Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma.

OBJECTIVE: The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcriptome, and protein expressions. METHODS: The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequencing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry. RESULTS: The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningiomas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expression of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. CONCLUSIONS: The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predictive of survival and exhibited significant correlations with EZH2 expression.

Assessing the Capabilities of Transcranial Magnetic Stimulation (TMS) to Aid in the Removal of Brain Tumors Affecting the Motor Cortex: A Systematic Review.

Introduction: The brain tumor is frequently related to severe motor impairment and impacts the quality of life. The corticospinal tract can sometimes be affected depending on the type and size of the neoplasm, so different tools can evaluate motor function and connections. It is essential to organize surgical procedures and plan the approach. Functional motor status is mapped before, during, and after surgery. Studying corticospinal tract status can help map the functional areas, predict postoperative outcomes, and help the decision, reducing neurological deficits, aiming to preserve functional networks, using the concepts of white matters localization and fibbers connections. Nowadays, there are new techniques that provide functional information regarding the motor cortex, such as transcranial magnetic stimulation (TMS), direct cortical stimulation (DCS), and navigated TMS (nTMS). These tools can be used to plan a customized surgical strategy and the role of motor evoked potentials (MEPs) is well described during intra-operative, using intraoperative neuromonitoring. MEPs can help to localize primary motor areas and delineate the cut-off point of resection in real-time, using direct stimulation. In the post-operative, the MEP has increased your function as a predictive marker of permanent or transitory neurological lesion marker. Methods: Systematic review performed in MEDLINE via PUBMED, EMBASE, and SCOPUS databases regarding the post-operative assessment of MEP in patients with brain tumors. The search strategy included the following terms: (("Evoked Potentials, Motor"[Mesh]) AND "Neoplasms"[Mesh]) AND "Transcranial Magnetic Stimulation"[Mesh] AND "Brain Tumor"[Mesh]), the analysis followed the PRISMA guidelines for systematic reviews, the review spanned until 06/04/2021, inclusion criteria were studies presenting confirmed diagnosis of brain tumor (primary or metastatic), patients >18 y/o, using TMS, Navigated TMS, and/or Evoked Potentials as tools in preoperative planning or at the intra-operative helping the evaluation of the neurological status of the motor cortex, articles published in peer-reviewed journals, and written in English or Portuguese. Results: A total of 38 studies were selected for this review, of which 14 investigated the potential of nTMS to predict the occurrence of motor deficits, while 25 of the articles investigated the capabilities of the nTMS technique in performing pre/intraoperative neuro mapping of the motor cortex. Conclusion: Further studies regarding motor function assessment are needed and standardized protocols for MEPs also need to be defined.

Evaluation of Computed Tomography Scoring Systems in the Prediction of Short-Term Mortality in Traumatic Brain Injury Patients from a Low- to Middle-Income Country.

The present study aims to evaluate the accuracy of the prognostic discrimination and prediction of the short-term mortality of the Marshall computed tomography (CT) classification and Rotterdam and Helsinki CT scores in a cohort of TBI patients from a low- to middle-income country. This is a post hoc analysis of a previously conducted prospective cohort study conducted in a university-associated, tertiary-level hospital that serves a population of >12 million in Brazil. Marshall CT class, Rotterdam and Helsinki scores, and their components were evaluated in the prediction of 14-day and in-hospital mortality using Nagelkerk's pseudo-R 2 and area under the receiver operating characteristic curve. Multi-variate regression was performed using known outcome predictors (age, Glasgow Coma Scale, pupil response, hypoxia, hypotension, and hemoglobin values) to evaluate the increase in variance explained when adding each of the CT classification systems. Four hundred forty-seven patients were included. Mean age of the patient cohort was 40 (standard deviation, 17.83) years, and 85.5% were male. Marshall CT class was the least accurate model, showing pseudo-R 2 values equal to 0.122 for 14-day mortality and 0.057 for in-hospital mortality, whereas Rotterdam CT scores were 0.245 and 0.194 and Helsinki CT scores were 0.264 and 0.229. The AUC confirms the best prediction of the Rotterdam and Helsinki CT scores regarding the Marshall CT class, which presented greater discriminative ability. When associated with known outcome predictors, Marshall CT class and Rotterdam and Helsinki CT scores showed an increase in the explained variance of 2%, 13.4%, and 21.6%, respectively. In this study, Rotterdam and Helsinki scores were more accurate models in predicting short-term mortality. The study denotes a contribution to the process of external validation of the scores and may collaborate with the best risk stratification for patients with this important pathology.

