients with advanced tumors followed by invasion of the periventricular structures of the dominant hemisphere. Pyramidal symptoms de novo or their deterioration was noted in 32 (28%) patients. At the same time, clinical regression of ICH symptoms was observed in all patients at discharge. Postoperative neurological disorders are shown in Table 4.
All patients were evaluated in accordance with Karnofsky scale before and after surgery (Fig. 9).
A comparison of postoperative complications with localization and lateralization of the tumor revealed some features. Memory impairment, mental disorders and mutism were more common in patients with anterior type of the neoplasm (type A and/or B). Pyramidal symptoms and speech impairment were common in patients with median and posterior tumors (type C and/or D) (Table 5).
Analysis of treatment outcomes depending on dimensions of tumors showed that severe focal symptoms developed in patients with advanced neurocytomas (Table 6).
Postoperative mortality. Postoperative mortality rate was 4.3% (5 patients). The main cause of death is hemorrhage into residual tumor, edema and dislocation of the brain stem and circulatory disturbance in the brain stem. Two out of five patients underwent revision of surgical wound due to hemorrhage into residual tumor and lateral ventricle within 24 hours after resection of neoplasm. Redo surgery was followed by temporary positive dynamics (regression of stem symptoms and circulatory stabilization). One patient died from sepsis associated with multiple organ failure.
Discussion
It is generally recognized that resection is preferable method of treatment of neurocytoma. According to various authors, resection is possible in about 50% of all cases [5, 12—15]. In our clinic, we have twice analyzed surgical outcomes in patients with central neurocytomas [5]. These data demonstrate improvement of the treatment of this complex pathology (Table 7).
Complexity of resection of these tumors is determined by their localization, dimensions and features of blood supply. According to most authors, hemorrhagic complications, impaired cerebrospinal fluid circulation and deterioration of neurological symptoms are common in postoperative period [5,7, 9—10, 13, 16]. The most dangerous complication in early postoperative period is hemorrhage into residual tumor followed by hematoma in the bed of excised neoplasm. This event often requires revision of surgical wound and debridement of hematoma. In our opinion, delayed evacuation of hematoma after 5—6 days improves patient's condition if hematoma was not eliminated in acute period for any reason [5]. Li-Feng Chen et al. reported intensive blood supply of the tumor, the presence of multiple small abnormal arteries without smooth muscle elements and multiple cavernous veins as the main causes of postoperative hemorrhage [10]. On the one hand, complete resection of tumor associated with infiltration of periventricular tissues is dangerous and may be followed by serious complications. On the other hand, hemorrhage into residual tumor with subsequent intraventricular hematoma is the most common and dangerous complication. Leenstra J.L. et al. reported similar outcomes after complete and subtotal resection of neurocytoma [12]. Sharma M.C. et al. consider that safe maximal resection is optimal strategy for local control and long-term outcomes [13]. Imber B.S. et al. reported that postoperative stereotactic radiotherapy may be preferred for long-term control of tumor growth in case of impossible complete resection of neurocytoma due to high risk of complications [14]. Great number of complications and low quality of resections were noted in earlier publications [7, 9, 13, 17, 18]. It should be noted that tumors were diagnosed later at that time. As a result, large neoplasms were predominant diagnostic findings. According to multiple-center study of the treatment of neurocytoma (France, 2013), surgical treatment is followed by postoperative complications in 66% of cases (pyramidal symptoms and/or speech impairment — 39%, memory impairment — 29%, hydrocephalus — 26%) [19]. Optimization of surgical treatment and improvement of microsurgical technique significantly reduced early postoperative morbidity and postoperative mortality [4, 6, 10, 11, 20]. Another dangerous complication in early postoperative period is occlusion of pathways for cerebrospinal fluid cerculation. According to Soliman W.S. et al., the main reason of hydrocephalus is separation of CSF pathways of the lateral ventricles caused by residual tumor or blood clots [21]. Our experience and recent data show that incidence of postoperative hydrocephalus has significantly decreased (almost by half compared with earlier publications) [6, 8—10]. This is the result of more thorough microsurgical resection of neurocytoma. As we noted earlier, the choice of adequate surgical approach is one of the most important requirements for successful resection of neurocytoma. In our sample, transcortical approach through the premotor cortex was more common, while anterior transcallosal access was rarer. Haipeng Qian determines the choice of approach considering localization of tumor and severity of hydrocephalus [4]. Transcortical approach was preferable in patients with severe hydrocephalus, large asymmetrical tumors and neoplasms occupying almost all lateral ventricle. We prefer transcallosal approach in patients with anterior tumors of the lateral ventricle. This is especially true for median neoplasms. In rare cases, combined (transcallosal and transcortical) or bilateral transcortical approaches are needed in patients with giant neurocytoma. In all cases, the choice of approach is based on a thorough analysis of localization and dimensions of tumor using 3D reconstruction of MRI and CT data.
To date, near 500 patients with central neurocytomas are reported in the literature. The main representative samples and treatment outcomes for recent years are presented in Table 8.
Our data obtained in recent years are comparable with the results of other authors [4, 6, 10]. This experience suggests that postoperative morbidity is still high despite the undoubted progress in surgical treatment of central neurocytoma. The main approach for improvement of the outcomes in patients with central neurocytoma is an early diagnosis of these tumors. Surgery for small intraventricular neoplasms is accompanied by the best prognosis.
We have analyzed early postoperative outcomes in this article. However, follow-up data, validity and admissibility of redo interventions, effectiveness of radiotherapy are also essential. The second part of our research will be devoted to these problems.
Authors’ participation:
Concept and design of the study — A.N., D.I., S.A.
Collection and analysis of data — S.A.
Writing the text — S.A., A.N., A.Yu.
Editing — A.N., D.I., A.Yu.,S.A.
The authors declare no conflict of interest.