Category Archives: Neurooncology

Update: Cystic metastases

Cystic metastases

Epidemiology

The development of cystic brain metastases remains a relatively rare occurrence.

Etiology

Metastatic brain tumors are normally composed of cystic components, however, the reasons for the cyst formation have not been clearly investigated 1). Stem 2) reported that the brain cyst fluid protein always presents in the inflammatory exudates. Cumings 3) also reported that the cyst fluid formation may be correlated with the tumor degeneration. Gardner et al 4) found that fluid accumulating in brain tumors runs in the normal drainage route, since there are no lymphatic vessels in the tumors.

Gamma knife radiosurgery (GKRS) is occasionally a useful tool for maintaining good brain status in patients with brain metastases (METs). Conversely, Ishikawa et al. experienced patients with delayed cyst formation (DCF) several years after GKRS, a complication not previously reported 5).

Differential diagnosis

The main challenge in discrimination between intracranial cystic lesions is to differentiate benign inflammatory cystic lesions (as cerebral abscess) from malignant cystic lesions (as cystic metastases and cystic glioma) which have totally different management.

Cerebral abscess.

Hydatid cyst.

Other intra-axial cysts, e.g. intracranial arachnoid cyst, neuroglial cyst, porencephalic cyst.

The most common tumors are, hemangioblastoma, pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma.

Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma 6).

Treatment

In a review, Kim et al. describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes 7).

Case series

2017

Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively.

The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p=0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction.

For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst 8).

2016

Lee et al. retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy.

The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage.

According to this results, they suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor 9).


A study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24-72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life 10).

2014

Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).

Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months.

Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time 11).

2013

Ebinu et al. reviewed a prospectively maintained database of brain metastases patients treated between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.

A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.

This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates 12).

2012

Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined.

Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement.

The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases 13).

2009

Hydrofiber dressing is a sodium carboxymethylcellulose hydrocolloid polymer with high fluid-absorptive capacity. This material was originally used as a dressing for exudative wounds. Hydrofiber dressing was used for 8 patients with cystic-type metastatic brain tumor. Tumor removal was performed after hydrofiber dressing was inserted into the cyst cavity to transform the tumor into a solid-type tumor.

Transformation of cystic-type metastatic brain tumors into smaller solid-type tumors using hydrofiber dressing facilitated en bloc resection of tumor. The dressing also absorbed residual cyst fluid and was thus also effective in preventing intraoperative dissemination of tumor cells. This approach enabled ideal en bloc resection in all patients. There were no adverse events.

These findings suggest hydrofiber dressing may be useful in surgery for cystic-type metastatic brain tumors 14).

2008

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor.

Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients.

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis 15).

Case reports

2015

A study describes the first case of histopathologically-confirmed brainstem metastasis originating from lung adenosquamous carcinoma, and discusses the outcomes of treatment by stereotactic aspiration combined with gamma knife radiosurgery (GKRS). A 59-year-old female presented with a cystic mass (15×12×13 mm; volume, 1.3 cm3) located in the pons, two years following surgical treatment for adenosquamous carcinoma of the lung. The patient received initial GKRS for the lesion in the pons with a total dose of 54.0 Gy, however, the volume of the mass subsequently increased to 3.9 cm3 over a period of three months. Computed tomography-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 2.0 cm3 of yellow-white fluid. Histology confirmed the diagnosis of adenosquamous carcinoma. Aspiration provided immediate symptomatic relief, and was followed one week later by repeat GKRS with a dose of 12.0 Gy. The patient survived for 12 months following the repeat GKRS; however, later succumbed to the disease after lapsing into a two-week coma. The findings of this case suggest that stereotactic aspiration of cysts may improve the effects of GKRS for the treatment of cystic brainstem metastasis; the decrease in tumor volume allowed a higher radiation dose to be administered with a lower risk of radiation-induced side effects. Therefore, stereotactic aspiration combined with GKRS may be an effective treatment for brainstem metastasis originating from adenosquamous carcinoma 16).

2009

A 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient’s previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated 17).


Cystic brain metastases from small-cell lung carcinomas are exceedingly rare and neurosurgical operations are not suitable for those cases considering invisible micrometastases. A 34-year-old female patient presented with small-cell lung carcinoma that metastasized to the brain as a solitary cyst with a thin wall 24 months after a good partial response to initial chemoradiotherapy. The brain mass volume and the main symptom of left hemiplegia, which made the Karnofsky performance status (KPS) fall to 30%, did not respond to whole brain irradiation. Therefore, an Ommaya reservoir was inserted, which dramatically improved the KPS to 70%. This minimally invasive surgical strategy is suitable even for patients with a poorer KPS bearing cystic brain metastases 18).

References

1)

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated? Stereotact Funct Neurosurg. 1999;72 Suppl 1:38-44. PubMed PMID: 10681689.
2)

Stem K. Chemical study of fluids obtained from cerebral cysts: Report on 56 cases. Brain. 1939;62:88. doi: 10.1093/brain/62.1.88.
3)

CUMINGS JN. The chemistry of cerebral cysts. Brain. 1950 Jun;73(2):244-50. PubMed PMID: 14791790.
4)

GARDNER WJ, COLLIS JS Jr, LEWIS LA. Cystic brain tumors and the blood-brain barrier. Comparison of protein fractions in cyst fluids and sera. Arch Neurol. 1963 Mar;8:291-8. PubMed PMID: 13946556.
5)

Ishikawa E, Yamamoto M, Saito A, Kujiraoka Y, Iijima T, Akutsu H, Matsumura A. Delayed cyst formation after gamma knife radiosurgery for brain metastases. Neurosurgery. 2009 Oct;65(4):689-94; discussion 694-5. doi: 10.1227/01.NEU.0000351771.46273.22. PubMed PMID: 19834373.
6)

Ramanathan N, Kamaruddin KA, Othman A, Mustafa F, Awang MS. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report. Malays J Med Sci. 2016 May;23(3):92-4. PubMed PMID: 27418876; PubMed Central PMCID: PMC4934725.
7)

Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. Review. PubMed PMID: 25977901; PubMed Central PMCID: PMC4426272.
8)

