Quantification of tumor induced motor cortical plasticity using navigated transcranial magnetic stimulation in patients with adult-type diffuse gliomas.

Introduction: The evaluation of brain plasticity can provide relevant information for the surgical planning of patients with brain tumors, especially when it comes to intrinsic lesions such as gliomas. Neuronavigated transcranial magnetic stimulation (nTMS) is a non-invasive tool capable of providing information about the functional map of the cerebral cortex. Although nTMS presents a good correlation with invasive intraoperative techniques, the measurement of plasticity still needs standardization. The present study evaluated objective and graphic parameters in the quantification and qualification of brain plasticity in adult patients with gliomas in the vicinity of the motor area. Methods: This is a prospective observational study that included 35 patients with a radiological diagnosis of glioma who underwent standard surgical treatment. nTMS was performed with a focus on the motor area of the upper limbs in both the affected and healthy cerebral hemispheres in all patients to obtain data on motor thresholds (MT) and graphical evaluation by three-dimensional reconstruction and mathematical analysis of parameters related to the location and displacement of the motor centers of gravity (ΔL), dispersion (SDpc) and variability (VCpc) of the points where there was a positive motor response. Data were compared according to the ratios between the hemispheres of each patient and stratified according to the final pathology diagnosis. Results: The final sample consisted of 14 patients with a radiological diagnosis of low-grade glioma (LGG), of which 11 were consistent with the final pathology diagnosis. The normalized interhemispheric ratios of ΔL, SDpc, VCpc, and MT were significantly relevant for the quantification of plasticity (p < 0.001). The graphic reconstruction allows the qualitative evaluation of this plasticity. Conclusion: The nTMS was able to quantitatively and qualitatively demonstrate the occurrence of brain plasticity induced by an intrinsic brain tumor. The graphic evaluation allowed the observation of useful characteristics for the operative planning, while the mathematical analysis made it possible to quantify the magnitude of the plasticity.

Role of neutrophil-lymphocyte ratio as a predictive factor of glioma tumor grade: A systematic review.

Gliomas are the main type of intra-axial primary brain tumors. We performed a systematic review of studies on the neutrophil-to-lymphocyte ratio (NLR) and its role in the prognosis of patients with gliomas. An English-language literature-based search, using the PubMed and Biblioteca Virtual em Saúde databases, was conducted for papers published until May 2, 2020. The quality of the selected articles was stratified using the Newcastle-Ottawa scale's criteria. We found 137 publications for a query string. After applying the inclusion criteria, 13 articles were selected. Seven studies assessed overall survival and found high NLR values associated with poor overall survival. Six studies approached the issue of tumor grading and differential diagnosis and demonstrated that patients with high NLR values were diagnosed with high-grade gliomas. NLR is a low-cost method and an effective prognostic factor associated with tumor grading and OS in patients with gliomas.

Is neutrophil-lymphocyte ratio a useful tool for predicting outcome in subarachnoid hemorrhage? A systematic review.

Ruptured intracranial aneurysms, as the leading cause of spontaneous subarachnoid hemorrhage (aSAH), represents an emergency with high morbi-mortality. The comprehension of the underlying pathology that involves inflammatory and immune responses, through the neutrophil-to-lymphocyte ratio (NLR), could help to predict complications such as delayed cerebral ischemia (DCI) or rebleeding and the functional outcome. Systematic review of English-based literature through PubMed and Biblioteca Vitural em Saúde (BVS) to find papers discussing the use of NLR in the aSAH setting. Area-under-curve (AUC) of receiver operating characteristics (ROC), cutoff value, sensitivity, and specificity were retrieved. From 53 articles included, 4 papers were evaluated after exclusion criteria. Rebleeding could be predicted with a NLR cutoff value of 9.88 (sensitivity 72.3%, specificity 63.3%). The mean cutoff value for DCI was 12.85, with sensitivity 66.3% and specificity 75.8%. Finally, a worse 3-month functional outcome could be predicted with a mean sensitivity of 73.3% and a mean specificity of 54%. NLR is a new issue in scientific community, especially neurosurgery. The current understanding points to a multifactorial process after aSAH that emerges as alterations on the NLR. As a measurement readily available and cost-effect after admission of the patient, its use signals that patients that need expedite surgical treatment or more aggressive treatment for vasospasm. As other medical subspecialties already use this ratio to predict outcomes, the literature reviewed by this paper constitute the earliest clues that higher NLR predicts re-bleeding, DCI, and functional outcome.

Clinical outcome assessments of motor status in patients undergoing brain tumor surgery.

