Postmortem brain 7T MRI with minimally invasive pathological correlation in deceased COVID-19 subjects

Background Brain abnormalities are a concern in COVID-19, so we used minimally invasive autopsy (MIA) to investigate it, consisting of brain 7T MR and CT images and tissue sampling via transethmoidal route with at least three fragments: the first one for reverse transcription polymerase chain reaction (RT-PCR) analysis and the remaining fixed and stained with hematoxylin and eosin. Two mouse monoclonal anti-coronavirus (SARS-CoV-2) antibodies were employed in immunohistochemical (IHC) reactions. Results Seven deceased COVID-19 patients underwent MIA with brain MR and CT images, six of them with tissue sampling. Imaging findings included infarcts, punctate brain hemorrhagic foci, subarachnoid hemorrhage and signal abnormalities in the splenium, basal ganglia, white matter, hippocampi and posterior cortico-subcortical. Punctate brain hemorrhage was the most common finding (three out of seven cases). Brain histological analysis revealed reactive gliosis, congestion, cortical neuron eosinophilic degeneration and axonal disruption in all six cases. Other findings included edema (5 cases), discrete perivascular hemorrhages (5), cerebral small vessel disease (3), perivascular hemosiderin deposits (3), Alzheimer type II glia (3), abundant corpora amylacea (3), ischemic foci (1), periventricular encephalitis foci (1), periventricular vascular ectasia (1) and fibrin thrombi (1). SARS-CoV-2 RNA was detected with RT-PCR in 5 out of 5 and IHC in 6 out 6 patients (100%). Conclusions Despite limited sampling, MIA was an effective tool to evaluate underlying pathological brain changes in deceased COVID-19 patients. Imaging findings were varied, and pathological features corroborated signs of hypoxia, alterations related to systemic critically ill and SARS-CoV-2 brain invasion.

Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54–0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

A Clinical Semantic and Radiomics Nomogram for Predicting Brain Invasion in WHO Grade II Meningioma Based on Tumor and Tumor-to-Brain Interface Features

BackgroundBrain invasion in meningioma has independent associations with increased risks of tumor progression, lesion recurrence, and poor prognosis. Therefore, this study aimed to construct a model for predicting brain invasion in WHO grade II meningioma by using preoperative MRI.MethodsOne hundred seventy-three patients with brain invasion and 111 patients without brain invasion were included. Three mainstream features, namely, traditional semantic features and radiomics features from tumor and tumor-to-brain interface regions, were acquired. Predictive models correspondingly constructed on each feature set or joint feature set were constructed.ResultsTraditional semantic findings, e.g., peritumoral edema and other four features, had comparable performance in predicting brain invasion with each radiomics feature set. By taking advantage of semantic features and radiomics features from tumoral and tumor-to-brain interface regions, an integrated nomogram that quantifies the risk factor of each selected feature was constructed and had the best performance in predicting brain invasion (area under the curve values were 0.905 in the training set and 0.895 in the test set).ConclusionsThis study provided a clinically available and promising approach to predict brain invasion in WHO grade II meningiomas by using preoperative MRI.

Pediatric meningioma with rhabdoid features developed at the site of skull fracture: illustrative case

BACKGROUND Pediatric meningiomas are rare, and only a few cases attributed to trauma and characterized by development at the site of bone fracture have been reported. Both pediatric and traumatic meningiomas have aggressive characteristics. OBSERVATIONS An 11-year-old boy who sustained a head injury resulting from a left frontal skull fracture 8 years previously experienced a convulsive attack. Imaging revealed a meningioma in the left frontal convexity. Total removal of the tumor with a hyperostotic section was successfully achieved. Intraoperative investigation showed tumor invasion into the adjacent frontal cortex. Histologically, the surgical specimen revealed a transitional meningioma with brain invasion and a small cluster of rhabdoid cells. This led to a final pathological diagnosis of an atypical meningioma with rhabdoid features. The postoperative course was uneventful, and no recurrence of the tumor was found after 2 years without adjuvant therapy. LESSONS This is the first report of a pediatric meningioma with rhabdoid features occurring at the site of a skull fracture. Meningiomas that contain rhabdoid cells without malignant features are not considered to be as aggressive as rhabdoid meningiomas. However, the clinical course must be carefully observed for possible long-term tumor recurrence.