Oshima A, Kimura T, Akabane A, Kawai K. Optimal implantation of Ommaya reservoirs for cystic metastatic brain tumors preceding Gamma Knife radiosurgery. J Clin Neurosci. 2017 May;39:199-202. doi: 10.1016/j.jocn.2016.12.042. Epub 2017 Jan 20. PubMed PMID: 28117259.
9)

Lee SR, Oh JY, Kim SH. Gamma Knife radiosurgery for cystic brain metastases. Br J Neurosurg. 2016;30(1):43-8. doi: 10.3109/02688697.2015.1039489. Epub 2015 May 11. PubMed PMID: 25958957.
10)

Wang H, Qi S, Dou C, Ju H, He Z, Ma Q. Gamma Knife radiosurgery combined with stereotactic aspiration as an effective treatment method for large cystic brain metastases. Oncol Lett. 2016 Jul;12(1):343-347. Epub 2016 May 18. PubMed PMID: 27347148; PubMed Central PMCID: PMC4907086.
11)

Jung TY, Kim IY, Jung S, Jang WY, Moon KS, Park SJ, Lim SH. Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic brain metastases. Stereotact Funct Neurosurg. 2014;92(4):234-41. doi: 10.1159/000362935. Epub 2014 Aug 19. PubMed PMID: 25138737.
12)

Ebinu JO, Lwu S, Monsalves E, Arayee M, Chung C, Laperriere NJ, Kulkarni AV, Goetz P, Zadeh G. Gamma knife radiosurgery for the treatment of cystic cerebral metastases. Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):667-71. doi: 10.1016/j.ijrobp.2012.06.043. Epub 2012 Aug 9. PubMed PMID: 22885145.
13)

Higuchi F, Kawamoto S, Abe Y, Kim P, Ueki K. Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component. J Neurosurg. 2012 Dec;117 Suppl:17-22. doi: 10.3171/2012.7.GKS121001. PubMed PMID: 23205784.
14)

Okuda T, Teramoto Y, Yugami H, Kataoka K, Kato A. Surgical technique for a cystic-type metastatic brain tumor: transformation to a solid-type tumor using hydrofiber dressing. Surg Neurol. 2009 Dec;72(6):703-6; discussion 706. doi: 10.1016/j.surneu.2009.07.045. Epub 2009 Oct 15. PubMed PMID: 19836065.
15)

Franzin A, Vimercati A, Picozzi P, Serra C, Snider S, Gioia L, Ferrari da Passano C, Bolognesi A, Giovanelli M. Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis. J Neurosurg. 2008 Aug;109(2):259-67. doi: 10.3171/JNS/2008/109/8/0259. PubMed PMID: 18671638.
16)

DU C, Li Z, Wang Z, Wang L, Tian YU. Stereotactic aspiration combined with gamma knife radiosurgery for the treatment of cystic brainstem metastasis originating from lung adenosquamous carcinoma: A case report. Oncol Lett. 2015 Apr;9(4):1607-1613. Epub 2015 Feb 16. PubMed PMID: 25789009; PubMed Central PMCID: PMC4356421.
17)

Zigouris A, Pahatouridis D, Mihos E, Alexiou GA, Nesseris J, Zikou AK, Argyropoulou MI, Goussia A, Voulgaris S. Solitary cystic cerebral metastasis from transitional cell carcinoma of the bladder. Acta Neurol Belg. 2009 Dec;109(4):322-5. PubMed PMID: 20120215.
18)

Takeda T, Saitoh M, Takeda S. Solitary cystic brain metastasis of small-cell lung carcinoma controlled by a stereotactically inserted Ommaya reservoir. Am J Med Sci. 2009 Mar;337(3):215-7. doi: 10.1097/MAJ.0b013e3181833847. PubMed PMID: 19204557.

Update: Atypical meningioma

Atypical meningioma (AM)

Atypical (WHO Grade IImeningiomas comprise a heterogeneous group of tumors, with histopathology delineated under the guidance of the WHO and a spectrum of clinical outcomes.

In atypical meningiomas bone involvement and large meningioma peritumoral edema are associated with increased tumor progression.

Classification

Intracranial atypical meningiomas

Spinal atypical meningiomas

Epidemiology

Approximately 15-20% of meningiomas are atypical, meaning that the tumor cells do not appear typical or normal. Atypical meningiomas are neither malignant (cancerous) nor benign, but may become malignant.

Treatment

The treatment of atypical meningioma remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis.

In a study, Sun et al. review the English-language literature on the management and clinical outcomes using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies, the authors did find evidence for the following clinical strategies:

1) maximal safe resection

2) active surveillance after gross-total resection

3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radio resistant features 1).

Postoperative radiotherapy

Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection despite data that suggests that close observation remains reasonable in the setting of aggressive microsurgical resection.

The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear.

Conformal, high dose radiotherapy resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma 2).

Role of necrosis

Adjuvant radiation therapy or external beam radiation therapy (EBRT) improved local control after stereotactic radiosurgery STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs 3).

Necrosis may be a negative predictor of radiation response regardless of radiation timing or modality 4).

Recurrence

Grade II atypical meningiomas tend to recur and grow faster.

Retrospective series supports the observation that postoperative radiotherapy likely results in lower recurrence rates of gross totally resected atypical meningiomas.

Patients older than 55 years and those with mitoses noted during pathological examination had a significant risk of recurrence after GTR; for these patients, postoperative radiotherapy is recommended 5).

After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival 6).

A multicenter prospective trial will ultimately be needed to fully define the role of radiotherapy in managing gross totally resected atypical meningiomas 7).

Study limitations, including inadequate statistical power, may underlie the studies’ inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors 8).

Brain invasion and high mitotic rates may predict recurrence. After gross total resection (GTR) of AMs, EBRT appears not to affect progression free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR 9).

Outcome

The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles.

The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Metaanalysis for the existing literature is needed 10).

Case series

2017

The National Cancer Database was used to identify 2515 patients who were diagnosed with AM between 2009 and 2012 and underwent STR or GTR with or without adjuvant RT. Propensity score matching was first applied to balance covariates including age, year of diagnosis, sex, race, histology, and tumor size in STR or GTR cohorts stratified by adjuvant RT status. Multivariate regression according to the Cox proportional hazards model and Kaplan-Meier survival plots with log-rank test were then used to evaluate OS difference associated with adjuvant RT.