Dural-based lesions: is it a meningioma?

PURPOSE: Meningiomas are the most common extra-axial intracranial neoplasms with typical radiological findings. In approximately 2% of cases, histopathological reports reveal different neoplasms or non-neoplastic lesions that can closely mimic meningiomas. We describe radiological features of meningioma mimics highlighting imaging red flags to consider a differential diagnosis. METHODS: A total of 348 lesions with radiological diagnosis of meningiomas which underwent to surgical treatment or biopsy between December of 2000 and September of 2014 were analyzed. We determined imaging features that are not a typical finding of meningiomas, suggesting other lesions. The following imaging characteristics were evaluated on CT and MRI: (a) bone erosion; (b) hyperintensity on T2WI; (c) hypointensity on T2WI; (d) bone destruction; (e) dural tail; (f) leptomeningeal involvement; (g) pattern of contrast enhancement; (h) dural displacement sign. RESULTS: We have a relatively high prevalence of meningioma mimics (7.2%). Dural-based lesions with homogeneous contrast enhancement (52%) are easily misdiagnosed as meningiomas. Most lesions mimic convexity (37.5%) or parafalcine (21.9%) meningiomas. We have determined five imaging red flags that can alert radiologists to consider meningioma mimics: (1) bone erosion (22.2%); (2) dural displacement sign (36%); (3) marked T2 hypointensity (32%); (4) marked T2 hyperintensity (12%); (5) absence of dural tail (48%). The most common mimic lesion in our series was hemangiopericytomas, followed by lymphomas and schwannomas. CONCLUSION: The prevalence of meningioma mimics is not negligible. It is important to have awareness on main radiological findings suggestive of differential diagnosis due to a wide range of differentials which lead to different prognosis and treatment strategies.

Cognitive Assessment in Patients with Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health problem inWestern countries. ATBI brings many negative consequences, including behavioral and cognitive changes, which affect social adjustment and the performance of functional activities. Cognitive evaluation after TBI is a complex issue in what pertains to definition of the most appropriate questionnaires for clinical use in a comprehensive analysis of the condition of the patient. In this paper, we described a critical review of the main cognitive assessment tests currently used in clinical and research settings in patients with TBI.

Rare acute idiopathic subdural hematoma: A case report and literature review.

BACKGROUND: Acute spontaneous subdural hematoma is rare. For patients under 40 years of age, we found only five previous reports. Here, we have presented a sixth case study. CASE DESCRIPTION: A 27-year-old male initially presented with a high-intensity headache without any neurological deficits. The brain computed tomography revealed a left frontoparietal lesion, consistent with an acute epidural hematoma. However, the bone window examination showed no fracture, and at surgery, this lesion proved to be an acute subdural hematoma. Additional studies, including cerebral angiography, brain magnetic resonance imaging, and a complete coagulation work-up, were all negative. CONCLUSION: This case report and literature review focused on the rarity of acute idiopathic/spontaneous subdural hematomas.

