Monday, February 25, 2013

Estimating and communicating prognosis in advanced neurologic disease

Prognosis can no longer be relegated behind diagnosis and therapy in high-quality neurologic care. High-stakes decisions that patients (or their surrogates) make often rest upon perceptions and beliefs about prognosis, many of which are poorly informed. The new science of prognostication—the estimating and communication "what to expect"—is in its infancy and the evidence base to support "best practices" is lacking. We propose a framework for formulating a prediction and communicating "what to expect" with patients, families, and surrogates in the context of common neurologic illnesses. Because neurologic disease affects function as much as survival, we specifically address 2 important prognostic questions: "How long?" and "How well?" We provide a summary of prognostic information and highlight key points when tailoring a prognosis for common neurologic diseases. We discuss the challenges of managing prognostic uncertainty, balancing hope and realism, and ways to effectively engage surrogate decision-makers. We also describe what is known about the nocebo effects and the self-fulfilling prophecy when communicating prognoses. There is an urgent need to establish research and educational priorities to build a credible evidence base to support best practices, improve communication skills, and optimize decision-making. Confronting the challenges of prognosis is necessary to fulfill the promise of delivering high-quality, patient-centered care.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline

Objective:

In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors.

Methods:

Neurocognitive assessment at baseline included Trail Making Tests A/B, a modified Rey-Osterreith Complex Figure, California or Hopkins Verbal Learning Test, Digit Span, and Controlled Oral Word Association. DVH analysis was performed for multiple neuroanatomical targets considered to be involved in cognition. The %v10 (percent of ROI receiving 10 Gy), %v40, and %v60 were calculated for each ROI. Factor analysis was used to estimate global cognition based on a summary of performance on individual cognitive tests. Stepwise regression was used to determine which dose volume predicted performance on global factors and individual neurocognitive tests for each ROI.

Results:

Regions that predicted global cognitive outcomes at doses <60 Gy included the corpus callosum, left frontal white matter, right temporal lobe, bilateral hippocampi, subventricular zone, and cerebellum. Regions of adult neurogenesis primarily predicted cognition at %v40 except for the right hippocampus which predicted at %v10. Regions that did not predict global cognitive outcomes at any dose include total brain volume, frontal pole, anterior cingulate, right frontal white matter, and the right precentral gyrus.

Conclusions:

Modeling of radiation-induced cognitive decline using neuroanatomical target theory appears to be feasible. A prospective trial is necessary to validate these data.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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Sunday, February 24, 2013

Instagram Neurosurgery Blog more 2,000 followers #medicine #medicina #neurosurgery #neurocirurgia #medstudent #neurology

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Thursday, February 21, 2013

Stereotactic Radiosurgical Salvage Treatment for Locally Recurrent Esthesioneuroblastoma

imageBACKGROUND: Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor considered to be radiation sensitive. Local recurrence may be treated in a variety of ways, including stereotactic radiosurgery (SRS); however, little information on its effectiveness is available. OBJECTIVE: To determine whether SRS is effective in providing local control for recurrent ENB. METHODS: This was a retrospective single-institution experience including 109 patients with ENB treated at the Mayo Clinic (1962-2009). Sixty-three patients presented with Kadish stage C disease, and 21 patients developed local recurrence. Of these 21 patients, 7 patients underwent SRS at our institution and an additional patient underwent SRS after transnasal biopsy. Therefore, a total of 8 patients are reported. RESULTS: The median age at time of local recurrence was 50 years. All patients had Kadish C disease at initial diagnosis. Six of 8 patients were found to have Hyams grade 3 disease; the remaining 2 patients had grade 2 disease. The median treatment volume was 8.4 cm3 (mean, 18.9 cm3; range, 1.4-76.3 cm3), and the median dose to the tumor margin was 15 Gy (mean, 14.4 ± 2.2 Gy; range, 10-18 Gy). Of the 16 treatments, 13 had adequate follow-up to assess treatment response, with 92% achieving local control over a median follow-up of 42 months from the time of SRS. Five lesions decreased in size, 7 lesions stabilized, and only 1 lesion had in-field progression. There were no documented complications secondary to SRS. CONCLUSION: SRS appears to be a reasonable and safe option for treatment of intracranial recurrence of ENB. ABBREVIATIONS: EBRT, external beam radiotherapy ENB, esthesioneuroblastoma SRS, stereotactic radiosurgery







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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New Gene Identified That Causes Inherited Spinal Meningiomas

Genetic medicine experts from Manchester Biomedical Research Centre at Saint Mary's Hospital and The University of Manchester have identified a new gene responsible for causing an inherited form of tumour, known as spinal meningioma. Professor Richard Marias, Director of the Paterson Institute Meningiomas are the commonest form of tumour affecting the brain and spine...