GTR is associated with improved OS compared with STR. In the subgroup analysis, adjuvant RT in patients who underwent STR demonstrated significant association with improved OS compared with no adjuvant RT (adjusted hazard ratio [AHR] 0.590, P = .045); however, adjuvant RT is not associated with improved OS in patients who underwent GTR (AHR 1.093, P = .737).

Despite the lack of consensus on whether adjuvant RT reduces recurrence after surgical resection of AM, our study observed significantly improved OS with adjuvant RT compared with no adjuvant RT after STR 11).

2016

Real-Peña et al published 27 patients with pathological diagnosis of atypical meningioma, and who had a minimum follow-up time of 6 months after diagnosis. Later prognostic factors (age <50years, male gender, bone involvement, peri-lesional swelling, tumour volume, location, Ki67/MIB-1) were evaluated after the stratification of patients undergoing complete resection in recurrencies and non-recurrencies. Univariate analysis was performed using Mann-Whitney test, χ(2) homogeneity test/Fisher exact test. Finally, multivariate analysis was performed using binary logistic regression to obtain the values for R(2) Nagelkerke and the Hosmer-Lemeshow to evaluate the goodness of fit.

The uni- and multivariate analysis showed no statistically significant differences between recurrent and non-recurrent subgroups of patients undergoing complete resection. It is noted in the results that for each year of age above 50 years, the risk of recurrence is decreased by 5.8%.

Although current prognostic factors may show an increased risk of recurrence once patients are stratified by the two most important factors (pathology and extent of resection), those factors are insufficient to predict the ultimate outcome of patients affected by this pathology 12)


Endo et al., reviewed 45 patients with atypical meningioma who underwent surgical intervention between January 2000 and December 2013. The mean age of the patients and mean follow-up period was 58.7 years and 81.0 months, respectively. Analyses included factors such as patient age, gender, location and size of tumor, extent of surgical resection (Simpson Grading System), and MIB-1 index (LI). Univariate analysis was used to detect prognostic factors associated with recurrence and survival.

The 5-year recurrence-free rate for all 45 patients was 58.4 %; 5- and 10-year survival rates were 83.2 % and 79.9 %, respectively. In univariate analyses, age >60 years, and MIB-1 LI correlated with disease recurrence, whereas age >60 years, subtotal surgical resection, MIB-1 LI, and indication for radiotherapy correlated with death. MIB-1 LI levels higher than 12.8 % and 19.7 % predicted recurrence and death, respectively. In our cohort, 26 patients received postoperative radiotherapy including conventional radiation (n = 21) or gamma knife radiosurgery (n = 5). Postoperative radiotherapy did not decrease recurrence rates in our cohort (p = 0.63). Six and two patients who died during the study period underwent conventional radiation and radiosurgery, respectively.

Age, male gender, extent of surgical resection, and higher MIB-1 LI influenced the outcome of atypical meningioma. In our cohort, postoperative radiotherapy failed to provide long-term tumor control. Following incomplete surgical resection of atypical meningioma in elderly patients, adjuvant postoperative radiotherapy may not be an ideal treatment option, particularly when MIB-1 LI is higher than 19.7 % 13).


44 WHO Grade II and 9 WHO Grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.

For WHO Grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58% and 36%, respectively. For WHO Grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (p = 0.14), respectively. Overall, 7 of 44 Grade II patients and 8 of 9 Grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for Grade II and III meningioma were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.

SRS for adjuvant and salvage treatment of WHO Grade II meningioma by a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future work should contribute additional study toward the radiation naïve and the local management of malignant meningioma 14).


A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned 15).

2015

Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed.

Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up.

For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome 16).


A retrospective analysis of the patients operated at the Clinic of Neurosurgery, Clinical Center of Serbia, Belgrade, between January 1st 1995 and December 31th 2006 was performed. In that period 88 lesions met the histological criteria for atypical (75) and anaplastic (13) meningioma. Postoperative radiotherapy was conducted in 63.6% of patients.

At a median follow-up of 67.4 months in all patients the overall survival was 68 months and five-year survival was about 54.5%. The median survival was 76 months with surgery and adjuvant radiotherapy and 40 months with surgery alone (Log rank=7.4; p=0.006). Recurrent disease occurred in 58 patients (65.9%). Median time between first surgery and tumor recurrence in patients undergoing radiotherapy was 51 months, while in non-irradiated group 24 months (Log rank=17.7; p˂0.001). Multivariate analysis identified as recurrence-predicting factors anaplastic histotype (hazard ratio=2,9; p=0,003) and postoperative radiotherapy (hazard ratio=4,5; p<0,001).

The addition of adjuvant radiotherapy to surgery for atypical and anaplastic meningiomas resulted in a clinically meaningful and statistically significant survival benefit 17).

Case reports

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported.

Dehghan Harati et al. add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases 18).

References

1)

Sun SQ, Hawasli AH, Huang J, Chicoine MR, Kim AH. An evidence-based treatment algorithm for the management of WHO Grade II and III meningiomas. Neurosurg Focus. 2015 Mar;38(3):E3. doi: 10.3171/2015.1.FOCUS14757. PubMed PMID: 25727225.
2)

Hug EB, Devries A, Thornton AF, Munzenride JE, Pardo FS, Hedley-Whyte ET, Bussiere MR, Ojemann R. Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neurooncol. 2000 Jun;48(2):151-60. PubMed PMID: 11083080.
3)

Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR, Kim AH. Management of atypical cranial meningiomas, part 2: predictors of progression and the role of adjuvant radiation after subtotal resection. Neurosurgery. 2014 Oct;75(4):356-63. doi: 10.1227/NEU.0000000000000462. PubMed PMID: 24932708.
4)

Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Simpson JR, Robinson CG, Chicoine MR, Perrin RJ, Huang J, Kim AH. Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes. Neurosurgery. 2016 Jul;79(1):23-32. doi: 10.1227/NEU.0000000000001160. PubMed PMID: 26645969.
5)

Lee KD, DePowell JJ, Air EL, Dwivedi AK, Kendler A, McPherson CM. Atypical meningiomas: is postoperative radiotherapy indicated? Neurosurg Focus. 2013 Dec;35(6):E15. doi: 10.3171/2013.9.FOCUS13325. PubMed PMID: 24289123.
6)

