Early tumor-related hemorrhage after stereotactic radiosurgery of brain metastases: Systematic review of reported cases.

OBJECTIVE: Early (within 72 h) tumor-related hemorrhage (TRH) after stereotactic radiosurgery (SRS) of brain metastases (BM) has been reported only occasionally. Systematic review of such cases was done. METHODS: Literature search was performed through PubMed according to PRISMA guidelines using combination of the following medical subject headings: "hemorrhage," "stereotactic radiosurgery," and "brain metastasis." RESULTS: In total, 7 case reports and 8 clinical series, which noted early TRH after SRS of BM were identified. Scarce and inconsistent data precluded their precise synthesis and statistical analysis. BM of renal cell carcinoma comprised around one-third of reported cases. In 4 patients with multiple BM, TRH after SRS was noted simultaneously in several irradiated tumors. Considering 17 reported cases overall, in 3 patients TRH occurred during SRS session itself, in 4 within several minutes upon completion of treatment, in 7 within several hours thereafter, and in 3 on the third posttreatment day. Out of 11 reported cases providing detailed outcome, 6 patients died shortly after the ictus, 2 others were severely disabled at discharge, and 3 demonstrated good-to-moderate recovery. Overall, among evaluated series the median rates of early TRH after SRS for BM were 0.8% per patient (range, 0.4 - 1.9%) and 0.3% per tumor (range, 0.05 - 0.8%). CONCLUSION: Early TRH is very rare, but potentially life-threatening complication of SRS for BM; thus, its risk (while extremely low) and possible consequences should be discussed at the time of obtaining informed consent.

Gamma Knife Radiosurgery for Pituitary Adenomas Invading the Cavernous Sinus: Tokyo Women's Medical University Experience.

Total surgical removal of a pituitary adenoma (PA) invading the cavernous sinus (CS) is challenging and carries a significant risk of postoperative complications. As an alternative treatment strategy, after incomplete resection, such tumors may undergo stereotactic radiosurgery-in particular, Gamma Knife surgery (GKS). Treatment planning based on advanced neuroimaging (e.g., thin-slice 3-dimensional postcontrast constructive interference in steady state (CISS) images) allows clear visualization of the target microanatomy, which results in highly conformal and selective radiation delivery to the lesion with preservation of adjacent functionally important neurovascular structures. In the Tokyo Women's Medical University experience of GKS for 43 nonfunctioning and 46 hormone-secreting PA invading the CS, with a minimum follow-up period of 5 years (mean 76 months, range 60-118 months), the tumor control rate has reached 97%, and a significant volume reduction (≥50%) has been seen in 24% of lesions. In cases of hormone-secreting neoplasms, normalization (in 18 patients; 39%) or improvement (in 22 patients; 48%) of endocrinological function has been noted. Importantly, such effects have been sufficiently durable. Complications have been extremely rare and limited to transient cranial nerve palsy (in 2% of cases). Notably, no patient in our series has had a new pituitary hormone deficit after irradiation. Thus, subtotal resection followed by GKS may be considered a valuable alternative to aggressive surgery for a PA invading the CS.

Pituitary Radiosurgery for Management of Intractable Pain: Tokyo Women's Medical University Experience and Literature Review.

Surgical or chemical hypophysectomy has historically shown good effectiveness in management of intractable pain but has often been accompanied by serious complications. In contrast, high-dose irradiation of the pituitary gland and stalk provides comparable analgesic effects and is associated with minimal morbidity. Although its physiological mechanism remains elusive, pituitary radiosurgery using the Gamma Knife has demonstrated high clinical efficacy and safety in cases of both cancer pain and noncancer pain. According to the available data, this treatment provides at least a temporary analgesic effect in >80% of patients, usually within hours to days after the procedure. Although the pain relief is most prominent and durable in cases of metastatic bone disease, it is not limited to that pathological condition or to cases of hormone-dependent cancers. Nevertheless, the low-quality studies reported to date cannot support any meaningful clinical recommendations on use of pituitary radiosurgery. Therefore, additional well-elaborated clinical and basic investigations, preferably performed in a multi-institutional and prospective fashion, are clearly needed and may bolster further developments of this highly promising treatment modality.