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
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Brain Metastases from Esophageal Cancer- Clinical Review of 26 Cases

Available online 19 February 2013
Publication year: 2013
Source:World Neurosurgery

Objective For the rarity incidence, patients with esophageal cancer metastasized to the central nervous system have rarely reported. The aim of our study was to assess the frequency of brain metastasis from primary esophageal cancer, and to detect the clinical characteristics, diagnosis and prognosis. Methods A retrospective analysis of the medical files was carried out in a series of 26 consecutive patients with central nervous system involvement treated at our institution between 2000 and 2010 from 1612 esophageal primary carcinoma. The clinical history, image, and pathologic findings were analyzed. Results Among the 26 patients, 12 initially presented with a single cerebral metastatic lesion, and 14 had multiple brain lesions. There were 4 patients with adenocarcinoma, 22 with squamous cell carcinoma. Five of them received surgery followed with whole brain radiation, 5 underwent stereotactic radiosurgery, and 13 received whole brain radiation, 3 patients received chemotherapy treatment. The median survival period was 4.2 months, one year survival rate was 5.8%. Conclusions This retrospective study of 1612 patients with esophageal carcinoma at a single medical centre, indicated that 1.61% (26/1612) of these patients had a diagnosis of brain metastasis. The prognosis is poor for the brain metastasis of esophageal carcinoma. Solitary brain lesion, surgery and good KPS may indicate a well prognosis. 








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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[18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that gl

Background

To assess the sensitivity and specificity of [18F]-fluoro-ethyl-l-tyrosine (18F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.

Methods

We retrospectively evaluated 18F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). 18F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).

Results

Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed 18F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher 18F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). 18F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.

Conclusions

18F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood–brain barrier and 18F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis

Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor–related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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Wednesday, February 20, 2013

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Júlio Leonardo B. Pereira
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Monday, February 11, 2013

Primary adult infradiaphragmatic craniopharyngiomas: Clinical features, management and outcomes in o

Available online 8 February 2013
Publication year: 2013
Source:World Neurosurgery

Objective : This study was designed to evaluate the clinical, radiologic, histologic and surgical outcome characteristics of this disease treated in a single institution. Methods : 16 adult patients underwent trans-sphenoidal microsurgery from October 2005 to December 2010 at Neurosurgical Center of Beijing Tiantan Hospital. The clinical, radiological, operative, and pathological findings of the patients were reviewed retrospectively. Results : Pituitary dysfunction was presented in 12 patients, visual acuity and/or field deterioration was found in 11 patients, and headache was complained in 8 patients. Hyperprolactinemia was presented in 7 of 9 female patients. All lesions were resected by transsphenoidal microsurgery as the primary procedure.A GTR was achieved in 3 of 16 patients, a radical subtotal resection was attained in the rest 13 patients. 9 cases were histologically classified as adamantinous subtype. After a mean follow-up of 50 months, 2 patients experienced recurrence. All female patients who had hyperprolactinemia experienced a gain of function postoperatively. 6 patients experienced new diabetes insipidus. Visual field improved or normalized in 8 of 9 patients. Visual acuity improved in 1 cases and worsened in 1 patient. Conclusion : Primary adult infradiaphagmic craniopharyngiomas are relatively rare lesions occurring in young adults. Pituitary dysfunction, visual acuity and/or field deterioration and headache were the most common chief symptoms. Transsphenoidal surgery, including tearing the cyst walls off the diaphragma sellae and protecting normal pituitary tissue as much as possible, is recommended. Though at the risk of impairing the function of anterior pituitary ,trans-sphenoidal surgery results in a high rate of both visual field and hyperprolactinemia improvement with a low associated risk of recurrence. In terms of pathological aspects, the adamantinous subtype was more common.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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Clinicopathological study of pineal parenchymal tumors of intermediate differentiation (PPTID)