Aghi MK, Carter BS, Cosgrove GR, Ojemann RG, Amin-Hanjani S, Martuza RL, Curry WT Jr, Barker FG 2nd. Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation. Neurosurgery. 2009 Jan;64(1):56-60; discussion 60. doi: 10.1227/01.NEU.0000330399.55586.63. PubMed PMID: 19145156.
7)

Komotar RJ, Iorgulescu JB, Raper DM, Holland EC, Beal K, Bilsky MH, Brennan CW, Tabar V, Sherman JH, Yamada Y, Gutin PH. The role of radiotherapy following gross-total resection of atypical meningiomas. J Neurosurg. 2012 Oct;117(4):679-86. doi: 10.3171/2012.7.JNS112113. Epub 2012 Aug 24. PubMed PMID: 22920955.
8)

Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ, James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol. 2014 May;16(5):628-36. doi: 10.1093/neuonc/nou025. Epub 2014 Apr 2. PubMed PMID: 24696499; PubMed Central PMCID: PMC3984561.
9)

Sun SQ, Kim AH, Cai C, Murphy RK, DeWees T, Sylvester P, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR. Management of atypical cranial meningiomas, part 1: predictors of recurrence and the role of adjuvant radiation after gross total resection. Neurosurgery. 2014 Oct;75(4):347-55. doi: 10.1227/NEU.0000000000000461. PubMed PMID: 24932707.
10)

Hammouche S, Clark S, Wong AH, Eldridge P, Farah JO. Long-term survival analysis of atypical meningiomas: survival rates, prognostic factors, operative and radiotherapy treatment. Acta Neurochir (Wien). 2014 Aug;156(8):1475-81. doi: 10.1007/s00701-014-2156-z. Epub 2014 Jun 26. PubMed PMID: 24965072.
11)

Wang C, Kaprealian TB, Suh JH, Kubicky CD, Ciporen JN, Chen Y, Jaboin JJ. Overall survival benefit associated with adjuvant radiotherapy in WHO grade II meningioma. Neuro Oncol. 2017 Mar 24. doi: 10.1093/neuonc/nox007. [Epub ahead of print] PubMed PMID: 28371851.
12)

Real-Peña L, Talamantes Escribá F, Quilis-Quesada V, González-Darder JM. [Prognostic variability in atypical meningioma with complete resection. Proposed treatment algorithm]. Neurocirugia (Astur). 2016 Jan-Feb;27(1):15-23. doi: 10.1016/j.neucir.2015.08.003. Spanish. PubMed PMID: 26687847.
13)

Endo T, Narisawa A, Ali HS, Murakami K, Watanabe T, Watanabe M, Jokura H, Endo H, Fujimura M, Sonoda Y, Tominaga T. A study of prognostic factors in 45 cases of atypical meningioma. Acta Neurochir (Wien). 2016 Sep;158(9):1661-7. doi: 10.1007/s00701-016-2900-7. Epub 2016 Jul 28. PubMed PMID: 27468919.
14)

Zhang M, Ho AL, D’Astous M, Pendharkar AV, Choi CY, Thompson PA, Tayag AT, Soltys SG, Gibbs IC, Chang SD. CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World Neurosurg. 2016 Apr 20. pii: S1878-8750(16)30092-4. doi: 10.1016/j.wneu.2016.04.019. [Epub ahead of print] PubMed PMID: 27108030.
15)

Jenkinson MD, Waqar M, Farah JO, Farrell M, Barbagallo GM, McManus R, Looby S, Hussey D, Fitzpatrick D, Certo F, Javadpour M. Early adjuvant radiotherapy in the treatment of atypical meningioma. J Clin Neurosci. 2016 Jan 8. pii: S0967-5868(15)00663-3. doi: 10.1016/j.jocn.2015.09.021. [Epub ahead of print] PubMed PMID: 26775147.
16)

Wang YC, Chuang CC, Wei KC, Hsu YH, Hsu PW, Lee ST, Wu CT, Tseng CK, Wang CC, Chen YL, Jung SM, Chen PY. Skull base atypical meningioma: long term surgical outcome and prognostic factors. Clin Neurol Neurosurg. 2015 Jan;128:112-6. doi: 10.1016/j.clineuro.2014.11.009. Epub 2014 Nov 24. PubMed PMID: 25486076.
17)

Pisćević I, Villa A, Milićević M, Ilić R, Nikitović M, Cavallo LM, Grujičić D. The influence of adjuvant radiotherapy in atypical and anaplastic meningiomas: a series of 88 patients in a single institution. World Neurosurg. 2015 Mar 10. pii: S1878-8750(15)00128-X. doi: 10.1016/j.wneu.2015.02.021. [Epub ahead of print] PubMed PMID: 25769488.
18)

Dehghan Harati M, Yu A, Magaki SD, Perez-Rosendahl M, Im K, Park YK, Bergsneider M, Yong WH. Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma. Neuropathology. 2017 Aug 18. doi: 10.1111/neup.12409. [Epub ahead of print] PubMed PMID: 28833600.

Atlas of Endoscopic Neurosurgery of the Third Ventricle: Basic Principles for Ventricular Approaches and Essential Intraoperative Anatomy

Atlas of Endoscopic Neurosurgery of the Third Ventricle: Basic Principles for Ventricular Approaches and Essential Intraoperative Anatomy

Atlas of Endoscopic Neurosurgery of the Third Ventricle: Basic Principles for Ventricular Approaches and Essential Intraoperative Anatomy

By Roberto Alexandre Dezena

List Price: $199.00

ADD TO SHOPPING CART

This book describes in practical terms the endoscopic neurosurgery of the third ventricle and surrounding structures, emphasizing aspects of intraoperative endoscopic anatomy and ventricular approaches for main diseases, complemented by CT / MRI images. It is divided in two parts: Part I describes the evolution of the description of the ventricular system and traditional ventricular anatomy, besides the endoscopic neurosurgery evolution and current concepts, with images and schematic drawings, while Part II presents a collection of intraoperative images of endoscopic procedures, focusing in anatomy and main pathologies, complemented by schemes of the surgical approaches and CT / MRI images.

The Atlas of Endoscopic Neurosurgery of the Third Ventricle offers a revealing guide to the subject, addressing the needs of medical students, neuroscientists, neurologists and especially neurosurgeons.