What Tactics Should a Surgeon Choose to Treat a Black Extracerebral Tumor? A Case Report of Psammomatous Melanotic Schwannoma of the Meckel Cave and Literature Review.

BACKGROUND: Neoplasms located in the Meckel cave account for 0.2%-0.5% of all intracranial tumors. This area is the site of many types of pathologic lesions, most often trigeminal nerve schwannomas and meningiomas. Melanin-containing tumors are rare in this area. These tumor types can be suspected if the magnetic resonance characteristics of a tumor has some differences in comparison with other types of central nervous system neoplasms. In fact, differential diagnosis of melanotic tumors is based mainly on the histopathologic criteria and immunohistochemical profile. This article presents a case report of melanotic schwannoma of the Meckel cave and a literature review of the problem. CASE DESCRIPTION: A 23-year-old man underwent a 2-stage surgery for a dumbbell pigmented mass lesion located in the Meckel cave. No signs of recurrence were seen on follow-up magnetic resonance imaging (MRI) 3.5 years after the operation. CONCLUSIONS: Melanin-containing tumor can be suspected in the presence of radiologic characteristics, such as a hyperintense MRI signal on T1-weighted images and a hypointense signal on T2-weighted images. If a black extracerebral tumor is detected, the main course of surgical treatment is maximal excision despite it possibly being a malignant melanoma and the temptation to perform partial resection because of an unfavorable prognosis. Chemotherapy can be justified in the presence of an aggressive melanotic schwannoma.

Pathology and Genetics of Gliomas.

Current World Health Organization (WHO) classification of the neuroepithelial tumors is cell lineage-oriented and based on a presumed developmental tree of the central nervous system (CNS). It defines three main groups of gliomas, namely astrocytomas, oligodendrogliomas, and ependymomas, and additionally presumes their 4-tiered histopathological grading (WHO grades I to IV). Nevertheless, the impact of tumor pathology on clinically related parameters may be frequently much better predicted by genetics, than by histological appearance of the lesion. Recent studies have revealed several major molecular alterations typical for different types of neoplasms, such as IDH1/IDH2 mutations in diffusely infiltrating gliomas, mutations of TP53 and ATRX in astrocytomas, 1p/19q co-deletion in oligodendrogliomas, mutations of TERT promoter in oligodendrogliomas and IDH wild-type glioblastomas, and mutations or fusions of BRAF in circumscribed astrocytomas, particularly in children. Identification of those and several other genetic abnormalities in the tumor is clinically important and may help clinicians to determine proper treatment strategy and to predict prognosis. Therefore, the updated WHO classification of CNS tumors (2016) considers not only phenotype, but also some genetic characteristics of gliomas.

Imaging of Intracranial Gliomas.

Combined use of contemporary radiological modalities, particularly integration of structural, metabolic, and functional imaging, provides optimal multifaceted information for detailed characterization of intracranial gliomas. It allows differentiation of the tumor from non-neoplastic pathology, its non-invasive histopathological typing and grading, prediction of patient prognosis and clinical course of the disease, detailed planning of surgical resection or biopsy, critical postoperative assessment of the residual lesion, effective surveillance during follow-up with evaluation of effectiveness of the adjuvant therapy and timely identification of recurrence, and even insights into molecular signatures of the neoplasms. Therefore, advanced neuroimaging is one of the most important cornerstones of the modern neuro-oncology.

Rationale for Aggressive Resection and General Surgical Principles for Intracranial Gliomas.