Available online 8 February 2013
Publication year: 2013
Source:World Neurosurgery

Object Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities and only limited data are available regarding their pathologic features and biologic behaviors. Because grading criteria of pineal parenchymal tumors (PPTs) has yet to be established, the treatment strategy and prognosis of PPTIDs remain controversial. We describe the clinicopathological study of six patients with PPTID and compare responses for the treatment and prognosis with cases of pineocytoma (PC) and pineoblastoma (PB). From this analysis, we attempt to clarify the treatment strategy for PPTIDs. Methods This study included 15 patients with PPTs, consisting of 6 PCs, 6 PPTIDs, and 3 PBs. We focused on the six patients with PPTIDs. All PPTID cases were treated surgically and radiotherapy and chemotherapy were administered as adjuvant therapies in some cases. For histopathological study, we have already reported.8 Briefly, we examined mitotic figures and necrosis by H&E staining and immunohistochemical markers such as neuronal markers (synaptophysin (SY), neurofilament (NF), and NeuN) and a MIB-1 labeling index (LI) was determined. Results In the PPTID cases, the extent of resection was variable and the recurrence rates among patients varied according to stage and treatment. All PC patients underwent total resection with no recurrence. All PB patients underwent resection and adjuvant therapy with radiotherapy and chemotherapy. There were no recurrences in patients with PC or PB. The results of histopathological findings have been already reported.8 Briefly, the results indicated no mitotic figure or necrosis in any of the six cases of PPTID, but those features were observed in PB cases. All cases even including PC and PB were immunopositive for neuronal markers. The MIB-1 LI of PPTID was 3.5%, whereas that was 0% in PC and 10.5% in PB. Conclusions Good radiosensitivity of PPTIDs was observed in our series. Because there are cases with discrepancies between images and pathological findings, it is very difficult to determine the proper treatment strategy for PPTIDs. Proliferative potential was correlated with WHO grade, although the immunoreactivity of neuronal markers did not correlate with the histological grade.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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Clinical Outcomes of Gamma Knife Radiosurgery in the Salvage Treatment of Patients with Recurrent Hi

Available online 9 February 2013
Publication year: 2013
Source:World Neurosurgery

Background Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external-beam radiation therapy and chemotherapy when compared to patients treated with external-beam radiation therapy and chemotherapy alone. In recent years, Gamma Knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of Gamma Knife radiosurgery for patients who suffer from this malignancy. Methods Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing Gamma Knife radiosurgery for patients with high-grade glioma were reviewed. Results After assessing patient age, Karnofsky Performance Status, tumor histology, and extent of resection, Gamma Knife radiosurgery is a viable, minimally-invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that Gamma Knife radiosurgery provides patients with a high local tumor control rate and a median survival following tumor recurrence ranging from 13 to 26 months. Gamma Knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated Gamma Knife radiosurgery due to its potential to limit treatment-associated morbidity. Conclusions Gamma Knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating patients in specific clinical situations.








Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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An Updated Assessment of the Risk of Radiation Induced Neoplasia Following Radiosurgery of Arteriove

Available online 9 February 2013
Publication year: 2013
Source:World Neurosurgery

Object Gamma Knife radiosurgery (GKRS) is a minimally invasive technique employed in the treatment of intracranial arteriovenous malformations (AVM's). Patients experience a low incidence of complications following treatment. As the long-term follow-up data became available, some late adverse effects have been reported. However, the exact incidence of radiosurgically induced neoplasia is not known. Methods At UVA, imaging and clinical outcomes of 1309 patients with intracranial AVM's treated with GKRS have been reviewed. AVM patients underwent magnetic resonance imaging (MRI's) every 6 months for 2 years and then annually following GKRS. When the nidi were no longer visible on MRI, angiography was performed to verify the obliteration of AVM's. Patients were thereafter recommended to continue MRI's every 3-5 years to detect any long-term complications. A subset of 812, 358, and 78 patients had neuro-imaging and clinical follow-up of at least 3, 10, and 15 years respectively. Results The authors report the occurrence of 3 cases of radiosurgically induced neoplasia. More than 10 years after GKRS, 2 patients were found to have an incidental, uniformly enhancing, dural based mass lesion near the site of the AVM with radiological characteristics of a meningioma. As the lesions have shown no evidence of mass effect, they are being followed with serial neuro-imaging. A third patient was found to have neurological decline from a tumor in immediate proximity to an AVM previously treated with proton beam radiosurgery and GKRS. The patient underwent resection demonstrating a high grade glioma. The 3, 10, and 15-year incidence of a radiation-induced tumor is 0% (0/812), 0.3% (1/358), and 2.6% (2/78) respectively. The cumulative rate of radiosurgically induced tumors in those with a minimum of 10 year follow up is 3 in 4692 person-years or 64 in 100,000 person-years. Thus, patients had a 0.64% chance of developing a radiation induced tumor within 10 or more years following GKRS. If we calculate rates based on a subset of 78 patients with neuro-imaging and clinical follow-up of at least 15 years, the cumulative rate was 3.4%. These are the 2nd, 3rd, and 5th reported cases of radiation induced tumors following GKRS for an AVM. Conclusions Although radiosurgery is generally considered a safe modality in the treatment of AVM's, radiation induced neoplasia is a rare but serious adverse event. The possibility of GKRS induced tumors underscores the necessity of long-term follow-up in AVM patients receiving radiosurgery.