Product Details

  • Original language: English
  • Number of items: 1
  • Dimensions: 11.41″ h x .88″ w x 8.51″ l,
  • Binding: Hardcover
  • 271 pages

About the Author

Roberto Alexandre Dezena: MD from the Federal University of Triângulo Mineiro, Uberaba, Brazil (2003), completed his residency training in Neurosurgery at Santa Casa de Misericórdia de Ribeirão Preto, Brazil (2009), achieved his PhD in Neurosurgery at Ribeirão Preto Medical School of University of São Paulo, Brazil (2011), and his Postdoctoral Fellowship at Federal University of Triângulo Mineiro, Uberaba, Brazil (2014). In Brazil, is Full Member of Brazilian Society of Neurosurgery (SBN) and Brazilian Academy of Neurosurgery (ABNc). Internationally, is Fellow of World Federation of Neurosurgical Societes (WFNS), Active Member of both International Society for Pediatric Neurosurgery (ISPN) and International Federation of Neuroendoscopy (IFNE), and Full Member of both Latin American Federation of Neurosurgery Societes (FLANC) and Latin American Group of Studies in Neuroendoscopy (GLEN). Fellow of University of Tübingen, Germany, and University of Hiroshima, Japan. Currently is Chief of Division of Neurosurgery at Clinics Hospital, Neurosurgery Residency Director, and Professor of Postgraduate Program in Health Sciences and Postgraduate Program in Applied Biosciences, all in Federal University of Triângulo Mineiro, Uberaba, Brazil. Main neurosurgical areas in vascular and neuro-oncology microneurosurgery, endoscopic neurosurgery, pediatric neurosurgery, spinal surgery and neurotrauma. Main research areas in endoscopic neurosurgery, pediatric neurosurgery, neurotrauma, experimental cerebral ischemia and basic neurosciences. Editorial Board Member of International Journal of Anesthesiology Research (Phaps), Journal of Neurology and Stroke (Medcrave), EC Neurology (EC), and International Journal of Pediatrics and Children Health (Savvy). Reviewer of several online international scientific journals, highlighting World Neurosurgery (WFNS), Neurological Research (Maney) and Journal of Neurosurgical Sciences (Minerva).

 

Update: Trigeminal schwannoma radiosurgery

Stereotactic radiosurgery (SRS) is an effective and minimally invasive management option for patients with residual or newly diagnosed trigeminal schwannomas. The use resulted in good tumor control and functional improvement 1).

Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment 2).

Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required 3).

Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas 4).

It is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision 5).

Case series

2013

The records of 52 patients who underwent stereotactic radiosurgery (SRS) for trigeminal schwannoma were reviewed using a retrospective study. The median patient age was 47.1 years (range, 18-77); 20 patients (38.5%) had undergone prior tumor resection and 32 (61.5%) underwent radiosurgery on the basis of imaging diagnosis only. The most frequent presenting symptoms were facial numbness (29 patients), jaw weakness (11 patients), facial pain (10 patients) and diplopia (4 patients). Fifty-two cases with solid tumors were mainly solid in 44 cases (84.6%), mostly cystic in 2 cases (3.8%), and cystic and solid mixed in 6 cases (11.5%). Two cases of mostly cystic tumor first underwent stereotactic cystic fluid aspiration and intracavitary irradiation, and then had MRI localization scan again for gamma knife treatment. The mean tumor volume was 7.2 ml (range, 0.5-38.2). The mean prescription radiation dose was 13.9 Gy (range, 11-17), and the mean prescription isodose configuration was 47.9%.

At a mean follow-up of 61 months (range, 12-156), neurological symptoms or signs improved in 35 patients (67.3%), 14 patients (26.9%) had a stable lesion, and worsening of the disease occurred in 2 patients (3.8%). On imaging, the schwannomas almost disappeared in 8 (15.4%), shrank in 32 (61.5%), remained stable in 5 (9.6%), and increased in size in 7 patients (13.5%). Tumor growth control was achieved in 45 (86.5%) of the 52 patients.

SRS is an effective and minimally invasive management option for patients with residual or newly diagnosed trigeminal schwannomas. The use of SRS to treat trigeminal schwannomas resulted in good tumor control and functional improvement 6).

2009

The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1-82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5-18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12-20 Gy).

At an average of 6 years (range 7.2-147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs.

Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment 7).

2007

Phi et al. reviewed the clinical records and radiological data in 22 consecutive patients who received GKS for a trigeminal schwannoma. The median tumor volume was 4.1 ml (0.2-12.0 ml), and the mean tumor margin dose was 13.3 +/- 1.3 Gy at an isodose line of 49.9 +/- 0.6% (mean +/- standard deviation). The median clinical follow-up period was 46 months (range 24-89 months), and the median length of imaging follow-up was 37 months (range 24-79 months).

Tumor growth control was achieved in 21 (95%) of the 22 patients. Facial pain responded best to radiosurgery, with two thirds of patients showing improvement. However, only one third of patients with facial hypesthesia improved. Six patients (27%) experienced new or worsening cranial neuropathies after GKS. Ten patients (46%) showed tumor expansion after radiosurgery, and nine of these also showed central enhancement loss. Loss of central enhancement, tumor expansion, and a tumor in a cavernous sinus were found to be significantly related to the emergence of cranial neuropathies.

The use of GKS to treat trigeminal schwannoma resulted in a high rate of tumor control and functional improvement. Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required 8).


Twenty-six patients with trigeminal schwannomas underwent GKS at the University of Virginia Lars Leksell Gamma Knife Center between 1989 and 2005. Five of these patients had neurofibromatosis and one patient was lost to follow up. The median tumor volume was 3.96 cm(3), and the mean follow-up period was 48.5 months. The median prescription radiation dose was 15 Gy, and the median prescription isodose configuration was 50%. There was clinical improvement in 18 patients (72%), a stable lesion in four patients (16%), and worsening of the disease in three patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained stable in 10 patients (40%), and increased in size in three patients (12%). These results were comparable for primary and adjuvant GKSs. No tumor growth following GKS was observed in the patients with neurofibromatosis.

Gamma Knife surgery affords a favorable risk-to-benefit profile for patients harboring trigeminal schwannomas. Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas 9).