The neurosurgical management of sinonasal malignancies involving the anterior skull base: a 28-year experience at The MD Anderson Cancer Center

OBJECTIVE Sinonasal malignancies that extend to the anterior skull base frequently require neurosurgical intervention. The development of techniques for craniofacial resection revolutionized the management of these neoplasms, but modern and long-term data are lacking, particularly those related to the incorporation of endoscopic techniques and novel adjuvant chemotherapeutics into management schema. The present study was performed to better define the utility of surgical management and to determine factors related to outcome. METHODS Patients who underwent surgery between 1993 and 2020 were included in this retrospective cohort study. Only patients with greater than 6 months of clinical and radiological follow-up were included. Outcome measures included progression, survival, and treatment-related complications. RESULTS Two hundred twenty-five patients were included. The mean clinical follow-up was 6.5 years. The most common histological diagnosis was olfactory neuroblastoma (33%). Overall, metastatic disease and brain invasion were present in 8% and 19% of patients, respectively, at the time of surgery. A lumbar drain was used in 54% of patients. When stratified by decade, higher-stage disease at surgery became more frequent over time (15% of patients had metastatic disease in the 3rd decade of the study period vs 4% in the 1st decade). Despite the inclusion of patients with progressively higher-stage disease, median overall survival (OS) remained stable in each decade at approximately 10 years (p = 0.16). OS was significantly worse in patients with brain invasion (p = 0.006) or metastasis at the time of surgery (p = 0.014). Complications occurred after 28% of operations, but typically resulted in no long-term negative sequelae. Use of a lumbar drain was a significant predictor of complications (p = 0.02). Permanent ophthalmological disabilities were observed after 4% of surgical procedures. One patient died during the perioperative period. Finally, major complications (Clavien-Dindo grade ≥ IIIb) decreased from 27% of patients in the 1st decade to 10% in the 3rd decade (p = 0.007). CONCLUSIONS The surgical management of sinonasal malignancies with anterior skull base involvement is effective and generally safe. Surgical management, however, is only one facet of the overall multimodal management paradigms created to optimize patient outcomes. Survival outcomes have remained stable despite more extensive disease at surgery in patients who have presented in recent decades. The safety of such surgery has improved over time owing to the incorporation of endoscopic surgical techniques and the avoidance of lumbar spinal drainage with open resection.

Immunohistochemical expression of HGF and cMET in meningiomas

Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlike gliomas they are still graded according to their histopathological picture. Many growth factors and tyrosine kinase receptors have been studied in meningiomas in an attempt for prognostic stratification of patients, also to find a suitable targeted therapy for meningiomas. Aim of the study To correlate the immunohistochemical expression of HGF and cMET with the different WHO grades of meningioma in addition to brain invasion. Materials and methods This study included 60 cases of meningiomas (WHO grade I, n = 30 and WHO grade II & III, n = 30), brain invasion was present in 14 cases. Results HGF, cMET & HGF/cMET co-expression were positive in 60.0%, 65.0% and 58.3% respectively of the cases; WHO grade I meningioma showed positivity in 30.0%, 33.3% and 30.0% of the cases respectively in contrast with 90.0%, 96.7% and 86.7% of the cases of WHO grades II & III meningiomas respectively. The relation was statistically highly significant (p- value: &lt;0.001). As regards cases with brain invasion the expression of HGF, cMET and HGF/cMET co-expression was found in 92.9%, 100.0% and 92.9% respectively in comparison with 50.0%, 54.3% and 47.8% in the rest of the cases of meningiomas respectively; the relation was statistically significant (p- value: 0.004). Conclusion The results suggest that HGF/cMET pathway may play a role in the progression of meningiomas from WHO grade I to higher grades II & III.

The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensin-converting enzyme (ACE2) expression cells. Of interest herein is the ability of the virus to exhibit neurotropism. However, there is limited information on how this virus invades the brain. With this contribution, we explore how, in the context of a microbial co-infection using a cryptococcal co-infection as a model, SARS-CoV-2 could reach the brain. We theorise that the secretion of proteases by disseminated fungal cells might also activate the S2 domain of the viral spike glycoprotein for membrane fusion with brain endothelial cells leading to endocytosis. Understanding this potential invasion mechanism could lead to better SARS-CoV-2 intervention measures, which may also be applicable in instances of co-infection, especially with protease-secreting pathogens.