Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Meningioma: Molecular Updates from the 2021 WHO Classification of CNS Tumors and Imaging Correlates.

Meningiomas, the most common primary intracranial neoplasms, account for over a third of primary CNS tumors. While traditionally viewed as benign, meningiomas can be associated with considerable morbidity, and specific meningioma subgroups display more aggressive behavior with higher recurrence rates. The risk stratification for recurrence has been primarily associated with the World Health Organization (WHO) histopathological grade and extent of resection. However, a growing body of literature has highlighted the value of molecular characteristics in assessing recurrence risk. While maintaining the previous classification system, the 5th edition of the 2021 WHO CNS tumor (CNS5) book expands upon the molecular information in meningiomas to help guide management. The WHO CNS5 stratifies meningioma into three grades (1-3) based on histopathology criteria and molecular profile. pTERT mutations and CDKN2A/B deletions now signify a grade 3 meningioma with increased recurrence risk. Tumor location also correlates with underlying mutations. Convexity and most spinal meningiomas carry 22q deletion and/or NF2 mutations, while skull base meningiomas have AKT1, TRAF7, SMO, and/or PIK3CA mutations. MRI is the primary imaging modality for diagnosing and treatment planning of meningiomas, while DOTATATE-PET imaging offers supplementary information beyond anatomical imaging. Herein, we review the evolving molecular landscape of meningiomas, emphasizing imaging/genetic biomarkers, and treatment strategies relevant to neuroradiologists.ABBREVIATIONS: AKT1=AKT serine/threonine kinase 1; BAP1=BRCA1-associated protein 1; CDK4/6=Cyclin-dependent kinases 4 and 6; KLF4=Krüppel-like factor 4; NF2=Neurofibromatosis type 2; PIK3CA=Phosphatidylinositol-4,5-Bisphosphate 3-Kinase catalytic subunit alpha; POLR2A=RNA polymerase II subunit A; SMO: Smoothened, frizzled class receptor; SMARCB1=SWItch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1; TERT=Telomerase reverse transcriptase; TRAF7=TNF receptor-associated factor 7.

Glial Fibrillary Acidic Protein Astrocytopathy: Review of Pathogenesis, Imaging Features, and Radiographic Mimics.

Glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described autoimmune inflammatory disorder of the CNS characterized by the presence of specific antibodies targeting the intracellular filament protein in mature astrocytes. The pathogenesis is heterogeneous and poorly understood, with around 20%-34% of cases occurring as a paraneoplastic syndrome, most frequently associated with ovarian teratomas. It presents clinically as acute or subacute encephalomyelitis, and the diagnosis relies on imaging and detection of GFAP-Immunoglobulin (GFAP-IgG) in the CSF. Characteristic imaging findings include linear perivascular enhancement in the white matter extending in a radial pattern. Other imaging findings include periependymal enhancement, longitudinally extensive cord signal changes, intramedullary enhancement, optic neuritis, and papillitis. There is significant imaging overlap with other neuroinflammatory diseases like neuromyelitis optica spectrum disorder and lymphoproliferative conditions. GFAP astrocytopathy is characteristically responsive to steroids with, however, a significant rate of relapse. Currently, literature on this novel entity is limited with no established diagnostic criteria or standard treatment regimen. This comprehensive review explores the clinical, radiographic, and histopathologic aspects of GFAP astrocytopathy, shedding light on its complex nature and potential diagnostic challenges. The paper highlights the neuroimaging findings with a focus on differentiating GFAP astrocytopathy from other neuroinflammatory disorders.

Updates from the International League Against Epilepsy Classification of Epilepsy (2017) and Focal Cortical Dysplasias (2022): Imaging Phenotype and Genetic Characterization.

The International League Against Epilepsy (ILAE) is an organization of 120 national chapters providing the most widely accepted and updated guidelines on epilepsy. In 2022, the ILAE Task Force revised the prior (2011) classification of focal cortical dysplasias to incorporate and update clinicopathologic and genetic information, with the aim to provide an objective classification scheme. New molecular-genetic information has led to the concept of "integrated diagnosis" on the same lines as brain tumors, with a multilayered diagnostic model providing a phenotype-genotype integration. Major changes in the new update were made to type II focal cortical dysplasias, apart from identification of new entities, such as mild malformations of cortical development and cortical malformation with oligodendroglial hyperplasia. No major changes were made to type I and III focal cortical dysplasias, given the lack of significant new genetic information. This review provides the latest update on changes to the classification of focal cortical dysplasias with discussion about the new entities. The ILAE in 2017 updated the classification of seizure and epilepsy with 3 levels of diagnosis, including seizure type, epilepsy type, and epilepsy syndrome, which are also briefly discussed here.

Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma.

Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 WHO (CNS5) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma. Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wildtype and H3-wildtype) as the basic cornerstone, with elimination of the IDH-mutated category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histological features are absent, many lower grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wildtype, astrocytomas to GBM. The three molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/-10); TERT promoter mutation; epidermal growth factor receptor (EGFR) amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wildtype, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 ("molecular GBM") with important prognostic implications. Despite at an early stage, there is active ongoing research on the unique MRI features of molecular GBM. This paper highlights the differences between "molecular" and "histopathological" GBM, with the aim of providing a basic understanding about these changes.ABBREVIATIONS: GBM=Glioblastoma; TERT=telomerase reverse transcriptase; EGFR=epidermal growth factor receptor; MGMT= methylguanine-DNA methyltransferase; NGS= next-generation sequencing; IDH= isocitrate dehydrogenase.

Newly Recognized Genetic Tumor Syndromes of the CNS in the 5th WHO Classification: Imaging Overview with Genetic Updates.

The nervous system is commonly involved in a wide range of genetic tumor-predisposition syndromes. The classification of genetic tumor syndromes has evolved during the past years; however, it has now become clear that these syndromes can be categorized into a relatively small number of major mechanisms, which form the basis of the new 5th edition of the World Health Organization book (beta online version) on genetic tumor syndromes. For the first time, the World Health Organization has also included a separate chapter on genetic tumor syndromes in the latest edition of all the multisystem tumor series, including the 5th edition of CNS tumors. Our understanding of these syndromes has evolved rapidly since the previous edition (4th edition, 2016) with recognition of 8 new syndromes, including the following: Elongator protein complex-medulloblastoma syndrome, BRCA1-associated protein 1 tumor-predisposition syndrome, DICER1 syndrome, familial paraganglioma syndrome, melanoma-astrocytoma syndrome, Carney complex, Fanconi anemia, and familial retinoblastoma. This review provides a description of these new CNS tumor syndromes with a focus on imaging and genetic characteristics.

Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-ß Therapy.

Alzheimer disease (AD) is the most common form of dementia worldwide. Treatment of AD has mainly been focused on symptomatic treatment until recently with the advent and approval of monoclonal antibody (MAB) immunotherapy. U.S. Food and Drug Administration-approved drugs such as aducanumab, as well as upcoming newer-generation drugs, have provided an exciting new therapy focused on reducing the amyloid plaque burden in AD. Although this new frontier has shown benefits for patients, it is not without complications, which are mainly neurologic. Increased use of MABs led to the discovery of amyloid-related imaging abnormalities (ARIA). ARIA has been further classified into two categories, ARIA-E and ARIA-H, representing edema and/or effusion and hemorrhage, respectively. ARIA is thought to be caused by increased vascular permeability following an inflammatory response, leading to the extravasation of blood products and proteinaceous fluid. Patients with ARIA may present with headaches, but they are usually asymptomatic and ARIA is only diagnosable at MRI; it is essential for the radiologist to recognize and monitor ARIA. Increased incidence and investigation into this concern have led to the creation of grading scales and monitoring guidelines to diagnose and guide treatment using MABs. Cerebral amyloid angiopathy has an identical pathogenesis to that of ARIA and is its closest differential diagnosis, with imaging findings being the same for both entities and only a history of MAB administration allowing differentiation. The authors discuss the use of MABs for treating AD, expand on ARIA and its consequences, and describe how to identify and grade ARIA to guide treatment properly. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center See the invited commentary by Yu in this issue.

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies.

Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC0-24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood-brain barrier reaching therapeutic levels in CSF.

Sinonasal Schwannomas: Imaging Findings and Review of Literature.