Júlio Leonardo B. Pereira
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An MRI technique to evaluate tumor–brain adhesion in meningioma: Brain-surface motion imaging

Available online 9 February 2013
Publication year: 2013
Source:World Neurosurgery

Objective We examined the effectiveness of a newly-developed magnetic resonance imaging (MRI) technique, brain surface motion imaging (BSMI), in the preoperative evaluation of tumor-brain adhesion in meningioma surgery. Methods Cine phase-contrast MRI was used to measure cerebrospinal fluid (CSF) pulsations and heart rates at two different time points to create a subtraction image in meningioma patients who underwent BSMI. With no tumor-brain adhesion, a gap was observed in the tumor-brain movements resulting in an outline of the tumor in BSMI. If adhesion was evident, no outline was observed. Patients were evaluated as "exact" if the presence or absence of edema in T2-weighted MR images, BSMI findings, and intraoperative findings all matched, as "effected" when only BSMI findings and intraoperative images matched, and as "false" when BSMI findings and intraoperative findings did not match. Results BSMI judged 27 patients as "adhesion (+)" and 33 as "adhesion (-)", while surgical findings evaluated 22 as "adhesion (+)" and 38 as "adhesion (-)". The sensitivity and specificity were both high, at 95.5% and 84.2%, respectively. Forty-one of 60 patients were evaluated as "exact," 12 as "effected", and seven as "false". World Health Organization tumor grade assessment of "effected" subjects included 16.7% in grade 1 and 36.4% in grade 2. Conclusion BSMI was shown to be effective in evaluating adhesion between the meningioma and the brain, allowing safe and effective removal planning to be carried out preoperatively.








Júlio Leonardo B. Pereira
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Wednesday, February 6, 2013

Data in trials and their published papers do not always agree, finds analysis

An analysis that compared clinical trial documents that were released because of a lawsuit with the corresponding papers published in medical journals has generated further concern about the...







Júlio Leonardo B. Pereira
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Cancer's caregiver crisis of control

We hear that a loved one has cancer, and we're suddenly terrified, dazed, confused and physically stricken. The initial cancer diagnosis throws most cancer caregivers into an immediate crisis of control.







Júlio Leonardo B. Pereira
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Imaging Biomarker Dynamics in an Intracranial Murine Glioma Study of Radiation and Antiangiogenic Th