Given the infiltrative nature of gliomas, controversy has long persisted over the value of their aggressive surgical removal. Nevertheless, in recent decades, the balance of opinion in neurosurgical oncology has shifted from a more nihilistic view that led to many patients' receiving stereotactic biopsy or very limited debulking of lesions for tissue diagnosis only, to more extensive tumor resections which relieve mass effect, lower intracranial pressure, reduce accompanying brain edema, and attenuate dependence on steroids. Achieving a clinically significant cytoreduction makes adjuvant therapy more successful, and ultimately helps to preserve or improve neurological function. Moreover, increased extent of brain tumor removal results in prolongation of progression-free survival and overall survival of patients and improves their quality of life. The beneficial effect of high resection rate may be noted even in selected cases of recurrent neoplasms. However, optimizing an aggressive surgical strategy for intracranial gliomas requires specific skills, availability of advanced intraoperative technological modalities, and the presence of a highly qualified multidisciplinary team of medical professionals for pre-, intra-, and postoperative care of such patients.

Neurophysiological Monitoring and Awake Craniotomy for Resection of Intracranial Gliomas.

Aggressive resection of intracranial gliomas has a positive impact on patients' prognosis, but is associated with a risk of neurological complications. For preservation of brain functions and avoidance of major postoperative morbidity various methods of intraoperative neurophysiological monitoring have been introduced into clinical practice. At present, somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), and electrocorticography (ECoG) are used routinely during neurosurgical procedures. To maximize the efficacy of these neurophysiological techniques, it is most preferable to apply total intravenous anesthesia with continuous infusion of propofol and opioids and avoidance of long-acting muscle relaxants. Surgery for brainstem gliomas requires specific mapping with direct electrical stimulation (DES), corticobulbar tract MEP monitoring, and free-running electromyography (EMG) of the various muscles innervated by the cranial nerves. Awake craniotomy and intraoperative mapping of language and sensorimotor functions with DES allow precise identification of the functionally important neuronal structures and have become standard techniques for removal of cerebral neoplasms affecting eloquent cortical areas and subcortical pathways. Overall, contemporary neurophysiology plays a very important role in guidance of brain tumor surgery, in which it helps to maximize the extent of resection and to minimize the risk of permanent neurological morbidity.

Concept of robotic gamma knife microradiosurgery and results of its clinical application in benign skull base tumors.

The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.

Do we really still need an open surgery for treatment of patients with vestibular schwannomas?

BACKGROUND: Gamma Knife surgery (GKS) should be considered a standard treatment option for small and medium-sized vestibular schwannomas (VSs). It results in a tumor control rate similar to that seen with microsurgery and provides better preservation of facial nerve function and hearing. METHODS: From December 2002 to April 2011, a total of 260 patients with VS underwent GKS using Leksell Gamma Knife model 4C with an automatic positioning system. There were 30 Koos stage I tumors, 112 stage II, 100 stage III, and 18 stage IV. All patients were treated with the use of high-resolution magnetic resonance imaging; creation of the highly precise conformal and selective multi-isocenter dose planning with small collimators, carefully sparing adjacent cranial nerves of any excessive irradiation; and creation of a wide 80 % isodose area within the tumor while applying a low marginal dose (mean 11.9 Gy) at the 50 % isodose line. RESULTS: Among 182 patients who were followed for more than 3 years after treatment, the tumor control and shrinkage rates were 98.4 % and 76.4 %, respectively. Volume reduction of >50 % was marked in 54.9 % of VSs. Preservation of facial nerve function and hearing at the pretreatment level was noted in 97.8 % and 87.9 %, respectively. There was marked improvement of facial nerve function and hearing after GKS in 2.2 % and 3.8 %, respectively. There was no major morbidity. CONCLUSION: Due to contemporary technological and methodological achievements GKS can be focused not only on growth control but on shrinking the VS, with possible reversal of the neurological deficit.

Gamma knife treatment strategy for metastatic brain tumors.