INTRODUCTION: Clinical outcome assessment (COA) is an important instrument for testing the effectiveness of treatments and for supporting healthcare professionals on decision-making. This review aims to assess the use of COAs, and the evaluation time points of motor status in patients with brain tumor (BT) undergoing surgery. METHODS: We performed a scoping review through MEDLINE, EMBASE, and LILACS databases, looking for original studies in primary or secondary BT, having motor function status as the primary outcome. EXCLUSION CRITERIA: mixed sample, BT recurrence, and an unspecific description of motor deficits evaluation. RESULTS: Nine studies met the eligibility criteria. There were 449 patients assessed. A total of 18 scales evaluated these BT patients, 12 performance outcomes measures (PerfO) tested motor function. Four scales were the clinician-reported outcome measures (ClinRO) found in this review, two assessed performance status, and two rated ambulation. Two patient-reported outcome measures (PRO) appraised functionality. CONCLUSIONS: A variety of instruments were used to assess BT patients. Rehabilitation studies are more likely to associate the use of PerfO and PRO concerning motor and functional status. The use of specific validated scales to the BT population was rare. The lack of a standardized approach hampers the quality of BT patient's assessment.

Multiple and mirror intracranial aneurysms: study of prevalence and associated risk factors.

OBJECTIVE: Multiple intracranial aneurysms (MIA) account for 30% of all intracranial aneurysms, while mirror aneurysms, a subgroup of MIA, are present in 5% of all patients with cerebral aneurysms. We investigated the risk factors associated with the presence of multiple and mirror intracranial aneurysms. METHODS: 1404 patients, 314 males (22.4%) and 1090 female (77.6%) were enrolled for this study. Diagnosis was performed with a digital subtraction angiography (DSA). Multiplicity was defined as the presence of two or more aneurysms and mirror aneurysms as one pair of aneurysms involving bilateral corresponding arteries. Patients were followed-up from September 2009 till August 2018. Individuals' characteristics such as sex, age, smoking, hypertension and use of contraceptives were evaluated. RESULTS: Five hundred and twelve patients (36.4%) were diagnosed with MIA, approximately 4%/year. We observed 203 pairs of mirror aneurysms, accounting for 406 aneurysms (13% of the population). There was an increased frequency of females with multiple (p < 0.001, OR = 1.883, 95% CI = 1.386-2.560) and mirror aneurysms (p < 0.001, OR = 2.828, 95% CI = 1.725-4.636). Smoking was associated with multiplicity (p< 0.001, OR = 1.458, 95% CI = 1.160-1.833), as well as advanced age (p < 0.001, OR = 1.938, 95% CI = 1.438-2.611), but there was no significant relation with presence of mirror aneurysms. We observed higher frequency of baby aneurysms (<3mm) in the group of patients with MIA, while giant aneurysms (>25 mm) were most found in patients with only one aneurysm (p < 0.001). No differences between patients who used contraceptives against patients who did not use were found (p = 0.600). CONCLUSIONS: Gender and smoking, known risk factors to the development of a single intracranial aneurysm, are proportionally increased in patients with MIA. Hypertension and oral contraceptives were not associated with multiplicity.

A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18, IL17A, and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease.

Background: Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism profiles and cardiomyopathy or T. cruzi parasitemia, as well as the impact of HIV infection on cardiopathy. Methods: Two hundred twenty-six patients and 90 control individuals were analyzed. IL1B rs1143627 T>C, IL6 rs1800795 C>G, IL17A rs2275913 G>A, IL18 rs187238 C>G, and IL18 rs1946518 C>A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by PCR. Results: Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The IL6 rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between IL17A rs2275913 AA and IL18 s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). IL18 rs1946518 AA and IL1B rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for IL18 rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively). Conclusions: Our data support a protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the IL6 CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.

Cavernous carotid aneurysms do not influence the occurrence of upstream ipsilateral aneurysm.

OBJECTIVE: Cavernous carotid aneurysms (CCA) comprehend around 5% of all intracranial aneurysms. The main risk factors for an intracranial aneurysm seem not to influence the incidence of CCAs. The aim of this study was to investigate the association of CCAs and the presence of upstream aneurysms. METHODS: 1403 patients, admitted in Hospital das Clinicas de São Paulo, Brazil, from September 2009 to August 2018, enrolled this study. Diagnosis was performed with Digital Subtraction Angiography (DSA). Upstream aneurysm was defined as an intracranial aneurysm on anterior cerebral circulation, ipsilateral to the CCA (if present) or crossing the midline (e.g. anterior communicating artery). RESULTS: 177 individuals were diagnosed with CCA (12.6% of the population), totalizing 225 aneurysms (10% of the total number of aneurysms, 2253). No association was found between CCA and UA (p= .090, OR: 1.323, 95% CI: 0.957-1.828). Studying only patients with CCA, multivariable analysis showed smoking as the only factor associated with UA (p= .010, OR: 0.436, 95% CI: 0.232-0.821). CONCLUSIONS: Cavernous carotid aneurysms were present in 12% of our population, mostly in female. They seem to be independent of the modifiable risk factors already associated with intracranial aneurysms. A higher frequency of mirror aneurysms was seen in this location. CCA did not influence the presence of ipsilateral and anterior circulation aneurysms.