2001

A patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed. Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy. The patient underwent radiosurgery seven weeks later. The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery.

Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision 10).

References

1) , 6)

Sun J, Zhang J, Yu X, Qi S, Du Y, Ni W, Hu Y, Tian Z. Stereotactic radiosurgery for trigeminal schwannoma: a clinical retrospective study in 52 cases. Stereotact Funct Neurosurg. 2013;91(4):236-42. doi: 10.1159/000345258. Epub 2013 Mar 26. PubMed PMID: 23548989.
2) , 7)

Kano H, Niranjan A, Kondziolka D, Flickinger JC, Dade Lunsford L. Stereotactic radiosurgery for trigeminal schwannoma: tumor control and functional preservation Clinical article. J Neurosurg. 2009 Mar;110(3):553-8. PubMed PMID: 19301456.
3) , 8)

Phi JH, Paek SH, Chung HT, Jeong SS, Park CK, Jung HW, Kim DG. Gamma Knife surgery and trigeminal schwannoma: is it possible to preserve cranial nerve function? J Neurosurg. 2007 Oct;107(4):727-32. PubMed PMID: 17937215.
4) , 9)

Sheehan J, Yen CP, Arkha Y, Schlesinger D, Steiner L. Gamma knife surgery for trigeminal schwannoma. J Neurosurg. 2007 May;106(5):839-45. PubMed PMID: 17542528.
5) , 10)

Ardjomand N, Can B, Schaffler G, Eustacchio S, Scarpatetti M, Pendl G. [Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery]. Wien Klin Wochenschr. 2001 Aug 16;113(15-16):605-9. German. PubMed PMID: 11571839.

Update: Epidermal growth factor receptor

The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). Mutations affecting EGFR expression or activity could result in cancer.

Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors.


The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibody against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled 1).

This is in sharp contrast with the observations in EGFR-mutant lung cancer.


The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is the cell-surface receptor for members of the epidermal growth factor family (EGF-family) of extracellular protein ligands.

Overexpression of epidermal growth factor receptor (EGFR) in glioblastoma multiforme (GBM) secondary to EGFR gene amplification is associated with a more aggressive tumor phenotype and a worse clinical outcome.


Epidermal growth factor receptor (EGFR), pMAPK, 4E-BP1, p4E-BP1, pS6, eIF4E, and peIF4E expression levels were evaluated using immunohistochemistry. Expression levels were semiquantitatively evaluated using a histoscore. Immunohistochemistry and PCR were used for IDH1 mutations. Statistical analysis was based on the following tests: chi-square, Student’s t, Pearson correlation, Spearman’s rho, and Mann-Whitney; ROC and Kaplan-Meier curves were constructed. A significant increase was observed between grades for expression of total and phosphorylated 4E-BP1 and for eIF4E, Ki67, EGFR, and cyclin D1. Although expression of EGFR, eIF4E, and Ki67 correlated with survival, only peIF4E was an independent predictor of survival in the multivariate analysis. Combining the evaluation of different proteins enables us to generate helpful diagnostic nomograms. In conclusion, cell signaling pathways are activated in DIAs; peIF4E is an independent prognostic factor and a promising therapeutic target. Joint analysis of the expression of 4E-BP1 and peIF4E could be helpful in the diagnosis of glioblastoma multiforme in small biopsy samples 2).


Ren et al., analyzed the microarray and proteomics profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the Kininogen 1 (KNG1). Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR 138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0.05 for all), which resulted in the upregulation of oncogenic EGFR signaling in both cell lines, and stimulated angiogenic processes in cultured iHECs and zebrafish and mouse xenograft models of glioblastoma-induced angiogenesis. Angiogenic transduction of iHECs occurred via the uptake of U87-derived exosomes enriched in miR-138, with the siRNA-mediated knockdown of KNG1, CTU1, KIAA1274, or RAX increasing the level of miR-138 enrichment to varying extents and enhancing the angiogenic effects of the U87-derived exosomes on iHECs. The competing endogenous RNA network of KNG1 represents potential targets for the development of novel therapeutic strategies for glioblastoma 3).

EGFRvIII

Fluorophore/nanoparticle labeled with anti-EGFR antibodies

Senders et al., systematically review all clinically tested fluorescent agents for application in fluorescence guided surgery (FGS) for glioma and all preclinically tested agents with the potential for FGS for glioma.

They searched the PubMed and Embase databases for all potentially relevant studies through March 2016.

They assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5 aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives. 4).

References

1)

Westphal M, Maire CL, Lamszus K. EGFR as a Target for Glioblastoma Treatment: An Unfulfilled Promise. CNS Drugs. 2017 Aug 8. doi: 10.1007/s40263-017-0456-6. [Epub ahead of print] PubMed PMID: 28791656.
2)

Martínez-Sáez E, Peg V, Ortega-Aznar A, Martínez-Ricarte F, Camacho J, Hernández-Losa J, Ferreres Piñas JC, Ramón Y Cajal S. peIF4E as an independent prognostic factor and a potential therapeutic target in diffuse infiltrating astrocytomas. Cancer Med. 2016 Jul 20. doi: 10.1002/cam4.817. [Epub ahead of print] PubMed PMID: 27440383.
3)

Ren Y, Ji N, Kang X, Wang R, Ma W, Hu Z, Liu X, Wang Y. Aberrant ceRNA-mediated regulation of KNG1 contributes to glioblastoma-induced angiogenesis. Oncotarget. 2016 Oct 14. doi: 10.18632/oncotarget.12659. PubMed PMID: 27764797.
4)

Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, Broekman ML. Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir (Wien). 2017 Jan;159(1):151-167. doi: 10.1007/s00701-016-3028-5. Review. PubMed PMID: 27878374; PubMed Central PMCID: PMC5177668.

Update: Bing Neel syndrome

Bing Neel syndrome is a rare disease manifestation of Waldenstrom macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells 1).

This infiltration increases blood viscosity, which impairs blood circulation through small blood vessels of the brain and the eye. Some scientists proposed that a person diagnosed with BNS is typically classified into Group A and Group B depending on whether or not plasma cells are present within the brain parenchymaleptomeninges, dura, and/or the cerebrospinal fluid (CSF).

