Category Archives: Neurooncology

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


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).


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).


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).


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).


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).


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).



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.

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.

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.

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).


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).


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).


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


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


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).


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


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


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


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


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).


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.


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.


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.


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.


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.


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).


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.


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.


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.


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.

Book: Complex Surgical Cases of the Limbic System

Complex Surgical Cases of the Limbic System
By Sepehr Sani

Complex Surgical Cases of the Limbic System

List Price: $90.00


The limbic system (also known as the paleomammalian brain) is a collection of brain structures located in the middle of the brain. It is not a discrete system itself but rather a collection of structures-anatomically related but varying greatly in function. The limbic system is the centre for emotional responsiveness, motivation, memory formation and integration, olfaction, and the mechanisms to keep ourselves safe ( This book is a guide to surgical procedures for the limbic system. Beginning with an overview of brain embryology and anatomy, each of the following sections covers surgical approaches for disorders in different parts of the limbic system. Procedures are explained in a step by step approach, with emphasis on anatomical markers and avoidance of complications. The final chapters discuss brain mapping during surgery, giant and unusual tumours, and vascular lesions. Authored by a team of highly experienced, Illinois and Wisconsin-based neurosurgeons, the book is enhanced by anatomical dissections, operative photographs and illustrations, and includes a DVD ROM demonstrating surgical procedures. Key points * Guide to surgical procedures for the limbic system * Step by step approach with emphasis on anatomical markers and avoidance of complications * Highly experienced, Illinois and Wisconsin-based author team * Includes DVD ROM demonstrating surgical procedures

Product Details

  • Original language: English
  • Dimensions: 9.50″ h x .0″ w x 6.30″ l,
  • Binding: Hardcover
  • 180 pages

Editorial Reviews

About the Author
Sepehr Sani MD Assistant Professor, Department of Neurosurgery, Rush University Medical Centre, Chicago, IL, USA Mustafa K Baskaya MD Department of Neurological Surgery, University of Wisconsin-Madison School of Medicine, Madison, WI, USA Richard W Byrne MD Chairman, Department of Neurosurgery, Rush University Medical Centre, Chicago, IL, USA

Update: Maffucci syndrome

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome).

Additionally, neuroendocrine tumors including pituitary adenomas have been described in patients with Maffucci syndrome.

The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma. However, hematopoietic malignancies arising in Maffucci syndrome are rare 1)


The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2)2).

Case series


Cerebral MRI was routinely performed in Ollier-Maffucci patients followed-up in tertiary centers. Patients with previous history of skull base or intracranial tumors were excluded from the study. Clinical and radiological datas were retrospectively collected. The occurrence rate and nature of abnormal cerebral MRIs were determined.

Twelve patients were included. A glioma-looking lesion was found in one patient (8%), while skull base lesions were evidenced in 3 others (25%). A regular MRI follow-up was recommended for each patient, with a time interval varying between 1year and 3years depending on the likelihood of tumoral evolutivity, as infered from the MRI findings.

All in all, the high rate of intracranial and skull base lesions with a malignant potential warrants to include cerebral MRI in the routine follow-up of Ollier-Maffucci patients 3).

Case report


A report describes a patient with Maffucci syndrome who presented with skull base tumors and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors.

This report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction 4).

A 39-year-old woman who was diagnosed with Maffucci syndrome together with intrahepatic cholangiocarcinoma (IHCC). Heterozygous somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes are associated with a number of different tumor types (e.g. IHCC) and also with Maffucci syndrome. For IHCC, mutations in IDH1/IDH2 are associated with higher survival rates. IHCC tissue as well as normal liver tissue and peripheral blood were analyzed for IDH1/IDH2-mutations in our patient. In the tumor sample, we identified a recurrent somatic IDH1-mutation affecting Arg132, while in normal liver tissue and peripheral blood, no variants were detected, as expected.

This case report presents the second patient in the literature exhibiting the features of Maffucci syndrome along with cholangiocarcinoma. This supports the hypothesis that IDH1/2-mutations, which can be present in different types of tumor tissue simultaneously, arise during embryonic development in a mosaic pattern; as a result, a more aggressive follow-up is proposed in patients with Maffucci syndrome to exclude neoplasms 5).


First case of Maffucci syndrome associated with a pituitary adenoma and a probable brainstem glioma

A 35-year-old woman with Marfucci syndrome (diagnosed when she was 22 years old) who presented with complaints of decreased visual acuity and visual field defect. Neuroimaging revealed a pituitary macroadenoma and a suspected brainstem tumor. The macroadenoma was partially removed. There were no postoperative complications and the patient experienced rapid improvement in visual acuity. On follow-up examination 2 years later, the lesion in the pons showed the same dimensions. No sarcomatous changes of enchondromas or hemangiomas occurred. To the authors’ knowledge, including the present case, only 7 cases of Maffucci syndrome associated with glioma and 7 cases associated with pituitary adenoma have been reported in the literature. This report emphasizes that patients with this disease are at a higher risk for primary intracranial tumors and reinforces the concept of the multiplicity of tumors that may arise in this syndrome. It also underscores the importance of early diagnosis, regular clinical surveillance, and follow-up studies of these patients 6).