Purpose: There is a growing need for noninvasive biomarkers to guide individualized spatiotemporal delivery of radiation therapy (RT) and antiangiogenic (AA) therapy for brain tumors. This study explored early biomarkers of response to RT and the AA agent sunitinib (SU), in a murine intracranial glioma model, using serial magnetic resonance imaging (MRI).Methods and Materials: Mice with MRI-visible tumors were stratified by tumor size into 4 therapy arms: control, RT, SU, and SU plus RT (SURT). Single-fraction conformal RT was delivered using MRI and on-line cone beam computed tomography (CT) guidance. Serial MR images (T2-weighted, diffusion, dynamic contrast-enhanced and gadolinium-enhanced T1-weighted scans) were acquired biweekly to evaluate tumor volume, apparent diffusion coefficient (ADC), and tumor perfusion and permeability responses (Ktrans, Kep).Results: Mice in all treatment arms survived longer than those in control, with a median survival of 35 days for SURT (P<.0001) and 30 days for RT (P=.009) and SU (P=.01) mice vs 26 days for control mice. At Day 3, ADC rise was greater with RT than without (P=.002). Sunitinib treatment reduced tumor perfusion/permeability values with mean Ktrans reduction of 27.6% for SU (P=.04) and 26.3% for SURT (P=.04) mice and mean Kep reduction of 38.1% for SU (P=.01) and 27.3% for SURT (P=.02) mice. The magnitude of individual mouse ADC responses at Days 3 and 7 correlated with subsequent tumor growth rate R values of −0.878 (P=.002) and −0.80 (P=.01), respectively.Conclusions: Early quantitative changes in diffusion and perfusion MRI measures reflect treatment responses soon after starting therapy and thereby raise the potential for these imaging biomarkers to guide adaptive and potentially individualized therapy approaches in the future.







Júlio Leonardo B. Pereira
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The Role of Postoperative Radiation Therapy in the Treatment of Meningeal Hemangiopericytoma—Experie

Purpose: The aim of this study was to examine the effect of postoperative radiation therapy (RT) on cause-specific survival in patients with meningeal hemangiopericytomas.Methods and Materials: The Surveillance, Epidemiology, and End Results database from 1990-2008 was queried for cases of surgically resected central nervous system hemangiopericytoma. Patient demographics, tumor location, and extent of resection were included in the analysis as covariates. The Kaplan-Meier product-limit method was used to analyze cause-specific survival. A Cox proportional hazards regression analysis was conducted to determine which factors were associated with cause-specific survival.Results: The mean follow-up time is 7.9 years (95 months). There were 76 patients included in the analysis, of these, 38 (50%) underwent gross total resection (GTR), whereas the other half underwent subtotal resection (STR). Postoperative RT was administered to 42% (16/38) of the patients in the GTR group and 50% (19/38) in the STR group. The 1-year, 10-year, and 20-year cause-specific survival rates were 99%, 75%, and 43%, respectively. On multivariate analysis, postoperative RT was associated with significantly better survival (HR = 0.269, 95% CI 0.084-0.862; P=.027), in particular for patients who underwent STR (HR = 0.088, 95% CI: 0.015-0.528; P<.008).Conclusions: In the absence of large prospective trials, the current clinical decision-making of hemangiopericytoma is mostly based on retrospective data. We recommend that postoperative RT be considered after subtotal resection for patients who could tolerate it. Based on the current literature, the practical approach is to deliver limited field RT to doses of 50-60 Gy while respecting the normal tissue tolerance. Further investigations are clearly needed to determine the optimal therapeutic strategy.







Júlio Leonardo B. Pereira
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Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tu

Journal of Neurosurgery, Volume 118, Issue 2, Page 243-249, February 2013.
Object Awake craniotomy for removal of intraaxial tumors within or adjacent to eloquent brain regions is a well-established procedure. However, awake craniotomy failures have not been well characterized. In the present study, the authors aimed to analyze and assess the incidence and causes for failed awake craniotomy. Methods The database of awake craniotomies performed at Tel Aviv Medical Center between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if conversion to general anesthesia was required, or if adequate mapping or monitoring could not have been achieved. Results Of 488 patients undergoing awake craniotomy, 424 were identified as having complete medical, operative, and anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these 424 patients were considered failures. The main causes of failure were lack of intraoperative communication with the patient (n = 18 [4.2%]) and/or intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p < 0.001) and treatment with phenytoin (p = 0.0019) were related to failure due to lack of communication. History of seizures (p = 0.03) and treatment with multiple antiepileptic drugs (p = 0.0012) were found to be related to failure due to intraoperative seizures. Compared with the successful awake craniotomy group, a significantly lower rate of gross-total resection was achieved (83% vs 54%, p = 0.008), there was a higher incidence of short-term speech deterioration postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was longer (4.9 ± 6.2 days vs 8.0 ± 10.1 days, p < 0.001). Significantly more major complications occurred in the failure group (4 [14.8%] of 27) than in the successful group (16 [4%] of 397) (p = 0.037). Conclusions Failures of awake craniotomy were associated with a lower incidence of gross-total resection and increased postoperative morbidity. The majority of awake craniotomy failures were preventable by adequate patient selection and avoiding side effects of drugs administered during surgery.