Evaluation of Head Computed Tomography Assessment of Brain Swelling after Acute Traumatic Brain Injury: A Pilot study

Objective To evaluate the interobserver reliability of a new scale created for quantitatively assessing brain swelling in traumatic brain injury (TBI) patients using the computed tomography (CT) findings in three levels. Methods Computed tomography scans of severe head injury patients were randomly selected from a tertiary hospital image database and evaluated by independent groups of neurosurgeons, neurosurgery residents, radiologists, and intensivists from the same hospital. Each specialist assessed the tomographic findings, applying zero to six points in a new scale. The Kappa coefficient was calculated to assess interobserver agreement. Results The highest reliability coefficient was obtained by the neurosurgeons group (0.791; 95% confidence interval [CI]: 0.975­0.607; p < 0.001), followed by the neurosurgery residents group (0.402; 95%CI: 0.569­0.236; p < 0.001) and by the radiologists group (0.301; 95%CI: 0.488­0.113; p < 0.002). The lowest coefficient was found among the intensivists (0.248; 95%CI: 0.415­0.081; p » 0.004). Conclusion The proposed scale showed good reliability among neurosurgeons, and moderate overall reliability. This tomographic classification might be useful to better assist severe TBI victims, allowing to identify the worsening or amelioration of brain swelling, which should be further investigated. The scale seems to be feasible, even in low income countries,where the costof intracranial pressure (ICP)monitoring is higher than thatofCTs.

Computed tomography angiography accuracy in brain death diagnosis.

OBJECTIVE: The present study was designed to answer several concerns disclosed by systematic reviews indicating no evidence to support the use of computed tomography angiography (CTA) in the diagnosis of brain death (BD). Therefore, the aim of this study was to assess the effectiveness of CTA for the diagnosis of BD and to define the optimal tomographic criteria of intracranial circulatory arrest. METHODS: A unicenter, prospective, observational case-control study was undertaken. Comatose patients (Glasgow Coma Scale score ≤ 5), even those presenting with the first signs of BD, were included. CTA scanning of arterial and venous vasculature and transcranial Doppler (TCD) were performed. A neurological determination of BD and consequently determination of case (BD group) or control (no-BD group) was conducted. All personnel involved with assessing patients were blinded to further tests results. Accuracy of BD diagnosis determined by using CTA was calculated based on the criteria of bilateral absence of visualization of the internal cerebral veins and the distal middle cerebral arteries, the 4-point score (4PS), and an exclusive criterion of absence of deep brain venous drainage as indicated by the absence of deep venous opacification on CTA, the venous score (VS), which considers only the internal cerebral veins bilaterally. RESULTS: A total of 106 patients were enrolled in this study; 52 patients did not have BD, and none of these patients had circulatory arrest observed by CTA or TCD (100% specificity). Of the 54 patients with a clinical diagnosis of BD, 33 met the 4PS (61.1% sensitivity), whereas 47 met the VS (87% sensitivity). The accuracy of CTA was time related, with greater accuracy when scanning was performed less than 12 hours prior to the neurological assessment, reaching 95.5% sensitivity with the VS. CONCLUSIONS: CTA can reliably support a diagnosis of BD. The criterion of the absence of deep venous opacification, which can be assessed by use of the VS criteria investigated in this study, can confirm the occurrence of cerebral circulatory arrest.Clinical trial registration no.: 12500913400000068 (clinicaltrials.gov).

Chronic subdural hematoma with sudden clinical uncal herniation and coma: case report

Context: Chronic subdural hematomas are frequent diseases in neurosurgery units. Decreased level of consciousness is observed in 28 to 100 percent of cases, nevertheless in rare cases are seen comatous patients. We describe a case of a patient with clinical uncal herniation elapsed by a chronic subdural hematoma. Case report: Patient with previous diagnosis of breast cancer, presented sudden occurrence of a headache followed by decreasing level of consiousness the day before reaching our service. The patient was taken than to another Hospital at 1:00 AM in Glasgow Coma Scale (GCS) 13, with isochonic pupils. At 7:00 AM the GCS went to 7 and the pupils became anisochonic L > R and than transferred to our Unit and immediatly submitted to a computed tomohraphy scanning of the head that showed a chronic subdural hematoma with midline shift. The patient promptly was taken to surgical room and treated with a single burr hole with drainage of hypertensive chronic subdural hematoma. The level of consiousness increased few hours after surgery, being in GCS 15 just 6 hours after, without motor deficits. Conclusion: In spite of commonly progressive evolution chronic subdural hematomas can present with herniation, becoming itself a neurosurgical emergency.