OBJECTIVE: Schwannomas are common nerve sheath tumors and may occur anywhere in the body. 4% of head and neck schwannomas occur in the sinonasal cavity, and fewer yet have an intracranial component, making these presentations extremely rare. Furthermore, schwannomas present with nonspecific imaging signs and can only be definitively differentiated via histopathologic review, leading to misdiagnosis as various nasal tumors. We aim to conduct a review of published literature on sinonasal schwannomas with and without intracranial extension and provide additional case representations. METHODS: A literature review was conducted using the PubMed Database with the terms "sinonasal schwannoma," "intracranial," "anterior skull base," and "schwannoma." Results were reviewed, and additional cases identified were referenced and included in the study. Inclusion criteria were any case with intracranial extension of the schwannoma. There were no exclusion criteria. Review data was compiled into Excel and used for data analysis and comparison. Additionally, a search was done within our institution to identify additional cases of sinonasal schwannoma. RESULTS: We identified 17 cases of sinonasal schwannoma with intracranial extension, five from our institution and twelve from literature. Analysis revealed: 8 females (47%), 9 males (53%), 9 patients presented with headaches (53%), 6 patients presented with anosmia (35%), 4 patients presented with nasal obstruction (24%), and 2 patients with no symptoms (12%). Mean age and median were 39.4 ± 10.1 and 40, respectively. For treatment, 4 patients underwent endoscopic resection (24%), 11 underwent craniotomy (65%), and data was unavailable for 2 patients. Post-treatment complications occurred in 6 patients, 5 had CSF leaks (29%) and 1 had a hematoma (6%). CONCLUSION: We identified and discussed 17 cases of sinonasal schwannoma with intracranial extension. We hope our review provides insight for clinicians to maintain schwannoma as a potential differential when evaluating nasal and anterior skull base masses.

A novel technique for safe percutaneous biopsy of a petrous apex lesion.

Lesions within the skull base are the most challenging targets for percutaneous biopsy due to the likelihood of encountering a critical structure along any needle trajectory. Due to ICA proximity, the petrous apex is considered unsafe. We describe a novel percutaneous CT-guided approach for biopsying a petrous apex lesion via a contralateral mandibular condylar notch (subzygomatic approach). To our best knowledge, this approach has not been reported and can be safely employed with thorough planning.

Central Vein Sign in Multiple Sclerosis: A Comparison Study of the Diagnostic Performance of 3T versus 7T MRI.

BACKGROUND AND PURPOSE: An early and accurate diagnosis of multiple sclerosis remains challenging in clinical neurology. Established diagnostic methods have less than desirable sensitivity and specificity. An accurate, noninvasive diagnostic test for MS could have a major impact on diagnostic criteria. We compared the frequency of detection of the central vein sign (CVS) in white matter lesions of MS and controls on 7T T2*-weighted and SWI to 3T SWI. Additionally, we assessed the diagnostic performance of 7T T2*, 7T SWI, and 3T SWI for MS. MATERIALS AND METHODS: A retrospective case-control study was performed of patients with MS having both 7T MRI and 3T MRI. A control group of patients without MS was selected. Diagnosis of MS was established by board-certified neurologists with fellowship training in autoimmune neurology in line with the 2017 McDonald criteria. Percentage of lesions with a CVS was blindly measured for each technique. Diagnostic performance was computed by sensitivity, specificity, and positive and negative likelihood ratios (LRs). RESULTS: Sixty-one patients with MS (903 lesions) and 39 controls (1088 lesions) were included. 7T T2* showed significantly more CVS (87%) than both 7T SWI (73%) and 3T SWI (31%) (all P < .001). CVS was identified in the control group in ≤6% of lesions on all sequences. Using a threshold of >40% of lesions with CVS on 7T T2* and >15% on 7T SWI, both sequences had an accuracy = 100%, sensitivity = 100%, specificity = 100%, infinite positive LR, and zero negative LR. Using an optimal threshold of >12%, 3T SWI had an accuracy = 96.0%, sensitivity = 93.4%, specificity = 100%, infinite positive LR, and negative LR = 0.066. CONCLUSIONS: 7T MRI had 100% sensitivity and specificity for the diagnosis of MS and is superior to 3T. Future revisions to MS diagnostic criteria may consider recommendations for 7T MRI and inclusion of CVS as a biomarker.

Spinal gout diagnosed by dual-energy CT: A case report.