From 1993 to 2011, a total of 3,095 patients with brain metastases underwent Gamma Knife radiosurgery (GKS) at Tokyo Women's Medical University. Follow-up information on 2,283 of these patients was available for retrospective analysis. The cases were separated into three groups according to the treatment period, the model of the Gamma Knife used, main goals of treatment, and technical nuances of radiosurgery. In the latest cohort of patients treated with the Leksell Gamma Knife model 4C with automatic positioning system, an optimized treatment strategy was applied. It was based on highly selective dose planning, with the use of multiple small isocenters located within the bulk of the mass, which was done for prevention of the excessive irradiation of the perilesional brain and avoidance of its posttreatment edema. In cases of large cystic tumors, selective coverage of the contrast-enhancing capsule with chain-like application of multiple small isocenters was done. Introduction of the new treatment strategy did not affect the 1-year tumor control rate, which was consistently >90 %. However, it did result in a statistically significant reduction of severe posttreatment peritumoral brain edema (from 15.5 % to 6.3 %; P < 0.0001). In conclusion, recent technical and methodological achievements of GKS seemingly do not affect its high efficacy in cases of brain metastasis with regard to tumor control. However, it may result in a prominent reduction of treatment-associated -morbidity, which is particularly important in patients with large and/or critically located neoplasm.

Optimal visualization of multiple brain metastases for gamma knife radiosurgery.

BACKGROUND: Optimal management of metastatic brain disease requires precise detection and detailed characterization of all intracranial lesions. METHODS: We analyzed an experience with 3200 brain MRI investigations performed at 1.5 T and 3.0 T for identification and/or evaluation of intracranial metastases. Usually axial T1- and T2-weighted images and contrast-enhanced T1-weighted images in axial and coronal and/or sagittal projections were obtained. Fluid-attenuated inversion recovery and diffusion-weighted imaging were sometimes used as well. Routinely, 0.2 mmol/kg of gadoteridol (ProHance®) was administered intravenously, but the dose was reduced to 0.1 mmol/kg in elderly patients or in patients with mild renal dysfunction. FINDINGS: Magnetic resonance imaging (MRI) provided excellent information on tumor location; interrelations with functionally important intracranial structures; type of growth; vascularity; recent, old or multiple hemorrhages within or in the vicinity of the mass; presence of peritumoral edema; necrotic changes; subarachnoid dissemination; meningeal carcinomatosis. However, without administration of gadoteridol or without contrast enhancement, small metastatic tumors could not be reliably distinguished from brain lacunes. Some metastases (malignant melanoma, thyroid cancer, endocrine carcinoma, small cell lung carcinoma) may demonstrate specific neuroimaging features. Non-metastatic -multiple brain lesions caused by vascular, inflammatory, demyelinative or lymphoproliferative diseases require a thorough differential diagnosis with metastatic brain tumors based not only on neuroimaging but on additional analysis of various clinical data. CONCLUSION: Contemporary MRI techniques provide excellent options for detection, detailed characterization, and differential diagnosis of metastatic brain tumors, which is extremely important when choosing the optimal treatment strategy, particularly with Gamma Knife radiosurgery.

Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

BACKGROUND: Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. METHODS: Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. RESULTS: Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. CONCLUSION: Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Differentiation of tumor progression and radiation-induced effects after intracranial radiosurgery.

A number of intracranial tumors demonstrate some degree of enlargement after stereotactic radiosurgery (SRS). It necessitates differentiation of their regrowth and various treatment-induced effects. Introduction of low-dose standards for SRS of benign neoplasms significantly decreased the risk of the radiation-induced necrosis after -management of schwannomas and meningiomas. Although in such cases a transient increase of the mass volume within several months after irradiation is rather common, it usually followed by spontaneous shrinkage. Nevertheless, distinguishing tumor recurrence from radiation injury is often required in cases of malignant parenchymal brain neoplasms, such as metastases and gliomas. The diagnosis is frequently complicated by histopathological heterogeneity of the lesion with coexistent viable tumor and treatment-related changes. Several neuroimaging modalities, namely structural magnetic resonance imaging (MRI), diffusion-weighted imaging, diffusion tensor imaging, perfusion computed tomography (CT) and MRI, single-voxel and multivoxel proton magnetic resonance spectroscopy as well as single photon emission CT and positron emission tomography with various radioisotope tracers, may provide valuable diagnostic information. Each of these methods has advantages and limitations that may influence its usefulness and accuracy. Therefore, use of a multimodal radiological approach seems reasonable. Addition of functional and metabolic neuroimaging to regular structural MRI investigations during follow-up after SRS of parenchymal brain neoplasms may permit detailed evaluation of the treatment effects and early prediction of the response. If tissue sampling of irradiated intracranial lesions is required, it is preferably performed with the use of metabolic guidance. In conclusion, differentiation of tumor progression and radiation-induced effects after intracranial SRS is challenging. It should be based on a complex evaluation of the multiple clinical, radiosurgical, and radiological factors.