Akiyama M, Yamaoka M, Mikami-Terao Y, Ohyama W, Yokoi K, Arakawa Y, Takita J, Suzuki H, Yamada H. Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome. Int J Hematol. 2015 Dec;102(6):723-8. doi: 10.1007/s12185-015-1892-z. Epub 2015 Oct 27. PubMed PMID: 26508204.


Pansuriya TC, van Eijk R, d’Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011 Nov 6;43(12):1256-61. doi: 10.1038/ng.1004. PubMed PMID: 22057234; PubMed Central PMCID: PMC3427908.


Mandonnet E, Anract P, Martin E, Roujeau T, Spena G, Cormier-Daire V, Duffau H, Baujat G; Collaborators. Brain and skull base MRI findings in patients with Ollier-Maffucci disease: A series of 12 patient-cases. Clin Neurol Neurosurg. 2017 Jul 18;160:147-151. doi: 10.1016/j.clineuro.2017.07.011. [Epub ahead of print] PubMed PMID: 28750360.


Hao S, Hong CS, Feng J, Yang C, Chittiboina P, Zhang J, Zhuang Z. Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome. J Neurosurg. 2016 Jun;124(6):1562-7. doi: 10.3171/2015.4.JNS15191. Epub 2015 Oct 16. PubMed PMID: 26473790.


Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H. Maffucci syndrome and neoplasms: a case report and review of the literature. BMC Res Notes. 2016 Feb 27;9(1):126. doi: 10.1186/s13104-016-1913-x. PubMed PMID: 26920730; PubMed Central PMCID: PMC4769492.


Ruivo J, Antunes JL. Maffucci syndrome associated with a pituitary adenoma and a probable brainstem tumor. J Neurosurg. 2009 Feb;110(2):363-8. doi: 10.3171/2008.8.JNS08150. Review. PubMed PMID: 18976063.

Update: Amelanotic melanoma

Primary amelanotic melanoma is a special subtype of Primary melanocytic neoplasm, which is especially rare.

Very few cases of amelanotic variation of primary melanoma in the CNS were reported on. General guidelines or recommendations to establish this diagnosis do not exist.

Sun et al. established intracranial and subcutaneous melanoma models using cultured malignant cells derived from amelanotic melanoma. The median survival times in a mouse model with intracranial tumors was 20 days, but a mouse model with subcutaneous tumors did not show cachexia until they were killed 28 days after inoculation with tumor cells. Histopathological analysis showed that a high karyokinesis phase and nuclear pleomorphism appeared in the intracranial model compared with the subcutaneous tumor model mice. The tumor boron concentration at 2.5 h after boronophenylalanine administration was 15.21±3.88 μg/g in an intracranial melanoma xenograft and 19.85±3.63 μg/g in a subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and shorter survival time than did subcutaneous melanoma when the same number of tumor cells were injected, and subcutaneous and intracranial amelanotic malignant melanoma tumors are both fitted for boron neutron capture therapy 1).

Case reports


Primary Amelanotic CNS Melanoma: Case Report and Literature Review 2).


Ma et al. report a case of intracranial amelanotic melanoma. Preoperative assessment revealed progressive right frontal mass. The patient underwent tumor resection. The pathologic analysis reported amelanotic melanoma of intermediate grade. The further examination of the whole brain and body was negative. The familial history was also negative. The patient recovered uneventfully and went on for radiotherapy and chemotherapy. After a follow-up period of 5 months, the patient was tumor-free.

This is the second report about primary CNS amelanotic melanoma. They summarized characteristics of the primary CNS melanocytic lesions and amelanotic melanoma with review of the literature and review of cases from the department 3).


A 69-year-old man presented with trigeminal neuralgia. 4 years previously he underwent tumor removal with an initial diagnosis of amelanotic malignant cutaneous melanoma; 1 year later, because of tumor recurrence, the patient underwent neck dissection, chemotherapy and radiation. Magnet resonance imaging (MRI) disclosed an enhancement of the Gasserian ganglion and tumor extension along the mandibular and maxillar nerves of the intracranial part of the trigeminal nerve suggestive of tumor. The intraoperative macroscopic appearance of the tumor was compatible with a neurinoma. Histopathological studies proved the tumor to be a desmoplastic neurotropic melanoma (DNM) that was related to the previously treated malignant melanoma 4).