Epidemiology

Bing–Neel syndrome (BNS) is an extremely rare neurologic complication of WM.

Clinical features

The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenström’s macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients 2).

Diagnosis

The diagnostic approach should be based on cerebrospinal fluid analysis and brain magnetic resonance imaging and Spinal magnetic resonance imaging 3).

Cerebral spinal fluid analysis with multiparameter flow cytometry to establish B cell clonality, serum protein electrophoresis and immunofixation for the detection and classification of a monoclonal protein as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88 4).

Treatment

It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies 5).

Prospective clinical trials on Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, constituting a significant step forward in delineating treatment outcome for this intriguing disease manifestation 6).

Case series

2015

Simon et al. retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenström macroglobulinemia in 36% of patients. When Waldenström macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenström macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenström macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies 7).

Case reports

2017

A 68-year-old male with right eye vision loss secondary to a compressive optic neuropathy from Waldenstrom macroglobulinaemia relapse in both cavernous sinuses. Central nervous system involvement is extremely uncommon in lymphoplasmacytic lymphoma. Known as Bing-Neel syndrome, this has not been previously reported to present simultaneously in bilateral cavernous sinuses. We discuss the pathophysiology, diagnostic and neuroradiological features of Bing-Neel syndrome. In this case, there was marked clinical and radiological response to chemotherapy. As outcomes following treatment for Waldenstrom macroglobulinaemia improve, greater awareness of its less common manifestations becomes important. Neurosurgical intervention may be indicated to obtain histological diagnosis or decompress critical structures 8).


Waldenstrom macroglobulinemia presenting as a bilateral subdural chronic hematoma 9).

2016

Intracranial venous sinus thrombosis as unusual presentation of Bing-Neel syndrome: case illustration 10).

2014

A case of Bing-Neel syndrome presenting as spinal cord compression 11).

2013

Tumoral Bing-Neel Syndrome presenting as a cerebellar mass 12).

2002

A 72-year-old man with Waldenstrom’s macroglobulinemia and central nervous system infiltration by malignant cells with tumor formation 13).

1995

A 68-year-old female presented with Waldenstrom’s macroglobulinemia with infiltration into the cerebral parenchyma manifesting as increased confusion, memory loss, and disorientation. She had a past history of Waldenstrom’s macroglobulinemia treated 3 years before. Magnetic resonance imaging showed a high intensity area on T2-weighted images in the left frontal lobe extending to the corpus callosum which was well enhanced by gadolinium-diethylenetriaminepenta-acetic acid. Direct infiltration of neoplastic cells was confirmed by biopsy. Immunohistochemical examination showed that mature plasmacytoid cells in the cerebral parenchyma were immunoglobulin M and lambda light chain antigen positive, but immature lymphocytes in Virchow-Robin space were negative. Monoclonal proliferation was confirmed by southern blot analysis. She became symptom free and the size of the lesion was dramatically reduced after 40 Gy irradiation. She showed no evidence of recurrence 3 years after irradiation. As no effective chemotherapy regimen for Bing-Neel syndrome has been established, irradiation is worth considering when neuroimaging suggests intracranial infiltration of neoplastic cells 14).

References

1) , 2) , 4) , 6)

Minnema MC, Kimby E, D’Sa S, Fornecker LM, Poulain S, Snijders TJ, Kastritis E, Kremer S, Fitsiori A, Simon L, Davi F, Lunn M, Castillo JJ, Patterson CJ, Le Garff-Tavernier M, Costopoulos M, Leblond V, Kersten MJ, Dimopoulos MA, Treon SP. Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. Haematologica. 2017 Jan;102(1):43-51. doi: 10.3324/haematol.2016.147728. Epub 2016 Oct 6. PubMed PMID: 27758817; PubMed Central PMCID: PMC5210231.

3) , 5) , 7)

Simon L, Fitsiori A, Lemal R, Dupuis J, Carpentier B, Boudin L, Corby A, Aurran-Schleinitz T, Gastaud L, Talbot A, Leprêtre S, Mahe B, Payet C, Soussain C, Bonnet C, Vincent L, Lissandre S, Herbrecht R, Kremer S, Leblond V, Fornecker LM. Bing-Neel syndrome, a rare complication of Waldenström macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French Innovative Leukemia Organization (FILO). Haematologica. 2015 Dec;100(12):1587-94. doi: 10.3324/haematol.2015.133744. Epub 2015 Sep 18. Review. PubMed PMID: 26385211; PubMed Central PMCID: PMC4666335.

8) , 12)

Pham C, Griffiths JD, Kam A, Hunn MK. Bing-Neel syndrome – Bilateral cavernous sinus lymphoma causing visual failure. J Clin Neurosci. 2017 Jul 29. pii: S0967-5868(16)31423-0. doi: 10.1016/j.jocn.2017.07.010. [Epub ahead of print] PubMed PMID: 28765059.

9)

Franzini A, Gribaudi G, Pirola E, Pluderi M, Goldaniga MC, Marfia G, Rampini PM. Waldenstrom macroglobulinemia presenting as a bilateral subdural chronic hematoma. J Clin Neurosci. 2017 Jun;40:89-91. doi: 10.1016/j.jocn.2017.02.032. Epub 2017 Mar 2. PubMed PMID: 28262409.

10)

Morabito R, Grasso G, Barresi V, La Spina P, Garufi G, Alafaci E, Salpietro FM, Longo M, Granata F, Alafaci C. Intracranial venous sinus thrombosis as unusual presentation of Bing-Neel syndrome: case illustration. J Neurosurg. 2016 Dec 2:1-2. doi: 10.3171/2016.9.JNS161678. [Epub ahead of print] PubMed PMID: 27911232.

11)

Rigamonti A, Lauria G, Melzi P, Mantero V, Vismara D, Rossi G, Tetto A, Salmaggi A. A case of Bing-Neel syndrome presenting as spinal cord compression. J Neurol Sci. 2014 Nov 15;346(1-2):345-7. doi: 10.1016/j.jns.2014.08.029. Epub 2014 Aug 28. PubMed PMID: 25201716.

13)

Delgado J, Canales MA, Garcia B, Alvarez-Ferreira J, Garcia-Grande A, Hernandez-Navarro F. Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature. Am J Hematol. 2002 Feb;69(2):127-31. Review. PubMed PMID: 11835349.