Júlio Leonardo B. Pereira
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Potential intracranial applications of magnetic resonance–guided focused ultrasound surgery

Journal of Neurosurgery, Volume 118, Issue 2, Page 215-221, February 2013.
Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.







Júlio Leonardo B. Pereira
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Seizure outcome of surgical treatment of focal epilepsy associated with low-grade tumors in children

Journal of Neurosurgery: Pediatrics, Volume 11, Issue 2, Page 214-223, February 2013.
Object Low-grade tumor (LGT) is an increasingly recognized cause of focal epilepsies, particularly in children and young adults, and is frequently associated with cortical dysplasia. The optimal surgical treatment of epileptogenic LGTs in pediatric patients has not been fully established. Methods In the present study, the authors retrospectively reviewed 30 patients (age range 3–18 years) who underwent surgery for histopathologically confirmed LGTs, in which seizures were the only clinical manifestation. The patients were divided into 2 groups according to the type of surgical treatment: patients in Group A (20 cases) underwent only tumor removal (lesionectomy), whereas patients in Group B (11 cases) underwent removal of the tumor and the adjacent epileptogenic zone (tailored surgery). One of the patients, who underwent 2 operations, is included in both groups. Follow-up ranged from 1 to 17 years. Results Sixteen (80%) of 20 patients in Group A had an Engel Class I outcome. In this group, 3 of 4 patients who were in Engel Classes II and III had temporomesial lesions. All patients in Group B had temporomesial tumors and were seizure free (Engel Class I). In this series, in temporolateral and extratemporal tumor locations, lesionectomy yielded a good seizure outcome. In addition, a young age at seizure onset (in particular < 4 years) was associated with a poor seizure outcome. Conclusions Tailored resection in temporomesial LGTs was associated with excellent seizure outcome, indicating that an adequate presurgical evaluation including extensive neurophysiological evaluation (long-term videoelectroencephalography monitoring) to plan appropriate surgical strategy is advised.







Júlio Leonardo B. Pereira
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Recurrent pediatric central nervous system low-grade gliomas: the role of surveillance neuroimaging

Journal of Neurosurgery: Pediatrics, Volume 11, Issue 2, Page 119-126, February 2013.
Object Pediatric low-grade glioma (LGG) is the most common brain tumor of childhood. Except for the known association of gross-total resection and improved survival rates, relatively little is known about the clinical and radiographic predictors of recurrent disease and the optimal frequency of surveillance MRI. The authors sought to determine the clinical and radiographic features associated with recurrent or progressive disease in a single-institutional series of children diagnosed with primary CNS LGG. Methods The authors performed a retrospective analysis of data obtained in 102 consecutive patients diagnosed at Rady Children's Hospital–San Diego between 1994 and 2010 with a biopsy-proven LGG exclusive of a diagnosis of neurofibromatosis. Tumor location, patient age, sex, and symptomatology were correlated with tumor progression or recurrence. Magnetic resonance imaging characteristics and neuroimaging surveillance frequency were analyzed in those children with progressive or recurrent disease. Results Forty-six of 102 children diagnosed with an LGG had evidence of recurrent or progressive disease between 2 months and 11 years (mean 27.3 months) after diagnosis. In the larger group of 102 children, gross-total resection was associated with improved progression-free survival (p = 0.012). The location of tumor (p = 0.26), age at diagnosis (p = 0.69), duration of symptoms (p = 0.72), histological subtype (p = 0.74), sex (p = 0.53), or specific chemotherapeutic treatment regimen (p = 0.24) was not associated with tumor progression or recurrence. Sixty-four percent of children with recurrent or progressive disease were asymptomatic, and recurrence was diagnosed by surveillance MRI alone. All children less than 2 years of age in whom the tumor was diagnosed were asymptomatic at the time of progression (p = 0.04). Thirteen percent (6 of 46) of the children had disease recurrence 5 years after initial diagnosis; all of them had undergone an initial subtotal resection. Tumor progression was associated with either homogeneous or patchy T1-weighted post–Gd administration MRI enhancement in 94% of the cases (p = 0.0001). Conclusions Children diagnosed with recurrent LGG may be asymptomatic at the time of recurrence. The authors' findings support the need for routine neuroimaging in a subset of children with LGGs, even when gross-total resection has been achieved, up to 5 years postdiagnosis. The authors found that T1-weighted MR images obtained before and after Gd administration alone may be sufficient to diagnose LGG recurrence and may represent an effective strategy worthy of further validation in a larger multiinstitutional cohort.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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The Cancer Genome Atlas expression profiles of low-grade gliomas