¹H-MRS of intracranial meningiomas: what it can add to known clinical and MRI predictors of the histopathological and biological characteristics of the tumor?

OBJECTIVE: The main goal of the present study was evaluation of proton magnetic resonance spectroscopy (¹H-MRS) in diagnosis of histopathologically aggressive intracranial meningiomas. METHODS: Single-voxel ¹H-MRS of 100 intracranial meningiomas was performed before their surgical resection. Investigated metabolites included mobile lipids, lactate, alanine, N-acetylaspartate (NAA), and choline-containing compounds (Cho). According to criteria of World Health Organization (WHO) 82 meningiomas were assigned histopathological grade I, 11 grade II, and 7 grade III. The MIB-1 index varied from 0% to 27.3% (median, 1.6%). In 43 cases tight adhesion of the tumor to the pia mater or brain tissue was macroscopically identified at surgery. The consistency of 49 meningiomas was characterized as soft, 26 as hard, and 25 as mixed. RESULTS: No one metabolic parameter had statistically significant association with histopathological grade and subtype, invasive growth, and consistency of meningioma. Univariate statistical analysis revealed greater ¹H-MRS-detected Cho content (P=0.0444) and lower normalized NAA/Cho ratio (P=0.0203) in tumors with MIB-1 index 5% and more. However, both parameters lost their statistical significance during evaluation in the multivariate model along with other clinical and radiological variables. It was revealed that non-benign histopathology of meningioma (WHO grade II/III) is mainly predicted by irregular shape (P=0.0076) and large size (P=0.0316), increased proliferative activity by irregular shape (P=0.0056), and macroscopically invasive growth by prominent peritumoral edema (P=0.0021). CONCLUSION: While ¹H-MRS may be potentially used for the identification of meningiomas with high proliferative activity, it, seemingly, could not add substantial diagnostic information to other radiological predictors of malignancy in these tumors.

Role of proton magnetic resonance spectroscopy in preoperative evaluation of patients with mesial temporal lobe epilepsy.

A retrospective study was conducted for evaluation of the role of single-voxel proton magnetic resonance spectroscopy (1H-MRS) in preoperative investigation of patients with mesial temporal lobe epilepsy (MTLE). Eighteen cases, including both non-lesional and lesional MTLE, were analyzed. Selective amygdalohippocampectomy was performed in 8 cases, selective amygdalohippocampectomy combined with lesionectomy in 6 cases, lesionectomy in 3 cases, and anterior temporal lobe resection in one case. The length of follow-up varied from 24 to 71 months (median, 35 months). Before surgery, (1)H-MRS disclosed decrease of N-acetylaspartate (NAA) content (P=0.01) and more frequent (P=0.07) presence of lactate (Lac) on the side of the epileptogenic zone. Decrease of NAA content below 0.75 and/or unilateral presence of Lac provided 86% (95% CI: 68%-100%) lateralization accuracy. Metabolic parameters did not differ in subgroups with hippocampal sclerosis and brain tumors. On the long-term follow-up 12 patients (67%) were free of disabling seizures. There was a trend (P=0.05) for worse seizure outcome in cases with significant bilateral metabolic alterations characterized by predominance of choline-containing compounds' peak on 1H-MR spectra on both sides. In conclusion, 1H-MRS-detected reduction of NAA content and unilateral presence of Lac in the mesial temporal lobe structures may serve as additional diagnostic clues for lateralization of the epileptogenic zone in MTLE. Metabolic imaging has limited usefulness for differentiation of the hippocampal sclerosis and low-grade intraaxial brain tumor. Presence of significant bilateral metabolic alterations in the mesial temporal lobe structures is associated with worse postoperative seizure control.