14)

Imai F, Fujisawa K, Kiya N, Ninomiya T, Ogura Y, Mizoguchi Y, Sano H, Kanno T. Intracerebral infiltration by monoclonal plasmacytoid cells in Waldenstrom’s macroglobulinemia–case report. Neurol Med Chir (Tokyo). 1995 Aug;35(8):575-9. PubMed PMID: 7566387.

Update: Temporalis muscle

Temporalis muscle

The temporal muscle, also known as the temporalis, is one of the muscles of mastication. It is a broad, fan-shaped muscle on each side of the head that fills the temporal fossa, superior to the zygomatic arch so it covers much of the temporal bone.

The skin flap is reflected forward to the level of the external auditory canal. The temporal muscle and the sternocleidomastoid muscles are exposed.

EAC: External auditory canal; ECM: Sternocleidomastoid muscle;TF: Temporal fascia.

When Gazi Yasargil first described standard techniques and procedures for pterional craniotomy (PC) in his publication in 1984, subgaleal dissection was used for separation and mobilization of the temporalis muscle. Because subgaleal dissection of the temporalis muscle bears significant risk of injury to the frontal branches of the facial nerve, various surgical techniques have been adopted such as interfascial and subfascial dissection. However, interfascial dissection is somewhat complex and time-consuming, and, because the facial nerve sometimes courses into the interfascial space, it still cannot eliminate the risk of facial nerve injury. Subfascial dissection is also time-consuming, and may result in injury to muscle fibers and intramuscular bleeding. These two techniques require transection of the temporalis muscle to leave a cuff for closure, which causes functional and cosmetic problems by muscle fibrosis and atrophy.

In neurosurgical procedures, avoiding damage of surrounding tissues such as muscle and periosteum during a craniotomy is important for esthetic and other reasons.

Matano et al. devised a protection tool using an amputated syringe barrel to cover the perforating drill and protect temporal muscle damage. This device made it possible to prevent damage to surrounding tissues, such as the muscle and periosteum, during cranial perforation. This method could be useful as it is cost-effective, simple, and versatile 1).


Effect of reflection of temporalis muscle has not been systematically researched. Thirty-nine patients were enrolled to assess the effect of reflection of temporalis muscle during cranioplasty CP after STC. Cranial index of symmetry was adopted to evaluate the aesthetic results, transcranial Doppler was used to assess change of cerebral blood flow (CBF), functional independence measurements were performed to monitor the improvement of neuronal function, and complications associated with CP were also recorded. The results displayed that reflection of temporalis muscle or not had no effect on the anesthetic results. Both operation ways could improve CBF and neuronal function. Cranioplasty with reflection of temporalis muscle could improve CBF and neuronal function more significantly. Furthermore, reflection of temporalis muscle would not increase complications associated with CP. Reflection of temporalis muscle during CP with titanium mesh after STC proves to be an effective and safe operation way 2).


Pterional craniotomy (PC) using myocutaneous (MC) flap is a simple and efficient technique; however, due to subsequent inferior displacement (ID) of the temporalis muscle, it can cause postoperative deformities of the muscle such as depression along the inferior margin of the temporal line of the frontal bone (DTL) and muscular protrusion at the inferior portion of the temporal fossa (PITF). Herein, we introduce a simple method for reconstruction of the temporalis muscle using a contourable strut plate (CSP) and evaluate its efficacy. Patients at follow-ups between January 2014 and October 2014 after PCs were enrolled in this study. Their postoperative deformities of the temporalis muscle including ID, DTL, and PITF were evaluated. These PC cases using MC flap were classified according to two groups; one with conventional technique without CSP (MC Only) and another with reconstruction of the temporalis muscle using CSP (MC + CSP). Statistical analyses were performed for comparison between the two groups.  Lower incidences of ID of the muscle (p < 0.001), DTL (p < 0.001), and PITF (p = 0.001) were observed in the MC + CSP than in the MC Only group. The incidence of acceptable outcome was markedly higher in the MC + CSP group (p < 0.001). ID was regarded as a causative factor for DTL and PITF (p < 0.001 in both). Reconstruction of the temporalis muscle using CSP after MC flap is a simple and efficient technique, which provides an outstanding outcome in terms of anatomical restoration of the temporalis muscle 3).


The minipterional craniotomy (MPT) provides a reliable and less invasive alternative to the standard pterional craniotomy. Furthermore, ruptured and unruptured anterior circulation aneurysms can safely and effectively be treated with limited bone removal which provides better cosmetic outcomes and excellent postoperative temporalis muscle function 4).

1)

Matano F, Mizunari T, Koketsu K, Fujiki Y, Kubota A, Kobayashi S, Murai Y, Morita A. Protection device made of amputated syringe for muscle protection during cranial perforation: a technical note. World Neurosurg. 2016 Jan 7. pii: S1878-8750(16)00002-4. doi: 10.1016/j.wneu.2016.01.001. [Epub ahead of print] PubMed PMID: 26773982.

2)

Jin Y, Jiang J, Zhang X. Effect of Reflection of Temporalis Muscle During Cranioplasty With Titanium Mesh After Standard Trauma Craniectomy. J Craniofac Surg. 2016 Jan;27(1):145-9. doi: 10.1097/SCS.0000000000002336. PubMed PMID: 26674916.

3)

Park JH, Lee YS, Suh SJ, Lee JH, Ryu KY, Kang DG. A Simple Method for Reconstruction of the Temporalis Muscle Using Contourable Strut Plate after Pterional Craniotomy: Introduction of the Surgical Techniques and Analysis of Its Efficacy. J Cerebrovasc Endovasc Neurosurg. 2015 Jun;17(2):93-100. doi: 10.7461/jcen.2015.17.2.93. Epub 2015 Jun 30. PubMed PMID: 26157688; PubMed Central PMCID: PMC4495087.

4)

Alkhalili KA, Hannallah JR, Alshyal GH, Nageeb MM, Abdel Aziz KM. The minipterional approach for ruptured and unruptured anterior circulation aneurysms: Our initial experience. Asian J Neurosurg. 2017 Jul-Sep;12(3):466-474. doi: 10.4103/1793-5482.180951. PubMed PMID: 28761525; PubMed Central PMCID: PMC5532932.