Only 15 cases of intracranial amelanotic melanoma have been reported until 2008. A yellowish mass was observed in the frontal lobe. The content of the cyst consisted of old hematoma, xanthochromic fluid and necrotic tissue, was evacuated and the cyst wall was totally resected. No abnormal pigmentation was noted in the cyst wall and surrounding brain tissue. The imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2-weighted signal intensity loss 5).


A 63-year-old woman with diplopia and bilateral ptosis underwent brain MRI that showed a pituitary mass with signal characteristics suggestive of adenoma. Within one week she had developed nearly complete bilateral ophthalmoplegia. A repeat MRI showed extension of the mass into both cavernous sinuses. Hypophysectomy disclosed an amelanotic melanoma. Extensive search for a primary source was unsuccessful. Despite local radiation treatment, the tumor continued to grow and the patient became blind and died within several months of diagnosis. There are seven reported cases of melanoma arising primarily in the sella turcica. Two cases of metastatic melanoma to the cavernous sinuses have been reported. Amelanotic melanoma has not been reported as a cause of cavernous sinus syndrome 6).


A thirty-four-year-old man was admitted to our hospital because of the disturbed visual acuity and pain on the eye movement of the right eye. He had prominent right eye and CT-scan and MRI of the brain disclosed a tumor which could be obviously distinguished from the extraocular muscles, optic nerve and the bulb of eye in the retrobulbar region. On operation we identified dark-red solid tumor which was 3.0cm in diameter, and diagnosed it malignant melanoma pathologically. Because postoperative study detected amelanotic melanoma in the white patch on the right upper extremity, this right orbital tumor was considered to be the metastasis of it from the right upper extremity. Metastatic malignant melanoma of the skin to the orbit is very rare, while most of the eye-associated malignant melanoma originates from uveal tract, special choroid, and conjunctiva. This case was the 26th case of these in the world and the first case in Japan, furthermore the 4th case in the world whose first symptoms were caused by the orbital metastasis 7).


Primary intracranial amelanotic melanoma was verified at autopsy in a 38-year-old male. Correct diagnosis of amelanotic melanoma needs electron microscopy or immunohistochemistry, since Masson staining is negative due to the absence of melanin pigment. We adopted the following criteria for clinical use: macroscopically not dark and microscopically negative for Masson staining, but ultrastructurally various melanoma types present. Although the clinical profile of this case is consistent with melanotic melanoma, the more detailed features of primary intracranial amelanotic melanoma require future study 8).


Sun T, Li Y, Wu T, Xie X, Chen G, Wei Y, Li B, Zhou Y, Du Z. Comparative analysis of pathology and boronophenylalanine uptake in experimental orthotopic and heterotopic amelanotic melanoma. Melanoma Res. 2014 Aug;24(4):315-21. doi: 10.1097/CMR.0000000000000086. PubMed PMID: 24915302.

Mayer S, Mauer UM, Mathieu R, Hackenbroch C, Knupfer J, Schulz C. Primary Amelanotic CNS Melanoma: Case Report and Literature Review. J Neurol Surg A Cent Eur Neurosurg. 2017 Jul 27. doi: 10.1055/s-0037-1604326. [Epub ahead of print] PubMed PMID: 28750450.

Ma J, Zhang Z, Li S, Chen X, Wang S. Intracranial amelanotic melanoma: a case report with literature review. World J Surg Oncol. 2015 May 12;13:182. doi: 10.1186/s12957-015-0600-z. Review. PubMed PMID: 25963017; PubMed Central PMCID: PMC4436165.

Hashemi M, Stark A, Hugo H, Mehdorn M. Intracranial trigeminal nerve metastasis of a desmoplastic neurotropic melanoma: case report. Cent Eur Neurosurg. 2009 May;70(2):91-4. doi: 10.1055/s-0028-1082065. Epub 2009 May 25. PubMed PMID: 19711263.

Cemil B, Emmez H, Oztanir N, Tokgoz N, Dogulu F. A cystic amelanotic melanoma metastasis to the brain: case report. Neurocirugia (Astur). 2008 Aug;19(4):365-7. PubMed PMID: 18726049.

Jacob S, Pye E, Hbahbih M, Messios N, Rajabally YA. Rapidly progressive bilateral ophthalmoplegia and enlarging sellar mass caused by amelanotic melanoma. J Neuroophthalmol. 2006 Mar;26(1):49-50. PubMed PMID: 16518168.

Toyoda H, Fukui K, Okabe H, Kitoh A, Iguchi I, Kanematsu I. [A case of malignant melanoma with orbital metastasis which caused the first symptoms]. No To Shinkei. 1992 Oct;44(10):929-33. Review. Japanese. PubMed PMID: 1285995.

Seki Y, Ohara K, Aiba T, Unakami M, Hara M. Primary intracranial amelanotic melanoma–report of an autopsy case. Neurol Med Chir (Tokyo). 1991 Dec;31(12):773-6. PubMed PMID: 1726225.