Polymorphism in the Promoter Region of the IL18 Gene and the Association With Severity on Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by Paracoccidioides spp. This mycosis has been associated with high morbidity and sequels, and its clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host. The T helper(Th)1 and Th17/Th22 cells are related to resistance and control of infection, and a Th2/Th9 response is associated with disease susceptibility. In this study, we focused on interleukin(IL)-12p35 (IL12A), IL-18 (IL18), and IFN-γ receptor 1 (IFNGR1) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze IL12A-504 G/T (rs2243115), IL18-607 C/A (rs1946518), and IFNGR1-611 A/G (rs1327474) single nucleotide polymorphisms (SNP). One hundred forty-nine patients with the acute form (AF), multifocal chronic (MC), or unifocal chronic (UC) forms of PCM and 110 non-PCM individuals as a control group were included. In the unconditional logistic regression analysis adjusted by ethnicity and sex, we observed a high risk of the IL18-607 A-allele for both AF [p = 0.015; OR = 3.10 (95% CI: 1.24-7.77)] and MC groups [p = 0.023; OR = 2.61 (95% CI: 1.14-5.96)] when compared with UC. The IL18-607 A-allele associated risk for the AF and MC groups as well as the protective role of the C-allele in UC are possibly linked to higher levels of IL-18 at different periods of the course of the disease. Therefore, a novel role of IL18-607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.

Evaluation of Changes in Preoperative Cortical Excitability by Navigated Transcranial Magnetic Stimulation in Patients With Brain Tumor.

Background: This prospective study aimed to evaluate the cortical excitability (CE) of patients with brain tumors surrounding or directly involving the corticospinal tract (CST) using navigated transcranial magnetic stimulation (nTMS). Methods: We recruited 40 patients with a single brain tumor surrounding or directly involving the CST as well as 82 age- and sex-matched healthy controls. The patients underwent standard nTMS and CE evaluations. Single and paired pulses were applied to the primary motor area (M1) of both affected and unaffected cerebral hemispheres 1 week before surgery. The CE parameters included resting motor threshold (RMT), motor evoked potential (MEP) ratio for 140 and 120% stimulus (MEP 140/120 ratio), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Motor outcome was evaluated on hospital discharge and on 30-day and 90-day postoperative follow-up. Results: In the affected hemispheres of patients, SICI and ICF were significantly higher than in the unaffected hemispheres (p=0.002 and p =0.009, respectively). The 140/120 MEP ratio of patients' unaffected hemispheres was lower than that in controls (p=0.001). Patients with glioblastomas (GBM) had a higher interhemispheric RMT ratio than patients with grade II and III gliomas ( p = 0.018). A weak correlation was observed among the RMT ratio and the preoperative motor score (R 2 = 0.118, p = 0.017) and the 90-day follow-up ( R 2 = 0.227, p = 0.016). Conclusion: Using preoperative nTMS, we found that brain hemispheres affected by tumors had abnormal CE and that patients with GBM had a distinct pattern of CE. These findings suggest that tumor biological behavior might play a role in CE changes.

Adjuvant Radiotherapy Did Not Reduce Recurrence of World Health Organization Grade I Meningiomas with Venous Sinus Involvement: A Propensity Score Adjusted Analysis and Literature Review.

BACKGROUND: Most meningiomas are classified as World Health Organization (WHO) grade I. Adjuvant radiation therapy (RT) is commonly recommended for subtotal resections with documented progressive regrowth of lesions with venous sinus involvement. We investigated if recurrence of WHO grade I meningiomas was influenced by adjuvant RT. METHODS: From 2000 to 2014, patients with grade I meningiomas with at least one venous sinus involvement and at least 4 years of follow-up were included. Demographics, venous sinus involvement, histology, and extent of resection (EOR) were characterized. Because patients undergoing RT tend to differ from those for whom adjuvant therapy was not prescribed, we used propensity scores to adjust for confounding variables. RESULTS: Sixty-two patients were included; of these, 18 (29.0%) had recurrences. The mean age was 52.8 ± 12.3 years, and 79.0% were women. A total of 34 cases (54.8%) were submitted to adjuvant RT. Adjuvant RT was more frequent in those who had tumor recurrence (77.8% vs. 45.5%, P = 0.020). RT was more frequent in superior sagittal sinus (SSS) invasion (76.5% vs. 50.0%, P = 0.030) and less prevalent after gross total resection (GTR) (32.4% vs. 67.9%, P = 0.005). Propensity score adjusted analysis suggested no adjuvant RT benefit (odds ratio [OR], 2.51; 95% confidence interval [CI], 0.68-9.28; P = 0.167), independent of the EOR. SSS involvement increased recurrence risk (OR, 12.69; 95% CI, 1.46-110.27; P = 0.021), whereas GTR tended to decrease it (OR, 0.26; 95% CI, 0.06-1.09; P = 0.065). CONCLUSIONS: Adjuvant RT does not seem to be a pivotal criterion to reduce the recurrence rate in patients with grade I meningioma, even when venous sinuses are involved.