Axial gout is an atypical presentation of gout caused by monosodium urate deposition in the axial skeleton. Spinal gout presents nonspecifically and can be a difficult diagnosis. The diagnosis of gout is a clinical one, with imaging and labs providing supporting evidence. Current imaging modalities such as magnetic resonance, computed tomography, and X-ray can be nonspecific and lead to invasive procedures for diagnosis. Dual-energy computed tomography allows clear visualization of urate collection and is a valuable tool to make a confident diagnosis of spinal gout. Here, we present a case of a man with longstanding severe gout in which dual-energy computed tomography played a key role in diagnosis.

Reductions in anxiety, depression and insomnia in health care workers using a non-pharmaceutical intervention.

The COVID-19 pandemic has caused significant medical and psychological challenges worldwide, and not only exceeded the capacity of hospitals and intensive care units but also an individuals' ability to cope with life. Health-care workers have continued to provide care for patients despite exhaustion, fear of transmission to themselves and their family, illness or death of friends and colleagues, and losing many patients. They have also faced additional stress and anxiety due to long shifts combined with unprecedented population restrictions, including personal isolation. In this study, we study the effect of an app-based Yoga of Immortals (YOI) intervention on mental health of healthcare workers. In this study, the health care workers were digitally recruited, and their psychological parameters were measured using validated questionaries. The participants were randomly grouped into control and test groups. The validated psychological measures were the Patient Health Questionnaire-8 (PHQ-8), Insomnia Severity Index (ISI) and generalized anxiety disorder (GAD-7) scales. The digital YOI intervention significantly reduced the anxiety, depression symptoms, and insomnia in healthcare workers of all age groups. In contrast, there was no improvement in the control group. This study details the effectiveness of an app-based YOI intervention in healthcare workers.

Clinical and imaging features of spinal extradural arachnoid cysts: a retrospective study of 50 cases.

PURPOSE: Spinal extradural arachnoid cysts (SEDACs) are thought to arise from leakage of CSF through a spinal dural defect. This study investigates the demographics and imaging spectrum of SEDACs at our academic institution and compares them with those reported in the literature. METHODS: Fifty cases with documented MRI diagnosis of SEDAC, Nabors criteria type I meningeal cyst (MC), were identified from retrospective review of imaging records between 1999 and 2020. Patient demographics, presenting symptoms, cyst characteristics, and management outcomes were studied. Statistical analysis was performed to determine associations between maximum cyst size and presenting symptoms along with other imaging findings. RESULTS: In all 50 subjects, SEDACs were solitary (single) and sporadic (non-familial). The majority were incidental (62%), located posteriorly (92%) and laterally (80%) in the thoracic and thoracolumbar regions (34%, 30%). They were associated with mild mass effect upon the thecal sac (50%) and bone remodeling (92%). Among symptomatic SEDACs, back pain and radiculopathy were the most reported (68%). Larger cysts were located caudally in the spinal canal, and were associated with greater thecal mass effect, bone remodeling, and septations. Four out of six subjects who underwent surgical management had complete or partial remission. One had cyst recurrence. CONCLUSION: In this largest series of SEDACs, most were discovered incidentally, stable over time, and located in the thoracic spine dorsal to the thecal sac. When symptomatic, back pain and radiculopathy were the most common presenting symptoms. Treatment with complete surgical excision may yield the best results for symptomatic lesions.

Plain language summary: use of isavuconazole in Chinese patients with an invasive fungal disease.

WHAT IS THIS SUMMARY ABOUT?: Invasive aspergillosis (also known as IA) is a type of fungal infection, caused by a species of fungus called Aspergillus, that can be life threatening. Isavuconazole and voriconazole belong to a group of antifungal drugs called triazoles that are recommended for treating IA. In the USA and in Europe, isavuconazole is approved for treating patients with IA. In China, isavuconazole was recently being reviewed for approval for treating patients with IA. This study looked at whether isavuconazole works in the same way in healthy Chinese people as it does in healthy Western people. It also looked to see how well isavuconazole works and how many side effects it has compared with voriconazole in Chinese patients with IA. WHAT WERE THE RESULTS?: The results of this study showed that healthy Chinese people's bodies processed isavuconazole the same way as healthy Western people's bodies. The amount of drug in people's bodies did not change how well the drug worked or how many side effects there were. Isavuconazole worked as well as and had a similar number of side effects as voriconazole in treating Chinese patients with IA. WHAT DO THE RESULTS OF THE STUDY MEAN?: These findings show that isavuconazole may be a suitable treatment for Chinese patients with IA using the same dose that is used in Western patients.