Neurosurgical Focus, Volume 34, Issue 2, Page E8, February 2013.
Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic inter

Neurosurgical Focus, Volume 34, Issue 2, Page E9, February 2013.
Object The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence. Methods On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development. Results The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment. Conclusions The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low

Neurosurgical Focus, Volume 34, Issue 2, Page E7, February 2013.
Object Low-grade gliomas (LGGs) are indolent tumors that have the potential to dedifferentiate into malignant high-grade tumors. Recent studies have demonstrated that cerebellar low-grade tumors have a better prognosis than supratentorial tumors, although no study has focused on the risk factors for poor prognosis in cerebellar LGGs in adults. The authors of the current study aimed to address both of these concerns by using a large cohort derived from a national cancer registry and a smaller cohort derived from their institution's experience. Methods Adults with diagnosed Grade I and Grade II gliomas of the cerebellum were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox proportional hazard models were used to predict rates of survival, and the log-rank test was applied to evaluate differences in Kaplan-Meier survival curves. An institutional cohort was created by isolating all patients whose surgical pathology revealed an LGG of the cerebellum. Excluded from analysis were patients in whom a glioma was first diagnosed under the age of 18 years and those whose tumors could not be definitively determined to arise from the cerebellum. Results Data from the local cohort (11 patients) demonstrated that the most common presenting symptom was headache, which occurred in more than 70% of the cohort. Approximately half of the patients in this cohort had symptomatic improvement after treatment. Results from the SEER cohort (166 patients) revealed that adults with Grade I gliomas were slightly younger than those with Grade II tumors (p < 0.01), but no other demographic differences were observed. Patients with Grade I tumors were twice as likely to undergo gross-total resection (54% vs 21%), and those with Grade II gliomas were much more likely to receive postoperative radiation (3% vs 48%). Five-year survival was greater in the patients with Grade I gliomas than in those with Grade II lesions (91% vs 70%). Multivariate analysis revealed that an age ≥ 40 years (HR 7.30, 95% CI 3.55–15.0, p < 0.0001) and Grade II tumors (HR 2.76, 95% CI 1.12–6.84, p = 0.028) were risk factors for death, whereas female sex was protective (HR 0.28, 95% CI 0.14–0.59, p < 0.001). Log-rank tests revealed that a cerebellar location was protective (p < 0.0001), but this relationship was only true for Grade II tumors (p < 0.0001). Survival in patients with Grade I gliomas was not different based on the various lesion locations (p = 0.21). Conclusions Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved survival in patients with cerebellar Grade II gliomas.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
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The molecular biology of WHO Grade II gliomas

Neurosurgical Focus, Volume 34, Issue 2, Page E1, February 2013.
The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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Intraoperative cortical mapping of visuospatial functions in parietal low-grade tumors: changing per

Neurosurgical Focus, Volume 34, Issue 2, Page E4, February 2013.
Object The aim of this study was to explore the feasibility of intraoperative visuospatial mapping with the same criteria currently used to define essential language areas. Methods The authors compared surgical procedures in 2 patients with similar tumors (Grade II oligodendroglioma in the right parietal lobe) undergoing awake, image-assisted surgery for lesion removal with intraoperative neurophysiological monitoring. The line bisection task was used in both patients but with different criteria. Results In the first case, the authors respected any area, even within the tumor, where significant interference was found (a stimulation-induced error in 2 of 3 applications defined an essential area). In the second case, they removed 1 essential area located in the tumor and recorded an uneventful clinical response soon thereafter. They continued to monitor the patient without stimulation and stopped the resection when the patient was close to the criteria valid for defining spatial neglect. The signs of spatial neglect were present for 3 days postoperatively and then cleared spontaneously. Subtotal tumor removal was achieved in both cases. Conclusions Evidence in the present study reveals that areas for visuospatial functions cannot be assessed with the same criteria used for language functions, since essential areas located in the tumor can be safely removed.







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
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